LAW: Getting Soft on “Hard” Drugs?

The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

Early in the 20th Century, what are now called controlled substances were regularly available for retail purchase. Over the course of the last 100 years, the regulation of many drugs has become stricter and, since 1970, are subject to the restraints of the Controlled Substances Act. In 1996, some states began easing restrictions on the use and possession of marijuana. More recently, many municipalities and a few states (and some counties) have decriminalized the possession of an increasing number of controlled substances. This continuing education activity will review the national and international regulatory oversight of controlled substances and discuss the characteristics of some of the recent international, state, and local actions that have reduced penalties and continue the trend towards a more public health emphasis on drug control.

INTRODUCTION

Congress, in order to reduce the black market in illegal drugs, should begin taking incremental steps toward making drugs less of a criminal justice responsibility and more of a public health responsibility.¹

--Former Baltimore Mayor Kurt L. Schmoke

Has the time arrived for the incremental steps that Mayor Schmoke envisioned more than 30 years ago? One does not need to look any further than marijuana, which has been a tightly controlled substance in the U.S. for more than 85 years but is rapidly gaining acceptance as a medical product and a permissible intoxicant.^2,3 It is likely that many pharmacists are supportive of this regulatory movement and may even have “experimented” with this Schedule I drug while in school. But what about something like cocaine? “That won’t happen,” you say? Then you should be aware that Oregon passed a law in 2020 that reduced the penalty for the unauthorized possession of less than two grams of cocaine to the payment of a small fine.⁴

Other states, municipalities, and countries have also begun taking steps towards loosening or eliminating penalties for prohibited recreational substances, in some cases including other drugs currently listed in Schedule I of the Controlled Substances Act (CSA). Is this the start of a new national trend leading to a relaxation of restrictions on previously controlled substance and perhaps even to someday permit retail sales? Will the future of drug control start to look more like the 1890s than the 1990s?

This continuing education activity will review national and international regulation of controlled substances and some changes that governments are enacting or considering to loosen their control. Do these events indicate that society’s view of controlled substances and use disorders—and pharmacy’s role—are evolving?

Pause and Ponder: Will biennial controlled substance inventories and the familiar red “C” go the way of manual typewriters and become relics of a bygone era?

REGULATION OF CONTROLLED SUBSTANCES

Historical Perspective

In the 19^th Century, what we now call controlled substances were readily available in retail locations. In the 1890s, the Sears and Roebuck catalog (that’s the 19^th Century Amazon for our younger readers) offered a syringe and a small amount of cocaine for purchase for $1.50⁵ (equivalent to about $50 today). Individuals could also order the tonic, Wine of Coca, a mixture of coca-leaf extract and Bordeaux wine, which was promoted as “a genuine rich wine ... well known throughout Europe for its strengthening and nourishing qualities” at retail for 95 cents.⁵ In addition to cocaine, consumers could also openly purchase morphine and heroin from catalogs, apothecaries, and physicians.⁵

The popularity of cocaine-infused beverages, tonics, and powders grew in the late 1800s, and were generally held to have therapeutic value for a variety of conditions, including headache and fatigue, constipation, nausea, asthma, and impotence.⁶ Most pharmacy personnel are probably aware that a pharmacist in Atlanta, John Pemberton, took advantage of prohibition being enacted in parts of Georgia and replaced the wine in Wine of Coca with a sugary syrup and added a kola-nut extract containing caffeine in 1886.⁷ He named the concoction Coca-Cola and described it as a temperance drink.⁷

Although frequently denied by the company, Coca-Cola contained a small amount of cocaine (and likely the precursor, ecgonine) and became one of the world’s most popular tonic/beverage sold at retail, often at pharmacy soda fountains.^6,8 Early in the 20^th Century, public opinion about cocaine began to turn negative and the company (by then owned by another pharmacist, Asa Candler), tried to remove cocaine from the beverage but it would not become completely cocaine-free until 1929 when newer extraction methods were developed.⁶

Recently, the well-known billionaire, Elon Musk, jokingly(?) tweeted “Next I’m buying Coca-Cola to put the cocaine back in.”⁸ Current legislative changes discussed below suggest that this notion is not so far-fetched.

During the early part of the 20^th Century, there were no federal agencies that regulated medical and pharmacy practice, and physicians could freely prescribe cocaine and morphine as treatment for pain.⁹ Drug abuse became increasingly common and emerged as a significant social and public health issue, and a less permissive attitude towards drugs began to take hold.⁹

The first federal law to ban the non-medical use of a substance was the Smoking Opium Exclusion Act in 1909; it prohibited the possession, importation, and use of opium for smoking, although it could continue to be used medically.¹⁰ A more significant step was the passage of the Harrison Narcotic Tax Act in 1914 which regulated “narcotics” (defined as opiates and cocaine) by imposing a special tax upon anyone who produced, imported, manufactured, sold, dispensed, distributed, or compounded these substances.¹¹ Note that the act was an economic regulation to comply with treaty obligations and did not directly prohibit the use nor sale of opiates and cocaine.¹

The Harrison Act required physicians and pharmacists who prescribed or dispensed “narcotics” to be registered and pay a fee of $1 to $24 per year^11,12 (equivalent to $29 to $700 today). The act mandated special order forms and record keeping whenever narcotic drugs were sold. They could only be provided from packages bearing a government stamp.¹²

By using the federal government’s taxing power to restrict the use of opiates to professional practices, the Harrison Act effectively created the first class of prescription drugs.¹¹ (The Food Drug and Cosmetic Act in 1938 formally established prescription-only drugs and the 1951 Durham-Humphrey Act [sponsored by two pharmacist-legislators] gave the U.S. Food and Drug Administration (FDA) authority to designate which drugs would require prescriptions.¹³)

After 1919, oversight by the Treasury Department expanded to define the scope of professional practice.¹¹ Previously, physicians interpreted terms in the act such as “legitimate medical purposes,” “professional practice,” and “prescribed in good faith” to mean that they could provide narcotics to ease the suffering of withdrawal in addicts who were regarded as having a disease.¹² However, the Treasury Department interpreted the Harrison Act to mean that any prescription for an addict for the purpose of relieving the trauma of addiction was illegal, and the Courts supported this position.¹² Consequently, the only source available for an addict to obtain narcotics was through illegal means.¹²

The law also established the first federal narcotics agents, although their enforcement powers were limited. The Federal Bureau of Narcotics (FBN) was established in 1930 and was given the authority to enforce the Harrison Act and other anti-drug laws and later also oversaw the Marijuana Tax Act (see below).¹⁴ President Herbert Hoover appointed Harry J. Anslinger to be Commissioner of Narcotics, a position he would hold under four U.S. presidents for more than three decades. He became the face of the government’s hardline approach to eradicate drug abuse.¹⁴

Later, the 18^th Amendment of the Constitution and the Volstead Act banned the manufacture, transportation, or sale of alcohol in 1919.^10,15 (By this time, many states had already banned the sale of alcohol.) Prohibition was overturned by the 21^st Amendment in 1933.

By 1930, 30 states had also prohibited the use of marijuana, beginning with California in 1913 and Utah in 1914.¹⁶ (Ironically, California became the first state to approve the medical use of marijuana 83 years later.) In 1937, Congress passed the Marihuana Tax Act which was modeled after the Harrison Act.⁵⁵ The law didn’t specifically criminalize the use or possession of marijuana, but it required practitioners register and pay a tax, and imposed a fine of up to $2000 (about $40,000 today) and five years in prison for non-payment.^10,17 There is a widely held feeling that the push for stricter control of marijuana was fueled by non-health concerns. Those concerns included

commercial interests
anti-immigrant and racial bias
exaggerated fear about violence and crime
hysteria about the drug’s alleged contribution to moral decay, and
pressure from the Federal Bureau of Narcotics

All of these factors played major roles in the push for stricter control of marijuana.^17,18 Such feelings persist today and are part of the effort towards deregulation. The Act was ruled unconstitutional in 1969 in a suit brought by Harvard psychology professor and psychedelic guru, Timothy Leary.¹⁹

Today, drugs subject to abuse are regulated by the Controlled Substances Act (CSA), signed into law by then-President Richard Nixon in 1970, which, among other things, established the now-familiar five schedules. This will be discussed further below.

REGULATION OF RECREATIONAL DRUGS – INTERNATIONAL

The United States is a party to three United Nations (U.N.) drug control treaties²⁰:

the 1961 Single Convention on Narcotic Drugs
the 1971 Convention on Psychotropic Substances, and
the 1988 Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.

These are designed to establish effective control over international and domestic trafficking in opiates, coca leaf, cocaine, marijuana, stimulants, depressants, and hallucinogens by limiting the international production and trade of psychotropic substances and their chemical precursors.^9,20 The treaties also establish international mechanisms to monitor treaty adherence.²⁰ More than 95% of U.N. Member States are participants in these international treaties.²⁰ Under the CSA, treaty obligations may require the U.S. Attorney General to control or reschedule a substance if existing limits in the U.S. are less stringent than those required by a treaty.⁹

Despite these international agreements, more than two dozen countries have moved toward some form of decriminalization of recreational drugs.²¹ The SIDEBAR differentiates decriminalization and legalization.

SIDEBAR: Decriminalization and Legalization

Decriminalization is not the same as legalization.

When a drug is legalized, it may be restricted but there is no punishment for possession or use. Typically, regulations may exist regarding where and how the legal drug can be produced, sold, and consumed. Criminal or civil penalties may apply if production, sale, or consumption take place outside of regulations (think alcohol).

When a drug is decriminalized, possession and use are still “illegal” but, there are no criminal penalties (e.g., incarceration) for use or possession. Instead, there may be civil penalties (e.g., fines, or mandated treatment or educational programs), and usually, possession limits. In addition, use or possession do not lead to a criminal record that might affect employment, housing, or travel opportunities if a substance is decriminalized. Selling or manufacturing drugs would normally still carry criminal penalties.²²

Most people will bring up the Dutch city of Amsterdam when discussing lax drug policies. Indeed, people 18 years of age or older can purchase marijuana and other “soft” drugs (magic mushrooms, Salvia, Peyote cactus) legally and openly in coffee shops and other establishments in The Netherlands. .²³ Smoking tobacco products are also tolerated in public places except near schools or playgrounds.

Dutch drug policy rests on two principles.²³ (Note that Dutch policy applies nation-wide, but most people think of Amsterdam when this topic arises.) One is the fundamental belief that all human beings may decide about matters relating to their own health and includes acceptance of euthanasia for terminally ill patients. The other is that concealing socially negative phenomena does not cause those practices to disappear and instead makes them far more difficult to influence and control.

The Dutch divide drugs into two groups, soft and hard drugs, based on their human health impact. Hard drugs such as cocaine, LSD, morphine, and heroin are forbidden in the Netherlands. Soft drugs are tolerated but strict laws limit quantities, conditions of sale, and use. For example, driving under the influence of a soft drug is treated similarly to driving under the influence of alcohol. Large scale growing, processing, and trading in marijuana is forbidden, but Dutch courts bestow milder penalties than in most other countries.²³

Another frequently cited model is Portugal. On July 1, 2001, Portugal became the first country in the world to decriminalize all drugs, including methamphetamine and heroin, removing the distinction between soft and hard drugs.^24,25 Possession is decriminalized for personal use within certain limits, depending on the drug.²⁴ Generally, the limits are based on a hypothetical 10-day supply for an average individual.²⁵ Drug use became an administratively sanctionable misdemeanor under the responsibility of the Ministry of Health, rather than involving law enforcement.²⁵ The intent of the law was to focus police resources on those who profit from the drug trade, rather than their victims, while also providing a public health approach to drug users.²⁴

Individuals caught possessing drugs for personal use in Portugal are sent to a commission composed of health experts and a legal expert.²⁶ The commission evaluates the person’s drug use and, if necessary, will refer them to voluntary treatment. (While most treatment is voluntary, in some cases, the commission can choose to issue a fine or mandate some form of therapy.) Additionally, the country expanded access to treatment and harm reduction services like needle exchanges.²⁶

However, selling drugs is still illegal. Portuguese law considers it a crime if someone produces, buys, or transports an illicit drug that is above the legal amount for personal use.²⁴ For example, possession of more than 5 grams of hashish could potentially lead to arrest and prosecution for drug trafficking. A conviction for drug trafficking in Portugal can be subject to between one and five years in prison.²⁴

Beginning January 31, 2023, drug users 18 years of age and older in British Columbia, Canada who possess up to 2.5 grams of illegal drugs for personal use will not be arrested, charged, nor have their drugs confiscated.²⁷ Drugs include heroin, fentanyl, cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy). While those substances will remain illegal, police will offer users information on available health and social services. The province said it asked for the change in its request to the Canadian government for the drug laws exemption in order "to remove the shame that often prevents people from reaching out for life-saving help."²⁷

Canada’s intent is to use the province as a potential model for similar changes elsewhere in the country as part of a multi-faceted health-based strategy to end Canada’s drug overdose crisis, which reached record highs during the COVID-19 pandemic. The program has some exemptions; it will not apply to drug use on primary and secondary school grounds, child-care facilities, airports, or to members of Canada's military. The pilot program is set to run until January 31, 2026.²⁷

On the other hand, some countries have very harsh drug laws. In Malaysia, you can be fined, jailed, or deported for having drugs in your possession and those who sell drugs can be punished with death.²⁸ Execution is also the penalty for some drug crimes in China, Vietnam, and The Philippines. In Dubai, you can be imprisoned for possession of many prescription drugs that are legal in other parts of the world and failing a drug test can be grounds for incarceration even if the individual is not in possession of any drugs.²⁸ In Russia, even Americans in possession of vape cartridges containing hashish oil can be subject to arrest and detention, as WNBA star Brittney Griner discovered.²⁹

U.S. RECREATIONAL DRUG REGULATION

Controlled Substances Act

As noted above, in the early 1900s, drugs could be purchased at retail outlets with few, if any, limitations. Strong restrictions emerged later in the 20^th Century. In the 1960s, attention was being paid to a medical approach to preventing and treating drug abuse along with a powerful emphasis on law enforcement.⁹ By 1969, newly elected President Richard Nixon made reducing drug abuse, especially heroin abuse, one of his top priorities.⁹ Nixon feared that drugs were undermining the integrity of America’s youth and was convinced that abuse and addiction gave rise to crime, the biggest issue in his 1968 campaign.³⁰ Nixon sensed a need to restore control to a broken system and declared a “war on drugs.” Dismissing the current laws as “inadequate and outdated,” he called for a single, modern law to confine drug use to legitimate medical purposes.³⁰

One weapon in the war was the enactment of the CSA.⁹ The CSA was part (Title II) of an omnibus bill (a proposed law covering a number of diverse or unrelated topics) called the Comprehensive Drug Abuse Prevention and Control Act of 1970. The new legislation offered a more systematic approach to regulation of abused drugs and provided additional law enforcement resources.⁹

Congress, in enacting the CSA, dealt with two competing interests related to drug regulation.³¹ They recognized that while improper use of controlled substances can be detrimental to Americans' health and general welfare, many of these substances have a useful and legitimate medical purpose and are necessary to maintain health and well-being. The Act simultaneously aims to protect the public from the dangers of controlled substances while also ensuring access for legitimate purposes.³¹ To achieve both goals, the statute created two complementary legal schemes. One provision required individuals and entities working with controlled substances to register with the government, report certain information to regulators, and have a responsibility to prevent diversion and misuse of controlled substances.³¹ The act also contained provisions to prevent trafficking in controlled substances by establishing penalties for the production, distribution, and possession of controlled substances outside the legitimate scope of the registration structure.³¹ CSA policies that were intended to curtail illegitimate use of these drugs included prescription refill limitations, security standards, recordkeeping requirements, order forms, production quotas, and the registration of importers and exporters of controlled substances.^11,30 The new law was, however, not exclusively punitive; it eliminated mandatory minimum sentences for drug crimes.³⁰

Moreover, Title I of the comprehensive act had more of a public health focus.³⁰ It provided authority and funding to permit the Department of Health, Education, and Welfare to deliver prevention and treatment efforts through community mental health centers and public health service hospitals. It authorized the National Institute of Mental Health to increase substance abuse research and training.³⁰ It also protected subjects’ privacy rights under the care of approved researchers.

Over the next few decades, public concern over drug abuse increased and Congress responded by enacting policies that created a harsher system of drug control and served as a basis of the ensuing “War on Drugs.” ³⁰ Congress repeatedly amended the law to address the heightened concern, and it became more punitive and criminally focused and less directed towards rehabilitation and improved treatment.³⁰

A new Federal Agency, the Drug Enforcement Administration (DEA), was created in 1973 to enforce the new law. This was done in part to coordinate federal and state enforcement activities and to reduce inter-agency rivalries.^9,30 After the CSA was enacted, there were nearly 500,000 importers, exporters, manufacturers, distributors, and practitioners covered by the law, making the DEA the largest administrative agency in the U.S.¹¹

Scheduling

The centerpiece of the CSA, as pharmacists are aware, was the creation of a scheduling system that provided a means for assigning regulated substances into one of five categories based upon the drug’s medical risks, therapeutic use, and potential for abuse and dependence.^9,31 The classification system also establishes the obligations and penalties of the law.³¹ The most restrictive category is Schedule I which is comprised of drugs with high potential for abuse, but no accepted medical use.³² The placement of a drug in a schedule is fluid, and drugs can be moved to a different schedule, either up or down, added to the controlled substances list, or deleted.³⁰ Any individual, not just regulatory officials or health care providers, can request that the DEA add, remove, or change a drug’s scheduling.⁹

In determining into which schedule a drug or other substance should be placed, or whether a substance should be re-scheduled or decontrolled, certain factors must be considered. The DEA is required to seek a scientific and medical evaluation of the substance from the Department of Health and Human Services to apply what is known as the eight-factor test when determining scheduling.³² These factors are

(1) Its actual or relative potential for abuse
(2) Scientific evidence of its pharmacological effect, if known
(3) The state of current scientific knowledge regarding the drug or other substance
(4) Its history and current pattern of abuse
(5) The scope, duration, and significance of abuse
(6) What, if any, risk there is to the public health
(7) Its psychic or physiological dependence liability
(8) Whether the substance is an immediate precursor of a substance already controlled

These criteria help to stratify the seriousness of the public health concern among the controlled substances. Will new regulatory strategies remove these distinctions?

PAUSE AND PONDER: Do the “C” schedules serve a purpose?

DECRIMINALIZATION – STATE AND LOCAL ACTIONS

While the general trend at the federal level for the past five decades has been a toughening of the restrictions on abused drugs, especially opioids, one exception is marijuana. States have led the way by actively relaxing restrictions on marijuana, first by legalizing medical use and later permitting limited non-medical use.

The medical use of marijuana has been legalized in 37 states plus the District of Columbia (D.C.), Puerto Rico, Guam, the Northern Mariana Islands, and the U.S. Virgin Islands.³³ The medical marijuana movement began in California in 1996, but it wasn’t until 2012 that Colorado and Washington became the first two states to decriminalize the non-medical use of marijuana (for people 21 years of age or older).³³ (California voters had rejected a proposition in 2010.) In the 2022 election, two additional states, Maryland and Missouri, approved the recreational use of marijuana. bringing the total up to 21 (plus D.C.) although similar proposals were rejected in Arkansas, North Dakota, and South Dakota.³³

Beyond Marijuana

More recently, states and municipalities have gone beyond marijuana and have decriminalized other controlled substances. In May 2019, Denver, Colorado became the first governmental entity in the U.S. to decriminalize a (non-Cannabis) Schedule I drug, the psychedelic ingredient from mushrooms, psilocybin.³⁴ The proposal was placed on the municipal ballot after garnering almost 9500 petition signatures and was supported by 50.5% of voters in the election.³⁴ Denver was also the first major U.S. city to legalize the possession of small amounts of marijuana in 2005.³⁴

The new ordinance states that the “enforcement of any laws imposing criminal penalties for the personal use and personal possession of psilocybin mushrooms... shall be the lowest law enforcement priority in the City and County of Denver.” It mandates that “no department... shall use any city funds or resources to assist in the enforcement of laws imposing criminal penalties for the personal use and personal possession of psilocybin mushrooms by adults.”³⁵ Adult is defined as an individual 21 years of age or older.

One advocacy group (Decriminalize Denver) noted its support for the ordinance by stating that “Humans have used these mushrooms for thousands of years for healing, rites of passage, spiritual insight, strengthening community, and raising consciousness.” Decriminalize Denver has argued that “One arrest is too many for something with such low and manageable risks for most people, relative to its potential benefits.”³⁴ In contrast, opponents have warned that “Denver is quickly becoming the illicit drug capital of the world” and that the long-term health effects of these drugs are unknown.³⁴

Other municipalities have followed the same path as Denver. Oakland and Santa Cruz, California also decriminalized psilocybin in 2019 and 2020, respectively. In both cases, their respective City Councils took the action rather than mounting a referendum.^36,37 The Santa Cruz ordinance is very similar to what was enacted in Denver preventing resources from being used to investigate and arrest people 21 years of age and older solely for the personal use and possession of “entheogenic plants and fungi”³⁷ (a psychoactive, hallucinogenic substance or preparation especially when derived from plants or fungi and used in religious, spiritual, or ritualistic contexts³⁸). Community testimony from people sharing mental health struggles and treatment likely contributed to the Council’s decision. Santa Cruz later extended its policy and banned enforcement actions against individuals using peyote and other mescaline-containing cacti. Oakland also decriminalized mescaline cacti, ayahuasca and ibogaine.³⁹ The City Council in Ann Arbor, Michigan also unanimously approved mushroom decriminalization in 2020.⁴⁰

Voters in Washington D.C. also approved similar measures in 2020, termed the Entheogenic Plant and Fungus Policy Act, which would decriminalize natural psychedelics including magic mushrooms, ayahuasca, and mescaline, and makes arrests for their possession or use the lowest priority for DC police. Due to D.C.’s unique status, implementation of the act was delayed for Congressional review and approval. D.C. received approval in 2021 but not before one member of Congress threatened to derail the process.⁴¹

In late 2021, Seattle became the largest city (to date) to decriminalize Schedule I psychedelic drugs.^39,42 The City Council unanimously passed a resolution that “the investigation, arrest, and prosecution of anyone engaging in entheogen-related activities should be among The City of Seattle’s lowest enforcement priorities.” Its City Council asked the city’s police department to codify that practice as departmental policy.³⁹ The resolution was limited to natural substances, notably psilocybin and ayahuasca, and later peyote; it excluded synthetic materials such as LSD.^39,42 In support of its approval, the resolution noted both the therapeutic potential of psychedelics and protection of indigenous peoples who use these compounds for cultural and spiritual practices.⁴² More than 100 additional cities are moving to decriminalize psychedelic mushrooms.⁴³

States are also supporting decriminalization measures and Oregon is at the forefront of these activities. In the 2020 election, voters in the state passed two companion referenda that significantly changed the state’s drug policy. Measure 109 approved the use of a psychedelic mushroom for medical use by authorizing the Oregon Health Authority to create a program to permit licensed service providers to administer psilocybin-producing mushroom and fungi products to individuals 21 years of age or older.⁴⁴ The new law will allow anyone age 21 or older who passes a screening procedure to access the services for “personal development."⁴⁵ A client does not need to be diagnosed with or have any particular medical condition to receive psilocybin. Clients would complete a preparatory session and then attend a session at a psilocybin service center where they would receive and consume the psilocybin product under the supervision of the service facilitator.⁴⁴

Unlike the cities that decriminalized psychedelic drugs for personal use, the Oregon measure took a medical approach with the purpose of improving the physical, mental, and social well-being of people in the state and reducing the prevalence of mental illness conditions among adults who have not been helped by more mainstream therapies.^44,46 The measure restricts psilocybin sales to licensed service providers and does not permit sales directly to users. Individual counties can opt out of the program.⁴⁶

In the 2022 election, Colorado became the second state to approve psychedelics.⁴⁷ The proposition legalizes regulated access to natural medicines for people 21 years of age or older, including plants or fungi that impact an individual's mental health and provides civil and criminal immunity for providers and users.⁴⁷

Pharmacy staff should note that there is a growing interest in the potential therapeutic applications of psychedelic drugs to help many psychiatric disorders and these may become FDA-approved pharmaceutical products.⁴⁸

While several municipalities and states have authorized the decriminalization of mushrooms and other psychedelics and justified their actions due to their healing and spiritual value, there have been other movements to expand decriminalization beyond those with potential medical benefits.

In the same election that decriminalized mushrooms, voters in Oregon approved another measure (110) to become the first state to lighten penalties for possession of both large and small amounts of a wide assortment of scheduled substances.⁴

Under the new law, the penalty for possession of larger amounts of controlled substances was reduced from a felony offense to a Class A misdemeanor punishable by up to 364 days of imprisonment and a fine of up to $6,250. For possession of smaller amounts of controlled substances, the measure reduced the penalty from a criminal misdemeanor to a new, Class E violation, which is punishable by a $100 fine. In lieu of a fine, a person charged with a violation may instead complete a health assessment at an Addiction Recovery Center.⁴

The threshold differentiating large from small amount are defined for different substances. For cocaine, the Class E violation applies to unauthorized possession of less than two grams. For oxycodone, it is unauthorized possession of fewer than 40 pills, tablets, or capsules. Someone in possession of less than 1 gram heroin would be subject to the new Class E penalty.⁴ The new measure also removes penalty enhancements for possession of small amounts of controlled substances where the individual previously had a felony conviction or multiple previous convictions for possession.^4,45

The new program is loosely based on Portugal’s model, described above, but was modified in accordance with recommendations from Oregon’s recovery community.²⁶ Oregon’s approach will focus on diversion and harm reduction for people who use drugs while retaining punitive approaches for drug trafficking. A goal of the new program is to improve Oregon’s ranking as one of the worst states at providing treatment for addiction.²⁶ In 2016 and 2017, Oregon ranked first in the country for analgesic drug misuse, second in the U.S. for methamphetamine misuse, and fourth for cocaine and alcohol misuse while ranking 48th in access to treatment.²⁶ In all, almost 10% of the state’s population had a substance use disorder.

The state is expanding its addiction recovery centers and anyone will be able to access them whether or not they have received a citation.²⁶ The funding for expanded services will come from a higher than anticipated yield from marijuana taxes, which has exceeded $100 million per year.²⁶

Oregon’s program has produced mixed results. In the first year after decriminalization took place, police issued approximately 2000 citations, but, despite the waiver of the fine if a person calls the hotline for a health assessment and counseling, only 92 of those ticketed called the hotline and only 19 of them requested resources for services.⁵⁰ Almost half of people receiving a citation failed to make a court appearance. State health officials reported 473 opioid overdose deaths in the first 8 months of 2021, surpassing the total for all of 2020, and nearly 200 deaths more than the state saw in 2019.⁵⁰ The state also reported that visits to emergency rooms and urgent care centers for opioid overdose have been increasing. The Oregon Health Authority cites an upturn in fentanyl abuse and a pandemic-related downturn in reporting in 2020 as possible reasons for the disappointing results. In addition, Oregon’s inpatient facilities, detox clinics and recovery-focused nonprofits were adversely affected by issues related to COVID-19 including workforce shortages; there is uncertainty whether providers can adequately expand to meet increased needs.⁵¹

Pause and Ponder: Is there a role for pharmacists in improving outcomes?

However, it has also been suggested that the more lenient rules take away the threat of jail time that some individuals need to encourage them to get into recovery while fewer low-level offenders will be forced into court-ordered behavioral health services.⁵¹ Portugal takes a more robust approach than Oregon, having “dissuasion commissions” that pressure anyone caught using drugs, including marijuana, to seek treatment. Tools include fines, prohibiting drug users from visiting certain venues or from traveling abroad, seizure of personal property, community work, and having to periodically report to health services or other facilities.⁵⁰

California, Maine, and New Jersey, among others, have also been considering enacting decriminalization measures.^52,53 A bill pending approval in California would decriminalize most psychedelics. The bill would allow people aged 21 and older to possess psilocybin, DMT, ibogaine, mescaline, LSD, and MDMA for personal use and “social sharing.”⁵² The bill advanced to the final step of Assembly approval when the sponsor removed ketamine from the list of substances due to concerns over date rape. The bill prohibits sharing drugs with anyone under 21 years of age or possessing them on school grounds. It would also allow personal cultivation of mushrooms. Proponents touted the benefits to individuals who would be aided by the use of psychedelics to treat trauma including military veterans. Opponents argued that social sharing could result in more overdoses from contaminated products and give drug dealers a built-in defense.⁵²

PROS AND CONS

Why have states and municipalities chosen to decriminalize drugs? Although a detailed discussion of the benefits and detriments of lax drug policies is beyond the scope of this activity, it is worth briefly examining some of the arguments that have driven the move towards decriminalization. Table 1 describes the pros and cons frequently used to support the various arguments.

Table 1. Pros and Cons re: Decriminalization of Recreational Drugs^{1,16,54,55,56,57}

Justifications for decriminalization

Justifications for continuing prohibition of recreational drugs

· A sense that the “War on Drugs” is expensive, harmful to society, and not working

· The suggestion that a medical model will be more effective

· Decriminalization will reduce profits for drug traffickers

· More than half of people in prison have untreated substance use disorders and

o Imprisonment actually leads to increased illicit drug and medication misuse following a period of incarceration with a much higher risk of drug overdose upon release

o Relapse to drug use in someone with an untreated opioid use disorder can be fatal due to loss of opioid tolerance that may have occurred while the person was behind bars

o A criminal conviction or a record of imprisonment can significantly hamper a person’s employment prospects and other opportunities

· Risk of endorsing or encouraging risky behaviors

· Decriminalization would drive down the cost of drugs, making them more accessible

· Few non-violent users are actually imprisoned

· A black market will still exist for users under the permitted statutory age

· The current treatment infrastructure is inadequate to accommodate the anticipated increased demand

· The threat of incarceration is an incentive to seek treatment

· If restrictions are abandoned, other social costs will increase

As a proponent for decriminalization, Mayor Schmoke proposed that the abuse of drugs should be “dealt with as a moral and medical problem than as a criminal problem ... a problem for the surgeon general, not the attorney general.”¹ The number of people incarcerated for drug-law violations in state and federal prisons in the United States increased 12-fold between 1980 and 2018. Yet there is no statistically significant relationship between state drug imprisonment rates and three markers of state drug problems: self-reported drug use, drug overdose deaths, and drug arrests.⁵⁷

Pause and Ponder: Should recreational drugs be regulated like alcohol?

Many advocates recommend an approach similar to the policy in Portugal and treat illicit drug use the way most states regulate alcohol and marijuana, by making it legal for stores to sell such drugs to adults.⁵⁷ In Portugal, which has led the way towards decriminalization, the use of cocaine among young adults (15-34) is 0.3% compared with 2.1% in the European Union (EU) countries.⁵⁸ Amphetamine and MDMA use are also lower. The overall overdose death rate in Portugal is five times lower than in the EU (which has a lower rate than in the U.S.).⁵⁸ HIV infection rates among IV drug users have also dropped.⁵⁸

Where Will This Lead?

Are the localities decriminalizing recreational drug use an anomaly or do they represent the tip of the iceberg for liberalization of personal drug use? The movement could follow the path taken by marijuana.

States have pursued a pattern of first decriminalizing and/or allowing medical use of marijuana before finally proposing legalization.^16,59 States used their experiences with the intermediate steps as a means to anticipate the expected effects of total legalization.¹⁶ The liberalized marijuana policies in medical marijuana states exposed the public to more open marijuana use and may have changed attitudes towards the drug, along with a sense that prohibition is too costly.⁵⁹

Efforts are ongoing to legalize marijuana at the federal level. Congress is currently considering the Marijuana Opportunity Reinvestment and Expungement (MORE) Act. It would remove marijuana from the list of scheduled substances under the Controlled Substances Act and eliminate criminal penalties for an individual who manufactures, distributes, or possesses marijuana.³ It would also establish a process to expunge convictions and conduct sentencing review hearings for individuals previously convicted of federal cannabis offenses. It would establish and fund a grant program to provide resources to administer services for individuals adversely impacted by the War on Drugs, including job training, legal aid, reentry services, and health education programs and would levy a 5% tax on the sale of cannabis products.³

Will legalizing marijuana serve as a model for other C-I drugs to follow? Indeed, a bipartisan bill was recently introduced in the U.S. Senate calling on the DEA to reclassify breakthrough therapies such as psilocybin and 3,4-methylenedioxymethamphetamine (MDMA) as Schedule II drugs.⁶⁰

SUMMARY AND CONCLUDING COMMENTS

The pendulum of drug control may be swinging closer to the more lenient approach that existed 100 years ago. In a decade, the U.S. moved from no state permitting recreational use of marijuana to almost half of the states doing so, along with decriminalization being debated at the federal level. Will additional recreational drugs follow the same path? Several municipalities and a few states have already made significant strides in that direction. In particular, Oregon and the nation of Portugal have established programs making controlled substances a medical and public health issue rather than a law enforcement issue, although with mixed results. Will the distinction between “hard” and “soft” drugs disappear in the U.S., as more states adopt measures aimed at decriminalizing drugs?

If so, there will be many questions about how pharmacy may be affected. Will drugs for which there is some evidence for medical applications like cannabinoids and psychedelics such as psylocibin, find their way to the pharmacy shelf? If Oregon’s medical model for psychedelics is followed by other states, will it enable new opportunities for pharmacists? Will cocaine and heroin once again be available as OTC products in pharmacies?

It is important for pharmacy staff to stay abreast of regulatory changes in their own states and nationally. They should become part of the conversation about the direction such regulations should take.

Law: Getting Soft on “Hard” Drugs?

Post-test

After completing this activity, pharmacists and pharmacy technicians should be able to
• DESCRIBE regulation of controlled substances and how it has changed over time
• INDICATE how drugs are regulated internationally
• CHARACTERIZE state and local actions that are loosening the regulation of controlled substances
• DISCUSS the pros and cons of drug decriminalization

1. What was the first Schedule I drug (after marijuana) to be decriminalized by a U.S. city?
A. Cocaine
B. Psilocybin
C. Heroin

2. What is the guiding principle behind Amsterdam’s drug policy?
A. Individuals should be able to decide about matters relating to their own health
B. It is too expensive to try to crack down on the use of recreational drugs
C. Individuals need the threat of punishment in order to seek help for addiction

3. What was the first country to decriminalize all drugs?
A. Canada
B. The Netherlands
C. Portugal

4. Jose is talking with Mike. Jose says more than half of the people in American prisons have untreated substance use disorders and in these people, incarceration is associated with a much higher risk of drug overdose upon release. Jose also says a criminal conviction can significantly hamper a person’s employment prospects and other opportunities. Mike argues that the threat of incarceration is an incentive to seek treatment and few non-violent users are actually imprisoned. He says that the current treatment infrastructure is inadequate to accommodate the influx of people who would need treatment if Jose’s proposal passes. What positions are they arguing?
A. Jose is a proponent of legalization of all drugs; Mike is against legalization of drugs.
B. Jose supports decriminalization of all drugs; Mike is against decriminalization of drugs.
C. Jose supports legalization of all drugs, while Mike is a proponent of decriminalization.

5. The first significant regulation of opioids in the U.S. was the Harrison Act. What did this act do?
A. Empowered the FBI to seize all opioids entering the U.S. at all ports
B. Required pharmacists who dispensed “narcotics” to be registered and pay a fee
C. Prohibited the dispensing of cocaine from pharmacies or other healthcare venues

6. What significant change occurred as a result of the enactment of the CSA?
A. Possession of marijuana became illegal
B. The “C” Schedules were established
C. Public health remedies for addiction were curtailed

7. Many factors apply to the decision to control drugs under the CSA. Which of the following correctly describes one of these factors?
A. The CSA may require the DEA to comply with international treaty obligations when assigning a drug to a schedule
B. Only law enforcement or federal employees may ask the DEA to consider adding or deleting a drug from a schedule
C. The DEA must request a scientific/medical evaluation from the Centers for Disease Control and Prevention when deciding on scheduling

8. A young woman is stopped for speeding in Oregon and the officer sees she has a baggie with 12 Oxycontin tablets on the passenger’s seat, and she admits she does not have a prescription. The officer explains that under Oregon’s current laws, she may pay a fine for the unauthorized possession of small amounts of prescription opioids. What can she do in lieu of a monetary penalty?
A. Perform 20 hours of community service at an addiction recovery center
B. Attend an educational program about the risks of drug abuse
C. Complete a health assessment at an addiction recovery center

9. What was Oregon’s goal in decriminalizing the possession of controlled substances?
A. Raise revenue by taxing the sale of all recreational drugs
B. Improve the provision and use of addiction treatment services
C. Make sales from illegal sources economically unworkable

10. What would the proposed Marijuana Opportunity Reinvestment and Expungement (MORE) Act do?
A. Reclassify marijuana from the C-1 category to a C-II drug
B. Allow Medicare to pay for over-the-counter cannabidiol
C. Remove marijuana from the list of scheduled substances

Law: Getting Soft on “Hard” Drugs?

Post-test

1. What was the first Schedule I drug (after marijuana) to be decriminalized by a U.S. city?
A. Cocaine
B. Psilocybin
C. Heroin

3. What was the first country to decriminalize all drugs?
A. Canada
B. The Netherlands
C. Portugal

References

REFERENCES
1. Schmoke KL. An Argument in Favor of Decriminalization. Hofstra Law Rev. 1990; 18(3):501-525. Accessed March 21, 2023. https://scholarlycommons.law.hofstra.edu/cgi/viewcontent.cgi?article=1668&context=hlr
2. Support for Legal Marijuana Holds at Record High of 68%. Gallup. November 4, 2021. Accessed March 21, 2023. https://news.gallup.com/poll/356939/support-legal-marijuana-holds-record-high.aspx
3. H.R. 3884. MORE Act of 2020. 116th Congress (2019-2020). Accessed March 21, 2023.
https://www.congress.gov/bill/116th-congress/house-bill/3884
4. Lantz M, Nieubuurt B. Measure 110 (2020) Background Brief. State of Oregon Legislative Policy and Research Office. December 9, 2020. Accessed March 21, 2023.
https://www.oregonlegislature.gov/lpro/Publications/Background-Brief-Measure-110-(2020).pdf
5. Holzwarth L. The Most Unexpected Items People Used to Buy via Catalog. History Collection. January 31, 2019. Accessed March 21, 2023.
https://historycollection.com/the-most-unexpected-items-people-used-to-buy-via-catalog/10/
6. Palermo E. Does Coca-Cola Contain Cocaine? Live Science. December 13, 2016. Accessed March 21, 2023.
https://www.livescience.com/41975-does-coca-cola-contain-cocaine.html
7. Hamblin J. Why We Took Cocaine Out of Soda. Atlantic. January 31, 2013. Accessed March 21, 2023.
https://www.theatlantic.com/health/archive/2013/01/why-we-took-cocaine-out-of-soda/272694/
8. Browne E. Fact Check: Was There Ever Cocaine in Coca Cola, As Elon Musk Implied? Newsweek. April 29, 2022. Accessed March 21, 2023.
https://www.newsweek.com/elon-musk-tweet-twitter-coca-cola-cocaine-ingredient-1701864
9. Sacco LN. Drug Enforcement in the United States: History, Policy, and Trends. Congressional Research Service. October 2, 2014. Accessed March 21, 2023. https://fas.org/sgp/crs/misc/R43749.pdf
10. War on Drugs. History.com. Updated December 17, 2019. Accessed March 21, 2023.
https://www.history.com/topics/crime/the-war-on-drugs#:~:text=Drug%20use%20for%20medicinal%20and,had%20not%20yet%20been%20outlawed
11. Spillane JF. Debating the Controlled Substances Act. Drug Alcohol Depend. 2004;76(1):17-29.
12. Cantor DJ. The Criminal Law and the Narcotics Problem. J. Crim. L. Criminology & Police Sci. 1961;51(5):512-527. Accessed March 21, 2023.
https://scholarlycommons.law.northwestern.edu/cgi/viewcontent.cgi?article=4977&context=jclc
13. U.S. Food and Drug Administration. Milestones of Drug Regulation in the United States. Accessed March 21, 2023.
https://www.fda.gov/media/109482/download#:~:text=1951%20Durham%2DHumphrey%20Amendment%20defines,prescription%20by%20a%20licensed%20practitioner
14. Narcotics Enforcement in the 1930s. DEA Museum. Accessed March 21, 2023.
https://museum.dea.gov/exhibits/online-exhibits/anslinger/narcotics-enforcement-1930s
15. Volstead Act. Britannica. Accessed March 21, 2023.
https://www.britannica.com/topic/Volstead-Act
16. Dills A, Goffard S, Miron J, Partin E. The Effect of State Marijuana Legalizations: 2021 Update. Cato Institute. February 2, 2021. Accessed March 21, 2023.
https://www.cato.org/policy-analysis/effect-state-marijuana-legalizations-2021-update
17. Musto DF. The history of the Marijuana Tax Act of 1937. Arch Gen Psychiat. 1972; 26(2): 101-108. Accessed March 21, 2023. http://www.druglibrary.org/schaffer/hemp/history/mustomj1.html
18. Brecher EM. Marijuana is Outlawed. The Consumers Union Report on Licit and Illicit Drugs. Chapter 56. 1972. Accessed March 21, 2023. https://www.druglibrary.org/schaffer/library/studies/cu/cu56.html
19. Leary v. United States, 395 U.S. 6 (1969). Accessed March 21, 2023.
https://supreme.justia.com/cases/federal/us/395/6/
20. Rosen LW. International Drug Control Policy: Background and U.S. Responses. Congressional Research Service. March 16, 2015.
https://sgp.fas.org/crs/row/RL34543.pdf
21. Approaches to Decriminalizing Drug Use & Possession. Drug Policy Alliance. February 2015. Accessed March 21, 2023.
https://www.unodc.org/documents/ungass2016/Contributions/Civil/DrugPolicyAlliance/DPA_Fact_Sheet_Approaches_to_Decriminalization_Feb2015_1.pdf
22. Overview: Decriminalisation vs Legalisation. Alcohol and Drug Foundation. Accessed March 21, 2023.
https://adf.org.au/talking-about-drugs/law/decriminalisation/overview-decriminalisation-legalisation/
23. Amsterdam Drugs Laws. Amerstam.info. Accessed March 21, 2023.
https://www.amsterdam.info/drugs/
24. Silva L. Portugal Drug Laws under Decriminalization: Are Drugs Legal in Portugal? Portugal.com. April11, 2022. Accessed March 21, 2023.
https://www.portugal.com/op-ed/portugal-drug-laws-under-decriminalization-are-drugs-legal-in-portugal/
25. Rêgo X, Oliveira MJ, Lameira, C. et al. 20 Years of Portuguese Drug Policy - Developments, Challenges and the Quest for Human Rights. Subst Abuse Treat Prev Policy. 2021;16:Art 59. Accessed March 21, 2023.
https://substanceabusepolicy.biomedcentral.com/articles/10.1186/s13011-021-00394-7
26. Abraham R. How Oregon’s Radical Decriminalization of Drugs Was Inspired by Portugal. Next City. January 5, 2021. Accessed March 21, 2023.
https://nextcity.org/urbanist-news/how-oregons-radical-decriminalization-of-drugs-was-inspired-by-portugal?gclid=CjwKCAjwlqOXBhBqEiwA-hhitF2WD4yaDXh2LLfgppfmqe5xh5gl2q00t16uM6l0T8oDrbP38JipShoCN7sQAvD_BwE
27. BBC. Canada Trials Decriminalising Cocaine, MDMA and Other Drugs. BBC.com. June 1, 2022. Accessed March 21, 2023. https://www.bbc.com/news/world-us-canada-61657095
28. American Addiction Centers. The 20 Countries with the Harshest Drug Laws in the World. Updated July 16, 2021. Accessed March 21, 2023.
https://drugabuse.com/blog/the-20-countries-with-the-harshest-drug-laws-in-the-world/
29. Ganguli T, Abrams J, Bubola E. What We Know About Brittney Griner’s Case in Russia. NY Times. October 25, 2022. Accessed March 21, 2023.
https://www.nytimes.com/article/brittney-griner-russia.html#:~:text=Griner%2C%2031%2C%20who%20has%20played,a%20professional%20women%27s%20basketball%20team
30. Courtwright DT. The Controlled Substances Act: How a "Big Tent" Reform Became a Punitive Drug Law. Drug Alcohol Dependence. 2004;76(1):9–15.
31. Lampe JR. The Controlled Substances Act (CSA): A Legal Overview for the 117th Congress. Congressional Research Service. February 5, 2021. Accessed March 21, 2023.
https://sgp.fas.org/crs/misc/R45948.pdf
32. U.S. Drug Enforcement Administration. The Controlled Substances Act. Accessed March 21, 2023.
https://www.dea.gov/drug-information/csa
(8 factor) Ref 58
33. State Medical Cannabis Laws, National Conference of State Legislatures. Accessed March 21, 2023.
https://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx
34. Chavez N, Prior R. Denver Becomes the First City to Decriminalize Hallucinogenic Mushrooms. CNN. May 9 2019. Accessed March 21, 2023.
https://www.cnn.com/2019/05/08/us/denver-magic-mushrooms-approved-trnd
35. BallotPedia. Denver, Colorado, Initiated Ordinance 301, Psilocybin Mushroom Initiative (May 2019). Retrieved from:
https://ballotpedia.org/Denver,_Colorado,_Initiated_Ordinance_301,_Psilocybin_Mushroom_Initiative_(May_2019
Mush 51.
36. Kennedy M. Oakland City Council Effectively Decriminalizes Psychedelic Mushrooms. NPR. June 5, 2019. Accessed March 21, 2023.
https://www.npr.org/2019/06/05/730061916/oakland-city-council-effectively-decriminalizes-psychedelic-mushrooms
37. York JA. Santa Cruz Decriminalizes Natural Psychedelics. Santa Cruz Sentinel. January 29, 2020. Retrieved from: Accessed March 21, 2023.
https://www.santacruzsentinel.com/2020/01/29/santa-cruz-decriminalizes-natural-psychedelics/
38. “Entheogen.” Merriam-Webster.com Dictionary, Merriam-Webster. Accessed March 21, 2023.
https://www.merriam-webster.com/dictionary/entheogen
39. Adlin B. Seattle Becomes Largest U.S. City to Decriminalize Psychedelics. Marijuana Moment. October 4, 2021. Accessed March 21, 2023.
https://www.marijuanamoment.net/seattle-becomes-largest-u-s-city-to-decriminalize-psychedelics/
40. Stanton R. Why Ann Arbor Officials Decided to Decriminalize Psychedelic Mushrooms, Plants. Michigan Live. September 22, 2020. Accessed March 21, 2023.
https://www.mlive.com/news/ann-arbor/2020/09/why-ann-arbor-officials-decided-to-decriminalize-psychedelic-mushrooms-plants.html
41. Beaujon A. Magic Mushrooms are Decriminalized in DC as of Today. Washingtonian. March 15, 2021. Accessed March 21, 2023.
https://www.washingtonian.com/2021/03/15/magic-mushrooms-are-decriminalized-in-dc-as-of-today/
42. Miller C. Seattle City Council Votes in Favor of Decriminalizing Psychedelic Drugs. King 5. October 7, 2021. Accessed March 21, 2023.
https://www.king5.com/article/news/local/seattle/seattle-city-council-favor-decriminalize-psychedelic-drugs/281-23bee413-1898-41fd-8850-31ecc38ea621
43. Kelly D. Denver Dabbles with Magic Mushrooms, but Using them to Treat Mental Health Disorders Remains Underground. LA Times. April 5, 2021. Accessed March 21, 2023.
https://www.latimes.com/world-nation/story/2021-04-05/denver-dabbles-with-magic-mushrooms-but-using-them-to-treat-mental-health-disorders-remains-underground
44. Oregon Measure 109, Psilocybin Mushroom Services Program Initiative (2020). Ballotpedia. Accessed March 21, 2023.
https://ballotpedia.org/Oregon_Measure_109,_Psilocybin_Mushroom_Services_Program_Initiative_(2020)
45. Acker L. Oregon Becomes First Stat to Legalize Psychedelic Mushrooms. Oregonian. Updated November 4, 2020. Accessed March 21, 2023.
https://www.oregonlive.com/politics/2020/11/oregon-becomes-first-state-to-legalize-psychedelic-mushrooms.html
46. McInally M. Many Oregonians Will Have to Vote Again on Psilocybin. Oregon Capital Chronicle. August 8, 2022. Accessed March 21, 2023.
https://oregoncapitalchronicle.com/2022/08/08/many-oregon-voters-will-have-to-decide-again-on-a-psilocybin-program/
47. Martin S. In Colorado Election, Voters Legalize Psychedelic Mushrooms for Medicinal Purposes. USA Today. November 11, 2022. Accessed March 21, 2023.
https://www.usatoday.com/story/news/politics/2022/11/11/colorado-election-magic-mushrooms-health-approved/10669400002/
48. Nutt D, Erritoze D, Carhart-Harris R. Psychedelic Psychiatry’s Brave New World. Cell. 2020; 181: 21-28.
49. National Survey on Drug Use and Health. 2016-2017 National Survey on Drug Use and Health National Maps of Prevalence Estimates, by State. Accessed March 21, 2023.
https://www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHsaeMaps2017/NSDUHsaeMaps2017.pdf
50. Selsky A. Oregon's Pioneering Drug Decriminalization Law Draws Mixed Results. KGW8. April 4, 2022. Accessed March 21, 2023.
https://www.kgw.com/article/news/local/mixed-results-oregon-drug-decriminalization/283-0980d8b1-a514-425a-8989-889b027f5a95
51. Quinton S. Oregon’s Drug Decriminalization May Spread, Despite Unclear Results. Pew Stateline. November 3, 2021. Accessed March 21, 2023.
https://www.pewtrusts.org/en/research-and-analysis/blogs/stateline/2021/11/03/oregons-drug-decriminalization-may-spread-despite-unclear-results
52. Thompson D. California Advances Decriminalizing Psychedelic Substances. AP News. June 29, 2021.
Accessed March 21, 2023.
https://apnews.com/article/california-health-government-and-politics-c3eb439025f5f0b50090c73f22183cd0?utm_id=32439&sfmc_id=4213507
53. An Act to Make Possession of Scheduled Drugs for Personal Use a Civil Penalty. Maine Legislature Legislative Document 967. First Regular Session, 2021. Accessed March 21, 2023.
https://legislature.maine.gov/legis/bills/getPDF.asp?paper=HP0713&item=1&snum=130
54. Weatherburn D. Australian & New Zealand Journal of Criminology. 2014;47(2)176–189. Accessed March 21, 2023.
https://idhdp.com/media/362647/1408-weatherburn-article.pdf
55. ProCon.Org. Should Illegal Drugs Legalized? Accessed March 21, 2023.
https://aclu.procon.org/questions/should-illegal-drugs-be-legalized/
56. Volkow ND. Addiction Should be Treated, Not Penalized. Neuropsychopharmacology. 2021;46:2048-2050.
57. Gelb A. Pew Charitable Trust Letter to Chris Christie. June 19, 2017. Accessed March 21, 2023.
https://www.pewtrusts.org/~/media/assets/2017/06/the-lack-of-a-relationship-between-drug-imprisonment-and-drug-problems.pdf
58. Atkins S, Mosher C. Oregon Just Decriminalized All Drugs – Here's Why Voters Passed This Groundbreaking Reform. US News. December 10, 2020. Accessed March 21, 2023.
https://www.usnews.com/news/best-states/articles/2020-12-10/oregon-just-decriminalized-all-drugs-heres-why-voters-passed-this-groundbreaking-reform
59. History of Recreational Marijuana. ProCon.Org. Accessed March 21, 2023.
https://marijuana.procon.org/history-of-recreational-marijuana/
60. DeFuedis N. Congress Takes Another Look at Reclassifying Psilocybin and MDMA. Endpoints News. November 18, 2022. Accessed March 21, 2023.
https://endpts.com/push-to-reclassify-psilocybin-and-mdma-gains-bipartisan-support/

Pet Allergies

After completing this application-based continuing education activity, pharmacists will be able to

· Outline the causes of pet allergies in dogs, cats, and other less common species

· Differentiate between allergic sensitization, allergy, and cross sensitivity

· Paraphrase facts that prove that currently, hypoallergenic dogs and cats are a myth

· Compare nonpharmacologic, over the counter, and prescription treatments in terms of dosing, effectiveness, and cost

After completing this application-based continuing education activity, pharmacy technicians will be able to

· Outline the causes of pet allergies in dogs, cats, and other less common species

· Differentiate between allergic sensitization, allergy, and cross sensitivity

· Paraphrase facts that prove that currently, hypoallergenic dogs and cats are a myth

· Identify patients whose complaints indicate they may need referral to a pharmacist

In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

Dr. Li is a full time employee of Janssen Pharmaceutical of Johnson and Johnson and previously worked for Nest Bio and LegendBiotech. Dylan DeCandia does not have any relationships with ineligible companies and therefore has nothing to disclose.

Many American households have pets, and many others would like to have pets but family members have pet allergies. Allergies to cats and dogs are common (an estimated 15% to 30% of people are allergic to companion pets), and allergies to unusual or exotic pets have increased over the last decade. Pet allergy is an allergic reaction to proteins (allergens) found in animals’ skin cells (dander), saliva, urine, or sweat on their fur. Most animal allergens belong to one of three primary protein families. Pet allergies are currently incurable. The treatment goal is to control symptoms and improve patients’ functional status and well-being. Options include nonpharmacologic interventions like cleaning and bathing the pet and pharmacologic management with antihistamines, corticosteroids, anticholinergic nasal sprays, mast cell stabilizers, or leukotriene modifiers. Allergists will consider allergy-specific immunotherapy when medications and/or avoidance measures fail.

Introduction and Epidemiology

The American Pet Products Association (APPA) estimates that approximately 70% of Americans keep pets in their household, equating to 90.5 million homes. Dogs and cats are the most popular and live in around 69.0 and 45.3 million U.S. households, respectively, followed by 11.8 million households for freshwater fish, 9.9 million households for birds, and 3.5 million households for horses.¹ Public, residential, leisure, and specific occupational environments (e.g., farms, laboratories, pet shops) have high concentrations of pet allergens because of the high prevalence of community pet-keeping and Americans’ tendency to live indoors. Allergic reactions to pets have been recognized for at least 100 years.² Risk factors for developing asthma and rhinitis include allergies to furry animals, especially cats and dogs.³ Direct or second-hand pet exposure increases the likelihood of exacerbating disease in pet-sensitive people. However, evidence also shows that early childhood exposure to dogs or cats before one year of age may have protective effects in preventing allergic sensitization.⁴

Notably, allergies to unusual or exotic pets have increased over the last decade.⁵ In many urban areas, apartment complexes prevent owning large pets or charge a fee for owning cats and dogs, leading to the choice of smaller, more unusual animals. Some examples of uncommon pets are rodents (mice, rats [which allegedly make very good pets], guinea pigs, and other mammals like ferrets, pigs), amphibians (axolotl [a Mexican salamander], dart frogs, and fire belly newts), and reptiles (snakes).⁶ The allergic signs and symptoms or diseases associated with uncommon pets are like those manifested in cat and dog allergies. In addition, patients may present with respiratory symptoms induced by bird allergens and gastrointestinal symptoms after consuming bird eggs; this is called a bird-egg syndrome.⁷

Overall, the incidence of specific allergy to exotic or uncommon pets is unknown because literature only includes isolated cases or small series. In the United States, an estimated 15% to 30% of people are allergic to their pets.⁸ Among people with pet allergies, a fraction is sensitized to more than one animal. Moreover, according to the Asthma and Allergy Foundation of America, cat allergies are reported twice as often as dog allergies. Animals are also recognized as the third leading cause of allergic asthma, after mites and pollens.⁸ Many people adopt ferrets or rabbits, believing they are hypoallergenic. They are not, and pharmacy staff should be aware of that fact.^9,10 The most frequent allergic reactions result from inhalation, contact, or bites.

This continuing education activity summarizes knowledge of pet allergens, including those from uncommon pets; the allergy reaction mechanism and its signs and symptoms; current advances in diagnosis and treatment methods such as immunotherapy; and recommendations for patient education and counseling.

Pause and Ponder: When patients ask about medication for pet allergies, what kinds of questions should you ask?

PET ALLERGENS

Allergy Mechanisms

Compared with other conditions’ mechanisms, allergy mechanisms are simple and encompass three specific paths: allergic sensitization, allergy, and cross-reactivity.¹¹

Allergic sensitization is the presence of immunoglobulin E (IgE) antibodies to an allergen.
Allergy is the occurrence of reproducible symptoms or signs initiated by exposure to a defined stimulus at a dose tolerated by nonallergic persons and mediated by specific immunologic mechanisms. If no symptoms develop, a person could be sensitizing to a particular allergen but not be allergic.
Cross-reactivity is the process of IgE antibodies (originally developed against a given allergen) binding to homologous molecules originating from a different allergen source.

Characterizing Pet Allergens

Allergies to pets are common. Pet allergy is an allergic reaction to proteins (allergens) found in animals’ skin cells (dander), saliva, urine, or sweat on their fur.⁵ Allergens within the same protein family can cause cross-reactivity. Most allergens are spread via airborne particles. Dander contains allergens formed in sebaceous gland secretions and saliva. Secretions containing allergens adhere to the hair and stratum corneum of the skin. When an animal sheds, tiny particles disperse into the air and remain buoyant for an extended period of time. After the particles slowly settle onto the floor, furniture, or other items, they can be easily re-dispersed into the air. As a result, pet-sensitive people could experience allergy symptoms in the nose, eyes, and respiratory tract even if the pet is not present.⁵ Additionally, people can carry pet allergens that settled onto their clothing or hair.

For cats and dogs, the primary allergen sources are dander and saliva. Similarly, the primary allergen source in rabbits is saliva. In contrast, the primary allergen source is urine in rodents (e.g., mouse, rat,) and Mustelidae (ferrets and minks).

Rodents are an interesting case study. Most research laboratories experience a very high rate of staff turnover because lab workers develop allergies to rodents. Children who are exposed to rodent urine can develop this allergy, too. Male rodents produce a larger quantity of and more condensed urine than female rodents. This explains why people who commonly come in contact with male rodents are more likely to develop allergic symptoms. Allergy to rodents acts as an occupational hazard for researchers. Mouse urine is the most concentrated of all urines—far more concentrated than any other species.¹² One study showed that 30% of people exposed to mice and 13.7% of people exposed to rats suffered from allergy symptoms.¹² Symptoms range from conjunctivitis to asthma to skin reactions, which makes working with these animals difficult.

Most animal allergens belong to one of three primary protein families. Within the three families, lipocalin-like proteins and the serum albumin family are the two most widely studied. Other identified allergens are considered minor, including gelatins, immunoglobulins, and transferrins presented in secretions and dandruff. Knowledge of these allergens’ allergenicity and cross-activity is essential to improve treatment and prevent allergic reactions. Table 1 summarizes partially characterized pet allergens, including those generated by exotic pets, because not all allergens are fully characterized.⁵

Table 1. Summary of Characterized Pet Allergens^13-22

Common Name of Animal	Source	Allergen	Family
Dog	Dander, saliva, hair	Can f 1 (major allergen) Can f 2 Can f 4 Can f 6 Can f 3 Can f 5 Can f 7 Can f 8	Lipocalin Lipocalin Lipocalin Lipocalin Albumin Arginine esterase (kallikrein) Epididymal secretory protein E1 or Niemann Pick type C2 protein Cystatin
Cat	Sebaceous, anal, and salivary gland	Fel d 1 (major allergen) Fel d 2 Fel d 4 Fel d 7 Fel d 3 Fel d 5w Fel d 8 Fed d 6w	Uteroglobin Albumin Lipocalin Von Ebner gland protein Cystatin Cat IgA Latherin-like IgM
Horse	Dander, sublingual, submaxillary salivary glands, and urine	Equ c 1 (major allergen) Equ c 2 Equ c 4 Equ c 3 Equ c 6	Lipocalin Lipocalin Latherin Albumin Lysozyme
Chinchilla	Epithelia, saliva, urine	Chi La Chi Lb	Protein kinase inhibitor Lipocalin
Guinea pig	Epithelia, saliva, urine	Cav p 1 (major allergen) Cap p 2 (major allergen) Cap p 3 Cap p 4 Cap p 6	Lipocalin Lipocalin Lipocalin Serum albumin Lipocalin
Gerbil	Epithelial, salvia, urine, sleep bed	Mer un 23kDa Mer un 4	Lipocalin Serum albumin
Siberian hamster	Epithelial, saliva, urine	Phod s 1	Lipocalin
Rat		Rat n 1 (major allergen) Rat n 4 Rat n 7	Lipocalin; alpha-2u-glubulin Serum albumin Immunoglobulin
Mouse		Mus m 1 (major allergen) Mus m 2 Mus m 4 Mus m 7	Lipocalin; urinary prealbumin Unknown Serum albumin Immunoglobulin
Rabbit		Ory c 1 Ory c 2 Ory c 3 Ory c 4	Lipocalin Lipocalin Secretoglobin Lipocalin
Ferret		Mus p 17 Mus p 66	Unknown Serum albumin
Pig	Meat	Sus s 1 Sus s 5 Sus s 6	Serum albumin Lipocalin Serum albumin

Lipocalin Superfamily

More than 50% of allergens identified from furry animals belong to the lipocalin superfamily and are found in animal dander, saliva, and urine.²³ Lipocalins are large proteins and can induce IgE production in a large proportion of atopic individuals (people who have enhanced immune response to common allergens) who are exposed to the allergen source.²⁴

Serum Albumin Family

Serum albumin is a globular protein prone to participation in IgE-mediated cross-reactions.²⁴ Serum albumin is commonly found in pet dander and saliva and causes an allergic reaction by inhalation and ingestion.

Secretoglobin Superfamily

Secretoglobins are the most potent allergens in cats (e.g., Fel d 1) and other pets (e.g., rabbit Ory c 3). Produced by the skin, salivary and lacrimal glands, these proteins have an unknown function. Dried saliva and dandruff are spread as airborne particles and cause sensitization in susceptible people.²⁵

SIGNS AND SYMPTOMS OF PET ALLERGIES

The most frequently observed pet allergies result from inhalation, contact, and bites. The main allergic symptoms are similar across both common and uncommon pet types. They present as rhinitis, conjunctivitis, urticaria (red, itchy welts that result from a skin reaction), and lower and upper respiratory symptoms, which can be mild to severe and rarely cause anaphylactic shock.⁵

Hypoallergenic Pets

“Hypoallergenic” is defined as possessing decreased risk of causing an allergy in people, which means that hypoallergenic animals could still elicit allergies in humans.⁹ To make hypoallergenic animals, breeders or researchers combine breeds that produce less allergen (in dogs, breeders use breeds that shed less than other breeds, or have hair rather than fur). However, animals often have different mechanisms of allergenicity, so infrequent shedding does not solve all allergy problems.

In a dog allergen study, homes that included hypoallergenic dogs had no statistically significant difference in dog allergen levels compared to homes that included non-hypoallergenic dogs. The common allergen in dogs, Can f 1, was reported at similar levels in all groups.²⁵The frequency of shedding varies in different dog breeds, but all dogs can elicit allergies in humans.

The main allergen in cats, Fel d 1 protein, comes from their saliva and sweat glands. Because of its small size and adhesiveness, Fel d 1 floats around and sticks to everything, making it almost impossible to remove physically. In fact, Fel d 1 measures in at less than one-tenth the size of ribosome; it’s so small, it easily navigates its way deep into the lungs and can precipitate asthma.²⁶ For this reason, making a completely hypoallergenic cat has proven impossible, however vaccines to decrease the production of Fel d 1 protein have been studied; one vaccine is a combination of recombinant Fel d 1, tetanus toxoid protein, and a snippet of the coat of a plant virus.²⁷ Researchers are unsure as to the purpose of Fel d 1 in cats or why levels of Fel d 1 vary.

Ferrets—which are related to otters, minks, weasels—are considered hypoallergenic because they are less likely to cause an allergic reaction compared to other animals. However, they can still provoke allergies in people. Allergies to ferrets come from their hair, saliva, and urine. Ferret hair and saliva is usually easy to control because they shed infrequently and do not lick people like dogs and cats often do. However, urine is harder to control and can cause allergies when owners clean crates.⁹

Rabbits produce allergens through dander, hair from shedding, and saliva. They tend to shed more often than ferrets, around every three months, so keeping up with cleaning may be difficult. Rabbit hair isn’t naturally allergenic, but when rabbits lick their fur, they transfer a saliva protein that is contaminated with the protein allergen.¹⁰

DIAGNOSIS

Skin Prick Test

Allergists (allergy specialists) use skin prick tests together with medical history and physical examinations to rule out or confirm a suspected IgE-mediated animal allergy.²⁸ Manufacturers prepare skin prick tests by extracting natural allergens from animal hair, dander, and urine. The doctor or nurse will prick the patient’s skin on the forearm or upper back and determine if an allergic reaction occurs within 15 minutes. If a patient develops a red, itchy bump where the pet allergen extract is pricked into the skin, the patient is allergic to that pet allergen. Diagnosticians should first use a skin prick test as it is inexpensive, easy to use, and quick to perform. However, allergen concentrations and components are inconsistent, varying among similar commercial tests from different manufacturers. Healthcare providers should be aware that patients’ test results may be inconsistent if they use different skin prick tests at different times.²⁸

Serum-specific IgE Test

Allergists can use a serum-specific IgE (blood) test when patients’ symptoms and skin test results are contradictory or when patients’ skin conditions prevent a skin test. Serum-specific IgE tests can only determine if a patient is sensitized to a specific pet allergen, but it cannot determine if a patient is allergic to that allergen. Serum-specific IgE tests are highly sensitive, but prone to false-positive results. From this perspective, serum-specific IgE tests may be less accurate than skin prick tests.²⁹

Molecular Diagnosis

Recent scientific advances have allowed molecular diagnosis to differentiate patients who are allergic to a single species or sensitized due to cross-reactivity. This method can aid targeted recommendations for avoidance and assess the choice and composition of immunotherapy.²⁸

PET ALLERGY MANAGEMENT

Pet allergies cannot currently be cured. The treatment goal is to control symptoms and improve patients’ functional status and well-being.

Nonpharmacologic Treatment – Avoid & Minimize Allergen Exposure

Current recommendations for managing pet allergy symptoms start with exposure avoidance. Starting when animals are young, bathing them at least once weekly can reduce allergens and eliminate reactions in humans who are exposed to them (see SIDEBAR).³⁰ Immediate removal of animals from the household will not alleviate symptoms if the owner has carpeting and other pieces of furniture/items that the pet slept or sat on. Mammalian allergens are stable and can persist in house dust for up to six months.³² Additionally, using high-efficiency particulate air (HEPA) filters and mattress encasement, vacuuming, and chemically treating carpet are alternative methods for reducing exposure to contaminated materials, but may not reduce disease severity.³³

Pause and Ponder: When patients have pet allergies, which symptoms are best treated with antihistamines?

SIDEBAR: To Bathe or Not to Bathe…^26,31

Bathing a cat or dog regularly appears to reduce the quantity of allergen harbored by the pet. To effectively lower Can f 1 concentrations, owners need to bathe the animal at least twice every week because Can f 1 concentrations rise rapidly, approaching baseline concentrations within three days after washing. Twice-weekly bathing can reduce the amount of recoverable Can f 1 on dogs by more than 80%, but researchers note that ideally, one would bathe the dog two to three times every week. Airborne Can f levels can fall by ruff-ly 40% but will quickly escalate.

However, the beneficial effects of reducing allergen levels by regular bathing are more likely associated with dogs, because their allergen burden returns faster than that of cats. So, bathing animals reduces the amount of allergen far better than vacuuming.

But should companion animals be bathed so often?

Most cats are notoriously averse to bathing, although some breeds like water (i.e., the Bengal). Dogs vary in the response to bathing—some like it, others do not. People who plan to bathe their cats or dogs regularly should do three things:

Check with a veterinarian or a breed advocacy group. The American Kennel Club indicates that how often an owner should bathe a dog depends on the dog’s coat type and presence or absence of an undercoat (in the latter case, frequent bathing can affect a dog’s temperature regulation). Bathing an animal is not just about a human’s allergies, the animal’s health and welfare should be a primary concern.
Consider the labor and time involved in bathing a pet often, safely, and well.
Start when the animal is young.

An allergen reducing cat food (Pro Plan LiveClear) is now available, and its manufacturer indicates it reduces the number of allergens in cat hair and dander by 47% after three weeks of feeding.³⁴ It is produced using eggs that contain an anti-Fel d1 antibody. When cats consume the food, the egg powder binds to and neutralizes Fel d1 in the cat’s saliva.³⁴

Pharmacologic Treatment

When avoidance and reducing allergens are not enough, depending on the severity of signs, over the counter (OTC) medications like antihistamines or local/topical steroids may provide temporary relief of allergy symptoms.³⁵ Those symptoms include runny/itchy nose or throat, sneezing, and itchy, red or watery eyes. Combination products that contain both an antihistamine and a decongestant or an analgesic are available but should be used with caution due to the increased risk of adverse effects. Other allergy medications, besides the ones mentioned above, are used less often, including mast cell stabilizers and leukotriene antagonists. Table 2 summarizes common medications (both OTC and prescription) for treating mild to moderate allergy symptoms.³⁵

Table 2. Medications to Treat Allergy Symptoms³⁶

Medication	Mechanism of Action	Adverse Effects	Notes
Antihistamines
1^st generation (nonselective, more sedating) * Diphenhydramine, chlorpheniramine, clemastine 2^nd generation (less sedating, less drowsiness): Cetirizine,* desloratadine,* fexofenadine,* levocetirizine,* and loratadine* Azelastine has nasal spray* and eye drop formulation. Epinastine and olopatadine* are formulated as eye drops.	Blocks histamine and its binding to receptors, prevents histamine-caused redness, swelling, itching, and changes in secretions during an allergic response	· Drowsiness · Fatigue · Headache	The 2^nd generation antihistamines are preferred over 1^st generation based on safety and efficacy data.
Corticosteroids
Available as tablets, liquids, nasal spray, topical creams for skin allergies, topical eye drops for conjunctivitis. Some steroids include: beclomethasone, ciclesonide, fluticasone furoate,* mometasone, budesonide,* triamcinolone,* dexamethasone ophthalmic, prednisone, etc.	Anti-inflammatory effect	Short-term use: Weight gain, fluid retention, high blood pressure Long-term use: Growth suppression, diabetes, cataracts of the eye, osteoporosis, muscle weakness Side effects of inhaled steroids: Cough, hoarseness, fungal infection of the mouth	Highly effective for allergies but must be taken regularly. It may take 1 to 2 weeks before the full effect.
Decongestants
Available as nasal sprays, eye drops, liquids, and tablets Some decongestants include: pseudoephedrine,* phenylephrine,* and oxymetazoline* nasal sprays	Shrinks swollen nasal tissues and blood vessels to relieve the symptoms of nasal swelling, congestion, mucus secretion, and redness	· Increased blood pressure · Insomnia · Anxiety, feeling nervous, restlessness	Relieve congestion and are often prescribed with antihistamines for allergies Contraindicated in patients with severe coronary artery disease, severe hypertension, and who concomitantly use monoamine oxidase inhibitors Short-term use only (~5 days). Long-term use can make symptoms worse.
Combination Allergy Drugs
Some combination drugs include: cetirizine/pseudoephedrine,* fexofenadine/ pseudoephedrine,* diphenhydramine/ pseudoephedrine,* loratadine/pseudoephedrine,* pseudoephedrine/triprolidine* for nasal allergies, and naphazoline/pheniramine* for allergic conjunctivitis	Effects from each component	Side effects from each component	Use with caution due to increased risk of adverse effects
Anticholinergic Nasal Spray
Ipratropium bromide nasal spray to control nasal discharge	Antisecretory properties in the nasal mucosa	· Bitterness of the mouth · Dry nose, nosebleeds, or irritation · Dizziness · Headache · Sore throat · Respiratory tract infection	Some patients may feel better right away. For others, it may take 1 to 2 weeks before the medicine helps. It is important for patients to continue use of this medication as instructed.
Mast Cell Stabilizers
Available as eye drops for allergic conjunctivitis and nasal sprays for nasal allergy symptoms Some mast cell stabilizers include cromolyn sodium,* iodoxamide-tromethamine, nedocromil, pemirolast, etc.	Prevents histamine release from mast cells	Throat irritation, coughing, skin rashes For eye drops may cause blurred vision, stinging, and burning	For mild to moderate symptoms Not as effective as steroids
Leukotriene Modifiers
Montelukast*: Indicated for adults and pediatric patients six months or older with perennial allergic rhinitis. May be less effective than loratadine or cetirizine for reducing daytime nasal symptoms	Montelukast binds to leukotriene receptors in the human airway (smooth muscle cells and macrophages), preventing airway edema, smooth muscle contraction, and other respiratory inflammation	· Stomach pain or upset · Headache · Stuffy nose · Cough · Fever · Rash · Irritability	Warn patients to report behavior changes, including suicidal ideation or suicidal behavior Avoid concomitant use of aspirin or NSAIDs in aspirin-sensitive patients
*Indicates over the counter (OTC) medication

In general, for conditions eligible for self-care, e.g., allergic rhinitis, patients should start taking OTC allergy medications one week before they expect symptoms from a predictable exposure or as soon as possible before allergen exposure (for episodic exposure).³⁵ Prescribers should tailor the pharmacologic therapy and length of treatment based on symptoms and severity. Usually, complete relief takes two to four weeks. Intranasal steroids control nasal symptoms more effectively than antihistamines, as they inhibit multiple cell types and mediators, and should be recommended for moderate or persistent allergic rhinitis. Decongestants are effective in nasal congestion but have little effect on other symptoms. Intranasal and ocular preparations are available for nasal and eye symptoms. Intranasal cromolyn is the preferred initial choice for pregnant or lactating patients, as the body does not absorb it based on the route of administration. As mentioned in the table, fluticasone and triamcinolone nasal sprays are available over the counter.³⁵

If a patient has persistent allergies, allergy medication is more effective when taken regularly.³⁵ For example, if a patient with moderate or severe persistent allergic rhinitis has completed two to four weeks of treatment with intranasal corticosteroids or oral antihistamine and achieved symptomatic control, healthcare providers can optimize the treatment’s effect by reducing the dose and continuing treatment for one additional month. If a patient’s symptoms are uncontrolled after two to four weeks of OTC treatment, pharmacists should assess the patient’s adherence and refer for prescription therapy if necessary.³⁵

Pause and Ponder: Which providers in your area provide allergen-specific immunotherapy? What should patients expect if they take this route?

Allergy Immunotherapy

Allergen-specific immunotherapy has been used in pet allergies for years and has proven efficacy to help control symptoms and prevent disease progression. Allergists will consider allergy-specific immunotherapy when symptoms are uncontrolled by medications and/or avoidance measures, when adverse drug effects are intolerable, or when patients want to reduce long-term use of allergy medications.³⁷

The basis for allergen-specific immunotherapy is gradual reprogramming of the immune system to build a tolerance to allergens. This class comes in three forms:

Sublingual allergy immunotherapy (SLIT) tablets
SLIT drops, and
subcutaneous allergy immunotherapy (SCIT)

As of 2022, the FDA has approved four SLIT tablets to treat allergic rhinitis with or without allergic conjunctivitis caused by ragweed, northern pasture grasses, and dust mites in susceptible individuals; the FDA has not approved SLIT tablets for pet allergies.²²

SLIT drops are made from FDA-approved allergy extracts used to make SCIT shots. However, these extracts are only FDA-approved for injection use under the skin, and they are not approved for use under the tongue. Therefore, SLIT drops are not FDA-approved and are off-label in the United States, and Medicare or Medicaid does not cover these treatments in most cases. Despite not having FDA approval, patients can still receive SLIT drops from some prescribers who prepare a custom-mixed formulation but must pay out of pocket. Research indicates SLIT is safe and effective.³⁹

The FDA has approved SCIT for cat allergies, but not for other pet allergies. Patients who receive SCIT usually call it “allergy shots.” One systemic review evaluated 88 trials that enrolled 3,459 asthmatic patients and exposed them to SCIT. One case of deterioration in asthma symptoms was avoided for every three patients treated with SCIT (95% CI, 3-5), and one patient would avoid increasing symptomatic medication use for every four patients treated (95% CI, 3-6).⁴⁰ Another study found that SCIT can reduce the need for systemic steroids in allergic rhinitis patients.⁴¹ Usually, the patient receives a solution for injection with 10,000 bioequivalent allergy units (BAUs) per milliliter (standardized extract) of lyophilized cat hair and dander added to glycerol and human serum albumin (0.03%). A clinician administers one to two subcutaneous injections every week starting at low doses (1:10,000 dilution) and titrating up to a seemingly effective maintenance dosing. Then, the prescriber extends the injection interval gradually to every 2 weeks to 4 weeks. For cat allergens, the effective maintenance dose usually falls within the 1000 to 4000 BAU range.⁴²

SCIT sometimes can cause treatment-related systemic allergic reactions; however, near-fatal or severe reactions are rare, and most reactions are local and mild (swelling, pruritis, and redness at injection site).⁴³ SCIT should not be recommended to patients who have severe uncontrolled heart problems or asthma if they take beta-blockers, which are associated with more frequent reactions, more severe reactions, and reactions that are refractory to epinephrine. Additionally, allergy shots should not be recommended for pregnant women unless discussed with their obstetricians.⁴³

Both SCIT and SLIT require gradual up-titration of dosages with ongoing and multiple treatments and may take three to five years to reach desensitization. Also, for SCIT, based on its route of administration (subcutaneous injections are invasive), patients will need to visit the doctor's office more frequently and may experience the treatment-associated side effects.

SLIT has been increasingly recommended because of its ability to modify the immune system for the long term while reducing allergy symptoms. SLIT also showed a safer profile, only associated with mild mouth symptoms, and improved adherence compared to SCIT.⁴⁴ When compared to traditional allergy treatments, SLIT tablets showed similar clinical efficacy to nasal corticosteroids and greater clinical efficacy than second-generation antihistamines and montelukast.⁴⁵

What About Cost?

In adherent patients, SCIT and SLIT have proven to be an economically viable option. The annual cost of using SCIT depends on patients’ insurance: Medicare ($1021.70), Medicaid ($758.16), and the commercial average ($1722.24). Yearly treatment costs for SLIT are self-pay because treatment is not FDA approved and costs around $679.25.⁴⁶ Because SLIT drops are administered at home by patients, they tend to be more affordable than the cost of SCIT. Patient preference might be for a once monthly administration, rather than taking oral antihistamines daily.

OTC medications are less expensive than immunotherapy, but costs vary. In a comparison of second-generation antihistamines versus montelukast, levocetirizine (Xyzal) had the best efficacy per cost value. Generic fexofenadine (Allegra), although similar in efficacy, was more expensive than levocetirizine.⁴⁴

CONCLUSION

Healthcare providers should counsel patients about reducing allergen exposure and help patients to choose OTC medications for self-care based on individual patient needs and conditions to optimize treatment effects. Pharmacy staff should refer patients to allergists when necessary to identify the cause of their allergy symptoms. If a patient's allergy does not allow him or her to have pets at home and the patient owns a pet, suggest that the patient ask family members or friends about placement before contacting the local animal shelters.

Pet Allergies
Pharmacist Post-test
After completing this continuing education activity, pharmacists will be able to
1. Outline the causes of pet allergies in dogs, cats, and other less common species
2. Differentiate between allergic sensitization, allergy, and cross sensitivity
3. Paraphrase facts that prove that currently, hypoallergenic dogs and cats are a myth
4. Compare nonpharmacologic, over the counter, and prescription treatments in terms of dosing, effectiveness, and cost

1. What is the major allergen in dogs?
A. Can f 3
B. Can f 1
C. Fel d 1

2. When comparing allergy immunotherapies (SCIT, SLIT) and traditional allergy treatments, how do they differ?
A. Traditional allergy treatments are more clinically efficacious, SCIT and SLIT therapies should not be considered in treatment
B. Traditional allergy treatments are more effective, but with the recent FDA approval of SLIT, it should be considered more often
C. Although not FDA approved, SLIT showed similar clinical efficacy to nasal corticosteroids and more clinical efficacy to second-generation antihistamines in trials

3. What is the best way to define hypoallergenic animals?
A. Animals that are less likely to cause allergies in humans.
B. Animals that cannot cause allergies in humans
C. Animals that do not cause conjunctivitis, but other common symptoms may still occur

4. A mother brings her young son to the pharmacy and says that the allergist indicates he has an allergy to their cat. She asks what this means. What is the BEST answer?
A. Her son has immunoglobulin G (IgG) antibodies to an allergen.
B. Her son will experience reproducible symptoms when exposed to the cat.
C. Her son will have symptoms when exposed to any furry animal.

5. Lance, a college student who lives in a group house, comes in and says that he has tried several medications for allergic symptoms linked to his roommate’s three cats. The medications relieved the symptoms but caused so much drowsiness, he couldn’t study. His allergist is now recommending he start immunotherapy. What is the MOST LIKELY reason the allergist is making this recommendation?
A. Lances’ symptoms are uncontrolled by medications
B. Lance is experiencing intolerable adverse effects
C. Lance want to reduce his use of allergy medications.

6. Lance returns to the pharmacy to pick up his atenolol for hypertension and he said the allergist has asked him to decide if he wants to take SCIT or SLIT. He asks you which factors he should consider. What is the BEST answer?
A. Advise him to consider cost, dosing frequency, and route of administration
B. Advise him to consider cost and convenience alone as they are both effective
C. Advise him to tell his allergist he is taking a beta blocker, so SLIT is preferred

7. Emily and her mom come to the pharmacy and they are very excited. They are considering adopting a dog! Emily has asthma and multiple allergies, and the pediatrician has told them she is probably allergic to or will become allergic to dogs. As Mom chatters, she tells you that the 9-year-old dog, Raven, is an Alaskan Malamute (a breed that has a heavy undercoat) that weighs 95 pounds. She said that a friend told her that if she washes the dog two or three times a month, allergies will not be a problem. She says, “I think I can find time to wash a dog twice a month.” What is the MOST IMPORTANT FACT you should bring to her attention?
A. Before adopting Raven, check with a veterinarian or a breed advocacy group to determine if bathing is a good idea.
B. Bathing a pet two to three times a month is not frequent enough to reduce the allergen load—you have to bathe them two to three times a week.
C. Look for a younger Alaskan Malamute—maybe a puppy—so the dog will get used to being bathed so often.

8. Adele, who is 7 months pregnant, is experiencing an allergic reaction to a visiting ferret. She asks you to recommend an OTC product to reduce her nasal stuffiness and itchy eyes. Which is the BEST product to recommend?
A. Intranasal cromolyn
B. Oral levocetirizine
C. Oral diphenhydramine

9. Which of the following have similar effectiveness for pet allergies, but different cost effectiveness?
A. Fluticasone and fexofenadine
B. Montelukast and loratadine
C. Levocetirizine and fexofenadine

10. Which medication class should be used for no longer than five days at a time?
A. Decongestants
B. First generation antihistamines
C. Nasal corticosteroids

Pet Allergies

Pharmacy Technician Post-test

After completing this continuing education activity, pharmacy technicians will be able to
• Outline the causes of pet allergies in dogs, cats, and other less common species
• Differentiate between allergic sensitization, allergy, and cross sensitivity
• Paraphrase facts that prove that currently, hypoallergenic dogs and cats are a myth
• Identify patients whose complaints indicate they may need referral to a pharmacist

1. What is the major allergen in dogs?
A. Can f 3
B. Can f 1
C, Fel d 1

2. When comparing allergy immunotherapies (SCIT, SLIT) and traditional allergy treatments, how do they differ?
A. Traditional allergy treatments are more clinically efficacious, SCIT and SLIT therapies should not be considered in treatment
B. Traditional allergy treatments are more effective, but with the recent FDA approval of SLIT, it should be considered more OFTEN?
C. Although not FDA approved, SLIT showed similar efficacy to nasal corticosteroids and more clinical efficacy to second-generation antihistamines in trials

7. Emily and her mom come to the pharmacy, and they are very excited. They are considering adopting a dog! Emily has asthma and multiple allergies, and the pediatrician has told them she is probably allergic to or will become allergic to dogs. As Mom chatters, she tells you that the 9-year-old dog, Raven, is an Alaskan Malamute (a breed that has a heavy undercoat) that weighs 95 pounds. She said that a friend told her that if she washes the dog two or three times a month, allergies will not be a problem. She says, “I think I can find time to wash a dog twice a month.” What is the MOST IMPORTANT FACT should you bring to her attention?
A. Before adopting Raven, check with a veterinarian or a breed advocacy group to determine if bathing is a good idea.
B. Bathing a pet two to three times a month is not frequent enough to reduce the allergen load—you have to bathe them two to three times a week.
C. Look for a younger Alaskan Malamute—maybe a puppy—so the dog will get used to being bathed all the time.

8. Adele., who is 7 months pregnant, is experiencing an allergic reaction to a visiting ferret. She asks you to recommend an OTC product to reduce her nasal stuffiness and itchy eyes. Which is the BEST product to recommend?
A. Intranasal cromolyn
B. Oral levocetirizine
C. Oral diphenhydramine

10. Which medication class should be used for no longer than five days at a time?
A. Decongestants
B. First generation antihistamines
C. Nasal corticosteroids

2021-2022 APPA National Pet Owners Survey. Accessed January 17, 2022. https://www.americanpetproducts.org/press_industrytrends.asp
Ownby D, Johnson C. Recent Understandings of Pet Allergies [version 1; peer review: 2 approved]. F1000Research. 2016;5(108)doi:10.12688/f1000research.7044.1
Perzanowski MS, Rönmark E, Platts-Mills TA, Lundbäck B. Effect of cat and dog ownership on sensitization and development of asthma among preteenage children. Am J Respir Crit Care Med. 2002;166(5):696-702. doi:10.1164/rccm.2201035
Ownby DR, Johnson CC, Peterson EL. Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA. 2002;288(8):963-72. doi:10.1001/jama.288.8.963
Díaz-Perales A, González-de-Olano D, Pérez-Gordo M, Pastor-Vargas C. Allergy to uncommon pets: new allergies but the same allergens. Front Immunol. 2013;4:492-492. doi:10.3389/fimmu.2013.00492
Curin M, Hilger C. Allergy to pets and new allergies to uncommon pets. Allergol Select. 2017;1(2):214-221. Published 2017 Aug 4. doi:10.5414/ALX01842E
Villas F, Compes E, Fernández-Nieto M, Muñoz MP, Bartolome B, de las Heras M. Bird-egg syndrome caused by Agapornis species (lovebird). J Investig Allergol Clin Immunol. 2009;19(1):71-2.
Quirce S. Asthma in Alergológica-2005. J Investig Allergol Clin Immunol. 2009;19 Suppl 2:14-20.
Ferret allergies: Are ferrets hypoallergenic animals? Accessed July 12, 2022. https://friendlyferret.com/ferret-hypoallergenic-allergies/
Are rabbits hypoallergenic? All your questions answered. Hypoallergenic Home. Accessed July 12, 2022. https://hypoallergenichomes.com/hypoallergenic-pets/rabbits/
Konradsen JR, Fujisawa T, van Hage M, et al. Allergy to furry animals: New insights, diagnostic approaches, and challenges. J Allergy Clin Immunol. Mar 2015;135(3):616-25. doi:10.1016/j.jaci.2014.08.026
Kang SY, Won HK, Park SY, Lee SM, Lee SP. Prevalence and diagnostic values of laboratory animal allergy among research personnel [published online ahead of print, 2021 Jul 11]. Asian Pac J Allergy Immunol. 2021;10.12932/AP-220321-1094. doi:10.12932/AP-220321-1094
Grönlund H, Saarne T, Gafvelin G, van Hage M. The major cat allergen, Fel d 1, in diagnosis and therapy. Int Arch Allergy Immunol. 2010;151(4):265-74. doi:10.1159/000250435
Fernández-Parra B, Bisson C, Vatini S, Conti A, Cisteró Bahima A. Allergy to chinchilla. J Investig Allergol Clin Immunol. 2009;19(4):332-3.
De las Heras M, Cuesta-Herranz J, Cases B, et al. Occupational asthma caused by gerbil: purification and partial characterization of a new gerbil allergen. Ann Allergy Asthma Immunol. 2010;104(6):540-542.
De las Heras M, Cuesta J, De Miguel J, et al. Occupational rhinitis and asthma caused by gerbil. J Allergy Clin Immunol. 2002;109(1):S326.
Hunskaar S, Fosse RT. Allergy to laboratory mice and rats: a review of the pathophysiology, epidemiology and clinical aspects. Lab Anim. 1990;24(4):358-379.
Sathish JG, Sethu S, Bielsky M-C, et al. Challenges and approaches for the development of safer immunomodulatory biologics. Nat Rev Drug Discov. 2013;12(4):306-324.
Phipatanakul W. Rodent allergens. Curr Allergy Asthma Rep. 2002;2(5):412-416.
Gonzáles de Olano D, Pastor Vargas C, Cases Ortega B, et al. Identification of a novel 17-kDa protein as a ferret allergen. Ann Allergy Asthma Immunol.. 2009;103(2):177-178.
Posthumus J, James HR, Lane CJ, et al. Initial description of pork-cat syndrome in the United States. J Allergy Clin Immunol.. 2013;131(3):923-925.
FDA Allergen Extract Sublingual Tablet. Cited 21 February 2022 Accessed https://www.fda.gov/vaccines-blood-biologics/allergenics/allergen-extract-sublingual-tablets.
Jesner S. (2022, June 28). Sublingual immunotherapy faqs. Sublingual Immunotherapy FAQs. Accessed July 8, 2022. https://www.hopkinsmedicine.org/otolaryngology/specialty_areas/sinus_center/sublingual_immunotherapy.html#:~:text=Immunotherapy%20treats%20the%20cause%20of,as%20drops%20under%20the%20tongue.
Malandain H. IgE antibody in the serum--the main problem is cross-reactivity. Allergy. 2004;59(2):229-230. doi:10.1046/j.1398-9995.2003.00395.x
Nicholas CE, Wegienka GR, Havstad SL, et al. Dog allergen levels in homes with hypoallergenic compared with nonhypoallergenic dogs. Am J Rhinol Allergy. 2011;25(4):252-6. doi: 10.2500/ajra.2011.25.3606
Dance A. The race to deliver the hypoallergenic cat. Nature. 2020;588(7836):S7-S9. doi:10.1038/d41586-020-02779-3
Hypoallergenic cats. Blue Cross. (n.d.). Accessed July 8, 2022. https://www.bluecross.org.uk/advice/cat/hypoallergenic cats#:~:text=Despite%20popular%20belief%2C%20hypoallergenic%20cats,how%20much%20protein%20they%20produce
Skin prick tests. FoodAllergy.org. Accessed August 1, 2022. Skin Prick Tests - FoodAllergy.org
de Vos G. Skin testing versus serum-specific IgE testing: which is better for diagnosing aeroallergen sensitization and predicting clinical allergy?. Curr Allergy Asthma Rep. 2014;14(5):430. doi:10.1007/s11882-014-0430-z
Hodson T, Custovic A, Simpson A, Chapman M, Woodcock A, Green R. Washing the dog reduces dog allergen levels, but the dog needs to be washed twice a week. J Allergy Clin Immunol. Apr 1999;103(4):581-5. doi:10.1016/s0091-6749(99)70227-7
Latz K. How Often Should You Bathe Your Dog? Accessed July 13, 2022. https://www.akc.org/expert-advice/health/how-often-should-you-wash-your-dog/
Aalberse RC. Mammalian airborne allergens. Chem Immunol Allergy. 2014;100:243-247. doi:10.1159/000358862
Wood RA, Johnson EF, Van Natta ML, Chen PH, Eggleston PA. A placebo-controlled trial of a HEPA air cleaner in the treatment of cat allergy. Am J Respir Crit Care Med. 1998;158(1):115-120. doi:10.1164/ajrccm.158.1.9712110
Discover ProPlan LiveClear Allergen Reducing Cat Food. Purina. Accessed July 12, 2022. https://www.purina.com/pro-plan/cats/liveclear-cat-allergen-reducing-food
Scolaro KL. Chapter 11: Colds and Allergy. Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care, 20th Edition.
Product Information: SINGULAIR(R) oral tablets, oral chewable tablets, oral granules, montelukast sodium oral tablets, oral chewable tablets, oral granules. Merck & Co (Per FDA); 2012.
Clark J, White ND. Immunotherapy for Cat Allergies: A Potential Strategy to Scratch Back. Am J Lifestyle Med. 2017;11(4):310-313. doi:10.1177/1559827617701389
Allergenics. U.S. Food and Drug Administration. Accessed July 29, 2022. https://www.fda.gov/vaccines-blood-biologics/allergenics
Sublingual Immunotherapy. Johns Hopkins Medicine. Accessed July 13, 2022. https://www.hopkinsmedicine.org/otolaryngology/specialty_areas/sinus_center/sublingual_immunotherapy.html#:~:text=Immunotherapy%20treats%20the%20cause%20of,as%20drops%20under%20the%20tongue.
Abramson MJ, Puy RM, Weiner JM. Injection allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2010;(8):Cd001186. doi:10.1002/14651858.CD001186.pub2
Aasbjerg K, Torp-Pedersen C, Backer V. Specific immunotherapy can greatly reduce the need for systemic steroids in allergic rhinitis. Allergy. 2012;67(11):1423-9. doi:10.1111/all.12023
Ling M, Long AA. Pet dander and difficult-to-control asthma: therapeutic options. Allergy Asthma Proc. 2010;31:385-391.
Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1-55. doi:10.1016/j.jaci.2010.09.034
Goodman MJ, Jhaveri M, Saverno K, Meyer K, Nightengale B. Cost-effectiveness of second-generation antihistamines and montelukast in relieving allergic rhinitis nasal symptoms. Am Health Drug Benefits. 2008;1(8):26-34.
Aboshady OA, Elghanam KM. Sublingual immunotherapy in allergic rhinitis: efficacy, safety, adherence and guidelines. Clin Exp Otorhinolaryngol. 2014 Dec;7(4):241-9. doi: 10.3342/ceo.2014.7.4.241.
Hardin FM, Eskander PN, Franzese C. Cost-effective Analysis of Subcutaneous vs Sublingual Immunotherapy From the Payor's Perspective. OTO Open. 2021 Oct 25;5(4):2473974X211052955. doi: 10.1177/2473974X211052955.

Human Trafficking: Pharmacy’s Impact on Care

After completing this application-based continuing education activity, pharmacists will be able to

Review the history and current laws of human trafficking in the United States

Recognize common terms, warning signs, and/or vulnerabilities for human trafficking in pharmacy patients/customers

Describe pharmacists’ impact on identifying and supporting victims and survivors of human trafficking

Ensure proper referral, treatment, and counseling for common health risks associated with human trafficking

After completing this application-based continuing education activity, pharmacy technicians will be able to

Review the history and current laws of human trafficking in the United States

Recognize common terms, warning signs, and/or vulnerabilities for human trafficking in pharmacy patients/customers

Identify signs/signals of human trafficking red flags to notify pharmacists or law enforcement

Americans may widely underestimate human trafficking’s current extent in the United States because of stereotypes about traffickers, victims, and sex workers, and also because many Americans lack knowledge about this topic. Despite the general public’s lack of knowledge, trafficking reports are rapidly increasing in the United States today. Healthcare for trafficking victims and survivors is often complicated due to clinicians’ lack of sensitivity about a patient’s trafficking experiences. Because victims of human trafficking are highly likely to seek medical care while under a trafficker’s control, training healthcare providers to identify, handle, and report suspected human trafficking is critical. Without trafficking education, providers’ biases and misunderstanding of victim trauma may hinder the ability to develop a trusting patient-provider relationship. Pharmacy teams should know how to identify human trafficking while protecting victims’ safely, providing appropriate resources for victims to seek help, and assisting with individualized treatment selection.

Introduction

Human trafficking is a growing concern globally. Americans may widely underestimate human trafficking’s current extent in the United States (U.S.) because of stereotypes about traffickers, victims, and sex workers, and also because many Americans lack knowledge about this topic. Despite the general public’s lack of knowledge, trafficking reports are rapidly increasing in the United States today. The SIDEBAR defines terms associated with human trafficking.

SIDEBAR. Human Trafficking Definitions^1,2

Human Trafficking: Recruitment, transfer, transportation, or receipt of people through force, manipulation, fraud, or threats to achieve control over a person for exploitation
Sex worker: A person who voluntarily provides sex work regularly or occasionally in commercial exchange for money or goods. Sex work differs from sexual exploitation, or the forcing of a person to commit sexual acts.
Survivors: people who have escaped their trafficking situations
Survivor-informed practice: Including meaningful input from a diverse community of survivors at all stages of a program or project, including development, implementation and evaluation
Traffickers: people using force, manipulation, threats, or fraud to force victims into exploitative situations
Trauma-informed care: collaborating with community resources to empower individuals to determine their own futures
Venue: The place in which trafficking occurs; human trafficking does not necessarily involve crossing state or international borders
Victims: people currently in an exploitative situation

In 2010, Faith Robles, a 14-year-old teenager from Mexico, moved in with her boyfriend’s family in Queens, New York.³ The family promised her a job that would “change her life,” but she did not learn this involved sleeping with men against her will—sometimes up to 30 men daily—until after her boyfriend smuggled her into the U.S. At the time, Robles was unaware that her boyfriend and four of his relatives were involved in a human trafficking ring. After she arrived, the family threatened to kill her family and traffic her sister if she sought help from authorities or did not comply with their demands. Robles was a victim of sex trafficking for three and a half years, suffering multiple beatings, sexual assaults, and a broken jaw following an escape attempt. She was finally able to escape at age 17 when she sought help from police officers.³ Hearing from survivors like Faith Robles has helped healthcare providers develop interventions that are survivor-informed. This continuing education activity will cover several aspects of human trafficking as it relates to pharmacy using evidence collected by reliable organizations and researchers.

Unfortunately, many victims in the U.S. today share stories like Robles’. In August 2022, the Federal Bureau of Investigation (FBI) announced that they located and identified 84 minors who were victims of sex trafficking during a nationwide sex trafficking operation. FBI agents found an additional 141 adult victims. Human trafficking rates continue to increase in the U.S. Reports of human trafficking to the National Center for Missing and Exploited Children Tipline increased from 21.7 million to 29.3 million reports from 2020 to 2021.⁴ Readers should note that collecting and reporting data on human trafficking has some limitations; many cases of human trafficking are never reported.⁵ Sometimes it’s because the victims are afraid or under a trafficker’s strict control and cannot seek help. Sometimes, it's because people who might be able to help a victim do not recognize the problem or have no idea how to help. Sometimes, it’s because systems have not looked at the issue, determined what (if anything) the system’s responsibilities are, and established policies and procedures to prevent trafficking and provide help.

Readers should also note that to be considered human trafficking, the trafficker need not move a victim across state or international borders; thinking that movement is a necessary component of human trafficking is a common misperception. Current federal laws only require that the trafficker has met the criteria for the 3 elements of “act,” “means,” and “purpose.”⁶

ACT means that the trafficker has recruited, transported, transferred, harbors, or received a victim
MEANS indicates the trafficker has used threat or use of force, coercion, fraud, deception, abuse of a position of vulnerability, payments or benefits, or abduction
PURPOSE is very simple; the trafficker’s sole purpose is to exploit the victim

In short, these requirements indicate that someone who coerces an individual to provide sex or labor against their will in exchange for housing or drugs would be considered a human trafficker, as doing so is exploitation. Someone who moves victims from place to place is also a trafficker, and in some states, people or organizations that knowingly harbor traffickers and their victims would also be complicit in human trafficking.^7,8

In 2019, the National Human Trafficking Hotline reported California, Texas, and Florida as the top states for human trafficking with 1,507, 1,080, and 896 reported cases, respectively.⁹ Human trafficking often occurs along highways that provide access to easy getaways and quick transportation; many traffickers move their victims often to avoid detections. The busiest interstates in the U.S. include I-5 in the West, I-95 in the East, and I-80 stretching from California to New Jersey. The Polaris Project (see SIDEBAR) asserts that common trafficking venues include illicit massage parlors, informal underground businesses, and hotels and motels along major highways. For this reason, the National Association of Truck Stop Operators and large hotel chains, such as Marriott, offer training to help employees identify and report human trafficking victims.¹⁰

Pause and Ponder: How likely is your pharmacy to interact with victims or survivors of human trafficking? Why?

SIDEBAR. The Polaris Project

The Polaris Project is a nonprofit social justice organization that fights sex and labor trafficking through the U.S. National Human Trafficking Hotline. Polaris uses survivor-driven trafficking data to improve trafficking identification, provides assistance for victims and survivors, and educates the community. More information on the Polaris Project can be found on its website (https://polarisproject.org/).¹¹

Polaris hosts the National Human Trafficking Hotline around the clock. Readers should make note of this resource, as it will often be the first and safest place to seek help when patients indicate or pharmacy staff suspects that an individual is being trafficked.

Web site: https://humantraffickinghotline.org/en in English
Web site: https://humantraffickinghotline.org/es in Spanish
1-888-373-7888
TTY: 711
Text* 233733

Human trafficking is a crime under federal and international law. The International Labor Organization estimates that the human trafficking “industry” generated $32 billion in 2005, making it the third largest source of income for organized crime.^12,13 Current estimates are unavailable but would clearly be much larger.Human trafficking victims can come from any background and may live for years under their trafficker’s control. Victims may be trafficked by their own family, friends, or acquaintances with or without the victim’s knowledge.^14,15

Human traffickers prey on others in reprehensible ways.¹⁶Policy makers, public health groups, and researchers have tried to understand the motives behind human trafficking to identify factors that would help develop anti-trafficking interventions. Many publications indicate traffickers become involved primarily for financial gain because the profits associated with human trafficking can be enormous. Many of the interventions currently employed identify traffickers by tracking large quantities of cash and banking patterns. Recent research has found that in some cases, traffickers make considerably less money than expected. These traffickers may be motivated by cultural norms, ideology, or religions that devalue human life. Traffickers may be former victims who go on to recruit and control others. And some traffickers simply have sociopathic tendencies.¹⁶

Traffickers use various tactics to manipulate victims, including¹⁴

Debt-bondage
Emotional manipulation
Lies or deceit
Subjecting victims to unstable or unpredictable conditions
Physical, sexual, or psychological violence
Threats against family members
Transporting victims to unfamiliar places to create a language barrier
Withholding documents

Pre-trafficking vulnerabilities for victims include poverty, trauma, domestic violence, learning difficulties, lack of educational or work opportunities, loss of family, community- or gender-based violence, and natural disasters.² Human trafficking survivors with vulnerabilities are at higher risk of re-victimization. The SIDEBAR describes types of human trafficking.

SIDEBAR. Types of Human Trafficking^15,^17,18

All forms of human trafficking include exploitation, abuse of vulnerable situations, psychological violence, and deprivation of freedom. Added physical and/or sexual violence is also common. Specific types of trafficking may include one or more of the following:

Sex trafficking: forcing someone to sell sex; more commonly affects women but often happens to children of both sexes
Forced labor: involuntary servitude, often in industries with large numbers of workers and little regulation; most common element of modern-day slavery
Domestic servitude: jobs related to domestic help; often hidden in plain sight
Debt bondage: begins with debt that the victim is unable to pay immediately; employer exploits the victim by adding additional expenses to increase debt
Other forms: forced marriage, organ removal for sale, and enforced crime

Readers should note that human trafficking differs from human smuggling. In human smuggling, the purported purpose is to transport or hide individuals who lack proper documentation (e.g., passports, driver’s licenses, or other identification) and circumvent officials without regard to immigration laws (a transportation-based crime).The people smuggled across borders often have chosen to be smuggled as a means to reach an otherwise inaccessible destination. Victims of human trafficking are generally held in circumstances against their will. Nevertheless, traffickers may also use victims’ immigration status and threaten to deport victims to coerce victims to do as they are told. In some cases, smuggling may lead to trafficking.

With 30% to 88% of U.S. trafficking victims seeking healthcare at least once during captivity, life-saving identification of trafficking victims in healthcare settings is crucial.¹⁹Several researchers have attempted to estimate how many victims seek healthcare, but because of the nature of the topic and the risk associated with disclosure, it’s been difficult. Two studies shed some light on victims’ contact with healthcare providers. In a meta-analysis of 420 victims, 50% to 98% of victims reported seeking healthcare services in diverse medical settings while they were captive.²⁰A second study found that roughly 63% of victims had visited emergency departments (ED) and identified hospitals and ED as their most frequent source of care.²¹Trafficking victims tend to use complaint-based episodic acute care services (e.g., minute clinics, urgent care centers, and ED) more often than long-term comprehensive primary care services.²² Each visit represents an opportunity to identify potential behaviors, injuries, or actions that may signal victimization. Several studies have documented that healthcare professionals tend to have limited recognition and knowledge of human trafficking.^23,24

No data is available about victims’ use of pharmacies, but pharmacy employees in community settings are likely to encounter human trafficking victims. Pharmacists and technicians should be prepared to recognize human trafficking signs for quick, appropriate, and life-saving action.

History of Human Trafficking in the United States

Let’s return to Faith Robles. Fortunately, Ms. Robles pressed charges against her boyfriend and his family for the damages and trauma she endured during captivity. In 2020, a judge sentenced Robles’ boyfriend and his family to prison terms of between 25 and 40 years under charges of “sex trafficking, sex trafficking conspiracy, sex trafficking of minors, interstate prostitution, alien smuggling, and money laundering conspiracy.”³However, if Robles had reported her case in the early 1970s, she would not have been able to press charges; the federal government did not incorporate human trafficking crimes into U.S. law until recently.

The first U.S. law for human trafficking was the 1974 Child Abuse Prevention and Treatment Act (CAPTA). CAPTA required states to establish child abuse reporting laws as a condition of receiving federal funds.²⁵ Mandated reporters and agencies to which people who observe or suspect abuse are to report vary by state law, but generally states require reporting in some capacity. Healthcare providers should always check their states’ applicable laws periodically so they know exactly what the state requires.

Mandated reporters are personnel who must report suspected or confirmed exploitation, abuse, or neglect of vulnerable populations. Alabama, Colorado, Connecticut, Hawaii, Oregon, Vermont, and Washington state laws specifically list pharmacists as mandated reporters for child victims. Other states list mandated reporters as “healthcare personnel” or people responsible for the care and/or treatment of child victims. Most states do not require mandatory reporting by healthcare personnel for victims 18 years old or older unless the adult is elderly or in some way vulnerable. States that do not require healthcare providers to report adult victims may do so because of the victims’ heightened safety risk, vulnerability, mistrust in authorities, and fear of their traffickers.²⁶ Federal law does not currently require states to mandate reporting for adults or provide funding to meet reporting requirements.

The Trafficking Victims Protection Act (TVPA) of 2000 created the first comprehensive federal law to address human trafficking. The TVPA offered immigration relief for human trafficking victims, creation of public educational programs for prevention of future trafficking, and increased prosecution of trafficking.^25,27 In January 2023, Congress reauthorized this Act. TVPA reauthorization added some additional coverage²⁸:

It increases protections for child survivors of human trafficking
It provides funding for state welfare agencies to identify and assist child victims of human trafficking and work more closely and efficiently with the juvenile justice system
It eliminates barriers to services for child victims of human trafficking: consent from a parent or guardian is no longer necessary to apply for ID and other forms of identification, making it easier for children to apply for benefits and services
It expands support for research concerning social media’s impact on human trafficking

In 2013, the U.S. Department of Health and Human Services (HHS) created the Stop, Observe, Act, and Respond (SOAR) program to provide human trafficking training to healthcare and related professionals. The program includes victim identification and implementation of best practices for necessary reporting, referrals, communication, and treatment. In 2018, the HHS required public posting of best practices on the HHS website for entities receiving federal grants.²⁹ SOAR’s program for individuals and groups are available at https://nhttac.acf.hhs.gov/soar/soar-for-individuals/soar-online.

In 2015, the Justice for Victims of Trafficking Act (JVTA) improved U.S. trafficking response. The law strengthened victim resources, including increasing individuals’ criminal liability if they buy commercial sex from victims, creation of the survivor-led U.S. Advisory Council on Human Trafficking, and a national strategy for combating human trafficking.³⁰

Current human trafficking reporting laws are inconsistent due to variations among states; federal law does not clearly define a “mandated reporter” and does not require healthcare providers to report trafficking victims 18 years old or older.²⁵The American Hospital Association; the law firm of Jones Day; and the Health, Education, Advocacy, Linkage (HEAL) Trafficking network have collated state-specific reporting requirements for healthcare providers on the HEAL Trafficking website (https://healtrafficking.org/wp-content/uploads/2021/01/Human-Trafficking-and-Health-Care-Providers_Legal-Requirements-for-Reporting-and-Education-02_25_21.pdf).²⁶

Pause and Ponder: What policies do you currently have in place to identify victims?

Healthcare Providers & Human Trafficking

Human trafficking victims are often in situations that compromise their health and safety. Most trafficked people seek healthcare from licensed providers at some point during their exploitation. Pharmacists and pharmacy technicians in outpatient settings may interact with victims without realizing their situation. Healthcare providers should be able to recognize possible victims and survivors confidently and take appropriate action to intervene if needed²;however, most health professionals report that they are unfamiliar with how to identify or respond to a trafficked person effectively.³¹

The Pharmacy Team in Action

Pharmacists’ involvement on the healthcare team is increasing and expanding from dispensing drugs to include medication and disease management and more expansive responsibilities. Pharmacy is unique because the available healthcare counseling is highly accessible by the public.

For safety and reporting, pharmacy team members should generally trust their instincts in a suspicious situation, especially when patients^2,31,32

Act as if under control of another person, i.e., another person accompanies the patient, speaks for them, or there is a lack of rapport between the patient and accompanying individual
Report a history of frequent address changes, vagueness about where they live and/or medical history
Are present at a time when they should be in school
Have poor or concerning physical appearance suggesting captivity, neglect, and/or physical harm, i.e., poor hygiene or inappropriate clothing for current weather conditions or for their age (i.e., clothing is more promiscuous or revealing than normal for a teen)
Present with illnesses or injuries not easily explained, especially repeated or partially treated concerns
Exhibit signs and symptoms of self-harm, suicidal ideation, depression, or drug or alcohol misuse

Many state laws require pharmacists to counsel patients on new prescriptions. Prescription filling patterns that may signal trafficking include frequent sexually transmitted infection (STI) treatment, no insurance coverage, cash-only payments, prescriptions routinely lost or stolen, or a medical history of prescriptions from acute care clinics rather than a primary care physician.³³Victims may be hesitant to access healthcare because of safety concerns and are more likely to self-treat using over the counter (OTC) medications. Table 1 lists frequently used or misused OTC products for self-treatment, and this information may assist pharmacists and pharmacy technicians with screening for potential victims. Upon suspicion of trafficking, pharmacists should try to screen the patient privately.

Table 1. OTC Products Frequently Used or Misused for Self-Treatment of Trafficking-Associated Medical Concerns^34,35

Health Concern	OTC Products
Mental health and substance abuse	St. John’s Wort Dextromethorphan Diphenhydramine Pseudoephedrine Phenylephrine
Sexual intercourse or urinary tract infection	Condoms Levonorgestrel (Plan B) Miconazole Pregnancy tests Phenazopyridine Genital anti-itch creams
Physical abuse	Painkillers (i.e. acetaminophen, ibuprofen, aspirin) First aid items (i.e., bandages, gauzes, antiseptics, Neosporin)

Privacy is essential to obtaining accurate and sensitive information that a victim might otherwise not be comfortable with sharing, especially for victims who fear for their safety and accompanied by an abuser. When pharmacy team members try to speak to the patient alone, they should remain calm and ask for privacy cautiously. The pharmacy team may emphasize the importance of privacy to the accompanying individual, perhaps by saying, “I’m going to step in here and speak to [patient’s name] alone because these are deeply personal health issues.” Note that this approach doesn’t ask a question—which might give the trafficker wiggle room to argue—but instead states a fact in a neutral manner. However, pharmacy staff should not push if they experience push-back from the suspected trafficker. Most pharmacies have a separate space for consultation or vaccinations that they may use when patients need privacy or to review sensitive information.

Pause and Ponder: What are some ways your pharmacy team can work to improve health outcomes for victims and survivors of human trafficking?

Avoiding Bias + Using the Correct Language

Pharmacy team members should be aware of their language when speaking to victims; personal biases may perpetuate stereotypes and influence clinical decision making for therapy or diagnoses.

Well-intentioned but poorly informed organizations or people can perpetuate stereotypes that are not evidence-based or all-encompassing.Understanding bias and perpetuated stereotypes reduces barriers to optimal healthcare. Stereotypes associated with trafficking including victim appearance, location, traffickers, or current situations prevent victims from escaping and/or receiving treatment.¹Table 2 addresses common stereotypes or myths associated with human trafficking in the United States. Pharmacy team members should question, acknowledge, and resolve their personal biases towards trafficking to reduce stigmatizing language and shame.

Table 2. Common Human Trafficking Myths vs Reality^1,36

Myth	Reality
Human trafficking victims are always undocumented foreign women or children.	Victims can be any age, sex, ethnicity, or legal status. Sensationalized imagery of victims in the media, such as on TV or in the news, creates bias and provides an inconsistent narrative. Researchers estimate as many as half of all victims and survivors are male, but healthcare professionals are less likely to identify males as victims.
All commercial sex is human trafficking.	Commercial sex is not human trafficking if the patient is an adult and gives informed consent for all activities involved.
Traffickers always hold victims against their will.	Victims may stay involved in trafficking due to lack of resources to leave, fear for their safety, or manipulation by the trafficker. Victims may face shame from their trauma, including cultural attitudes about prostitution, debt, poor health conditions because of captivity, or working conditions.
Labor trafficking is only an issue in developing countries.	Labor trafficking occurs in the U.S. but is reported less often than sex trafficking.
Human trafficking is always a violent crime.	Human trafficking rarely includes physical force such as kidnapping. Most traffickers manipulate victims through psychological means such as defrauding, manipulating, or threatening vulnerable populations.
If individuals consented to be in their initial situation, they are not victims of trafficking.	Initial consent to commercial sex or labor prior to force, manipulation, or fraud is irrelevant if the situation becomes one of coercion and exploitation later.

Healthcare providers should always use strength-based language to avoid victim blaming. For example, providers should refrain from using the term “child pornography,” and instead refer to it as “child sexual abuse materials.”¹For sex trafficking victims, they should refer to sexual acts during captivity as “exploitation” rather than “prostitution.”

Victims may experience intense shame surrounding their experiences that limits their ability to seek medical attention. Healthcare equity for trafficking victims starts with establishing trust. To gain trust, providers should identify and eliminate unconscious biases to improve service accessibility and health outcomes.

HEALTH CONSEQUENCES FOR VICTIMS

Traffickers often expose victims to numerous health risks before, during, and after exploitation and may restrict victims’ access to care. A key indicator of human trafficking is delayed care. Many patients have reasons to delay care (e.g., lack of insurance, no transportation, or difficult access to care), but delayed care in combination with other flags may indicate a patient is in trouble.^37,38 Victims’ lack of access to proper care and poor environmental conditions may lead to deterioration or exacerbation of conditions.³⁹

Mental Health and Addiction

Due to mental exhaustion from trauma, most victims face debilitating mental health issues. Victims may present with signs and symptoms of posttraumatic stress disorder (PTSD), depression, anxiety, dissociation, and substance use disorders. Serious symptoms warranting need for behavioral health therapy may include

Difficulty sleeping
Feeling detached or withdrawn
Guardedness
Hopelessness
Recurrent thoughts of trauma
Sudden emotional reaction when reminded of trauma
Suicidal ideation
Tendency to startle easily

Drug or alcohol addiction may exacerbate victim vulnerability, be used as a coping mechanism, or be a part of the trafficker’s tactic to keep victims hostage. An anti-trafficking service provider reported that 66% of victims claimed their substance use led to being trafficked, while 4.5% claimed their substance use began after being trafficked.⁴⁰ Substance use throughout victimization occurred in 84.3% of victims, with the most common substances used being alcohol, marijuana, cocaine, and opioids.⁴⁰ Due to high mortality rates from opioid overdoses, patients who are or have been trafficked warrant screening for opioid addictions.

Healthcare providers need to engage in trauma-informed care when helping victims of human trafficking.⁴¹ The experience of trauma overwhelms the victim’s ability to cope and healthcare providers need to recognize trauma’s impact on victims. They need to employ a trauma-informed approach. A trauma-informed approach has four components⁴¹:

Realizing trauma’s pervasive impact and the potential paths victims can follow for recovery
Recognizing trauma’s signs and symptoms in individuals, families, staff, and others involved in the system
Responding in a manner that fully integrates knowledge about trauma into policies, procedures, and practices
Taking care to communicate in ways that actively avoid retraumatization

A trauma-informed approach means collaborating with community resources to empower individuals to determine their own futures.⁴¹ Using the NHTRC hotline is a good way to initiate contact with community resources, as its staff is trained to help healthcare providers determine and identify the next best steps when trafficking is suspected or reported.

The Substance Abuse and Mental Health Services Administration (SAMHSA) supplies additional information on child trauma-informed care for patient and provider use (https://www.samhsa.gov/childrens-awareness-day/child-traumatic-stress-resources).⁴⁰

Unprotected Sexual Intercourse

Victims of sex trafficking are at elevated risk for STIs and unwanted pregnancies. Pharmacists should attempt to counsel victims of sex trafficking on proper testing or screening, including the common signs and symptoms of various STIs, types of tests, and when and how to test. The CDC lists specific STI treatment guidelines on its website (https://www.cdc.gov/std/treatment-guidelines/default.htm).⁴²

Monkeypox (now called Mpox) has been an emerging concern particularly for men who have sex with men. Monkeypox presents as a painful rash accompanied by fever, lethargy, muscle aches, and headaches.⁴³ More information on monkeypox presentation, treatment and prevention can be found in UConn’s You Asked For It CE titled, “Go Bananas: Peel Away the Unknowns of Monkeypox.”

In female patients of childbearing age who have had recent unprotected sexual intercourse, pharmacists may recommend OTC emergency contraceptive pills (ECPs), or an intrauterine device (IUD) or “morning after” pill if allowed by state law.

Copper IUDs are a highly effective emergency contraceptive when inserted up to five days after sexual intercourse. This extended period for use and high efficacy rate may be beneficial for victims of human trafficking who may not have immediate access to emergency contraceptives, but IUD insertion can be expensive, and the trafficker may not allow the victim to see a qualified provider. The most common side effects for IUDs are heavy menstrual bleeding, spotty menstruation, or abdominal discomfort. Because victims of sex trafficking may have increased risk for STIs, victims should generally be tested and/or treated for STIs prior to IUD insertion and monitored after insertion.⁴⁴

ECPs contain either levonorgestrel or ulipristal acetate (UPA) with 1.2% and 1.2-2.1% efficacy, respectively. UPA-containing ECPs are more effective between 72 and 120 hours post-intercourse than levonorgestrel-containing ECPs. Side effects may include nausea, vomiting, fatigue, and irregular vaginal bleeding.⁴⁴

More information on emergency contraception eligibility criteria and safety is located on the World Health Organization’s (WHOs) website.⁴⁴ In any emergency contraceptive, efficacy decreases as the time between intercourse and treatment increases. Pharmacists should inform patients that contraceptives do not induce abortions.

Physical Abuse

Victims may be vulnerable to physical abuse in captivity. Common signs of physical abuse are bruises, wounds, fractures, internal injuries, chronic pain, or head, neck and back injuries. Physical abuse may also present as substantial weight loss, dehydration, malnutrition, increased vulnerability to illness, and insomnia. Physical abuse is a medical emergency; if a patient’s safety is in danger, the pharmacy must report the situation to authorities immediately if the patient is a minor. States may require pharmacists to report abuse of an adult under state-specific mandatory reporting laws.

Acting on Human Trafficking

Upon suspicion or confirmation of trafficking, pharmacy technicians should alert the pharmacist and pharmacists should try to see the patient alone when possible. All involved staff must remain vigilant about everyone’s safety and avoid directly challenging the victim and/or accompanying individual. Direct confrontation, or raising the suspicion of an accompanying individual, can put a victim at risk of additional harm. It’s critical to note repeatedly that intervention can be dangerous. Most authorities indicate that the best action is to call the National Human Trafficking Hotline at 1(888) 3737-888 or call 911.³⁸

In instances that involve language barriers, pharmacists should advise the accompanying individual that professional interpreters may be needed instead of relying on ad hoc interpreters (untrained children [who should only be used in emergencies], friends, family, or untrained staff).^45-51 The reasons for working alongside interpreters (and interpreters prefer healthcare providers use the term “working alongside” rather than “using” to reflect that this is a collaborative endeavor) are evidence-based. Ad hoc interpreters are more likely to make mistakes, violate confidentiality rules, and increase risk of adverse outcomes. Professional interpreters are also fluid speakers and need not stop and think or reformulate language before translating. Untrained interpreters often leave out the niceties of language—niceties that increase trust and cultural understanding between patient and provider. When using an interpreter, the clinician should address the patient directly and seat the interpreter next to or slightly behind the patient.^45-51 Readers who want to learn more about the nuances of professional interpretation may be interested in What’s in a Word? A Guide to Understanding Interpreting and Translation, available online for free at https://www.ncihc.org/assets/documents/publications/Whats_in_a_Word_Guide.pdf.

Pharmacists and technicians should be patient, compassionate, and sensitive to build trust and gather sufficient information. Since 2011, the Institute of Medicine and the U.S. Department of Health and Human Services have recommended screening for intimate partner violence and abuse by asking patients, “Do you feel safe at home?” at each visit.⁵² In 2013, the U.S. Preventive Services Task Force also made this recommendation. Although the question was meant to identify intimate partner violence, it has identified other types of abuse. This question surprises many patients, and many healthcare practitioners find it uncomfortable to ask. Pharmacy staff might ask this question, but it probably should not be the first question to the suspected victim. Saving this and similar questions should come after establishing some rapport with the patient and the patient seems comfortable. Regardless, patients may not answer truthfully or at all, but just asking the question let’s victims know that someone cares, and help is available.⁵²When interviewing patients, pharmacists should ask “trauma-informed” questions but consider the harmful effect of reliving traumatic experiences.² Table 3 provides additional appropriate example questions when screening patients for human trafficking.

Table 3. Example Screening Tool for Suspicion of Human Trafficking^2,14,17

Are you limited as to who you can talk to and when?
Do you have the freedom to leave your current job?
Do you have to ask permission for necessities, such as eating or using the bathroom?
Do you owe your employer money or other debts?
Has anyone ever physically hit, threatened, or raped you or anyone you work with for any reason?
Has anyone ever forced you into sexual intercourse for work?
Has anyone threatened your family?
Has anyone threatened you with deportation?
Is someone else controlling your money or finances?
Is someone else in control of where you are allowed to go?
Is someone else in control of your identification documents, including your birth certificate or passports?
Was someone else in control of your travel arrangements to the U.S.?
What is your working or living condition like?

Healthcare providers may be unable to help patients involved in human trafficking—affected individuals may be too afraid to engage. Individuals need to be able and willing to help themselves. Providers should also offer patients choices; if the patient does not verbalize immediate danger, pharmacists can gently discuss reporting to police, non-government organizations, or helplines. When patients do not want to act, healthcare providers should prioritize care for the patient’s health conditions, gain the victim’s trust, and document clearly. Pharmacy teams should write down any information that may be helpful in an investigation, including time of day, address, and vehicle information, if available.

Providers must always consider security risks. Pharmacy staff should never attempt to confront a potential human trafficker or victim directly. They should try to arrange follow-up with patients and document their contact information. Pharmacists may also ask for consent to call the patient’s primary care provider.

That said, pharmacy teams need to follow statutory and healthcare organization procedures at all times. Again, the National Human Trafficking Resource Center (NHTRC) hotline is available for pharmacy teams to use and pharmacy personnel can call the hotline for guidance. The NHTRC helps providers identify local resources and coordinate with social service organizations. It’s hotline is available 24/7 at 1 (888) 3737-888 or text HELP or INFO to “BeFree” (233733). Pharmacists may choose to submit an anonymous tip online on the NHTRC website (https://humantraffickinghotline.org/report-trafficking).³³ If the patient is a minor or in imminent danger, a staff member should stay with the patient, remain calm, and contact 911 or the local police department when it is safe to do so.

Providers should do their best to ensure proper self-care after a stressful or intense situation.

Conclusion

Faith Robles is now a spokeswoman, advocate, and aftercare provider for victims of human trafficking which demonstrates that victims, when they can access help, can survive and flourish.⁵³ Pharmacy teams should remain vigilant when encountering suspicious circumstances. Trafficking victims may have multiple health issues because of their trauma and abuse. Pharmacy team members can easily recognize signs of human trafficking through prescription, disease, or behavioral patterns. Individualized screening and determination of the type of trafficking involved is necessary for treatment recommendations and referrals. Pharmacy teams should address victims’ concerns while considering the patient’s health, safety, and personal hardships. Pharmacies may advocate for federal and/or local legislation focused on trafficking prevention and education to drive large-scale change.

PHARMACIST POSTTEST

Learner Questions for Pharmacists
Learning Objectives
At the end of this continuing education activity, pharmacists will be able to
• Review the history and current laws of human trafficking in the United States
• Recognize common terms, warning signs, and/or vulnerabilities for human trafficking in pharmacy patients/customers
• Describe pharmacists’ impact on identifying and supporting victims and survivors of human trafficking
• Ensure proper referral, treatment, and counseling for common health risks associated with human trafficking

1. Which of the following statements describes the Trafficking Victims Protection Act (TVPA) of 2000?
a. TVPA was the first law to address child trafficking reporting laws
b. TVPA offers immigration relief for victims and survivors of human trafficking
c. TVPA created the US Advisory Council on Human Trafficking

2. Which of the following is a federal law and a state-specific law that addresses healthcare providers’ responsibilities regarding human trafficking?
a. Reporting of human trafficking victims 17 years old or younger
b. Specific definitions of “mandated reporters”
c. Mandated human trafficking training for healthcare workers

3. Which act included increased individuals’ criminal liability if they buy commercial sex from victims?
a. The Child Abuse Prevention and Treatment Act (CAPTA)
b. The Stop, Observe, Act, and Respond (SOAR) to Health and Wellness Act
c. The Justice for Victims of Trafficking Act (JVTA)

4. Which action may result in increased harm for human trafficking victims when accompanied by an individual?
a. Asking to see the patient alone during private exams because your state requires prescription counseling
b. Allowing the accompanied individual to act as an interpreter when there is a language barrier
c. Staying aware of your own safety when encountering a victim and accompanying individual
5. Which of the following situations during counseling may suggest a patient may be a victim of human trafficking?
a. A 37-year-old female patient approaches the consulting window alone asking to pick up her birth control prescription 2 days earlier than allowed by insurance
b. A patient calls the pharmacy asking about selection of vaginal itch creams and pregnancy tests three separate times within one month
c. A smiling 9-year-old patient accompanied by his legal guardian picking up a new prescription for an albuterol inhaler for the child

6. When heightening awareness of human trafficking, what do healthcare providers need to know?
a. Human trafficking victims are likely to seek healthcare at least once during captivity
b. Human trafficking victims are predominately female adults aged 25 to 34
c. Traffickers often force victims into trafficking through physical force such as kidnapping

7. A young woman visits the pharmacy accompanied by a man who seems to hover and intervene in your conversations with the woman. You are able to gently pry her away and interview her in the counseling room. She tearfully says that 4 days ago she had unprotected sexual intercourse with a man who told her he may have an STI after they had sex. Which emergency contraceptive would you choose for her?
a. Ulipristal acetate (UPA) emergency contraceptive pills
b. Levonorgestrel emergency contraceptive pills
c. Refer her for a copper intrauterine device

8. A young male who is unkempt and has a prescription for an antibiotic used to treat syphilis listens intently as you counsel him on how to take the medication. You ask him how he has been feeling in general in an attempt to build trust. He says that his clothes have gotten tight, has missed school because he sleeps heavily all night and oversleeps often, and he periodically experiences headache, fatigue, dizziness and thirst. Which symptom set may indicate he may be a victim of human trafficking?
a. His clothes have gotten tight
b. Oversleeping
c. Headache, fatigue, dizziness and thirst

9. Alex, Ben, and Carrie each describe symptoms that seem to suggest opioid addictions. Alex, 17, says that he has used heroin since he was 12. Ben, 42, says that he currently has little access to opioids and needs treatment to reduce craving. Carrie, 15, says that she uses alcohol when her “friend” cannot find opioids for her. Which patients are most in need of screening for possible human trafficking?
a. Alex and Ben
b. Ben and Carrie
c. Carrie and Alex

10. The lead technician comes to you and says that she tried to complete medication reconciliation for a young woman. She is 16 years old and has just been admitted to the emergency department for abdominal pain that started with a diagnosis of chlamydia two weeks ago. Now, she may have pelvic inflammatory disease. The patient does not speak English. The woman’s companion said that he would translate for her because she has antisocial personality disorder. Choose the BEST way to approach this dilemma.
a. Say, “Are you aware that your actions seems suspicious? Either let us talk to her in private or we are going to call the police”
b. Say, “We have called a translator, and we’ll speak to [patient’s name] alone because these are deeply personal health issues.”
c. Say, “You have a choice here. We can use the hospital translator with or without you present, and you can take your friend and leave AMA.”

Learner Questions for Pharmacy Technicians
At the end of this continuing education activity, the pharmacy technician will be able to
• Review the history and current laws of human trafficking in the United States
• Recognize common terms, warning signs, and/or vulnerabilities for human trafficking in the pharmacy
• Identify signs/signals of human trafficking red flags to notify pharmacists or law enforcement

4. Which of the following is a pre-trafficking vulnerability for victims?
a. Natural disasters
b. High insurance copays
c. Well-paying occupation

5. Which of the following types of trafficking matches its definition below?
a. Forced Labor: involuntary servitude, often from industries with large numbers of workers and little regulation
b. Domestic servitude: begins with debt that cannot be paid immediately; employer exploits the victim by adding additional expenses to increase debt
c. Debt bondage: forcing someone to sell sex
6. Which of the following OTC products are human trafficking victims most likely to use or misuse?
a. Esomeprazole (Nexium)
b. Oxymetazoline (Sinex)
c. Acetaminophen (Tylenol)

7. Which statement below is a common myth regarding human trafficking in the United States?
a. Labor trafficking exists in the United States, but public health officials less often report labor trafficking compared to sex trafficking
b. All commercial sex is human trafficking
c. Human trafficking rarely uses physical force such as kidnapping

8. Select the patient interaction that should prompt you to inform your pharmacist of potential human trafficking.
a. A young adult patient who hands you a handwritten list of their prescriptions and medical history
b. An adolescent whose breath smells of alcohol and is dressed in shorts and a tank top for 10⁰F weather in January
c. A female patient asking to fill her birth control 2 days earlier than her insurance will cover because she’s going on vacation to Miami tomorrow
9. Three patients confirm that they are human trafficking victims but state that they are not in imminent danger and ask you not to contact authorities. You MUST contact the authorities for one patient under federal law. Which one is it?
a. An 18-year-old patient who has not showered in 3 weeks
b. An 11-year-old patient accompanied by her father
c. A 23-year-old patient taking medications for his anxiety disorder
10. Upon suspicion of human trafficking, which of the following is an appropriate intervention for pharmacy technicians?
a. Directly confront the individual accompanying the victim and tell them to stay where they are while you get the pharmacist
b. When alone with the patient, start a discussion with in-depth questions about their trauma for a more detailed background
c. Prioritize everyone’s safety, inform the pharmacy team of the situation, and call the authorities when appropriate

REFERENCES

References

Jessica L. Peck, Jordan Greenbaum & Hanni Stoklosa (2021): Mandated Continuing Education Requirements for Health Care Professional State Licensure: The Texas Model, Journal of Human Trafficking, DOI: 10.1080/23322705.2021.1981708 [Epub ahead of print]
Hunt J, Witkin R, Katona C. Identifying human trafficking in adults. BMJ. 2020; 371 doi:10.1136/bmj.m4683 [Epub ahead of print]
Rasmussen A. 'I Will Never Forgive You': Sex Trafficking Survivor Helps Put Her Captors Behind Bars. CrimeFeed. Published July 2022. Accessed January 5, 2023. https://www.investigationdiscovery.com/crimefeed/id-shows/on-tv0/in-pursuit-with-john-walsh/articles/raymond-dean-holley-easter-sunday-child-sex-abuse-fugitive
Chen S. FBI locates 121 minors, 141 adults in nationwide human trafficking bust. Axios. Published August 15, 2022. Accessed January 5, 2023. https://www.axios.com/2022/08/15/fbi-human-trafficking-operation-recovery
Gaps in Reporting Human trafficking incidents result in significant undercounting. National Institute of Justice. August 4, 2020. Accessed January 5, 2023. https://nij.ojp.gov/topics/articles/gaps-reporting-human-trafficking-incidents-result-significant-undercounting
The Trafficking Victims Protection Act of 2000. U.S. Department of Health & Human Services, Office on Tafficking in Persons. Accessed January 5, 20232. https://www.acf.hhs.gov/archive/otip/policy-guidance/state-letter-01-13
Van Steenwyk J. Human trafficking: What landlords & property managers must know. All Property Management web site. Accessed January 5, 2023. https://www.allpropertymanagement.com/blog/post/human-trafficking-facts-for-landlords/
Landlords Coercing Tenants Unable to Pay Rent to Provide Sex: Sex Trafficking or Not? Polaris web site. Accessed January 5, 2023. https://polarisproject.org/blog/2020/05/landlords-coercing-tenants-unable-to-pay-rent-to-provide-sex-sex-trafficking-or-not/
Where does human trafficking happen? DeliverFund. Published June 9, 2022. Accessed January 5, 2023. https://deliverfund.org/the-human-trafficking-problem-in-america/where-does-human-trafficking-happen/
Datta M. Sex trafficking in the US: Four questions answered. Phys.org. Published March 8, 2019. Accessed January 5, 2023. https://phys.org/news/2019-03-sex-trafficking.html
The Polaris Project. About Us. Accessed January 5, 2023. https://polarisproject.org/about-us/.
Dovydaitis T. Human trafficking: the role of the health care provider. J Midwifery Womens Health. 2010;55(5):462-467.
Feingold D. Human trafficking. Foreign Policy. 2005; 150:26-30.
Zimmerman C, Borland R. Caring for Trafficked Persons: Guidance for Health Providers. International Organization for Migration. 2009. Accessed January 5, 2023. https://www.iom.int/caring-trafficked-persons-guide-health-providers
Polaris. Human Trafficking Trends in 2020 An analysis of data from the U.S. National Human Trafficking Hotline. Accessed January 5, 2023. https://polarisproject.org/wp-content/uploads/2022/01/Human-Trafficking-Trends-in-2020-by-Polaris.pdf
Clark MC. Questioning the Notion of Financial Gain as the Primary Motivation of Human Traffickers. Anti-Trafficking Rev. 2022;18:180-184.
Leslie J. Human trafficking: Clinical assessment guideline. J Trauma Nursing. 2018;25(5):282-289.
Human trafficking vs human smuggling. US Immigration and Customs Enforcement. Published Summer 2017. Accessed January 5, 2023. www.ice.gov/sites/default/files/documents/Report/2017/CSReport-13-1.pdf
Stoklosa H, Showalter E, Melnick A, Rothman EF. Health Care Providers’ experience with a protocol for the identification, treatment, and referral of human-trafficking victims. J Human Trafficking. 2016;3(3):182-192.
Armstrong S, Greenbaum VJ. Using Survivors' Voices to Guide the Identification and Care of Trafficked Persons by U.S. Health Care Professionals: A Systematic Review. Adv Emerg Nurs J. 2019;41(3):244-260. doi:10.1097/TME.0000000000000257
Lederer LJ, Wetzel CA. The health consequences of sex trafficking and their implications for identifying victims in healthcare facilities. Ann Health Law. 2014;23(1);61-87.
Wallace C, Lavina I, Mollen C. Share our stories: An exploration of the healthcare experiences of child sex trafficking survivors. Child Abuse Negl. 2021;112:104896. doi:10.1016/j.chiabu.2020.104896
McAmis NE, Mirabella AC, McCarthy EM, et al. Assessing healthcare provider knowledge of human trafficking. PLoS One. 2022;17(3):e0264338. doi: 10.1371/journal.pone.0264338
Recknor FH, Gemeinhardt G, Selwyn BJ. Health care provider challenges to the identification of human trafficking in health care settings: a qualitative study. J Human Trafficking. 2018;4(3):1-18. doi: 10.1080/23322705.2017.1348740
Jones Day White Paper. Human Trafficking and Health Care Providers: Legal Requirements for Reporting and Education. Published August 2020. Accessed January 5, 2023. https://healtrafficking.org/wp-content/uploads/2021/01/Human-Trafficking-and-Health-Care-Providers_Legal-Requirements-for-Reporting-and-Education-02_25_21.pdf.
Kirschner F, Godspeed T, Baker C, Lynch S, Jones H. Human trafficking and Health Care Providers: Legal Requirements for Reporting and Education. HEAL Trafficking: Health, Education, Advocacy, Linkage. Accessed January 5, 2023. https://healtrafficking.org/2021/01/legal-requirements-for-reporting-and-education/
Federal law. National Human Trafficking Hotline. Accessed January 5, 2023. https://humantraffickinghotline.org/what-human-trafficking/federal-law.
Delgado A. The trafficking victims protection act is signed into law. January 9, 2023. Accessed February 17, 2023. https://www.ecpatusa.org/blog/2023/1/4/trafficking-victims-protection-act-signed-into-law
The SOAR to Health and Wellness Act of 2018, Pub L. No. 115-398 § 132 Stat. 5329 (2018).
Human trafficking laws & regulations. US Department of Homeland Security. Accessed January 5, 2023. https://www.dhs.gov/human-trafficking-laws-regulations.
Nordstrom B. Multidisciplinary Human Trafficking Education: Inpatient and Outpatient Healthcare Settings. J Human Trafficking. 2020;8(2):184-194
Indicators of Human Trafficking. Homeland Security Blue Campaign. Accessed January 5, 2023. https://www.dhs.gov/blue-campaign/indicators-human-trafficking
Palombi L, Ochten H, Patz C. The Pharmacists’ Role in Identifying and Supporting Victims of Human Trafficking. Human Trafficking. 2019;5(3):255-266.
Terrie Y. Promote the Safe and Proper Use of OTC Drugs . Pharmacy Times . 2019;85(4).
Trygstad T, DiMaggio T, Ogurchak J, Arakelians S, Gallagher A, James D. 2022 Survey of Pharmacists' OTC Recommendations. OTC Guide. (2022):3-60. Accessed January 5, 2023. https://cdn.sanity.io/files/0vv8moc6/pharmacytimes/86326ebdabcad93c75193a50a94fb30cf4e10661.pdf/2022OTCGuide_EditorialPagesOnly-R1%20(2).pdf
Myths & Facts. National Human Trafficking Hotline. Published May 3, 2019.Accessed January 5, 2023. https://humantraffickinghotline.org/what-human-trafficking/myths-misconceptions
Baldwin SB, Eisenman DP, Sayles JN, Ryan G, Chuang KS. Identification of human trafficking victims in health care settings. Health Hum Rights. 2011;13(1):E36-E49.
Schuette, B., (2015). Michigan attorney general. Human trafficking “Red Flags” for health care professionals. Accessed December 5, 2022. https://www.michigan.gov/ag/-/media/Project/Websites/AG/human-trafficking/Updated-Red-Flags-for-Responders/Red_Flags_-_Health_Care_598573_7.pdf?rev=827954e5cf9647ca9fc9369046759735
Stoklosa H, MacGibbon M, Stoklosa J. Human trafficking, mental illness, and addiction: Avoiding diagnostic overshadowing. AMA Journal of Ethics. 2017;19(1):23-34.
Resources for Child Trauma-Informed Care. Substance Abuse and Mental Health Services Administration. Accessed January 5, 2023. https://www.samhsa.gov/childrens-awareness-day/child-traumatic-stress-resources
Zarnello L. Implementing trauma-informed care across the lifespan to acknowledge childhood adverse event prevalence: best clinical practices. Nurse Pract. 2023;48(2):14-21. doi:10.1097/01.NPR.0000000000000002
Workowski K, Bachmann L, Chan P, et.al. STI treatment guidelines. Centers for Disease Control and Prevention. Published July 22, 2021. Accessed January 5, 2023. https://www.cdc.gov/std/treatment-guidelines/default.htm
MPox. Ceneters for Disease Control and Prevention. Accessed January 5, 2023. https://www.cdc.gov/poxvirus/monkeypox/index.html
World Health Organization. Emergency contraception. Published November 9, 2021. Accessed January 5, 2023. https://www.who.int/news-room/fact-sheets/detail/emergency-contraception
Juckett G, Unger K. Appropriate use of medical interpreters. Am Fam Physician. 2014;90(7):476-480.
Karliner LS, Jacobs EA, Chen AH, Mutha S. Do professional interpreters improve clinical care for patients with limited English proficiency? A systematic review of the literature. Health Serv Res. 2007;42:727-754.
Flores G, Laws MB, Mayo SJ, et al. Errors in medical interpretation and their potential clinical consequences in pediatric encounters. Pediatrics. 2003;111:6-14.
Jacobs EA, Lauderdale DS, Meltzer D, Shorey JM, Levinson W, Thisted RA. Impact of interpreter services on delivery of health care to limited-English-proficient patients. J Gen Intern Med. 2001;16:468-474.
What's in a Word? A Guide to Understanding Interpreting and Translation in Healthcare. Los Angeles, CA: National Health Law Program; 2010. Accessed January 5, 2023. https://www.ncihc.org/assets/documents/publications/Whats_in_a_Word_Guide.pdf
Jackson JC, Nguyen D, Hu N, Harris R, Terasaki GS. Alterations in medical interpretation during routine primary care. J Gen Intern Med. 2011;26:259-264.
Nápoles A, Santoyo-Olsson J, Karliner L, Gregorich SE, Pérez-Stable EJ. Inaccurate language interpretation and its clinical significance in the medical encounters of Spanish-speaking Latinos. Med Care. 2015;53:940-947.
Scott M. Doctors asking about domestic violence is important, but daunting. December 16, 2015. Accessed February 7, 2023. https://whyy.org/segments/doctors-asking-about-domestic-violence-is-important-but-daunting/
Dahlia's Hope. Accessed January 5, 2023. https://www.dahliashope.org/

Patient Safety: Seven Secrets for Patient Safety with Dietary Supplements

After completing this application-based continuing education activity, pharmacists will be able to

· Discuss the importance of knowing about a patient’s dietary supplement usage

· Identify commonly used dietary supplements, their regulation, and the value of certification

· Recognize potential medication-dietary supplement interactions

· Demonstrate the ability to locate different sources of information about dietary supplements

After completing this application-based continuing education activity, pharmacy technicians will be able to

· Discuss the importance of knowing about a patient’s dietary supplement usage

· Identify commonly used dietary supplements, their regulation, and the value of certification

· Recognize potential medication-dietary supplement interactions

· Recognize the need for pharmacist counseling when a patient is taking a dietary supplement

Consumer consumption of dietary supplements is at an all-time high. Available products number in the tens of thousands, generating millions in annual spending. Increasing interest in overall health and wellness, preventive medicine, and immune function contribute to the rise in usage. It is a common misconception that dietary supplements are safe because they are “natural.”
Ingestion of dietary supplements poses serious health risks including adverse reactions, drug interactions, and toxicity. Adulterated, mislabeled, and contaminated products exist in the marketplace, further increasing consumer risk. Existing federal regulation and oversight for supplements differs from prescription and over-the-counter medications, occurring primarily on a post-marketing basis. Self-reporting by consumers, healthcare professionals, and industry personnel identifies these issues. Patients often omit dietary supplements from medication histories, leaving healthcare professionals unaware that patients are using them. While misinformation abounds on the Internet, many online clinically-backed sources exist.

Introduction

Consuming natural substances to produce a desired effect on the body dates back thousands of years to ancient Egypt, Rome, China, and many other cultures. Records from early Mesopotamia include written formulas using many oils still in use today, including cedar, cypress, and licorice. Around 300 B.C., the Greek philosopher Theophrastus described the medicinal benefits of natural substances in his History of Plants. Throughout the centuries, many philosophers, scientists, and physicians continued collecting, combining, and documenting the use of natural products to treat different illnesses.¹

As the science of medicine developed, so did the science of pharmacology. Isolation of the active ingredients found in herbal substances lead to the development of synthetic compounds with similar properties. The first synthetic medication, chloral hydrate, derived from chloroform and discovered in the 1800s by German chemist Justus von Lieberg, is still in use today.²

Fast forward to modern day, and the interest and use of prescription medications, over-the-counter (OTC) products, and dietary supplements are at an all-time high. In 2020, consumers filled 6.3 billion prescriptions in the United States³ (U.S.) and purchased more than 6 billion OTC products.⁴ The dietary supplement market reached an unprecedented level in 2020 with a global spend of $61.2 billion. Experts predict it will reach $128.64 billion by 2028.⁵

The COVID-19 pandemic, caused by the SARS-CoV-2 acute respiratory coronavirus, significantly impacted our perception and approach to healthcare.⁶ More and more people use complementary and alternative approaches to healthcare than ever before.⁷ For example, sales of elderberry supplements more than doubled and zinc products quadrupled shortly after the pandemic's start.⁸

Pharmacists, widely recognized as drug information experts, and pharmacy technicians routinely field consumers' questions about dietary supplements. Many pharmacists lack the necessary knowledge or don't know where to look to answer these questions. Pharmacy schools educate future pharmacists on prescription and OTC medications with courses about nutrition and dietary supplementation, if offered, available as electives. This continuing education activity presents information about dietary supplements through a series of seven common pharmacy situations and lets learners in on seven secrets they can apply to their practices.

Situation: Continuing education is a professional requirement many pharmacists find tedious. Looking through the UCONN online CE library and seeing a new continuing education activity entitled ‘Seven Secrets of Patient Safety with Dietary Supplements,’ a pharmacist remarks to the pharmacy team, "What a waste, no one even takes dietary supplements."

Secret #1: Almost 60% of people in the United States used a dietary supplement in the last 30 days.^11,12

Dietary supplements crowd the aisles in drug stores, supermarkets, warehouse clubs, and even corner convenience stores. The sheer number of products is staggering. The Dietary Supplement Database (DSLD) is an online, searchable database developed by the Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH). The database contains product labeling information on dietary supplements sold in the United States, including both on and off-market products. DSLD currently lists more than 140,000 labels.⁹

In the early 1960s, the National Center for Health Statistics began a program named the National Health and Nutrition Examination Survey (NHANES). NHANES is a continuous program focusing on various health and nutritional measurements and assesses adults' and children's health and nutritional status in the U.S.¹⁰ Scientific and technical journals publish the study results.

One section of the program assesses dietary supplement use among adults. Results from the 2017-2018 NHANES show that^11,12

57.6% of adults 20 years or older used a dietary supplement in the past 30 days
Women (63.8%) had a higher utilization than men (50.8%)
Use of dietary supplements increased with age, with women 60 years or older reporting the highest usage at 80.2%
Use of multiple dietary supplements increased with age
Most common dietary supplements used by all age groups include multivitamin-mineral supplements, vitamin D, and omega-3 fatty acids

The Council for Responsible Nutrition (CRN) is a trade association for the dietary supplement and functional food industry. Annually, the CRN performs a survey gathering data on consumer use of dietary supplements. The 2019 survey conducted by the CRN underscored dietary supplement usage with the following results¹³:

77% of US adults take dietary supplements, including 79% of American women and 74% of males
Top reasons for taking supplements included:
- Energy
- Immune health
- Filling nutrient gaps
- Healthy aging
- Heart health

The COVID-19 pandemic significantly impacted our perception and approach to healthcare.⁶ As of August 5, 2022, SARS-CoV-2 has infected more than 580 million people worldwide.¹⁴ Interest in boosting our overall immunity and protecting ourselves from viral infections has dramatically increased as a result.⁷ Many vitamins and minerals play essential roles in proper immune function.^7,15 Sales of supplements associated with boosting immunity increased over the last two years, including vitamins C and D, zinc, omega-3, garlic, ginger, and turmeric.¹⁶

Table 1. Common Dietary Supplements and Potential Uses^7,17,18

Dietary Supplement	Potential Use
Black Cohosh	Menopausal symptoms
Calcium	Dyspepsia Osteoporosis Premenstrual syndrome
Echinacea	Prevention and treatment of the common cold Promotion of wound healing
Elderberry	Prevention of upper respiratory tract infections Reduction in duration and severity of symptoms of the common cold
Folic acid	Folate deficiency Kidney failure Neural tube defects
Ginkgo	Anxiety Dementia Memory improvement Premenstrual syndrome
Ginger	Dysmenorrhea Nausea and vomiting Osteoarthritis
Ginseng	Cognitive function Erectile dysfunction
Iron	Anemia Restless leg syndrome
Magnesium	Constipation Dyspepsia
Melatonin	Sleep disorders
Multivitamin with minerals	General supplementation
Omega-3 fatty acids	Alzheimer’s disease Cardiovascular disease Dementia Depression Reduction of triglycerides
Potassium	Hypokalemia Hypertension Kidney stones
Probiotics	Atopic dermatitis Antibiotic-associated diarrhea Irritable bowel syndrome
St. John’s Wort	Anti-depressant Menopausal symptoms
Turmeric	Allergic rhinitis Osteoarthritis Pruritis
Valerian	Insomnia
Vitamin A	Aging skin Healthy vision
Vitamin B-12	Vitamin B-12 deficiency
Vitamin C	Anemia Antioxidant effects Prevention of the common cold Vitamin C deficiency
Vitamin D	Osteomalacia Osteoporosis Vitamin D deficiency
Vitamin E	Alzheimer's disease Dysmenorrhea Premenstrual syndrome
Zinc	Acne Depression Diabetes Diarrhea Treatment of common cold

Eating a healthy diet is essential for good health and nutrition. The Dietary Guidelines for Americans advise professionals, including policymakers, health care providers, and nutrition educators, about what to eat to meet the body’s nutritional needs. It emphasizes eating a diet rich in nutrient-dense foods, such as fruits and vegetables, as the best way to meet the body’s nutritional needs. The guideline identifies specific populations in which dietary supplementation may be necessary, such as women who are pregnant or lactating and adults older than 50.¹⁹

In addition to these defined special populations, many pharmacy patients may find it necessary to take specific vitamins or minerals due to medication-induced nutrient deficiencies.

Table 2. Examples of Nutrient Depletion Induced by Medications^7,17

Nutrient	Medication(s)	Mechanism
Vitamin D	Anticonvulsants	Increase hepatic metabolism
	Bile acid sequestrants	Decrease absorption
	Orlistat	Decrease absorption
Magnesium	Estrogens	Decrease serum levels by increasing uptake into tissues
	Loop diuretics	Increase excretion
	Proton pump inhibitors	Decrease absorption
Vitamin B₁₂	Biguanides	Decrease absorption
	Proton pump inhibitors	Decrease absorption
	H-2 blockers	Decrease absorption
Potassium	Loop diuretics	Increase excretion
	Thiazide diuretics	Increase excretion
	Corticosteroids	Increase excretion

The pharmacist's dismissal of dietary supplement education is understandable. No one wants to waste precious time on irrelevant continuing education. However, the facts presented here illustrate the need for pharmacist education on dietary supplements.

Pause and ponder: A patient presents information about taking lemon and baking soda tea to prevent COVID-19 infection and asks you if it really works. How would you approach this conversation?

Situation: Sunday afternoons sometimes (but not often!) present the opportunity to catch up on administrative activities. While completing an inventory reconciliation of the vitamin section, a technician inquires, "Why does the FDA approve so many different products?" Looking up distractedly from the CII safe count, the pharmacist pauses, then replies in a weary voice, "You know, I’m not sure, probably just to make it more confusing for us."

Secret #2: Regulatory oversight of dietary supplements differs from prescription and OTC medications.

What is a Dietary Supplement?

On the most basic level, a dietary supplement is a substance consumed to add nutrients to a diet or to lower the risk of certain health problems. The use of natural substances has been around for millennia, but it is only within the last five decades that countries worldwide have formalized language and regulations around dietary supplements. Terminology, quality control, and safety assessment differ depending on the country and governing legislative body.²⁰

In 1994, the United States Congress passed the Dietary Supplement Health and Education Act (DSHEA), an amendment to the Food, Drug, and Cosmetic Act. DSHEA defines the term dietary supplement as a product intended for ingestion and containing an ingredient that supplements the diet. Dietary supplement labeling must include the term ‘dietary supplement’ or an equivalent term such as ‘herbal supplement’ or ‘magnesium supplement.’ DSHEA also stipulates that a dietary supplement must be free of contamination, adulteration, and properly labeled.²¹ We will discuss dietary supplement product integrity and labeling later in this activity.

According to DSHEA, dietary supplements include vitamins, minerals, herbs, other botanicals, amino acids, and live microbials (probiotics).Dietary supplements are available in many different formulations including tablets, capsules, soft gels, gel caps, powders, and liquids.²¹

DSHEA defined the term ‘new dietary ingredient’ as an ingredient that meets the above criteria and was unavailable in the U.S. before October 15, 1994. If manufacturers want to market a product containing a new dietary ingredient, they must notify the U.S. Food and Drug Administration (FDA) before marketing. The FDA then reviews the product for safety but not effectiveness.²¹

Regulation of Dietary Supplements

The FDA and the Federal Trade Commission (FTC) share regulation and oversight of dietary supplements. The FDA is responsible for the information provided on dietary supplement product labeling, including the package labeling, product inserts, and information available at the point of sale. The FTC monitors dietary supplement advertising, ensuring advertisements are truthful, substantiated, and not misleading. Both agencies have the authority to address violations and work together to ensure their efforts are consistent with one another.²²

The FDA does not have the authority to approve dietary supplement products before manufacturers market, distribute, and sell them to consumers. Manufacturers are responsible for ensuring the products they produce and distribute meet all quality standards defined by federal law. Quality standards include²²

Ensuring the safety of the dietary ingredients used in the product
Following current Good Manufacturing Practices (cGMP)
Meeting all product labeling requirements
Ensuring substantiation of all claims made about the product
Ensuring products are free of adulteration or misbranding

cGMP, defined and regularly updated by the FDA, establish the minimum requirements for manufacturing, packaging, and labeling products to ensure product quality. cGMP includes guidance on obtaining quality ingredients, operating procedures, and quality controls.²³ Failure to follow cGMP results in possible product contamination.

While the FDA may not have the authority to approve dietary supplements before the product marketing and distribution, it can monitor products via post-marketing surveillance and auditing. The FDA routinely performs manufacturer inspections, monitors the marketplace, and investigates adverse event reports. Follow-up includes working with the manufacturer to bring the product into compliance, issuing warning letters, and recalling products.²¹

Reporting Issues with Dietary Supplements

Post-marketing surveillance is essential for documenting and monitoring any issues with dietary supplements. Information about severe reactions and product quality are important issues to report. The FDA Safety Reporting Portal is an online tool used to report safety issues on several categories of products, including pet or livestock foods, tobacco products, animal drugs, and dietary supplements.²⁴

The website address for the portal is https://safetyreporting.hhs.gov. Anyone can use the portal to report issues, including consumers, healthcare professionals, manufacturers, and researchers. Generating a new report starts on the home screen. The reporter chooses to file the report as a guest or by creating an account. Creating an account streamlines data entry and allows the reporting individual to save a draft of the report, follow up on a report, and view previous submissions.²⁴

Generation of an Individual Case Safety Report ID (ICSR) occurs after report submission. The ICSR allows the reporter to identify the report for future reference including submission of a follow-up report with additional information. FDA reviewers assess the seriousness of the reported issue and assign follow-up. Submission of this information allows the FDA to identify potentially dangerous products and potentially remove them from the market.²⁴

Traditionally, insurance companies limit coverage to prescription medications. Recent trends show an expansion of coverage to include some dietary supplements. Insurance coverage of dietary supplements blurs the regulatory differences between prescription medications and dietary supplements. Understanding the differences in oversight is beneficial and allows the pharmacy staff to counsel patients effectively.

Situation: While running back to the pharmacy after a much-needed bathroom break, a pharmacist stops when approached by a customer asking for advice about an iron supplement. Overhearing the inquiry, another customer comments, "You should buy that online; it’s cheaper, and the quality is just as good." The pharmacist nods assent, turns, and hurries back to the pharmacy amid the erupting sounds of chaos behind the counter.

Secret #3: Product integrity fluctuates between manufacturers and sources of dietary supplements.

Integrity of Dietary Supplements

The lack of government oversight opens the door for substandard products to flood the market. Poor ingredient quality, heavy metal or microbial contamination, adulteration, and mislabeling occur regularly. In the current economy, with rising prices, consumers are turning to less expensive options, and cheaper is not necessarily better, especially with dietary supplements.

In the literature, many studies exist that analyze dietary supplement product integrity. A study published in 2021 tested multiple bottles of 29 herbal supplements for consistency of ingredient activity and the presence of metal and fungal contaminants. The analysis showed inconsistent ingredient activity not only between bottles of the same product manufactured by the same company, but also between bottles manufactured by different companies. Assaying for metal contamination found zinc in 88% of bottles and nickel in 40% of bottles. In 37 of 58 bottles tested, fungal contamination was present, with 21 bottles having multiple strains.²⁵

Another study analyzed 41 dietary supplements for the presence of cadmium, lead, and mercury. Results revealed that 68.3% of samples contained contamination with cadmium and lead, and 29.3% with mercury.²⁶ One research team evaluated 121 dietary supplements along with 49 prescription drugs for levels of toxic element contamination. A small percentage of the dietary supplement products exceeded safety levels for mercury, lead, cadmium, arsenic, or aluminum. None of the prescription products exceeded these safety levels.²⁷

Adulterated products contain substances not listed on the product labeling, substitution of inferior materials for active ingredients, or may contain a lesser amount of ingredients. Weight loss, sports enhancement, and sexual function supplements commonly contain banned substances.²⁸

The FDA created and currently maintains the Health Fraud Product Database to increase awareness. This database contains information about products cited in warning letters, advisory letters, recalls, public notifications, and press announcements for various issues. Issues cited include products claiming to cure, treat, or prevent a disease and products containing undeclared ingredients or a new dietary ingredient.²⁹ The database is available in the consumer section of the FDA website at https://www.fda.gov/consumers/health-fraud-scams/health-fraud-product-database.

On January 2, 2022, the FDA issued a warning letter to the manufacturers of Nasitrol, a nasal spray based on the ingredient iota carrageenan. A review of the product’s website found claims that the product is intended to mitigate, prevent, treat, diagnose, or cure COVID-19 in people. Federal regulations define products making these claims as drugs and subject to review by the FDA before approval and subsequent marketing. As discussed earlier, this is in direct violation of federal regulations.³⁰

In another example, on July 15, 2022, the FDA issued a public notice advising consumers to refrain from purchasing Adam’s Secret Extra Strength Amazing Black, a product promoted for sexual enhancement. Laboratory analysis found that the product contained tadalafil, a prescription medication used for erectile dysfunction.³¹ Due to the potential for severe side effects such as hypotension, tadalafil administration requires medical supervision by a physician.³²

A study published in 2018 analyzed FDA warning letters issued from 2007 through 2016, using data from the Health Fraud Product Database. During this time frame, the FDA found 776 adulterated dietary supplements from 146 different companies. A total of 157 products contained more than one unapproved ingredient. Products marketed for sexual enhancement accounted for 45.5% of letters, weight loss 40.9%, and muscle building 11.9%. Unapproved ingredients included sildenafil in sexual enhancement, sibutramine in weight loss, and synthetic steroids or steroid-like ingredients in muscle building supplements.³³

One way for consumers to know they are purchasing a valid product is by looking for a certified product. The certification process involves an independent, third-party company testing a company’s products, offering quality assurance for dietary supplements. Parameters tested include³⁴

Product contains the ingredients stated on the label
Presence of harmful ingredients
Presence of contamination
Proper dissolution
cGMP followed during manufacture

Three independent, private, third-party certifying organizations operate in the United States: the US Pharmacopeial Convention (USP), NSF International, and Consumerlabs.com. All three companies offer product certification programs for a fee. Each company allows products passing certification to display a seal on product labeling. Table 3 summarizes information about each organization.

Table 3. Dietary Supplement Certification Organizations

Certifying Organization	US Pharmacopeial Convention	NSF International	Consumerlab.com
Website	www.usp.org www.qualitysupplements.org	www.nsf.org	www.consumerlab.com
Services offered	Dietary supplement verification program including GMP facility audits, product QCM process evaluation, and product testing	Product and ingredient certification GMP Certification Certified for Sport	Product reviews Quality Certification Program
Information available on the website	Program information, list of verified products, and educational resources	Program information, product search engine, and educational resources	Product reviews, health condition information
GMP = Good Manufacturing Practice

Source: adapted from reference 33

Online product ordering is a convenient shopping option rapidly gaining popularity in recent years, especially during the pandemic. While tempting to order the least expensive product, investigating the source and quality of dietary supplements available online is essential. Proactive training of the entire pharmacy team aids in providing patients with accurate information.

Situation: A weary technician finally finishes ringing out the last customer after two hours straight at the register. A sigh of relief quickly turns into a disgruntled groan as another customer approaches. With a bottle labeled ‘Menopausal Support’ in hand, the customer points to the bottle label and asks, "What does ‘proprietary blend’ mean?" The technician glances over her shoulder, sees the pharmacist engaged in an intense phone conversation, and replies to the customer, "The bottle label clearly lists the ingredients."

Secret #4: Federal regulations define required dietary supplement label information. Unfortunately, ambiguity still exists, making it challenging to identify exactly what the product contains.

Federal regulations define the information required on dietary supplement product labeling in detailed, specific terms. Product labeling must include³⁵

Product name
The term ‘dietary supplement’ or similar term (i.e., herbal supplement)
Name and location of the manufacturer, along with a domestic address and phone number for reporting serious adverse events
Nutrition labeling in the form of a “Supplement Facts” panel with the following information (see Figure 1):
- Serving size
- Number of servings per container
- Listing of each dietary ingredient in the product
- Amount of dietary ingredient per serving (Exception: ingredients in a proprietary blend)
- Amount per serving listed as a quantitative amount by weight, as a percentage of the Daily Value, or as both
A list of other ingredients not declared on the Supplement Facts label (usually excipients such as preservatives or dyes)
Net quantity of contents

Figure 1. Supplemental Facts Label (sourced from reference 36)

One area of ambiguity in dietary supplement product labeling is the listing of a proprietary blend. The term proprietary blend refers to a blend of dietary ingredients unique to a manufacturer and product. Federal labeling regulations allow the listing of proprietary blends on dietary supplement products, however, only the total weight of the blend is required, not the weight of individual ingredients.³⁵ There is no way for the healthcare professional or consumer to know exactly how much of a particular ingredient the proprietary blend contains.

Consumerlabs.com cautions consumers about products containing proprietary blends or formulas. In many instances, the blend's name sounds like a desired, expensive ingredient that is only a small part of the formula. Marketing of products containing proprietary blends may mislead the consumer with claims meant to impress the consumer and drive sales of the product.³⁷

FDA regulations do allow structure/function claims on dietary supplement labeling. Structure/function claims describe how a nutrient or dietary ingredient may affect or act to maintain the structure or function of the body.³⁵Examples of structure/function claims include³⁵

Calcium builds strong bones
Antioxidants maintain cell integrity
Fiber maintains bowel integrity

If a dietary supplement label contains a structure/function claim it must also contain the following statement: "This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease."³⁵

The example in this situation involved a product marketed for menopausal support. Menopausal symptoms affect more than 1 million women in the US annually and include symptoms such as hot flashes and sleep disturbances.³⁸ A search of the DSLD using the term ‘menopausal support’ and filtering for on-market products containing the ingredient ‘proprietary blend’ returned almost 3,000 products.⁹ This abundance of products illustrates the ambiguity that exists on dietary supplement labeling.

Pharmacy technicians are often the first line of contact at the pharmacy. Training and development of pharmacy technicians on the facts surrounding dietary supplements empower technicians, allowing them to answer factual questions and provide effective patient education.

Situation: The pharmacy phone constantly rings throughout the day, and today is no exception. The new COVID vaccine is out, and everyone wants to know if the pharmacy has it in stock. Answering yet another call, the technician is surprised when a patient asks to talk to the pharmacist, complaining about dizziness. The pharmacist checks the patient’s profile, finding no underlying causative medication. Further questioning the patient, the pharmacist uncovers the recent addition of melatonin at night for sleep.

Secret #5: Like prescription medications, dietary supplements have pharmacologic and physiologic effects on the body, potentially resulting in health risks and side effects.

Consumers perceive dietary supplements as safe due to their source from natural substances. While generally well tolerated, dietary supplements affect the body like prescription medications, capable of producing an undesired effect. Lack of regulatory oversight allows products to reach consumers without adequate safety evaluation.

Information describing adverse effects of dietary supplements is anecdotal, derived from case reports and reports submitted through the FDA Safety Reporting Portal. Most dietary supplements have not been studied in pregnant or lactating women or children.

A study published in 2015 evaluated ten years of emergency room data to assess the number of annual visits resulting from dietary supplement adverse events. The authors calculated an average of more than 23,000 emergency room visits stemmed from the consumption of dietary supplements, resulting in more than 2,000 hospitalizations annually.³⁹

Events in older adults accounted for the highest percentage of visits, with 40% of visits due to difficulty swallowing. Incidence in young adults aged 20 to 34 was significant at 28% and primarily involved weight loss and energy products. Side effects reported include heart palpitations, chest pain, and tachycardia.³⁹

Unsupervised child ingestions accounted for 21% of visits. Unlike prescription medications, regulations do not require child-resistant packaging for dietary supplements, except for iron-containing products.³⁹ The authors note the numbers evaluated in the study are likely underreported as patients do not always include dietary supplements with the current medication list.³⁹

Table 4. Adverse Effects of Common Dietary Supplements^7,17

Supplement	Adverse Effects
Black Cohosh	Breast tenderness, diarrhea, gastrointestinal upset, nausea/vomiting
Calcium	Burping, constipation, gastrointestinal upset
Echinacea	Diarrhea, constipation, gastrointestinal upset/pain, heartburn, nausea/vomiting, skin rashes
Ginseng	Gastrointestinal side effects, headache, sleep difficulty
Ginger	Burping, diarrhea, heartburn
Iron	Abdominal pain, constipation, diarrhea, nausea/vomiting
Magnesium	Diarrhea, gastrointestinal irritation, nausea/vomiting
Melatonin	Dizziness, drowsiness, headache
Omega-3 fatty acids	Bad breath, headache, heartburn, nausea, diarrhea, unpleasant taste
Potassium	Abdominal pain, burping, diarrhea, nausea/vomiting
St. John’s Wort	Diarrhea, dizziness, dry mouth, fatigue, headache, insomnia
Turmeric	Constipation, dyspepsia, gastrointestinal reflux, nausea/vomiting
Vitamin C	Abdominal cramping, heartburn, kidney stones (if history of kidney stones)
Zinc	Abdominal cramping, diarrhea, metallic taste, nausea/vomiting

Patients often fail to report usage of dietary supplements and most pharmacy software lacks the ability to note dietary supplement usage in the patient profile. In this situation, the pharmacist took the extra time to further question the patient about dietary supplement usage and successfully identified the causative agent.

Pause and Ponder: In what ways could you incorporate activities into the daily workflow to increase awareness of patients’ use of dietary supplements?

Situation: Today, the workload in the pharmacy is lighter than usual. With a grateful sigh, the pharmacist sinks onto a stool reaching for a quick snack. Then the phone rings… The caller is a triage nurse from the local hospital to verify a patient’s medication profile. Pulling up the profile, the pharmacist verifies the list of medications, including digoxin. The triage nurse confirms atrial fibrillation as the cause for admission, adding that the patient recently started taking St. John’s Wort for depression.

Secret #6: Some dietary supplements affect the CYP450 liver enzymes, potentially altering the pharmacokinetics of medications, leading to treatment failure and/or toxicity.

Dietary supplement-drug interactions

Drug-drug interactions result in altered absorption, metabolism, or excretion. Drug-dietary supplement interactions occur through the same pathways as those used by FDA-approved drugs. The cytochrome P450 (CYP P450) enzymes in the liver are responsible for the metabolism of most medications.^41,42 The ability of a drug to either induce or inhibit these enzymes is a significant factor in drug-drug interactions. The natural ingredients found in dietary supplements are capable of inhibition or induction, also having the potential to interact with medications.

St. John’s Wort, an herbal commonly taken for the relief of mild to moderate depression, induces the activity of CYP3A4.^43,44 This induction increases the clearance of medications metabolized by CYP3A4. Examples of medications cleared by CYP3A4 include alprazolam, atorvastatin, cyclosporine, oral contraceptives, oxycodone, and warfarin.^43,44 Patients need counseling about potential drug interactions with St. John’s Wort.

Limited clinical studies evaluating the impact of drug-dietary supplement interactions exist. Many interactions are theoretical, based on limited clinical evidence, animal research, and case reports.⁷

Table 5. Examples of Potential Drug-Dietary Supplement Interactions^7,17

Dietary Supplement	Medication	Interaction
Calcium	Quinolone and tetracycline antibiotics	Decreased antibiotic efficacy Take antibiotic 2 hours before or 4-6 hours after calcium
Calcium	Dolutegravir Elvitegravir	Reduced serum levels Take medication 2 hours before or 2 hours after calcium
Ginseng	Diabetes medications	Increase risk of hypoglycemia
Ginseng	Immunosuppressants	Decreased effectiveness of immunosuppressant
Ginkgo	Anticoagulants	Increased risk of bleeding
Iron	Quinolone and tetracycline antibiotics	Decreased levels of antibiotics due to decreased absorption Take antibiotics 2 hours before or 4-6 hours after iron
Magnesium	Bisphosphonates	Decreased absorption
Magnesium	Levodopa/carbidopa	Decreased bioavailability of levodopa/carbidopa
Niacin	Statins	Increased risk of myopathy or rhabdomyolysis
	Thyroid hormones	Antagonize the effects of thyroid hormone replacement
	Antihypertensive medications	Increased risk of hypotension due to niacin’s vasodilating effects
St. John’s Wort	Alprazolam	Decreased effects of alprazolam
	Oral Contraceptives	Decreased efficacy Counsel patients to use other forms of contraception
	Digoxin	Decreased levels of digoxin
	Omeprazole	Decreased effects of omeprazole
Valerian	CNS depressant drugs	Additive sedative effects
Vitamin B6	Phenytoin	Decrease levels and clinical effects of phenytoin
Vitamin D	Atorvastatin	Decreased absorption of atorvastatin
Vitamin E	Anticoagulants	Increased risk of bleeding
Zinc	Quinolone antibiotics	Decreased levels and effects of antibiotics Take antibiotic 2 hours prior or 4-6 hours after zinc

Pharmacy training emphasizes the importance of drug-drug interactions. It is important to remember that any substance introduced to the body, including food, beverages, and dietary supplements, has the potential to interact with medications.

Situation: It is another busy day in the pharmacy; prescriptions cover the bench, the phone rings constantly, and a pickup queue extends around the corner. A technician nervously approaches the pharmacist about a patient at the counter with a question regarding a supplement. The pharmacist throws down the spatula, muttering angrily about lacking the knowledge and training to answer the question properly. Sighing, he says, "I’ll just Google it."

Secret #7: Many websites provide clinically backed information on dietary supplements (and Google is not one of them!).

The vast amount of health information available via the Internet with just a few clicks of the keyboard is both a blessing and a curse. Google is now a verb, and a simple search returns millions of results in seconds. While this may seem like a blessing, the curse lies in the searcher's inability to recognize valid, accurate sources of information. In many searches, ads appear as search results adding to the confusion.

In addition to the Internet, consumers turn to social media for health information. Social media use increased from 27% in 2009 to 86% in 2019.⁴⁵ Information posted on social media provides communication about healthcare issues, potentially resulting in improved health care.⁴⁵ Unfortunately, inaccurate information abounds on the Internet and social media platforms, leading to consumer misinformation.^47-49

The FDA recently launched a new dietary supplement education initiative geared towards consumers, healthcare professionals, and teachers. The program, Supplement Your Knowledge, presents information about dietary supplements through a series of three videos. Educational materials, including fact sheets and infographics, are available in English and Spanish.⁵⁰

Many government agencies provide free access to information about dietary supplements and their side effects, toxicity, and drug interactions. There are also several paid subscription resources available. Table 6 lists many of the available information options.

Table 6. Sources of Information about Dietary Supplements

Resource	Website	Information
Dietary Supplement Education Program	https://www.fda.gov/food/healthcare-professionals/dietary-supplement-continuing-medical-education-program	Continuing medical education program Collaboration between FDA and AMA Series of 3 videos about dietary supplements Also contains links to educational materials and other websites with information about dietary supplements
Dietary Supplement Label Database	https://dsld.od.nih.gov	Current and historical label information on dietary supplement products marketed in the United States Useful to determine the contents of dietary supplement products
Food and Drug Administration	https://www.fda.gov/food/dietary-supplements/information-consumers-using-dietary-supplements	Information for consumers on using dietary supplements Links to educational resources and materials, consumer updates, alerts, recalls and other information
Google Scholar	https://scholar.google.com/	Source of information from many avenues including journals, books, and conference proceedings
Lexi-Comp Natural Products Database	Available via mobile app	Requires a paid subscription Alphabetical, searchable natural product database
Memorial Sloane Kettering Cancer Center	https://www.mskcc.org/cancer-care/diagnosis-treatment/symptom-management/integrative-medicine/herbs	Information on herbs, botanicals, and other products for both consumers and healthcare professionals Dietary supplement monographs IOS app: About Herbs Part of an online integrative medicine resource center
National Cancer Institute Office of Cancer Complementary and Alternative Medicine	https://cam.cancer.gov	Information for consumers and healthcare professionals about CAM as it relates to cancer therapy Information on current NCI CAM research
National Center for Complementary and Integrative Health	https://www.nccih.nih.gov	Information for both consumers and healthcare professionals about complementary health products and practices
National Library of Medicine - Medline Plus	https://medlineplus.gov/druginfo/herb_All.html	Online health information about drugs, herbs, and supplements for consumers Information sourced from the National Center for Complementary and Integrative Health and Natural Medicines Comprehensive Database
Natural Medicines Comprehensive Database	https://naturalmedicines.therapeuticresearch.com	Requires a paid subscription Professional monographs including information about effectiveness, safety, adverse effects, and interactions Information on specific commercial products Interaction checker Patient handouts in English, Spanish and French
Office of Dietary Supplements	https://ods.od.nih.gov	Information for both consumers and healthcare professionals General supplement information Information on supplements for specific purposes Fact sheets on dietary supplements and their ingredients
PubMed	https://pubmed.ncbi.nlm.nih.gov	Search engine for the National Library of Medicine Source of information from journals
United States Department of Agriculture	https://www.nutrition.gov/topics/dietary-supplements	Links to general information and resources on dietary supplements

Performing an Internet search via Google may seem like the quickest and easiest way to find the answer to an inquiry. Engaging with the patient, gaining additional information, and knowing where to look ultimately saves time. It is not necessary for one to be an expert in all dietary supplements, just to self-educate one supplement at a time.

Pause and Ponder: A patient shares the unfortunate news about a recent cancer diagnosis. He asks you about the use of herbs in the treatment of cancer. What advice would you give?

Conclusion

You may have noticed a recurring theme throughout this activity. Education. Dietary supplement education is essential to patient safety given the current usage patterns and accessibility of the retail pharmacy team. Education needs to include the entire pharmacy team. Technicians are often the first point of contact at the pharmacy, commonly fielding patient questions. Knowing when to answer questions and when to involve the pharmacist is a necessary skill. Understanding the differences in oversight, the physiological effects of dietary supplement consumption, and the potential for drug interactions allows effective management and counseling of patients. It is important for healthcare providers to solicit information regarding patient consumption of dietary supplements.

Sidebar: Tips for Counseling Patients about Dietary Supplements

Carefully inspect the product to ensure intact product labeling

Ensure the safety seal is intact

Check for an expiration date or best used by date

Check for customer service or return information before ordering

Buy direct from a reputable company; many reputable companies sell through Amazon, avoid 3^rd party resellers

Check for the presence of a third-party certification seal

Before purchase, check the company’s website for information on quality standards

Pay attention to the appearance and smell of the product upon opening

Child-resistant packaging is not a requirement for dietary supplements; advise on proper storage of product

Reinforce the importance of including dietary supplements on a current medication list

Seven Secrets for Patient Safety with Dietary Supplements

Pharmacist post-test

After completing this continuing education activity, pharmacists will be able to:

1. Discuss the importance of knowing about a patient’s dietary supplement usage (K)
2. Identify commonly used dietary supplements, their regulation, and the value of certification (K, or A?)
3. Recognize potential medication-dietary supplement interactions (K)
4. Demonstrate the ability to locate different sources of information about dietary supplements (A)

1. According to The National Health and Nutrition Examination Survey more than what percentage of adults have used a dietary supplement in the last 30 days?

A. 45%
B. 50%
C. 55%

2. Which of the following is a commonly used dietary supplement?

A. Boswellia
B. Turmeric
C. Quercetin

3. Which government agencies regulate dietary supplements?

A. USDA, FDA
B. FTC, DEA
C. FTC, FDA

4. Patient MW fills a new prescription for bumetanide. Which potential nutrient depletion may occur?

A. Magnesium
B. Vitamin D
C. Vitamin B12

5. While completing an inventory reconciliation of the vitamin section, a technician inquires, ‘Why does the FDA approve so many different products?’ Which of the following is the most appropriate answer?

A. ‘The FDA does not have the authority to approve dietary supplements, the FTC approves dietary supplements, including vitamins.’
B. ‘The FDA does not have the authority to approve dietary supplements before they are marketed, allowing manufacturers to flood the market with products.’
C. ‘You know, I’m not sure, probably just to make it more confusing for us.’

6. Which of the following companies offer independent third-party dietary supplement certification services?

A. Consumer Reports
B. NSF International
C. Certified Naturally Grown

7. Patient ED is a 58-year-old male new to your pharmacy. He provides the pharmacy team with a list of his current medications including:
• Warfarin 3 mg PO QD
• Atorvastatin 10 mg PO QD
• Donepezil 10 mg PO QHS
• Metformin 1,000 mg PO BID
Use of which of the following supplements would be cause for concern in this patient?

A. Ginkgo
B. Omega-3 fatty acids
C. Niacin

8. A patient calls with questions about a supplement recommended by a friend. The name of the supplement is Mind and Memory Essentials, and the patient does not know the product ingredients. Where would you go to find this information?

A. Dietary Supplement Label Database
B. Office of Dietary Supplements
C. United States Department of Agriculture

9. A patient asks you about the potential side effects of taking turmeric. Where would you go to find this information?

A. Google
B. PubMed
C. Office of Dietary Supplements

10. You are verifying a new birth control prescription for a patient, recalling that the patient strongly believes in alternative medicine and dietary supplementation. Thankfully her profile contains a list of dietary supplements. You see St. John’s Wort listed and suspect a drug-supplement interaction. Where would you go to find more information?

A. Natural Medicines Database
B. Google Scholar
C. National Library of Medicine

11. One of your regular patients stops by the counter to ask your opinion on a dietary supplement product purchased on the Internet. What should you assess when looking over the product?

A. Product labeling, color of bottle, structure/function disclaimer, certification
B. Certification, expiration date, product labeling, intact seal
C. Expiration date, product price, certification, product labeling

12. Pharmacy patient ML approaches the pharmacy counter to purchase several bottles of oral glucose tablets. When questioned, the patient reveals the recent occurrence of several hypoglycemic episodes. The patient confirms compliance with taking their prescription for metformin 1 gm PO BID. ML reports no changes in other prescriptions or dietary habits but does state they started taking a dietary supplement a few days ago but cannot recall the name. Which product would you suspect based on the information provided?

A. Vitamin E
B. Valerian
C. Ginseng

Pharmacy Technician

After completing this continuing education activity, pharmacy technicians will be able to:

1. Discuss the importance of knowing about a patient’s dietary supplement usage (K)
2. Identify commonly used dietary supplements (A)
3. Define dietary supplement oversight and different levels of quality (K)
4. Recognize the need for pharmacist counseling when a patient is taking a dietary supplement (K)

1. Why is it important to ask about a patient’s usage of dietary supplements?

A. It is not important to ask about dietary supplement usage.
B. To identify which dietary supplements the pharmacy should feature on the front counter.
C. Dietary supplements potentially interact with prescription medications.

2. Which of the following is a commonly used dietary supplement?

A. Boswellia
B. Turmeric
C. Quercetin

3. Which government agencies regulate dietary supplements?

A. USDA, FDA
B. FTC, DEA
C. FTC, FDA

4. A patient approaches the counter with 2 different magnesium products and asks your opinion on which to purchase. Which of the following is an appropriate answer?

A. Let’s look at these a little closer.
B. Neither, it’s better to buy supplements online.
C. The one that’s on sale.

5. Reasons for dietary supplementation include which of the following?

A. To supplement a poor diet.
B. Promotion of optimal immune health
C. No one needs to take dietary supplements.

6. Which of the following companies offer independent third-party dietary supplement certification services?

A. Consumer Reports
B. NSF International
C. Certified Naturally Grown

7. You are entering a new patient into the pharmacy system. In addition to asking about allergies, demographics, and current medications, what else should you ask?

A. How many hours of sleep do you average a night?
B. Do you take any over-the-counter medications or dietary supplements?
C. How many children do you have and how old are they?

8. You are finally heading out for a lunch break and walk past a pharmacy patient in the aisle looking at 2 different brands of St. John’s Wort. What should you do?

A. Keep going, you already punched out and only have 30 min to eat your lunch.
B. Stop and offer to accompany them to the pharmacy to talk to the pharmacist.
C. Stop and help them make a choice between the products.

9. A patient picks up a medication and purchases a bottle of magnesium at the same time. What should you do?

A. Advise the patient that there may be an interaction between the prescription and the magnesium.
B. Ring out the patient as usual.
C. Touch base with the pharmacist to make sure there are no potential interactions between the products.

10. Where should adverse reactions or issues with dietary supplements be reported?

A. FDA Safety Reporting Portal
B. Federal Trade Commission
C. Office of Dietary Supplements

References

1. Cragg GM, Newman DJ. Natural products: a continuing source of novel drug leads. Biochim Biophys Acta. 2013;1830(6):3670-3695. doi:10.1016/j.bbagen.2013.02.008

2. Jones AW. Early drug discovery and the rise of pharmaceutical chemistry. Drug Test Anal. 2011;3(6):337-344. doi:10.1002/dta.301

3. Aitken M, Kleinrock M. The Use of Medicines in the U.S. Spending and Usage Trends and Outlook to 2025. IQVIA Institute for Human Data Science. May 2021. Accessed August 5, 2022. https://www.iqvia.com/-/media/iqvia/pdfs/institute-reports/the-use-of-medicines-in-the-us/iqi-the-use-of-medicines-in-the-us-05-21-forweb.pdf

4. OTC Sales Statistics. Consumer Healthcare Products Association. Accessed June 22, 2022. https://www.chpa.org/about-consumer-healthcare/research-data/otc-sales-statistics

5. Dietary Supplements Market Size, Share & COVID-19 Impact Analysis, By Type (Vitamins, Minerals, Enzymes, Fatty Acids, Proteins, and Others), Form (Tablets, Capsules, Liquids, and Powders), and Regional Forecasts, 2021-2028. Fortune Business Insights. Accessed June 22, 2022. https://www.fortunebusinessinsights.com/dietary-supplements-market-102082

6. Moynihan R, Sanders S, Michaleff ZA, et al. Impact of COVID-19 pandemic on utilisation of healthcare services: a systematic review. BMJ Open. 2021;11(3):e045343. Published 2021 Mar 16. doi:10.1136/bmjopen-2020-045343

7. Dietary Supplements in the Time of COVID-19. Fact Sheet for Health Professionals. National Institutes of Health, Office of Dietary Supplements. Accessed July 20, 2022. https://ods.od.nih.gov/factsheets/COVID19-HealthProfessional/.

8. Adams KK, Baker WL, Sobieraj DM. Myth Busters: Dietary Supplements and COVID-19. Ann Pharmacother. 2020;54(8):820-826. doi:10.1177/1060028020928052

9. US Department of Health and Human Services, National Institutes of Health, Office of Dietary Supplements. Dietary Supplement Label Database (DSLD). Accessed August 5, 2022. https://ods.od.nih.gov/Research/Dietary_Supplement_Label_Database.aspx

10. About the National Health and Nutrition Examination Survey. National Center for Health Statistics. Accessed July 20, 2022. https://www.cdc.gov/nchs/nhanes/about_nhanes.htm

11. Mishra S, Stierman B, Gahche JJ, Potischman N. Dietary supplement use among adults: United States, 2017–2018. NCHS Data Brief, no 399. Hyattsville, MD: National Center for Health Statistics. 2021. DOI: https://doi.org/10.15620/cdc:101131external icon

12. Gahche JJ, Bailey RL, Potischman N, et al. Federal Monitoring of Dietary Supplement Use in the Resident, Civilian, Noninstitutionalized US Population, National Health and Nutrition Examination Survey. J Nutr. 2018;148(Suppl 2):1436S-1444S. doi:10.1093/jn/nxy093

13. 2019 CRN Consumer Survey on Dietary Supplements. Council for Responsible Nutrition. https://www.crnusa.org/2019survey. Published September 30, 2019. Accessed June 1, 2022.

14. Johns Hopkins Coronavirus Resource Center. https://coronavirus.jhu.edu/. Accessed August 5, 2022.

15. Calder PC, Carr AC, Gombart AF, Eggersdorfer M. Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients. 2020;12(4):1181. Published 2020 Apr 23. doi:10.3390/nu12041181

16. Hamulka J, Jeruszka-Bielak M, Górnicka M, Drywień ME, Zielinska-Pukos MA. Dietary Supplements during COVID-19 Outbreak. Results of Google Trends Analysis Supported by PLifeCOVID-19 Online Studies. Nutrients. 2020;13(1):54. Published 2020 Dec 27. doi:10.3390/nu13010054

17. Natural Medicines. Therapeutic Research Center. Accessed August 2, 2022. https://naturalmedicines.therapeuticresearch.com.

18. Office of Dietary Supplements Dietary Supplement Fact Sheets. Accessed August 2, 2022. https://ods.od.nih.gov/factsheets/list-all/

19. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th Edition. December 2020. Available at DietaryGuidelines.gov. https://www.dietaryguidelines.gov/sites/default/files/2021-03/Dietary_Guidelines_for_Americans-2020-2025.pdf

20. Thakkar S, Anklam E, Xu A, et al. Regulatory landscape of dietary supplements and herbal medicines from a global perspective. Regul Toxicol Pharmacol. 2020;114:104647. doi:10.1016/j.yrtph.2020.104647
21. FDA 101: Dietary supplements. United States Food and Drug Administration. Accessed July 31, 2022. https://www.fda.gov/consumers/consumer-updates/fda-101-dietary-supplements.
22. Questions and Answers on Dietary Supplements. U.S. Food and Drug Administration. Accessed July 31, 2022. https://www.fda.gov/food/information-consumers-using-dietary-supplements/questions-and-answers-dietary-supplements.

23. Facts About the Current Good Manufacturing Practices (cGMPs). U.S. Food and Drug Administration. Accessed July 22, 2022.
https://www.fda.gov/drugs/pharmaceutical-quality-resources/facts-about-current-good-manufacturing-practices-cgmps

24. Safety Reporting Portal. Food and Drug Administration. Accessed August 10, 2022. https://www.safetyreporting.hhs.gov/SRP2/en/Home.aspx?sid=da6dc761-7962-4743-82cd-2e62985492d0

25. Veatch-Blohm ME, Chicas I, Margolis K, Vanderminden R, Gochie M, Lila K. Screening for consistency and contamination within and between bottles of 29 herbal supplements. PLoS One. 2021;16(11):e0260463. Published 2021 Nov 23. doi:10.1371/journal.pone.0260463

26. Ćwieląg-Drabek M, Piekut A, Szymala I, et al. Health risks from consumption of medicinal plant dietary supplements. Food Sci Nutr. 2020;8(7):3535-3544. Published 2020 May 19. doi:10.1002/fsn3.1636

27. Genuis SJ, Schwalfenberg G, Siy AK, Rodushkin I. Toxic element contamination of natural health products and pharmaceutical preparations. PLoS One. 2012;7(11):e49676. doi:10.1371/journal.pone.0049676

28. Tucker J, Fischer T, Upjohn L, Mazzera D, Kumar M. Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings [published correction appears in JAMA Netw Open. 2018 Nov 2;1(7):e185765]. JAMA Netw Open. 2018;1(6):e183337. Published 2018 Oct 5. doi:10.1001/jamanetworkopen.2018.3337

29. Health Fraud Product Database. United States Food and Drug Administration. Accessed August 10, 2022. https://www.fda.gov/consumers/health-fraud-scams/health-fraud-product-database

30. Warning Letter: Amcyte Pharma, Inc. United States Food and Drug Administration. January 03, 2022. Accessed August 12, 2022. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/amcyte-pharma-inc-623474-01032022

31. Public Notification: Adam’s Secret Extra Strength Amazing Black contains hidden drug ingredient. United States Food and Drug Administration. July 15, 2022. Accessed August 12, 2022. https://www.fda.gov/drugs/medication-health-fraud/public-notification-adams-secret-extra-strength-amazing-black-contains-hidden-drug-ingredient

32. Coward, RM, Carson CC. Tadalafil in the treatment of erectile dysfunction. Ther Clin Risk Manag. 2008;4(6):1315-1329. Accessed October 3, 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643112/pdf/TCRM-4-1315.pdf

33. Tucker J, Fischer T, Upjohn L, Mazzera D, Kumar M. Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings [published correction appears in JAMA Netw Open. 2018 Nov 2;1(7):e185765]. JAMA Netw Open. 2018;1(6):e183337. Published 2018 Oct 5. doi:10.1001/jamanetworkopen.2018.3337

34. Akabas SR, Vannice G, Atwater JB, Cooperman T, Cotter R, Thomas L. Quality Certification Programs for Dietary Supplements. J Acad Nutr Diet. 2016;116(9):1370-1379. doi:10.1016/j.jand.2015.11.003

35. Dietary Supplement Labeling Guide, U.S. Food and Drug Administration. https://www.fda.gov/food/dietary-supplements-guidance-documents-regulatory-information/dietary-supplement-labeling-guide Accessed July 15, 2022.

36. Frequently Asked Questions for Industry on Nutrition Facts Labeling Requirements. United States Food and Drug Administration. Accessed August 12, 2022. https://www.fda.gov/media/99158/download

37. Cooperman, T. 6 Red Flags to Watch Out For When Buying Vitamins & Supplements. October 9, 2021. Accessed August 12, 2022. https://www.consumerlab.com/answers/what-to-watch-out-for-when-buying-vitamins-and-supplements/vitamin-and-supplement-red-flags

38. Research explores the impact of menopause on women’s health and aging. National Institute of Aging. May 6, 2022. Accessed September 6, 2022. https://www.nia.nih.gov/news/research-explores-impact-menopause-womens-health-and-aging

39. Geller AI, Shehab N, Weidle NJ, et al. Emergency Department Visits for Adverse Events Related to Dietary Supplements. N Engl J Med. 2015;373(16):1531-1540. doi:10.1056/NEJMsa1504267

40. Code of Federal Regulations. Title 16, Chapter II, Subchapter E, Part 1700. Amended September 6, 2022. Accessed September 6, 2022. https://www.ecfr.gov/current/title-16/chapter-II/subchapter-E/part-1700/section-1700.14

41. Zanger UM, Turpeinen M, Klein K, Schwab M. Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal Bioanal Chem. 2008;392(6):1093-1108. doi:10.1007/s00216-008-2291-6

42. Matura JM, Shea LA, Bankes VA. Dietary supplements, cytochrome metabolism, and pharmacogenetic considerations [published online ahead of print, 2021 Nov 4]. Ir J Med Sci. 2021;10.1007/s11845-021-02828-4. doi:10.1007/s11845-021-02828-4

43. Chrubasik-Hausmann S, Vlachojannis J, McLachlan AJ. Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content. J Pharm Pharmacol. 2019;71(1):129-138. doi:10.1111/jphp.12858

44. Zhou S, Chan E, Pan SQ, Huang M, Lee EJ. Pharmacokinetic interactions of drugs with St John's wort. J Psychopharmacol. 2004;18(2):262-276. doi:10.1177/0269881104042632

45. Chen J, Wang Y. Social Media Use for Health Purposes: Systematic Review. J Med Internet Res. 2021;23(5):e17917. Published 2021 May 12. doi:10.2196/17917

46. Moorhead SA, Hazlett DE, Harrison L, Carroll JK, Irwin A, Hoving C. A new dimension of health care: systematic review of the uses, benefits, and limitations of social media for health communication. J Med Internet Res. 2013;15(4):e85. Published 2013 Apr 23. doi:10.2196/jmir.1933

47. Swire-Thompson B, Lazer D. Public Health and Online Misinformation: Challenges and Recommendations. Annu Rev Public Health. 2020;41:433-451. doi:10.1146/annurev-publhealth-040119-094127

48. Chou WS, Oh A, Klein WMP. Addressing Health-Related Misinformation on Social Media. JAMA. 2018;320(23):2417-2418. doi:10.1001/jama.2018.16865

49. Suarez-Lledo V, Alvarez-Galvez J. Prevalence of Health Misinformation on Social Media: Systematic Review. J Med Internet Res. 2021;23(1):e17187. Published 2021 Jan 20. doi:10.2196/17187

50. Supplement Your Knowledge. Dietary Supplement Education Initiative. United States Food and Drug Administration. May 25, 2022. Accessed July 20, 2022. Reference the Supplement your knowledge program

Ketamine and Its Kissing Cousins

Ketamine is Food and Drug Administration-approved as a general anesthetic. Researchers found higher dose ketamine therapy had a more desirable adverse effect profile than the previously used anesthetic phencyclidine (PCP). N-methyl-D-aspartate (NMDA) antagonism from subanesthetic ketamine doses produces dissociative and analgesic effects. As such, prescribers are exploring off-label uses for ketamine in patients with agitation, depression, and pain while considering potential risks to multiple organ systems. Ketamine has the potential to cause complications and providers need to monitor patients closely. Illicit and inappropriate use by abusers and untrained law enforcement officers highlight ketamine’s potentially harmful effects. Educating patients and healthcare providers is vital to allow potential benefits while minimizing harm.

Introduction

Consider this: It’s 10:30 PM on a Friday night, 30 minutes before you leave for the weekend. Suddenly, from across the emergency department you hear, “Get OFF me! No, I have not t-t-taken anything! If you come ANY CLOSER, things are going to get physical!” Not a moment later, an order pops up for ketamine hydrochloride 500 mg intramuscularly (IM) for severe agitation. Concerned, a colleague asks you, “Is this safe? Is this effective? I have never seen a dose this high before. Isn’t this just for horses?”

Ketamine made its debut in human clinical practice in the 1960s when several chemists at Parke Davis Company were searching for an anesthetic with similar effects to phencyclidine (PCP). PCP, ketamine’s notorious kissing cousin, was a promising new anesthetic in the 1950s because of its dissociative effects. However, the chemists quickly became unimpressed with its adverse effect profile (i.e., long-lasting psychoactive effects after anesthesia). Humans experienced intense prolonged emergence delirium following PCP anesthesia, relegating its use to veterinary practice.¹ Chemists searched for a better anesthetic and found ketamine, which has similar dissociative effects without PCP’s negative consequences. Ketamine is a more desirable anesthetic because it has a shorter half-life (2.5 hours) compared to PCP (21 hours) and it causes less delirium.^1,2

Prescribers have begun using ketamine for several off-label uses and patients have also started using the drug or structural analogs in a variety of formulations illicitly. Pharmacists and technicians can ensure ketamine’s safe use by keeping current with new formulations and indications, both approved and unapproved. This continuing education activity will dive into the clinical and social consequences of ketamine use.

What’s Ketamine?

Ketamine is a schedule III-controlled substance approved by the U.S. Food and Drug Administration (FDA) for use as a general anesthetic for diagnostic and surgical procedures.²Ketamine is commercially available in the United States as a solution/injection under its brand (Ketalar) and as generic ketamine.² Healthcare providers most often use intravenous (IV) ketamine, but it may be used IM or compounded into an oral solution.

Healthcare providers also use ketamine off-label for analgesia, agitation, and major depressive disorder. These indications emanate from ketamine’s mechanism of action: it acts specifically on the N-methyl-D-Aspartate (NMDA) receptor as a non-competitive antagonist to block glutamate binding.³Glutamate, a major excitatory neurotransmitter, binds to receptors throughout the nervous system. The NMDA receptor is an ionotropic receptor responsible for the brain’s neuroplasticity, memory, learning, and recovery.^4-6 Blocking this receptor with high ketamine doses (ranging from 0.5 to 2 mg/kg) results in dissociation, decreases in spinal reflexes, and produces a cataleptic state (loss of voluntary movements and reduced consciousness) that is applicable to its current clinical use in anesthesia.² However, at low doses, ketamine can produce analgesia and stimulate new pathways within the brain that reduce depressive symptoms and improve mood.

Although ketamine has useful applications in medicine, prescribers must be aware of the adverse effects and risk factors associated with use and should consider how these effects apply to their patients before initiating the medication. Ketamine adversely impacts multiple organ systems (see Table 1), including but not limited to the cardiovascular system. Increases in blood pressure and heart rate are important cardiovascular effects associated with ketamine therapy.² These cardiovascular effects make it a drug of choice for anesthesia induction in patients with cardiovascular shock, where it anesthetizes patients while improving blood pressure and improving organ perfusion. However, clinicians must avoid ketamine use in patients with preexisting hypertensive conditions or other patients who have limited baroreceptor buffering capacity (baroreceptor buffering is the body’s ability to sense blood pressure) because of those same effects mentioned above.⁶

Table 1. General Adverse Effects of Ketamine^2,6

System	Adverse effects
Cardiovascular	Cardiac arrhythmias, increased blood pressure,* increased heart rate
Central nervous system	Prolonged emergence from anesthesia,* psychosis,* dissociation,* drug dependence, increased intracranial pressure
Dermatologic	Injection site irritation
Gastrointestinal	Nausea,* vomiting, anorexia
Genitourinary	Lower urinary tract dysfunction, bladder dysfunction
Respiratory	Laryngospasm,* respiratory depression,* apnea
Immunologic	Anaphylaxis
Other	Hypersalivation, diplopia (double vision), nystagmus (uncontrollable rapid eye movement)

*Common or serious adverse effects of ketamine use

Further contraindications include hypersensitivity to ketamine or its components.⁷ The American College of Emergency Physicians (ACEP) does not recommend ketamine use in patients with schizophrenia or in children younger than three months of age. The ACEP also advises against solely using ketamine as an anesthetic in procedures involving the pharynx, larynx, and bronchial tree. This recommendation primarily applies to patients with airway instability because ketamine can cause laryngospasms.⁵ Table 2 lists additional considerations in special populations.

Table 2. Special Population Considerations with Ketamine^2,6-8

Special population	Concerns	Recommendation
Pregnancy	Crosses the placenta; may have potential risk to fetus	Avoid use; evaluate benefits vs risk
Breastfeeding	Compatibility and safety unknown	Avoid breastfeeding to children with respiratory risk factors
Pediatrics	Can be given with anticholinergics to minimize hypersalivation	Refer to pediatric dosing. Avoid in infants < 3 months of age
Elderly	May be sensitive to dissociative adverse effects	Refer to adult dosing
Kidney dysfunction	No additional concerns	Refer to dosing parameters
Liver dysfunction	Hepatobiliary dysfunction with recurrent use	Refer to dosing parameters; monitor LFTs with repeated ketamine use
LFTs = liver function tests

Healthcare providers should monitor patients' vital signs closely during treatment with ketamine. Anesthesiologists and pharmacists must continuously watch patients undergoing surgical or diagnostic procedures for proper induction and maintenance of dissociative effects.² In patients who must take repeated doses of ketamine (e.g., for chronic pain management or psychiatric disorders), healthcare providers should order liver function tests at baseline and every one to two days during treatment.^2,6,9,10

Ketamine’s Kissing Cousins

As shown in Figure 1, ketamine is structurally related to many compounds. The drugs in Figure 1 antagonize the NMDA receptor and exhibit a dissociative effect.¹ PCP is one of the most notoriously abused drugs. Compared with ketamine, PCP is 10 times more potent and has a longer duration of action due to its strong affinity for the NMDA receptor. Both ketamine and PCP can replicate schizophrenia’s positive, negative, and cognitive symptoms and exacerbate underlying schizophrenia. But because ketamine has lower potency and a shorter duration of action, it induces fewer severe psychiatric effects than PCP.¹

Figure 1. Molecular structure of ketamine and structurally related dissociative drugs¹¹

Although ketamine’s labeling includes many precautions, it is an emerging option because of its therapeutic benefits. Xi Biopharmaceuticals is developing a sublingual wafer to treat acute pain while Janssen Pharmaceuticals has developed a nasal spray formulation for treatment resistant depression.^12,13 Table 3 compares the current ketamine formulations that are FDA-approved or under investigation.

Table 3. Ketamine Counterparts^12-14

Cousins	Formulation	Use & Dose	Approval or Trial Phase
Ketalar (ketamine hydrochloride)	Injectable	Anesthesia 0.25 – 0.35 mg/kg followed by CIVI 1 mg/kg/hr	FDA-approved
Wafermine (ketamine)	Sublingual Wafer	Acute Pain 25 mg, 50 mg & 75 mg PRN for 12 hrs	End-of-Phase 2 Clinical Trials
Spravato (esketamine)	Nasal Spray	Treatment Resistant Depressive Disorder 28 mg, 56 mg, 84 mg twice a week	FDA-approved
ABBREVIATION: CIVI = continuous intravenous infusion

ABUSE, ADDICTION, DEPENDENCE

Why is Ketamine Dangerous?

Long-term ketamine abuse is associated with memory, attention, and judgment impairment. The actual risk of ketamine abuse in the general population is low compared to other substances of abuse, but patients with polysubstance abuse disorder tend to use it.¹⁵ A study examining polysubstance abuse conducted in New York City found that polydrug use occurred because of an unexpected opportunity to use ketamine after already consuming other drugs. Researchers also determined that polysubstance abusers purposefully used ketamine with another substance to achieve an individually desired effect. Oftentimes polydrug-using events occurred within a group and each member contributed something: ketamine, knowledge, other drugs, or space to use drugs.¹⁶

Currently, ketamine is only commercially available as an injectable liquid. Dealers illegally sell ketamine as a recreational injectable substance or a white powder that resembles cocaine. The Department of Justice and Drug Enforcement Administration report that illegally distributed ketamine is diverted or stolen from veterinary clinics or smuggled into the United States from Mexico.¹⁷ Dealers can then synthesize ketamine into a powder or sell it as an injectable liquid.¹⁸ Prices average from $20-$25 per dose (50 mg to 100 mg).¹⁹ Drug abusers find ketamine’s dissociative sensations and hallucinations appealing. Users can inject liquid ketamine, or snort or smoke powdered ketamine.¹⁷ Ketamine is a popular drug to facilitate physical or sexual assault because it is a colorless, tasteless, and odorless liquid making it difficult for victims to detect. Additionally, ketamine is known to cause impaired coordination, confusion, and memory loss.²⁰

Ketamine’s IV administration started in the early 1990s. Injection events occur most frequently in large cities with high rates of homelessness, like New York City and Los Angeles.¹⁸ Researchers conducted a study with 213 people who abused IV ketamine.¹⁸ Among these users, 84% admitted to abusing ‘harder’ drugs first, with heroin predominating. Users reported their first ketamine injection happening among a group of people. This group often included people well known to them who provided knowledge and the materials for injecting.¹⁸

What attracts people to a dissociative drug with unknown psychoactive effects? Exactly that: the unknown. With most abused drugs, the user understands the effects they will experience. When someone takes ketamine, the reaction to each dose is unknown. Some users seek variety. Ketamine users have described an out of body experience that expands internal and external realms and realities.¹⁸ On the other hand, abusers also describe a “K-Hole”—an experience that they describe as near-death that results when they ingest too much ketamine.¹⁷

Timothy Wyllie, a spiritualist, describes ketamine doses as a curve over time through realms. He describes the domains abusers experience as they dose ketamine²¹:

The realm “I,” for internal reality, occurs at doses 30 to 75 mg roughly 10 minutes after injection.
The extraterrestrial reality realm, “They,” occurs at doses 75 to 150 mg approximately 15 minutes after injection.
The realm “We,” for network creation realm, occurs at doses from 150 to 300 mg mg approximately 15 minutes after injection.
An unknown realm exists at doses of more than 300 mg.

The doses studied for depression fall in the realm of internal reality. At these doses, users can see areas needing self-improvement that they were unaware they had the ability to fix. Drug users prefer subanesthetic doses but those that are higher than doses studied for treating depression. As the dose increases, users become so far removed from reality that “extraterrestrial” experiences begin.²¹

KETAMINE USES

Anesthesia

Patients unable to maintain and protect their airways require endotracheal intubation. Healthcare providers use ketamine as a sedative to facilitate rapid sequence induction and intubation (RSII), by inducing an anesthetized state, prior to paralyzing the patient. The decision to intubate is based on the patient’s Glasgow Coma Score.^22,23A score of 8 or less qualifies a patient to receive endotracheal intubation.²³ Healthcare providers follow a RSII strict algorithm, shown in Table 4, detailing the order in which medications should be administered based upon the onset and duration of action.

Table 4. Algorithm of Rapid Sequence Induction & Intubation^22,23

Step of RSII	What and Why	Medications Used
Premedication^*	Airway manipulation causes a sympathetic activation due to a pressor response. This sympathetic response leads to an increase in intracranial pressure and mean arterial pressure.	alfentanil, fentanyl, lidocaine, sufentanil
Sedation	Used to induce an anesthetic state before a paralytic is used and the airway manipulated. Crucial that a patient is properly sedated before paralyzed.	Also known as induction agents: etomidate, ketamine, midazolam, propofol
Paralytics^±	Neuromuscular blocking agents are given to relax pharyngeal and diaphragmatic muscles allowing for an endotracheal tube to be placed.	rocuronium, succinylcholine, vecuronium

*: Based upon time constraints/needs this step may be omitted

±: It is imperative to confirm a patient is properly sedated before beginning paralysis because if the patient is awake, they may feel the tube insertion

The drugs used in RSII possess unique characteristics, including IV use, quick onset, and short duration of action.²³ Traditionally, etomidate has been the gold standard for RSII, but ketamine is quickly becoming a commonly used alternative.²³ Table 5 highlights the differences between etomidate and ketamine.

Table 5. Comparison of Etomidate and Ketamine^22,23

	Etomidate	Ketamine
Dose for Induction	0.3 mg/kg	1.5 mg/kg or 0.1-0.5 mg/kg/min with 10% given as induction bolus
Onset of Action	10-15 seconds	< 30 seconds
Duration of Action	4-10 minutes	10-15 minutes
Benefits	Stable hemodynamic profile, decreases metabolic rate, decreases cerebral blood flow, increases generalized seizure threshold	Sedative and analgesic properties,^* cardiovascular and respiratory stimulation, and smooth muscle relaxation (beneficial in reactive airway disease, hypotensive, volume depleted, and septic patients)
Risks	Adrenal suppression, do not use in septic shock, lowers focal seizure threshold, increased incidence of ARDS	Potentiates effect of epinephrine, increases cardiac oxygen demand, may increase ICP,** emergent reactions, infusion related respiratory depression, hypersalivation
ABBREVIATIONS: ARDS = acute respiratory distress syndrome, ICP = intracranial pressure * Ketamine can be used as a combined premedication and induction step ** Data is conflicting, however, may not be suitable for patients with head trauma

The differences between etomidate and ketamine create a significant role in RSII for both drugs, but for different presenting conditions. Ketamine is gaining popularity for its use in septic patients, hypotensive patients, and those with reactive airway diseases. Choosing etomidate is preferable for patients with a hemodynamically stable profile and patients with traumatic brain injury where it could be cerebroprotective.

Analgesia (pain)

Ketamine’s use in pain management is controversial due to limited data, but this dataset is growing.^15,24 Before considering subanesthetic ketamine doses, prescribers should collaborate with patients and other clinical team members to try other approved pain regimens.²⁵ Using ketamine for its analgesic properties should be based on patient-specific criteria. The prescriber must assess the patient’s treatment goals, current medical conditions, pain types, and available protocols.

Ketamine is not discussed in available pain guidelines. Some literature recommends its use after unsuccessful trials of at least two opioids. Data supporting ketamine’s use in both acute and chronic pain management is mixed in its findings.^26,27 Most trials conclude ketamine can reduce acute pain exacerbations but note that prescribers must be cautious of its adverse effects.¹⁵ Data from small trials indicate using ketamine to overcome opioid withdrawal and opioid-induced-hyperalgesia (neuropathic pain) may be possible. Ketamine has a unique ability to counteract the unfavorable responses patients might experience on chronic high-dose opioids by its mechanism of action.^24,28 Overstimulated opioid receptors from high dose opioid use causes more hyperalgesia. Several small case reports describe patients on high-dose chronic opioid therapy who reduced their opioid doses after low-dose ketamine administration.²⁹

An open labeled audit determined that IV ‘burst’ ketamine therapy improved analgesia in neuropathic pain and painful bone metastases. Researchers enrolled 39 cancer patients who were refractory to opioid therapy. Patients received bursts of low-dose ketamine (100 to 500 mg/day) over three to five days and reported somatic and neuropathic pain relief for up to eight weeks.¹⁵

Limited evidence supports oral ketamine’s effect in chronic pain and most studies that examine its use are case reports or non-comparative trials. Compared to IV administration, lower oral ketamine concentrations are associated with analgesic effects. Oral ketamine has been associated with higher serum levels of its metabolite, norketamine. This metabolite seems to contribute to oral ketamine’s analgesic effects due to its shorter half-life and ability to reach much higher peak plasma concentrations than after IV administration. However, researchers have not extensively explored this in current literature.²⁹

Healthcare providers and patients face many hurdles when using ketamine for pain relief. Prescribers should avoid high ketamine doses that may cause a range of serious adverse effects. Unlike opioids, ketamine has a ceiling effect and maximum dose. Oral ketamine administration has a low bioavailability and is directly linked with a high rate of adverse effects.^15,27

Agitation

Due to ketamine’s dissociative properties, clinicians are increasingly using ketamine for treating pre-hospital and in-hospital agitation. Lacking a uniform definition for agitation, healthcare providers, institutions, and organizations may use different criteria to choose medication intervention in an agitated patient. Although the picture of agitation may change depending on the situation, validated scales like the Altered Mental Status Scale (AMSS) can define agitation’s severity.³⁰ The AMSS translates agitation into a quantifiable, real concept. The line between agitation and delirium is often unclear but has major ramifications for a patient’s treatment and outcome.³⁰ For example, excited delirium, an agitation subtype, classifies a patient’s agitation past the emotional component and includes psychomotor, metabolic, and contributing disease states as possible reasons for agitation.³⁰

As with most psychiatric disorders, identifying and treating agitation has been suboptimal. Since the 1980s, a popular cocktail of medications, known among emergency department physicians as the “B-52” order, has been the mainstay of agitation treatment in psychiatric facilities and emergency departments.³¹ When examining the B-52 order’s components, it is easy to see the correlation between the regimen and the American jet-powered strategic bomber from which it derives its name: Benadryl 50 mg IM, haloperidol 5 mg IM, lorazepam 2 mg IM.³¹ The B-52 order serves as a reminder of the suboptimal approach traditionally taken when confronted with an agitated patient.

Ketamine’s different routes of administration have benefits and disadvantages. Although less invasive, oral ketamine takes a longer time to reach the therapeutic range, something that is undesirable in an overly aggressive patient. Intravenous administration has the quickest onset but is the most invasive. Securing IV access may not always be possible. The IM route is the most often used method for agitation control for its quick “on/off” onset and duration of action, and its applicable dosage form.

A review explains ketamine’s uses and benefits in comparison to other, more traditional agitation treatments.³⁰ In terms of agitation efficacy, ketamine provides the same, if not better, response when compared to its more traditional counterparts.³⁰ Ketamine has a significantly faster onset of action when compared to haloperidol (5 minutes versus 17 minutes) and requires less redosing (5% of patients re-dosed versus 20% of patients re-dosed, respectively).³⁰ However, ketamine continues to show a higher incidence of adverse effects when compared to its anti-psychotic counterpart (percent incidence calculated from six studies where adverse events were recorded as a secondary outcome):³⁰

emergence reaction 12.3% (8/65 patients)
- An “emergence reaction” is an often hostile, psychiatric episode brought about by ketamine use
hypersalivation 31.8% (22/69 patients)
nausea and vomiting 8.5% (7/82 patients)
respiratory complications 7.6% (9/118 patients)

Although studies report a higher incidence of adverse reactions when using ketamine for agitation, it is important to consider study limitations: small patient populations, co-administration of drugs, and lack of adverse event reporting (only half of 12 studies included adverse reactions).³⁰ If used properly, ketamine can be a safe, quick-acting drug to stop agitation when compared to traditional treatments.

Some law enforcement agencies use ketamine. However, when they use ketamine improperly, or when adverse effects arise, ketamine can have dangerous consequences. Over a four-day period during late August of 2019 in Colorado, police gave 23-year-old Elijah McClain and 25-year-old Elijah McKnight excessive ketamine doses for agitation.³² McClain died from cardiac arrest and McKnight survived but required life support in the hospital.³² It is inappropriate to allow untrained police officers to inject ketamine as a law enforcement tool. However, police defend using ketamine saying suspects with mental health issues or suspects taking drugs can be belligerent and dangerous. A Minnesota whistleblower lawsuit filed by a former emergency medical services worker claims police pressured them to allow ketamine use uneccessarily.³² In Minneapolis, ketamine used by police rose from four incidents per year in 2015 to 62 in 2017.³² This marked increase in ketamine use is upsetting many healthcare professionals. Dr. Mary Dale Peterson, president of the American Society of Anesthesiologists, says that ketamine can have “dangerous complications,” just like any other anesthetic. Dr. Peterson points out that justifiably using ketamine occurs very rarely.³²

Whistleblowers cite complications from unwarranted ketamine use are associated with emergence reactions, and improper dosages.³² McClain died when he was given a ketamine dose for a 200-pound man but only weighed 143 pounds.³² Pharmacists can play a role in educating other healthcare professionals about proper dosing and management of ketamine’s serious adverse effects.

Major Depressive Disorders

Generally, major depressive disorder’s (MDD) treatment focuses on pathophysiology and regulates serotonin, norepinephrine, and dopamine.³² Medications such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibits (SNRIs), tricyclics, tetracyclics, and serotonin modulators all target an increase in synaptic neurotransmitter levels.³² Unfortunately, these drugs are not consistently effective for all patients, require an 8-week trial period, and have unfavorable adverse effects. For many providers and their patients, MDD treatment can feel like an awful waiting game—one that they sometimes lose.

Ketamine is becoming increasingly popular for its use in treating refractory depression. However, it requires healthcare providers to understand how it works to avoid putting patients into a “K-hole.” It offers a different approach to the current FDA-approved drugs for MDD. Ketamine prevents glutamate reuptake; excess glutamate produces an antidepressant effect. Ketamine, at subanesthetic doses, produces euphoria, and improves symptoms within 24 hours after infusion.^4,14,32,33 Depressive symptoms improve rapidly, but the effects last only a few days to weeks. As a result, ketamine is most useful as an adjunctive treatment option. Patients feel better for a brief period, giving their antidepressants a chance to start working.

In addition, prescribers have few options for patients with MDD who have suicidal behaviors and ideation. Ketamine seems promising for patients at an elevated risk for self-harm. The Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression trial examined ketamine’s potential benefits for 80 suicidal patients with MDD. The results of this randomized controlled study showed that ketamine was superior to midazolam in improving the Scale for Suicidal Ideation (SCI). Patients’ SCI scores improved 4.96 points within 24 hours after a ketamine infusion of 0.5 mg/kg over 40 minutes.³² This suggests clinical use of ketamine as an adjuvant agent for acute episodes of suicide ideation in patients maintained on guideline recommended therapy for MDD may be appropriate. However, patient safety remains a concern (e.g., dissociative effects, abuse potential, respiratory, and cardiovascular effects).

As mentioned earlier, esketamine (Spravato) is ketamine’s S-enantiomer and FDA-approved for treatment-resistant depression.³³ In the TRANSFORM-1 randomized controlled trial, the antidepressant/esketamine groups did not have a statistically significant change in Montgomery-Asberg Depression Rating Scale (MADRS) total score (from baseline to study day 28) when compared to the antidepressant placebo group.^34,35 However, the changes based on the MADRS were clinically meaningful and showed that esketamine has a beneficial role in treatment-resistant depression when used as an adjuvant agent.^36,37 The combination of esketamine with an antidepressant produced desirable outcomes while minimizing adverse effects. Although adverse effects were low, several adverse effects are possible: vertigo, nausea, vomiting, anxiety, sedation, abuse potential, increased blood pressure, dissociation, and suicidal thoughts/behaviors.³³

CONCLUSION

To paraphrase the father of toxicology, Paracelsus, it’s all about the dose. Ketamine is the poster child drug for this statement. Ketamine has the potential to be an important adjuvant therapy for the treatment of a range of conditions. Those listed in this CE—anesthesia, analgesia, and major depressive disorder—are currently the most studied disorders where ketamine and its derivatives may be useful. Due to ketamine’s dissociative and analgesic effects through NMDA antagonism, there may be additional future potential uses for ketamine in pain control and psychiatric disorders. Simply, ketamine treats not only the physical manifestations of these conditions but the emotional component that providers can easily overlook. However, the current data sets are small, many use rating scales instead of final health outcomes, and a larger and longer term series of trials are required to fully determine the place of ketamine in the treatment armamentarium for patients.

Pharmacists and other healthcare providers will need to distinguish between therapeutic use and addiction. Often, these lines are muddled. Providing education is a first step to preventing abuse. Usually, addiction is a manifestation of an untreated, or undertreated, medical condition. Pharmacist intervention helps patients and healthcare providers to make the safest, most informed decisions possible to ensure the best possible outcomes.

Pharmacist Post-Test
Objectives:
1. Identify patient populations in which ketamine use is justified based on its FDA approved indications and for off-labeled use where it has been sufficiently studied
2. Compare the different formulations of ketamine and its “kissing cousins”
3. Describe potential risks associated with ketamine use

1. Patient AV has a GCS score of 8 and requires intubation. He presents with volume depletion, hypotension, and sepsis. What drug would the anesthesiologist probably use for sedation?
a. Fentanyl
b. Etomidate
c. Ketamine

2. In which patients would you avoid recommending ketamine?
a. Patients with reactive airway disease
b. Patients with sepsis or hypotension
c. Patients with traumatic brain injury

3. Which formulation of esketamine is FDA-approved for treatment resistant depressive disorder?
a. Injectable
b. Nasal spray
c. Infusion

4. What is the most commonly used route of administration when using ketamine for agitation?
a. IV
b. IM
c. PO

5. A clinician asks you about ketamine’s adverse effects. What would you say to start?
a. Ketamine can cause cardiac arrythmias.
b. Ketamine can decrease blood pressure.
c. Ketamine can worsen peptic ulcers.

6. What is the correct order of administration for RSII medications?
a. Premedication, sedative, paralytic
b. Premedication, paralytic, sedative
c. Sedative, premedication, paralytic

7. When should prescribers monitor liver function in patients who receive repeated ketamine doses?
a. At baseline and every 1 to 2 months
b. At baseline and every 1 to 2 weeks
c. At baseline and every 1 to 2 days

8. What is a “K-hole?”
a. A networking experience
b. A near-death experience
c. An extraterrestrial experience

9. What is a limitation of using ketamine in MDD?
a. Depressive symptoms improve slowly
b. Requires an 8-week trial period first
c. Effects last only a few days to weeks

10. A police officer asks you to discuss ketamine and asks why you refer to similar drugs as “kissing cousins.” How would you explain it?
a. They all have similar potency and antagonize NMDA receptor
b. They are used in similar doses and act as a NMDA receptor agonist
c. They are structurally similar and antagonize NMDA receptor

Technician Post-Test
Objectives:
1. Identify patient populations in which ketamine use is justified based on its FDA approved indications and for off-labeled use where it has been sufficiently studied
2. Compare the different formulations of ketamine and its “kissing cousins”
3. Describe potential risks associated with ketamine use

1. In which patient should prescribers avoid using ketamine?
a. patient with serious peptic ulcer
b. patient older than 3 months old
c. patient with uncontrolled hypertension

2. What ketamine dose results in dissociation?
a. 0.1 to 0.5 mg/kg
b. 0.5 to 2 mg/kg
c. 2 to 3.5 mg/kg

3. What is a risk associated with using ketamine in RSII?
a. adrenal suppression
b. increase ARDS incidence
c. emergent reactions

4. What ketamine formulation is currently available by prescription?
a. sublingual tablet
b. injectable solution
c. 24-hour patch

5. What risk is associated with ketamine use?
a. exacerbates underlying schizophrenia
b. lowers focal seizure threshold
c. increases incidence of ARDS

6. What is a key difference between PCP and ketamine?
a. PCP has a shorter duration of action than ketamine
b. PCP is 10 time more potent than ketamine
c. PCP has less severe psychiatric effects than ketamine

7. What is a benefit of using ketamine for agitation in comparison to haloperidol?
a. faster onset
b. more redosing
c. fewer side effects

8. What is ketamine’s FDA-approved indication?
a. agitation
b. analgesia
c. anesthesia

9. What can be expected when people use oral ketamine?
a. high bioavailability
b. high rate of adverse effects
c. low plasma peak concentrations

10. What is ketamine’s role in RSII?
a. premedication
b. sedative
c. paralytic

References

1. Li L, Vlisides PE. Ketamine: 50 Years of modulating the mind. Front Hum Neurosci. 2016;10:612. Published 2016 Nov 29. doi:10.3389/fnhum.2016.00612

2. Ketalar. Prescribing information. Par Pharmaceutical; 2022. Accessed July 25, 2022. https://www.parpharm.com/pdfs/catalog/sterile/Ketalar_PI_20220613.pdf

3. Institute of Medicine (US) Forum on Neuroscience and Nervous System Disorders. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary. Washington (DC): National Academies Press (US); 2011.

4. Aleksandrova LR, Phillips AG, Wang YT. Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism. Journal of Psychiatry Neuroscience. 2017;42(4):222-229. DOI: 10.1503/jpn.160175.

5. Vyklicky V, Korinek M, Smejkalova T, et al. Structure, function, and pharmacology of NMDA receptor channels. Physiol Res. 2014;63(Suppl 1):S191-S203. doi:10.33549/physiolres.932678

6. Godwin SA, Burton JH, Gerardo CJ, et al. American College of Emergency Physicians. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2014;63(2):247-258.e18. doi:10.1016/j.annemergmed.2013.10.015[PubMed 24438649]

7. Ellingson A, Haram K, Sagen N, Solheim E. Transplacental passage of ketamine after intravenous administration. Acta Anaesthesiol Scand. 1977;21(1):41-44.[PubMed 842268]

8. Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006;60(7):341-348. doi:10.1016/j.biopha.2006.06.021

9. Zhu X, Kohan LR, Goldstein RB. substantial elevation of liver enzymes during ketamine infusion: a case report. A Pract. 2020;14(8):e01239. doi:10.1213/XAA.0000000000001239

10. Wilkinson ST, Sanacora G. Considerations on the Off-label Use of Ketamine as a Treatment for Mood Disorders. JAMA. 2017;318(9):793-794. doi:10.1001/jama.2017.10697

11. Ho JH, Dargan PI. Arylcyclohexamines (Ketamine, Phencyclidine, and Analogues). In: Critical Care Toxicology. Brent J, Burkhart K, Dargan P, Hatten B, Megarbane B, Palmer R, eds. Springer; 2016. https://doi.org/10.1007/978-3-319-20790-2_124-1

12. Lodge D, Mercier MS. Ketamine and phencyclidine: the good, the bad and the unexpected. Br J Pharmacology. 2015;172(17):4254-4276. doi:10.1111/bph.13222

13. Study of Wafermine™ for post-bunionectomy or abdominoplasty pain. ClinicalTrials.gov identifier: NCT03246971. Updated July 23, 2018. Accessed Jul 25, 2022. https://clinicaltrials.gov/ct2/show/study/NCT03246971

14. Treating major depressive disorder: a quick reference guide. American Psychiatric Association. Published October 2010. Accessed July 25, 2022. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd-guide.pdf

15. Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006;60(7):341-348. doi:10.1016/j.biopha.2006.06.021

16. Lankenau SE, Clatts MC. Patterns of polydrug use among ketamine injectors in New York City. Subst Use Misuse. 2005;40(9-10):1381-1397. doi:10.1081/JA-200066936

17. Drug Fact Sheet: Ketamine. Department of Justice and Drug Enforcement Administration. Published April 2020. Accessed July 25, 2022. https://www.dea.gov/sites/default/files/2020-06/Ketamine-2020.pdf

18. Lankenau SE, Sanders B, Bloom JJ, et al. First injection of ketamine among young injection drug users (IDUs) in three U.S. cities. Drug Alcohol Depend. 2007;87(2-3):183-193. doi:10.1016/j.drugalcdep.2006.08.015

19. Average Cost of Illicit Street Drugs. AddictionResource.net. Updated June 21, 2021. Accessed July 25, 2022. https://www.addictionresource.net/cost-of-drugs/illicit/

20. Świądro M, Stelmaszczyk P, Lenart I, Wietecha-Posłuszny R. The Double Face of Ketamine-The Possibility of Its Identification in Blood and Beverages. Molecules. 2021;26(4):813. Published 2021 Feb 4. doi:10.3390/molecules26040813

21. Morris, H. Hamilton’s Pharmacopeia Ketamine: Realms and Realities. [Video]. Vice TV. December 26, 2017. Accessed July 25, 2022. https://www.vicetv.com/en_us/video/hamiltons-pharmacopeia-ketamine-realms-and-realities/59cd5d0b7752d1ac3e90aacf

22. Kurdi MS, Theerth KA, Deva RS. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014;8(3):283-290. doi:10.4103/0259-1162.143110

23. Scarponcini TR, Edwards CJ, Rudis MI, Jasiak KD, Hays DP. The role of the emergency pharmacist in trauma resuscitation. J Pharm Pract. 2011;24(2):146-159. doi:10.1177/0897190011400550

24. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145-161.

25. Johnstone-Petty, M. Ketamine use for complex pain in the palliative care population. J Hosp Palliat Nurs. 2018;20(6):561-567. doi: 10.1097/NJH.0000000000000488.

26. Mercadante S, Caruselli A., Casuccio A. The use of ketamine in a palliative-supportive care unit: a retrospective analysis. Ann Palliat Med. 2018;7(2): 205-210. doi: 10.21037/apm.2018.01.01

27. Bell RF, Kalso EA. Ketamine for pain management. Pain Rep. 2018;3(5):e674. Published 2018 Aug 9. doi:10.1097/PR9.0000000000000674

28. Lalanne L, Nicot C, Lang JP, et al. Experience of the use of Ketamine to manage opioid withdrawal in an addicted woman: a case report. BMC Psychiatry. 2016;16(1):395. doi:10.1186/s12888-016-1112-2

29. Blonk MI, Koder BG, Van Den Bemt PMLA, Huygen FJPM. Use of oral ketamine in chronic pain management: a review. Eur J Pain. 2012;14(5): 466-472. https://doi-org.ezproxy.lib.uconn.edu/10.1016/j.ejpain.2009.09.005

30. Linder LM, Ross CA, Weant KA. Ketamine for the acute management of excited delirium and agitation in the prehospital setting. Pharmacotherapy. 2018;38(1):139-151. doi:10.1002/phar.2060

31. Lulla AA, Singh M. The Art of the ED Takedown. emDOCs.net - Emergency Medicine Education. Published March 4, 2015. Accessed July 25, 2022. http://www.emdocs.net/the-art-of-the-ed-takedown/

32. Young R, McMahon S. Some States Allow Authorities to Use Ketamine to Subdue Suspects in The Field. But Is It Safe? Some States Allow Authorities to Use Ketamine to Subdue Suspects in The Field. But Is It Safe? | Here & Now. Published September 8, 2020. Accessed July 25, 2022. https://www.wbur.org/hereandnow/2020/09/08/ketamine-police-safety-elijah-mcclain

33. Ketamine. In: Lexi-Drugs. Lexi-Comp, Inc. Updated July 20, 2022. Accessed July 25, 2022. http://usj-ezproxy.usj.edu:2099/lco/action/doc/retrieve/docid/patch_f/7135?cesid=a8n33eDrj1M&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dketamine%26t%3Dname%26acs%3Dfalse%26acq%3Dketamine#rfs

34. Montgomery-Asperg Depression Rating Scale. Accessed July 27, 2022. https://www.mdcalc.com/calc/4058/montgomery-asberg-depression-rating-scale-madrs

35. Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616-630. doi:10.1093/ijnp/pyz039

36. Spravato. Prescribing information. Janssen Pharmaceutical Companies; 2019. Accessed July 25, 2022. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf

37. Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616-630. doi:10.1093/ijnp/pyz039

Arthur E. Schwarting Symposium LIVE Event: Friday, April 17, 2026 OPENS SOON

The Arthur E. Schwarting Symposium is an educational conference focused on pharmacy practice for pharmacists in many settings.

Arthur E. Schwarting Symposium 2026

Five hours of live CE

2026 REGISTRATION

OPENS SOON

2026 Agenda

11:00am-12:00 pm

12:05-1:05 pm

1:10-2:10 pm

2:15-3:15 pm

3:20-4:20 pm

Handouts will be posted 72 hours prior to the event in 2 slide/page and 6 slide/page below:

11:00am-12:00 pm

12:05-1:05 pm

1:10-2:10 pm

2:15-3:15 pm

3:20-4:20 pm

“The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.”

Long-Acting Injectable Medication Products

Pharmacists possess the training and skills necessary to administer certain long-acting injectable (LAI) medications used in the management of mental illnesses and substance use disorders. Through collaborative practice agreements, pharmacists can administer Long Acting Injectables in almost every state. In some states, including the state of Connecticut, this occurs via collaborative agreements, and necessary injection and disease state training. Administration of these medications by pharmacists can increase accessibility of care for patients.

UConn has developed web-based continuing pharmacy education activity to enhance pharmacists’ skills and help them make sound clinical decisions about long acting injectables administration. This course includes eight hours of CPE (or eight hours of credit), required by the State of Connecticut. Successful completion of these eight hours (with four activities consisting of three hours online pre-requisite work and five hours of LIVE CE) will earn the pharmacist a Certificate in Long-Acting Injectables of Psychotropic Medication.

The three activities below are available separately for $17/hour each, or as pre-requisites for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program at $299 which includes both the prerequisites and the full day of LIVE training.

At the end of this application-based continuing education activity, the learner will be able to:

Compare and contrast among different long-acting injectable (LAI) medications currently available for the

treatment of schizophrenia, bipolar disorder and substance use disorders including:

· Dosing

· Generic and brand names

· Adverse effects

· Administration schedule

· Overlap with oral medications

· FDA-approved indications

If desired, pharmacists can register for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program

or for the individual activities. The Certificate consists of three activities in our online selection, and a 5 hour LIVE activity.

You may register for individual topics at $17/CE Credit Hour, or for the Entire LAIA Certificate at $299.00 which includes 5 hours of LIVE CE and the 3 online pre-requisites listed below.

You must register for ALL 4 activities to receive the bundled pricing of $299.00

Dr. Waters is a consultant with Janssen Pharmaceuticals. She will discuss all drugs without bias. All financial interests with ineligible companies (as noted) have been mitigated.

Guideline-Driven Treatment for Mental Illnesses and Substance Abuse Disorders

At the end of this application-based continuing education activity, the learner will be able to:

Describe first- and second-line treatment options for the following disease states:

· Schizophrenia

· Bipolar disorder

· Alcohol use disorder

· Opioid use disorder

Identify where long-acting injectable medications fit into treatment guidelines for each disorder

Apply clinical treatment guidelines to select optimal pharmacologic treatment for a patient diagnosed with these disorders

If desired, pharmacists can register for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program

or for the individual activities. The Certificate consists of three activities in our online selection, and a 5 hour LIVE activity.

You may register for individual topics at $17/CE Credit Hour, or for the Entire LAIA Certificate at $299.00 which includes 5 hours of LIVE CE and the 3 online pre-requisites listed below.

You must register for ALL 4 activities to receive the bundled pricing of $299.00

Dr. Waters is a consultant with Janssen Pharmaceuticals. She will discuss all drugs without bias. All financial interests with ineligible companies (as noted) have been mitigated.

Mental Illness and Substance Use Disorders: Background

If desired, pharmacists can register for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program

or for the individual activities. The Certificate consists of three activities in our online selection, and a 5 hour LIVE activity.

You may register for individual topics at $17/CE Credit Hour, or for the Entire LAIA Certificate at $299.00 which includes 5 hours of LIVE CE and the 3 online pre-requisites listed below.

You must register for ALL 4 activities to receive the bundled pricing of $299.00

Dr. Waters is a consultant with Janssen Pharmaceuticals. She will discuss all drugs without bias. All financial interests with ineligible companies (as noted) have been mitigated.

Hour 1: Mental Illness and Substance Use Disorders: Background

1. A 38-year-old patient with an unknown psychiatric history is dropped off at the emergency department by police after being found wandering the streets and knocking on doors at random. The patient admits that they believe they are being monitored by the FBI and that “the mafia” wants to recruit them as a spy. The patient is observed having a conversation with themselves while alone in the examination room.

Which of the following positive symptoms is the patient likely experiencing?
A. Psychosis and auditory hallucinations
B. Auditory hallucinations and delusions
C. Delusions and anhedonia
D. Paranoia and agitation

2. Which of the following is the correct term for fixed, false beliefs that patients with schizophrenia may experience?
A. Delusions
B. Hallucinations
C. Disorganized speech
D. Catatonia

3. A patient with schizophrenia has experienced both positive and negative symptoms for several years. They are now presenting with signs of mania, including pressured speech and grandiosity. Which of the following is true?
A. The patient’s diagnosis will likely change to schizoaffective disorder, bipolar type
B. The patient’s diagnosis will likely change to schizoaffective disorder, depressive type
C. The patient will now be diagnosed with schizophrenia and bipolar disorder
D. The patient will now be diagnosed with schizophrenia and major depressive disorder

4. Which of the following is true about bipolar disorder?
A. The most common time that patients are diagnosed is during childhood
B. Most patients are initially diagnosed with schizophrenia
C. It has a higher mortality rate than major depressive disorder
D. Type II bipolar disorder is associated with more severe episodes of mania than type I

5. Most patients with bipolar disorder spend the majority of their time in which mood phase?
A. Mania
B. Depression
C. Hypomania
D. Euthymia

6. A patient with bipolar disorder presents to their outpatient provider and reports that they believe they are on the verge of a “breakthrough” and will soon become a world-famous author once their manuscript is published. They have recently stopped going to work and have been writing “all day and all night” for the past week. They also report spending thousands of dollars on a new computer so that they have “the best equipment” with which to write their manuscript.
Which of the following symptoms of mania is the patient displaying?
A. Grandiosity, decreased need for sleep, increased goal directed activity
B. Flight of ideas, distractibility, grandiosity
C. Disorganized thoughts, decreased need for sleep, flight of ideas
D. Confusion, excessive spending, distractibility

7. Patient NP was diagnosed with bipolar disorder, type II approximately 5 years ago. They have rarely missed work due to hypomanic symptoms, and are generally able to perform all day-to-day activities without impairment. Following a breakup, NP begins to display signs of grandiosity, flight of ideas, decreased sleep, and increased spending. They also begin to hear the voice of their ex-partner telling them that they are worthless.

Which of the following is most appropriate?
A. NP’s diagnosis should be changed to bipolar disorder type I
B. NP’s diagnosis should remain the same
C. NP’s diagnosis should be changed to schizoaffective disorder
D. NP’s diagnosis should be changed to bipolar disorder, mixed type

8. Which of the following is a risk factor for the development of a substance use disorder?
A. Female gender
B. Age > 65 years
C. Co-occurring psychiatric disorder
D. Parenthood

9. Which type of opioid receptor contributes to the stimulation of the dopamine-related reward system?
A. Mu-opioid receptor
B. Kappa-opioid receptor
C. Delta-opioid receptor
D. Beta-opioid receptors

Law: Psychedelic Drugs: Can They Make the “Trip” to the Pharmacy Shelf?-RECORDED WEBINAR

The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

Pharmacists and Pharmacy Technicians are eligible to participate in this application-based activity and will receive 1.0 CE Hour for completing the activity (ACPE UAN 0009-0000-22-017-H03-P), passing the quiz with a grade of 70% or better, and completing an online evaluation. Statements of credit are available via the CPE Monitor online system and your participation will be recorded with CPE Monitor within 72 hours of submission.

Schwarting Webinar 2023 Post-Test

1. Review the development of the knowledge of the effects of psychedelic drugs and their potential use in psychiatry, with an emphasis on psilocybin.
2. Characterize the traditional legal classification of psychedelic drugs and modern reconsideration of their legal status.
3. Describe efforts at the state level to expand the medical use of psychedelic drugs.

The tryptamine class of psychedelic drugs (e.g., LSD, psilocybin) produce their psychedelic/therapeutic effects by acting as agonists of a neurotransmitter in the CNS. What is the relevant neurotransmitter system?

Serotonin
Dopamine
Glutamate

The FDA granted “breakthrough therapy” designation to psilocybin for treatment of a specific condition. What condition is it?

Schizophrenia
Treatment resistant depression
Post traumatic stress disorder

Which feature distinguishes a C-I drug from other controlled substances?

High potential for abuse, especially among hi-riskpopulations
Lack of accepted safety for use under medical supervision
No currently accepted medical use in treatment in the United States

Which state was the first to approve the use of psilocybin for medical use?

California
Oregon
Maryland

A patient considering psilocybin treatment for a psychiatric disorder asks you for advice; he is specifically interested in disadvantages of this type of therapy. What do you tell him?

Use of psychedelic therapy is time-and resource-intensive
Requires multiple treatments with a slow onset of activity
There is a high risk of autonomic side effects and addiction

In the state where medical use of psilocybin was first approved, which of the following statements describes its availability?

Psilocybin can be purchased at retail outlets including pharmacies
Psilocybin is available from any therapist throughout the state
Psilocybin is only available in state licensed clinics

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Introduction

SIDEBAR. Types of Human Trafficking15,17,18

History of Human Trafficking in the United States

Healthcare Providers & Human Trafficking

The Pharmacy Team in Action

For safety and reporting, pharmacy team members should generally trust their instincts in a suspicious situation, especially when patients2,31,32

Avoiding Bias + Using the Correct Language

Table 2. Common Human Trafficking Myths vs Reality1,36

HEALTH CONSEQUENCES FOR VICTIMS

Acting on Human Trafficking

Conclusion

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

About this Course

Target Audience

Pharmacist Learning Objectives

Bundle Options

Accreditation Statement

Grant Funding

Requirements for Successful Completion

Faculty

Faculty Disclosure

SIDEBAR. Types of Human Trafficking^15,^17,18

For safety and reporting, pharmacy team members should generally trust their instincts in a suspicious situation, especially when patients^2,31,32

Table 2. Common Human Trafficking Myths vs Reality^1,36