Cannabidiol as a treatment for craving and relapse inindividuals with cocaine use disorder: a randomizedplacebo-controlled trial, Violaine Mongeau-Pérusse, et al., 2021

Cannabidiol as a treatment for craving and relapse inindividuals with cocaine use disorder: a randomized placebo-controlled trial

Violaine Mongeau-Pérusse, Suzanne Brissette, Julie Bruneau, Patricia Conrod, Simon Dubreucq, Guillaume Gazil, EmmanuelStip & DidierJutras-Aswad

Addiction, 2021, 116, (9), 1-12.

Doi : 10.1111/add.15417



Background and Aims : Cocaine use disorder (CUD) is a significant public health concern for which no efficacious phar-macologicalinterventionsare available. Cannabidiol (CBD) has attracted considerable interest as a promisingtreatmentforaddiction. This study tested CBD efficacy for reducing craving and preventing relapse in people with CUD.DesignSingle-site double-blind randomized controlled superiority trial comparing CBD with placebo.

Setting and Participants : Centre Hospitalier de lUniversité de Montréal, Canada. Seventy-eight adults (14 women) with moderate to severe CUD partici-pated.InterventionParticipants were randomly assigned (1 : 1) by stratified blocks to daily 800 mg CBD (n=40)orplacebo (n= 38). Theyfirst underwent an inpatient detoxification phase lasting 10 days. Those who completed this phaseentered a 12-week outpatient follow-up.

Measurements : Primary outcomes were drugcue-induced craving during de-toxication and time-to-cocaine relapse during subsequent outpatient treatment.

Findings : During drugcue exposure,craving scores [mean ± standard deviation (SD)] increased from baseline by 4.69 (2.89) versus 3.21 (2.78) points, respec-tively, in CBD (n= 36) and placebo (n= 28) participants [confidence interval (CI) =0.33 to 3.04;P= 0.069; Bayes fac-tor = 0.498]. All but three participants relapsed to cocaine by week 12 with similar risk for CBD (n= 34) and placebo(n= 27) participants (hazard ratio = 1.20, CI = 0.652.20,P= 0.51; Bayes factor = 0.152). CBD treatment was well tol-erated and associated mainly with diarrhoea.

Conclusions : CBD did not reduce cocaine craving or relapse among people being treated for CUD.

Keywords : Addiction, cannabidiol, cocaine, craving, human, relapse



More than 18 million people world-wide use cocaine [1], and 16% of them will develop a cocaine use disorder (CUD) [2]. Given its association with high rates of healthand social problems [3], together with premature mortality[4], CUD has become a public health issue. An important factor predicting relapse is the intense desire (craving) to use cocaine [5]. CUD and related craving are mainly managed with psychosocial interventions such as cognitive behavioural therapy and contingency management. These strategies alone are often insufficient to induce behavioural changes or a reduction in cocaine use and relapse [6]. Several systematic reviews on CUD pharmacological treatments found weak efficacy evidence to improve cocaine craving and time to relapse [7,8]. Consequently, there is an urgent need to identify novel treatments to help individuals with CUD.

Pre-clinical findings suggesting that cannabinoids may decrease drug use [9,10] have motivated an enthusiasticcall for research into cannabidiol (CBD) as a promising intervention for CUD [1113]. CBD has a favourable tolerability profile [14] together with numerous physiological and neuroprotective properties. For example, it protects against cocaine-induced seizures and hepatotoxicity in animals [15]. Moreover, CBD possesses anxiolytic properties in clinical populations and can decrease autonomic arousal [16]. This is important, as stress is a potentcocaine-craving inducer [17] and a potential target fornew addiction interventions. The exact mechanism bywhich CBD impacts cocaine use is still unknown, but sev-eral have been hypothesized (e.g. hippocampalneurogenesis [18], reviewed here [12]).

Animal and human studies also reported CBD as apotential treatment for addictive disorders. Hence, sustained administration of CBD in rodents inhibits co-caine self-administration and context- and stress-induced reinstatement of cocaine-seeking behaviour [12,19]. Pre-clinical studies also demonstrated that CBD inhibits cue-induced heroin-seeking behaviours for up to 2 weeks following the last administration [20], while a smallrandomized clinical trial (RCT) showed that CBD decreases cue-induced craving and anxiety in individuals with heroin use disorder (HUD) [21]. Also, a recent RCT revealed that CBD was efficacious in reducing cannabis use in individuals with cannabis use disorder [22]. Finally, a cross-over RCT showed that CBD decreased attention bias of cigarette cues compared with placebo[23]. However, short-term treatment with 300 mg CBD was not effective in reducing craving in individuals withCUD [24]. However, it remains unclear whether individuals with CUD can benefit from a high dose of CBD in order to decrease their cocaine craving and, ultimately, the risk of relapse. In this RCT, we primarily aimed to test CBD efficacyin reducing drug–cue-induced craving and increasing time-to-cocaine relapse in recently abstinent individuals with CUD. Furthermore, we secondarily aimed to assess CBD efficacy in reducing stress-induced craving and cocaine use. We hypothesized that CBD would be superior to placebo in reducing drug–cue and stress-induced cravings, increasing time-to-cocaine relapse and decreasing co-caine use.