A randomized, double-blind, placebo-controlled, crossover study to evaluate the abuse potential of purified cannabidiol (CBD) in subjects with a history of recreational polydrug use (P1.266)

Objective: Assess the abuse potential of CBD.

Background: CBD is a cannabinoid in development to treat severe early-onset epilepsy and is currently a schedule I controlled substance in the United States.

Design/Methods: Healthy adult (ages 18–55) recreational polydrug users were recruited to assess CBD in a randomized, double-blind, 7-way crossover, single-dose study comparing CBD therapeutic (750 mg), mid (1500 mg), and supratherapeutic (4500 mg) doses with placebo and two active controls; dronabinol (DRO, 10 and 30 mg, schedule 3) and alprazolam (ALP, 2 mg, schedule 4). Visual analogue scales (VAS) for Drug Liking maximum effect (E_max) (primary endpoint) and Overall Drug Liking (ODL) (Emax/Emin) and Take Drug Again (TDA) as well as other secondary endpoints were measured.

Results: In total, 43 subjects were randomized (safety population) and 35 completed the study (completer population). For the primary endpoint of Drug Liking Emax, ALP and DRO both showed significantly greater response relative to placebo, demonstrating study validity (p<0.0001 for all comparisons). All three doses of CBD showed significantly decreased responses compared to ALP and DRO (p≤0.003). The lowest dose of CBD was not significantly different from placebo, whereas the two higher doses of CBD were significantly higher than placebo (p≤0.039) but the differences were not considered clinically relevant. For the secondary endpoint of ODL Emax, all 3 CBD doses were significantly lower than ALP and DRO (p≤0.004) and were not statistically different from that of placebo (p³0.09). For the endpoint of TDA Emax, all 3 doses of CBD were significantly less likely to be taken again than ALZ or DRO (p≤0.001). ). Two subjects on 30 mg DRO, 1 on 1500 mg CBD, and 2 on 4500 mg CBD discontinued due to adverse events.

Conclusions: CBD showed little or no signal for abuse potential compared with placebo, and less psychoactive effects than ALZ or DRO.

Study Supported by: Greenwich Research LTD

Disclosure: Dr. Schoedel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Altreos Research Partners, Inc. Dr. Schoedel has received research support from GW Pharmaceuticals, Inc. Dr. Etges has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GW Pharmaceuticals. Dr. Levy-Cooperman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Altreos Research Partners, Inc. Dr. Levy-Cooperman has received research support from GW Pharmaceuticals, Inc. Dr. Mills has nothing to disclose. Dr. Sellers has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Sellers provides independent scientific consulting services to the pharmaceutical and device industries and regulatory authorities through DL Global Partners Inc. Concerning abuse potential of new chemical entities and approved drugs. Confidentially a. Dr. Setnik has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with INC Research, GW Pharmaceuticals. Dr. Setnik has received research support from INC Research, GW Pharmaceuticals. Dr. Szeto has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with INC Research. Dr. Sommerville has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Greenwich Biosciences. Dr. Sommerville holds stock and/or stock options in Greenwich Biosciences, which sponsored research in which Dr. Sommerville was involved as an investigator. Dr. Sommerville holds stock and/or stock options in Johnson and Johnson.