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, 800 mg) 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 (7.5 hrs). 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, 800 mg) 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<.05). However, CBD was placebo-like on all measures collected (p>.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.

Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: A randomized, double-blind, controlled trial

“…Furthermore, in discrimination studies in rhesus monkeys, CBD did not substitute for a THC discriminative stimulus, indicating the lack of action by CBD at CB 1 receptors [25]. The minimal effects of CBD in this study are similar to those reported by Babalonis et al [13]. Although that study showed few significant effects of CBD, a lower range of doses were used (200, 400, and 800 mg) compared with the present study.…”

“…Assessment of the subjective effects of single doses allows one to make conclusions on the "recreational" abuse potential of a drug but does not assess its reinforcing or dependence (physical or psychological) potential. However, the trial was conducted in accordance with the human abuse potential study guidelines, and data presented are generally consistent with other human abuse potential studies of CBD and preclinical data [13,14,33].…”

“…In a study of CBD interactions with smoked marijuana in healthy users of recreational marijuana, CBD pretreatment did not alter the subjective, reinforcing, or cardiovascular effects of smoked marijuana [12]. Secondary analysis of the same study showed that CBD (at doses up to 800 mg) did not produce elevations in any subjective ratings of drug effect relative to placebo [13].…”

“…Based on the CNS-related adverse events (AEs) reported in CBD clinical trials and in accordance with US Food and Drug Administration (FDA) guidance [14], a human abuse potential study was conducted to evaluate the abuse potential of therapeutic and supratherapeutic single doses of an oral formulation of CBD. A previous human abuse potential study of CBD evaluated effects in recreational marijuana users [13]; however, as CBD had not demonstrated effects consistent with those of THC, recreational polydrug users were chosen for participation in this study to provide a broader range of drug experiences with which to compare any potentially novel euphoric effects of CBD. This population would also be the most susceptible population to abuse novel drugs with CNS effects and may exhibit a lower risk of false-negative responses than nondrug users who generally do not report liking or selfadministration of drugs of abuse [15,16].…”

Cannabidiol: A budding industry!

“…increased heart rate) and psychological (e.g. sedation and self-reported feelings of intoxication) effects of cannabis containing higher levels of THC (Martin-Santos et al 2012; Babalonis et al 2017).…”