Over the past several years, medicinal cannabis has become a focus of research and legislation, specifically regarding cannabidiol (CBD) oils and other CBD products. CBD is one of the most popular types of cannabinoids, and has been shown to reduce inflammation, convulsions, anxiety, and nausea.1

Chain pharmacies, including Walgreens and CVS, have decided to sell CBD products in their stores.2 The projected retail sales of CBD products are expected to reach $1.9 billion by 2020.3 Legislation regarding CBD products is evolving slowly, in attempt to catch up to this current movement.
 
CBD derived from any cannabis source was previously a Schedule I controlled substance; therefore, the current research of CBD was limited due to the Controlled Substances Act (CSA) formally making it illegal to cultivate, possess, sale, and distribute CBD. Under this law, researchers interested in studying CBD were required to register with the DEA and provide additional information, such as their qualifications, research protocol, and the institution where the research will take place.4

The 2014 Farm Bill was subsequently signed into law, which differentiated industrial hemp from marijuana, and authorized industrial hemp research by institutions of higher education or departments of agriculture in states where hemp cultivation was legalized.5 Later, the 2018 Farm Bill removed hemp from the CSA, paving the way for the legal cultivation, possession, sale, and distribution of hemp, thus streamlining research on hemp-derivatives, including CBD, and speeding up the development of new drugs.6

Hemp is regarded by the federal government as cannabis containing no more than 0.3% THC, which means that federally legal CBD, which must be derived from hemp or other lawful source, shall contain no more than 0.3% THC.5

CBD, when derived from marijuana, or “all parts” of the cannabis plant, remains a Schedule I substance.7 The 2018 Farm Bill also explicitly preserved the FDA’s authority to regulate any products containing hemp-derivatives under the U.S. Federal Food, Drug, and Cosmetic Act  (FDCA). FDA has not approved the use of CBD as a dietary supplement or food additive.8

Dr. Alex Capano, Chief Science Officer for Ananda, and a doctoral candidate focused on cannabinoid science, believes that CBD has many uses within the medical treatment realm. Among these include adjunctive therapy for patients on opioids to help them titrate down, pain management, and reducing withdrawal symptoms for narcotic users.9 Furthermore, Capano stated that a potential issue with CBD containing 0.3% THC or less includes drug testing for employers.

Some manufacturers are responding to the market demand by producing and marketing CBD that is THC-free. Even in this case, according to Capano, “there is still possibly an issue with drug testing due to CBD reactivity and false-positives. In addition, the THC-free CBD products are believed to have less therapeutic potential.”

With greater patient access to CBD, pharmacists will need to be prepared to address potential drug interactions to help patients use these products safely. The FDA has issued numerous warning letters instructing various manufacturers to halt production of OTC CBD products since 2016, due to significant discrepancies existing between the tested contents of products and strengths listed on the product labels. As some products were found to contain no trace of CBD compounds during quality testing, widespread mislabeling can easily occur in the absence of strict FDA enforcement.3,10

Furthermore, according to Capano, there is no standard production method among CBD manufacturers, which can lead to impurities being introduced into products. Therefore, microbiological, pesticide, and heavy metal contamination can lead to harmful effects. These risks can be mitigated by patients obtaining CBD products from reliable sources, such as pharmacies that have vetted vendors as trusted CBD suppliers.

Regarding interactions, in vitro studies have illustrated multiple potential drug interactions for CBD. The lack of standardized products somewhat limits the ability to make definitive statements from available research, but there is evidence that CBD is an inhibitor of many CYP450 enzymes including 2D6, 3A4, and 3A5, as well as a potent p-glycoprotein (P-gp) inhibitor.11 Since these are common enzymes of drug metabolism, and with the widespread adoption of CBD oil use by chronic pain patients, there exists a high potential for drug-drug interactions and safety concerns.

Research also suggests CBD use enhances the effect of opiates, and exhibits other interactions with barbiturates, fluoxetine, sedatives, and antihistamines, as well as having synergistic effects with alcohol.11

Community pharmacists are well-positioned to intervene clinically at the forefront of this health culture trend. While OTC products appear safe to many consumers, FDA warning letters to numerous manufacturers suggest otherwise.

Pharmacists are patient advocates to protect against adverse outcomes. They can assist with advising patients who present with quality concerns to use CBD products that provide certificates of analyses, and catch significant drug interactions before they occur. As such, it is important for pharmacists to stay abreast of ongoing research developments regarding CBD products. Staying current with emerging literature and evidence-based research on this topic is the best way for pharmacists to ensure they are continuing to provide the most competent and comprehensive care for their patients.


References
  1. Americans for Safe Access (Copyright 2018). Guide to using medical cannabis, Cannabis 101. https://www.safeaccessnow.org/usingmedicalcannabis. Accessed September 5, 2019.
  2. LaVito, A. Rite Aid will start selling CBD products. CNBC. https://www.cnbc.com/2019/04/11/rite-aid-will-start-selling-cbd-products-in-2-states.html. Published April 11, 2019. Accessed September 5, 2019.
  3. Corron J, Kight R. Regulatory status of cannabidiol in the United States: A perspective. Cannabis Cannabinoid Res. 2018; 3(1):190-194.
  4. DEA speeds up application process for research on schedule I drugs. DEA. https://www.dea.gov/press-releases/2018/01/18/dea-speeds-application-process-research-schedule-i-drugs. Published January 18, 2018. Accessed June 12, 2019.
  5. Sec. 7606 of the farm bill authorized hemp research and pilot programs. https://www.votehemp.com/laws-and-legislation/federal-legislation/sec-7606-of-the-farm-bill/. Accessed June 12, 2019.
  6. What does the 2018 farm bill mean for the hemp and CBD businesses? https://www.perkinscoie.com/en/news-insights/what-does-the-2018-farm-bill-mean-for-the-hemp-and-cbd-businesses.html. Published December 31, 2018. Accessed June 12, 2019.
  7. Hudak, J. The farm bill, hemp legalization and the status of CBD: An explainer. https://www.brookings.edu/blog/fixgov/2018/12/14/the-farm-bill-hemp-and-cbd-explainer/. Published December 14, 2018. Accessed June 12, 2019.
  8. FDA Regulation of Cannabis and Cannabis-Derived Products: Questions and Answers. FDA. https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm421168.htm#farmbill. Updated: April 2, 2019. Accessed September 5, 2019.
  9. Hurd YL, Springs S, Alishayev J, et al. Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: A double-blind randomized placebo-controlled trial. AM J Psychiat. 2019. DOI: 10.1176/appi.ajp.2019.18101191.
  10. Bonn-Miller MO, Loflin MJ, Thomas BF, et al. Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA.  2017;318(17):1708-1709. doi:10.1001/jama.2017.11909
  11. Opitz BJ, et al. The potential clinical implications and importance of drug interactions between anticancer agents and cannabidiol in patients with cancer. J Pharm Pract. 2019.