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

Violaine Mongeau-Pérusse, Suzanne Brissette, Julie Bruneau, Patricia Conrod, Simon Dubreucq, Guillaume Gazil, Emmanuel Stip, Didier Jutras-Aswad, Violaine Mongeau-Pérusse, Suzanne Brissette, Julie Bruneau, Patricia Conrod, Simon Dubreucq, Guillaume Gazil, Emmanuel Stip, Didier Jutras-Aswad

Abstract

Background and aims: Cocaine use disorder (CUD) is a significant public health concern for which no efficacious pharmacological interventions are available. Cannabidiol (CBD) has attracted considerable interest as a promising treatment for addiction. This study tested CBD efficacy for reducing craving and preventing relapse in people with CUD.

Design: Single-site double-blind randomized controlled superiority trial comparing CBD with placebo.

Setting and participants: Centre Hospitalier de l'Université de Montréal, Canada. Seventy-eight adults (14 women) with moderate to severe CUD participated.

Intervention: Participants were randomly assigned (1 : 1) by stratified blocks to daily 800 mg CBD (n = 40) or placebo (n = 38). They first underwent an inpatient detoxification phase lasting 10 days. Those who completed this phase entered a 12-week outpatient follow-up.

Measurements: Primary outcomes were drug-cue-induced craving during detoxication and time-to-cocaine relapse during subsequent outpatient treatment.

Findings: During drug-cue exposure, craving scores [mean ± standard deviation (SD)] increased from baseline by 4.69 (2.89) versus 3.21 (2.78) points, respectively, in CBD (n = 36) and placebo (n = 28) participants [confidence interval (CI) = -0.33 to 3.04; P = 0.069; Bayes factor = 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 = 0.65-2.20, P = 0.51; Bayes factor = 0.152). CBD treatment was well tolerated and associated mainly with diarrhoea.

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

Trial registration: ClinicalTrials.gov NCT02559167.

Keywords: Addiction; cannabidiol; cocaine; craving; human; relapse.

© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Figures

FIGURE 1
FIGURE 1
Consolidated Standards of Reporting Trials (CONSORT) flow‐chart of participants with cocaine use disorder (CUD) involved in this trial. Participants are considered lost to follow‐up when they missed two consecutive visits. *Other reasons for ineligibility included men with fertility problems (n = 2), immunocompromised participants (n = 2) and not currently moderate or severe CUD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria (n = 1). **One participant's consent form was lost. When asked, this participant refused to re‐consent, which ended her participation. This was reported to the data safety and monitoring board who requested that no data from this participant be used in the study. CBD = cannabidiol; n = number of participants
FIGURE 2
FIGURE 2
Cocaine craving among treatment groups. Bar chart illustrating mean changes in craving scores on the 10‐point visual analogue scale in each treatment group following a cocaine, a stress and a neutral cue imagery‐induced craving session. Standard deviations are indicated on the bars with vertical lines. CBD = cannabidiol; n = number of participants
FIGURE 3
FIGURE 3
Time‐to‐cocaine‐relapse and cocaine use among treatment groups. (a) Kaplan–Meier curves illustrating the proportion of participants without cocaine relapse in each treatment group during the 12‐week follow‐up period (Phase II) together with the number of participants at risk of relapse. (b) Bar chart illustrating similar cocaine use in both treatment groups during the follow‐up period. Standard deviations are indicated on the bars with vertical lines. CBD = cannabidiol; n= number of participants
FIGURE 4
FIGURE 4
Participants’ CBD blood levels among treatment groups. Box and whisker plots illustrating minimum, first quartile, median, third quartile and maximum CBD concentrations in each treatment group. Mean and outlier values are marked with diamonds and circles, respectively. In the CBD group, 9.00 a.m. CBD blood concentration evolved from (mean ± standard deviation) 37.14 ± 14.54 ng/ml on day 8 to 67.75 ± 71.20 ng/ml on week 4 and 74.57 ± 130.33 ng/ml on week 12. At 1.00 p.m. on day 9, CBD blood concentration was 553.82 ± 379.13 ng/ml in the CBD group. The single participant treated with placebo who tested positive for CBD had a CBD blood concentration of 0.06 ng/ml. CBD = cannabidiol; D = day; n = number of participants analyzed, including those with no detectable CBD; W = week

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