Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: A pilot randomized clinical trial

Abstract

Background: The current lack of pharmacological treatments for cannabis use disorder (CUD) warrants novel approaches and further investigation of promising pharmacotherapy. We previously showed that nabiximols (27 mg/ml Δ9-tetrahydrocannabinol (THC)/ 25 mg/ml cannabidiol (CBD), Sativex®) can decrease cannabis withdrawal symptoms. Here, we assessed in a pilot study the tolerability and safety of self-titrated nabiximols vs. placebo among 40 treatment-seeking cannabis-dependent participants.

Methods: Subjects participated in a double blind randomized clinical trial, with as-needed nabiximols up to 113.4 mg THC/105 mg CBD or placebo daily for 12 weeks, concurrently with Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT). Primary outcome measures were tolerability and abstinence, secondary outcome measures were days and amount of cannabis use, withdrawal, and craving scores. Participants received up to CDN$ 855 in compensation for their time.

Results: Medication was well tolerated and no serious adverse events (SAEs) were observed. Rates of adverse events did not differ between treatment arms (F1,39 = 0.205, NS). There was no significant change in abstinence rates at trial end. Participants were not able to differentiate between subjective effects associated with nabiximols or placebo treatments (F1,40 = 0.585, NS). Cannabis use was reduced in the nabiximols (70.5%) and placebo groups (42.6%). Nabiximols reduced cannabis craving but no significant differences between the nabiximols and placebo groups were observed on withdrawal scores.

Conclusions: Nabiximols in combination with MET/CBT was well tolerated and allowed for reduction of cannabis use. Future clinical trials should explore the potential of high doses of nabiximols for cannabis dependence.

Fig 1. Consort flow diagram.

Diagram shows the number of participants at each stage of the study.

Fig 2. Study medication rates/effects in cannabis use.

Circles (white placebo, black nabiximols) represent mean (+SEM). In a) self-titrated medication (sprays/day) as reported in the smoking diary. In b) total average cannabis intake (g) per week as reported in the timeline followback (TLFB) (week 0) and smoking diary (weeks 1–12). In c) mean percentage of days using cannabis (nabiximols n = 20–13, placebo n = 20–14).

Fig 3. High/low study medication effects in cannabis use.

Circles (white placebo, black nabiximols) represent mean (+SEM) for total cannabis intake (g) per week as reported in the timeline followback (TLFB) (week 0) and smoking diary (weeks 1–12). In a) high medication users’ subgroup (≥ 20 sprays on any treatment day) (n = 5 and 3 for nabiximols and placebo, respectively), in b) low medication users sub-group (< 20 sprays at any treatment day) (n = 8 and 11 for nabiximols and placebo, respectively).

Fig 4. Cannabis craving and withdrawal.

Circles (white placebo, black nabiximols) represent mean (+SEM). In a) cannabis withdrawal from the Cannabis Withdrawal Checklist (CWC). In b) craving for cannabis from the Marijuana Craving Questionnaire (MCQ). Generalized Linear Mixed Model (GLMM) analyses followed by one-way ANOVA, * (p < .05) vs nabiximols group.