Cannabis (Cannabis sativa) is “one of the most widely used and controversial substances worldwide.”1 The “vast majority” of cannabis use is recreational, although cannabis and cannabis-derived substances are increasingly being used for medical and complementary health purposes.2

Increased access has included the expansion of medical marijuana programs in approximately two-thirds of US states as well as “broad consumer marketing” and use of cannabidiol (CBD) products.2 Indeed, retail sales of hemp-derived CBD products in the United States reached $170 million in 2016, and are projected to grow at a 55% compound annual growth rate over the next 5 years to reach over $1 billion.3 A variety of cannabis products are now available, including high-potency herbal cannabis, mass-produced cannabis “edibles,” and cannabis oils, concentrates, and topical preparations.1  

The increased use of CBD has created some significant challenges because of a variety of factors. One is that CBD is one of many compounds derived from cannabis, with another compound being Δ9-tetrahydrocannabinol (THC), which is the psychoactive component.2 Another is a paucity of research; despite the increasing use of cannabis products—including CBD—and “rapid changes in the social, political, cultural and legal landscape…there is insufficient decision support provided by available evidence regarding CBD.”4 One reason for this is that potential researchers encounter a myriad of regulatory barriers, and practical obstacles that impede the research process.5 Clinicians “therefore face the challenge of keeping up with the evolving use of cannabis to better assess and treat use disorders and counsel patients who choose to use cannabis for medical or recreational purposes.”1

Joshua D Brown, PharmD, PhD, Assistant Professor, Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy.

Two of the many areas of unclarity and insufficient evidence are the potential adverse drug events (ADEs) of CBD and potential drug-drug interactions (DDIs) with other agents a patient may be taking. 

To shed light on this complex subject, MPR interviewed Joshua D Brown, PharmD, PhD, Assistant Professor, Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy. Dr Brown is the coauthor of a recent review article, “Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use.”

What motivated you to write your article?

We wrote the article to meet the need for cannabis-related education in the current environment in which cannabis products – especially CBD – are so easily accessible. Almost any patient could be using it recreationally or chronically for some type of medical condition, such as pain or insomnia.

This is a major problem from a safety perspective because cannabis has been regarded as a benign agent, which is assumed from its history of recreational use. People say, “Marijuana never killed anyone and no one has ever overdosed on it.” But when we look at the history of recreational users, they have traditionally been younger adults who don’t have serious conditions and are not taking multiple medications. So I think that we need a paradigm shift in the way we think about CBD and cannabis as a whole, not as a recreational illicit substance but as a medication.

CBD, THC, and other cannabinoids have the potential to interact with commonly used medications – at least hypothetically. If I were to hazard a guess, I would say that CBD might interact with at least one-half if not three-quarters of all medications, given its role as a potential inhibitor of certain enzymes that play a role in metabolizing other drugs. This can lead to potential ADEs and DDIs. CBD not only inhibits these enzymes but it also is itself metabolized by the enzymes, so one might say it is both a “perpetrator” and a “victim” of DDIs.

The potential for both ADEs and DDIs is related to the pharmacologic targets of CBD, its pharmacodynamic effects, and its impact on the metabolism, absorption, and elimination of other medications.