YAFI Online Programming // Disease State Management and Drug Therapy
A Tale of Two Products
After participating in this activity, pharmacists will be able to:
- Discuss cannabidiol and its known pharmacologic profile
- Identify FDA-approved indications for prescription cannabidiol and other indications in which research is promising
- Distinguish the FDA-approved canabidiol from various nonprescription products in terms of quality and risk/benefit profile
- Maximize the pharmacist's role in helping patients who are good candidates for prescription cannabidiol or use nonprescription cannabidiol products either with or without other prescription drug therapies
After participating in this activity pharmacists and pharmacy technicians will be able to:
- Discuss the basic facts about cannabidiol products
- Acquire reputable sources for patients who have an interest in cannabidiol to find information
- Distinguish between nonprescription and prescription cannabidiols
- Infer when to refer patients to the pharmacist for recommendations or referral
Release Date: May 15, 2019
Expiration Date: June 15, 2021
19YC44-XKP36 Pharmacy Technician
2.0 hours of CE
The U.S. Food and Drug Administration (FDA) approved a highly purified cannabidiol (CBD) product called Epidiolex (hereafter referred to as CBD-Rx) for the treatment of seizure disorders in Dravet's and Lennox-Gastaut syndromes. Patients with epilepsy are sensitive to small changes in antiepileptic drug concentrations. Due to CBD products' tendency to deviate from the dose on the label and the dose actually delivered, use of non-FDA approved CBD products is highly discouraged in people with epilepsy. CBD is well tolerated but like all drugs, poses risks to the consumer. CBD has benefits, adverse events, and drug interactions that the pharmacy team must assess; careful counseling is critical for optimal use. While the lay press and Internet touts CBD to treat or alleviate many ailments, the evidence for benefit is limited. The pharmacy team, with their high accessibility and deep respect in the community, should be an unbiased information source on the possible benefits and risks of CBD for various ailments. Pharmacists should discourage adding CBD to food and drink at this time.
|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 up to 0.2 CEU (2 contact hours) for completing the activity, passing the quiz with a grade of 70% or better, and completing an online evaluation. Statements of credit are available via the CPE Monitor on- line system and your participation will be recorded with CPE Monitor within 72 hours of submission
Grant funding: Greenwich Biosciences
Initial Release Date: May 15, 2019
Expiration Date: May 15, 2021
To obtain CPE credit, visit the UConn Online CE Center
Use your NABP E-profile ID and the session code 19YC44-JFK22 for pharmacists or 19YC44-XKP36 for pharmacy technicians to access the online quiz and evaluation.
First- time users must pre-register in the Online CE Center. Test results will be displayed immediately and your participation will be recorded with CPE Mon- itor within 72 hours of completing the requirements.
For questions concerning the online CPE activities, email firstname.lastname@example.org
C. Michael White, Pharm.D., FCP, FCCP; Professor and Chair, Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, CT and Director, HOPES Collaborative Group, University of Connecticut and Hartford Hospital, Hartford, CT.
The author has no actual or potential conflicts of interest associated with this article.
Disclosure of Discussions of Off-label and Investigational Drug Use
This activity may contain discussion of off label/unapproved use of drugs. The content and views presented in this educational program are those of the faculty and do not necessarily represent those of the University of Connecticut School of Pharmacy. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
In the United States, the 2018 Farm Bill legalized hemp production, a move that has given products derived from hemp—products that contain cannabidiol (CBD)—a boost. A recent news article disucssed CBD’s use by stressed-out parents.1 Various companies market CBD, an extract from hemp and marijuana plants, as able to help patients’ multiple ailments, including anxiety, pain, Parkinson’s disease, schizophrenia, and cancer. 2,3 Consumers may be drawn to CBD as it comes in multiple forms (e.g., oils, eye serums, gummies, etc).2,4 Even Willie Nelson has jumped on the CBD bandwagon—in July 2018, he released CBD infused-coffee beans.2
Full List of References
1. Caron C. CBD lures stressed-out parents looking to unwind. Accessed at https://www.nytimes.com/2019/04/12/parenting/cbd-oil safe.html, April 13, 2019.
2. Williams A. Why Is CBD Everywhere? The New York Times. October 27, 2018. Accessed at https://www.nytimes.com/2018/10/27/style/cbdbenefits.html?action=click&module=RelatedLinks&pgtype=Arti cle, April 13, 2019.
3. Gill LL. How to Shop for CBD. Consumer Reports. September 27, 2018. Accessed at https://www.consumerreports.org/marijuana/how-to-shop for-cbd/, April 13, 2019.
4. Caron, C. CBD Lures Stressed-Out Parents Looking to Unwind. The New York Times. April 12, 2019. Accessed at https://www.nytimes.com/2019/04/12/parenting/cbd-oil safe.html, April 13, 2019.
5. Atakan Z. Cannabis, a complex plant: different compounds and different effects on individuals. Ther Adv Psychopharmacol. 2012;2(6):241-254.
6. White CM. The pharmacologic and clinical effects of illicit synthetic cannabinoids. J Clin Pharmacol. 2017;57:297-304.
7. Satterlund TD, Lee JP, Moore RS. Stigma among California’s marijuana patients. J Psychoative Drugs. 2015;47:10-17.
8. Pisanti SA, Malfitano AM, Ciaglia E, et al. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol Ther. 2017;175:133-150.
9. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313:2456-2473.
10. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, can‐ nabidiol and Δ9‐tetrahydrocannabivarin. Br J Pharmacol. 2008;153:199-215.
11. Mandolini GM, Lazzaretti M, Pigoni A, et al. Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview. Epidemiol Psychiat Sci. 2018;2:327-335.
12. Perucca E. Cannabinoids in the treatment of epilepsy: heave evidence at last? J Epilep Res. 2017;7:61-76.
13. Cheng D, Spiro AS, Jenner AM, et al. Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer’s disease transgenic mice. J Alzheim Dis. 2014;42:1383-1396.
14. Veronesi B, Oortgiesen M. The TRPV1 receptor: target of toxicants and therapeutics. Toxicol Sci. 2006;89:1-3.
15. Oláh A, Tóth BI, Borbíró I, et al. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. J Clin Invest. 2014;124:3713-3724.
16. Mecha M, Feliú A, Iñigo PM, et al. Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors. Neurobiol Dis. 2013;59:141-150.
17. Epidiolex® (Cannabidiol) Prescribing Information. Greenwich Biosciences, Inc., Carlsbad, CA 92008. 2018.
18. Drug Enforcement Administration. Schedules of controlled substances: placement in schedule V of certain FDA-approved drugs containing cannabidiol; corresponding change to permit requirements. 21 CFR Parts 1308, 1312 [Docket No. DEA–486]. September 28, 2018. Federal Register 2018;vol 83, No. 189. Accessed at https://www.gpo.gov/fdsys/pkg/FR-2018-09 28/pdf/2018-21121.pdf, accessed April 10, 2019.
19. Epilepsy Foundation. Types of epilepsy syndromes. Accessed at https://www.epilepsy.com/learn/types-epilepsy-syndromes, April 15, 2019.
20. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the dravet syndrome. N Engl J Med. 2017;376:2011-2020.
21. Devinsky O, Patel AD, Cross JH, et al. Effect of cannabidiol on drop seizures in the lennox–gastaut syndrome. N Engl J Med. 2018;378:1888-1897.
22. Stockings E, Zagic D, Campbell G, et al. Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence. J Neurol Neurosurg Psychiatry. 2018;89:741-53.
23. Hess EJ, Moody KA, Geffrey AL, et al. Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex. Epilepsia. 2016;57:1617-1624.
24. Devinsky O, Marsh E, Friedma D, Thiele E, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurology. 2016;15:270-278.
25. Zuardi AW, Shirakawa I, Finkelfarb E, et al. Action of cannabidiol on the anxiety and other effects produced by delt 9-THC in normal subjects. Psychopharmacol. 1982;76:245-250.
26. Karniol IG, Shirakawa I, Kasinski N, et al. Cannabidiol interferes with the effects of delta 9-tetrahydrocannabidiol in man. Eur J Pharmacol. 1974;28:172-177.
27. Zuardi AW, Cosme RA, Graeff FG, et al. Effects of ipsapirone and cannabadiol on human experimental anxiety. J Psychopharmacol. 1993;7:82-88.
28. Martin-Santos R, Crippa JA, Batalla A, et al. Acute effects of a single, oral dose of d-9-tetrahydrocannabidiol (THC) and cannabidiol (CBD) administration in healthy volunteers. Curr Pharm Design. 2012;18:4966-4979.
29. Bergamaschi MM, Queiroz RH, Chagas MH, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment‐naıve Social phobia patients. Neuropsychopharmacology. 2011;36:1219-1226.
30. Linares IM, Zuardi AW, Pereira LC, et al. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. Braz J of Psychiat. 2019 Jan-Feb;41(1):9-14.
31. Zuardi AW, Rodrigues NP, Silva AL, et al. Inverted U-shaped dose-response curve of the anxiolytic effect of cannabidiol during public speaking in real life. Front Pharmacol. 2017;May 11;8:259.
32. Crippa JA, Zuardi AW, Garrido GE. Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology. 2004;29:417-426. 33. Bhattacharyya S, Morrison PD, Fusar-Poli P, et al. Opposite effects of Δ‐9‐tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology. 2010;35:764-774.
33. Bhattacharyya S, Morrison PD, Fusar-Poli P, et al. Opposite effects of Δ‐9‐tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology. 2010;35:764-774.
34. Das RK, Kamboj SK, Ramadas M, et al. Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology (Berl). 2013;226:781-792.
35. Arndt, DL, Harriet de Wit H. Cannabidiol does not dampen responses to emotional stimuli in healthy adults. Cannabis and Cannabinoid Res. 2017 Jun 1;2(1):105-113.
36. Hundal H, Lister R, Evans N, et al. The effects of cannabidiol on persecutory ideation and anxiety in a high trait paranoid group. J Psychopharmacol. 2018;32:276-282.
37. Hindocha C, Freeman TP, Schafer G, et al. Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: A randomised, double-blind, placebo-controlled study in cannabis users. Eur Neuropsychopharmacol. 2015;25:325-334.
38. Englund A, Morrison PD, Nottage J, et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J Psychopharmacol. 2013;27(1):19-27.
39. McGuire P, Robson P, Cubala WJ, et al. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: A multicenter randomized controlled trial. Am J Psychiatry. 2018;175:225-231.
40. Boggs DL, Surti T, Gupta A, et al. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacol. 2018;235:1923-1932.
41. Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational Psychiatry. 2012 Mar 20;2:e94.
42. Palmieri B, Laurino C, Vadalà M. Short-term Efficacy of CBDenriched hemp oil in girls with dysautonomic syndrome after human papillomavirus vaccination. IMAJ. 2017;19:79-84.
43. Cuñettia L, Manzoa L, Peyraubeb R, et al. Chronic pain treatment with cannabidiol in kidney transplant patients in Uruguay. Transplantation Proc. 2018;50(2):461-464.
44. Wade DT, Robson P, House H, et al. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003;17:21-9.
45. Chagas MH, Zuardi AW, Tumas V, et al. Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial. J Psychopharmacol. 2014;28:1088-1098.
46. Chagas MH, Eckeli AL, Zuardi AW, et al. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson’s disease patients: a case series. J Clin Pharm Ther. 2014 Oct;39(5):564- 566.
47. Oláh A, Tóth BI, Borbíró I, et al. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. J Clin Invest. 2014;124:3713-3724.
48. Ali A, Akhtar N. The safety and efficacy of 3% cannabis seeds extract cream for reduction of human cheek skin sebum and erythema content. Pak J Pharm Sci. 2015;28:1389-1395.
49. Oláh A, Markovics A, Szabó-Papp J, et al. Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrheic skin and acne treatment. Exp Dermatol. 2016 Sep;25(9):701-707.
50. Naftali T, Mechulam R, Marii A, et al. Low-dose cannabidiol is safe but not effective in the treatment for Crohn's disease, a randomized controlled trial. Dig Dis Sci. 2017;62:1615-1620.
51. Hande K. Cannabidiol: The need for more information about its potential benefits and side effects. Clin J Oncol Nurs. 2019;23:131-134.
52. Sulé-Suso J, Watson NA, van Pittius DG, et al. Striking lung cancer response to self-administration of cannabidiol: A case report and literature review. SAGE Open Med Case Rep. 2019;7:2050313X19832160.
53. Dall'Stella PB1, Docema MFL1, Maldaun MVC1, et al. Case report: Clinical outcome and image response of two patients with secondary high-grade glioma treated with chemoradiation, PCV, and cannabidiol. Front Oncol. 2019;8:643. doi: 10.3389/fonc.2018.00643.
54. Stott C, White L, Wright S, et al. A phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of rifampin, ketoconazole, and omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers. SpringerPlus. 2013;2:236.
55. Iffland K, Grotenherman F. An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis and Cannabinoid Res. 2017;2:139-154.
56. Geffrey AL, Pollack SF, Bruno PL, et al. Drug-drug interaction between clozabam and cannabadiol in children with refractory epilepsy. Epilepsia. 2015;56:1246-1251.
57. Bonn-Miller MO, Loflin MJ, Thomas BF, et al. Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA. 2017;318:1708- 1709.
58. Segall B. CBD oil poses risk for failed drug tests. WTHR TV. May 12, 2018. Accessed at https://www.wthr.com/article/cbdoil-poses-risk-for-failed-drug-tests, April 10, 2019.
59. Regan T. Woman says she failed drug test after taking CBD oil. WSB-TV. October 3, 2018. Accessed at https://www.wsbtv.com/news/local/atlanta/woman-says-shefailed-drug-test-after-taking-cbd-oil/846083743, April 10, 2019.
60. United Stated Food and Drug Administration. Warning letters and test results for cannabidiol-related products. Accessed at https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm4841 09.htm, April 10, 2019.
61. Hazekamp A. The trouble with CBD oil. Med Cannabis Cannabinoids. 2018;1:65-72. https://doi.org/10.1159/000489287.
62. ConsumerLab. CBD & Hemp Extract Supplements, Lotions, and Balms Review. April 1, 2019. Accessed at https://www.consumerlab.com/reviews/cbd-oil-hempreview/cbd-oil/, April 10, 2019.
63. US Pharmacopeia. US Pharmacopeia Verified Dietary Supplements. Accessed at https://www.qualitysupplements.org/verified-products/verified-products-listings, April 10, 2019.