Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers

Abstract

Background: Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability.

Methods: Healthy, frequent marijuana users (n=31) were enrolled in this within subject, randomized, placebo-controlled, double-blind, multisite study that administered oral cannabidiol (0, 200, 400, 800mg) alone and in combination with smoked marijuana (0.01%, 5.3-5.8% THC). Participants received one dose combination across 8 once-weekly outpatient sessions (7.5h). The primary findings on the drug interaction effects were previously reported (Haney et al., 2016). The present study is a secondary analysis of the data to examine the abuse liability profile of oral cannabidiol (200, 400, 800mg) in comparison to oral placebo and active smoked marijuana (5.3-5.8% THC).

Results: Active marijuana reliably produced abuse-related subjective effects (e.g., high) (p<0.05). However, CBD was placebo-like on all measures collected (p>0.05).

Conclusions: Overall, CBD did not display any signals of abuse liability at the doses tested and these data may help inform U.S. regulatory decisions regarding CBD schedule on the CSA.

Keywords: Abuse liability; CBD; Cannabidiol; Human; Smoked marijuana.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1

Peak ratings of the visual analog items “I feel high” (left panel) and “I feel a good drug effect” (middle panel) and estimates from a marijuana street value assessment (right panel) presented as a function of dose condition (n=31, ±SEM). Peak effect analyses detected a main effect of active marijuana (5.3-5.8% THC) on each measure. Tukey's post-hoc tests indicated that 1) active CBD doses were not significantly different from placebo CBD (p>.05) and 2) active marijuana condition was significantly different from each of the CBD dose conditions (0, 200, 400, 800 mg, collected under inactive marijuana [0.01% THC] conditions), as indicated by the asterisk (p<.05). The abbreviations on the graphs are as follows: MJ=active marijuana/placebo CBD, CBD 0= 0 mg CBD/placebo marijuana, CBD 200 = 200 mg CBD/placebo marijuana, CBD 400 = 400 mg CBD/placebo marijuana, CBD 800 = 800 mg CBD/placebo marijuana.