Is There a Place for Off-Label Pharmacotherapy in Cannabis Use Disorder? A Review on Efficacy and Safety.

BACKGROUND Cannabis use disorder (CUD) is setting an increasing demand on health services. Although there are objective physical symptoms of cannabis dependence, there is no validated pharmacotherapy for CUD treatment, which is mainly based on behavioral interventions. The goal of such pharmacotherapies in CUD may be abstinence or consumption reduction. Besides, a growing literature tests the efficacy of different drugs that have already been validated for other diseases, thus opening up possibilities for their off-label use. Here we led a systematic literature review to examine the level of evidence of their efficacy, indications and safety for off-label use to treat CUD. METHODS Systematic review via the PubMed, Web of Science, and ScienceDirect databases. RESULTS Although 43 relevant articles were found, only 13 were double-blind, randomized placebo-controlled trials, and only 4 of these 13 trials had positive results. These trials concerned dronabinol, nabiximols, N-acetylcysteine and gabapentin. CONCLUSION Given the small number of positive trials for each drug, there is no indication for routine off-label prescription in CUD. However, off-label prescribing may be an option in cases where behavioral therapies have failed. Benefit-risk balance is acceptable for N-acetylcysteine but remains to be confirmed for gabapentin, dronabinol and nabiximols.