“The flowering plants of the genus Cannabis, which mainly comprises the sativa and indica species, have been recognized for medical treatment for millennia.
Although Cannabis contains nearly 500 compounds from 18 chemical classes, its physiological effects derive mainly from a family of naturally occurring compounds known as plant cannabinoids or phytocannabinoids. Of the more than 100 phytocannabinoids that have been identified in Cannabis, among the most important and widely studied are its main psychoactive constituent, Δ9-tetrahydrocannabinol (Δ9-THC), and the most important nonpsychoactive component, cannabidiol (CBD). Other biologically active phytocannabinoids that have been isolated in Cannabis include Δ8-THC, cannabinol, Δ9-tetrahydrocannabivarin, and cannabidivarin.
In recent research, orally administered cannabidiol (CBD) showed a relatively high incidence of somnolence in a pediatric population. Previous work has suggested that when CBD is exposed to an acidic environment, it degrades to Δ9-tetrahydrocannabinol (THC) and other psychoactive cannabinoids. To gain a better understanding of quantitative exposure, we completed an in vitro study by evaluating the formation of psychoactive cannabinoids when CBD is exposed to simulated gastric fluid (SGF).
SGF converts CBD into the psychoactive components Δ9-THC and Δ8-THC. The first-order kinetics observed in this study allowed estimated levels to be calculated and indicated that the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a physiological response. Delivery methods that decrease the potential for formation of psychoactive cannabinoids should be explored.
Despite persistent challenges with dosing and administration, CBD-based therapies have a good safety profile and a potential for efficacy in the treatment of a variety of medical conditions. The rapidly evolving sciences of drug delivery and cannabinoid pharmacology may soon lead to breakthroughs that will improve access to the benefits of this pharmacological class of agents. In addition, current technologies, such as transdermal-based therapy, may be able to eliminate the potential for psychotropic effects due to this acid-catalyzed cyclization by delivering CBD through the skin and into the neutral, nonreactive environment of the systemic circulation.”