Review Article: What Do We Know About the Pharmacotheraputic Management of Insomnia in Cannabis Withdrawal: A Systematic Review

Background and Objectives: Sleep disturbance is one of the hallmarks of cannabis withdrawal. Studies have indicated that treatment of this key symptom may facilitate abstinence. In the present paper we aim to provide a systematic review of the extant literature on pharmacological management of sleep disturbance associated with cannabis withdrawal. Method: We conducted a systematic literature search across five electronic databases including PubMed, Psycinfo, MEDLINE, Cochrane review and Embase. Human studies using a pharmacological treatment for sleep disturbances associated with cannabis withdrawal were included. Review articles, case-series, open trials, posters, and editorials were excluded. Results: Seventeen publications, involving 562 participants, were included in this review. Major limitations involved small sample size, high dropout rate, methodological limitations, and heterogeneity of participants. Most of the studies were at high risk of bias, further downgrading the level of evidence. A meta-analysis was not performed due to lack of quantitative data, marked heterogeneity and low quality of the included studies. Conclusion: There is not sufficient evidence for any of the reviewed treatment options. Methodological limitations in a majority of the studies rendered their findings preliminary. Of the twelve investigated pharmacological agents, Gabapentin, Lofexidine, Mirtazapine, Quetiapine, and Zolpidem showed some primary benefits for treatment of sleep difficulties associated with cannabis withdrawal; however, future prospective studies are required to confirm such results. Scientific Significance: This review examines the current evidence for potential pharmacological options for treatment of cannabis withdrawal and associated sleep disturbance. It furthers our knowledge and provides groundwork for future research.