Cannabinoids in the Treatment of Insomnia Disorder: A Systematic Review and Meta-Analysis
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SYSTEMATIC REVIEW
Cannabinoids in the Treatment of Insomnia Disorder: A Systematic Review and Meta‑Analysis Chiranth Bhagavan1,2 · Stacey Kung3 · Marjan Doppen3 · Mary John3 · Iva Vakalalabure3,4 · Karen Oldfield3,4 · Irene Braithwaite3 · Giles Newton‑Howes1 Accepted: 1 November 2020 © Springer Nature Switzerland AG 2020
Abstract Background Insomnia is associated with significant comorbidity, disability and impact on quality of life and, despite advances in pharmacotherapy and psychotherapy, remains a significant burden to society. Cannabinoids are gaining acceptance for use as medicines in the treatment of insomnia disorder. Objective We conducted a systematic review and meta-analysis to evaluate the efficacy of cannabinoids in the treatment of insomnia disorder. Methods We performed a systematic review of the PubMed, Cochrane Library, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature Complete databases from inception to 5 December 2019, and again prior to data abstraction, for studies of cannabis-based products for the treatment of insomnia disorder in adults. Inclusion criteria were (1) clinical studies, (2) participants aged ≥ 18 years, (3) insomnia disorder either formally diagnosed against contemporaneous diagnostic criteria or quantified with validated instruments and (4) compared cannabis-based products with the standard of care, placebo or a sedative. No language restrictions were imposed. Non-primary research, animal studies and studies of cannabisinduced insomnia were excluded. Risk of bias was assessed using the RoB 2 tool for randomised controlled trials (RCTs) and Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I) tool for non-randomized trials. Heterogeneity was assessed with the I2 statistic. Results A total of five studies (two RCTs and three non-randomised studies) with 219 study participants were included, of which three could be combined. The three non-randomised studies contributed data on the Pittsburgh Sleep Quality Index Questionnaire score, showing a favourable effect of cannabinoids at ≤ 4 weeks of follow-up (mean difference − 1.89 [95% confidence interval {CI} − 2.68 to − 1.10]; n = 176) and at 8 weeks of follow-up (mean difference − 2.41 [95% CI − 3.36 to − 1.46]; n = 166). One double-blind crossover RCT (n = 32) reported that, compared with amitriptyline, nabilone—a synthetic analogue to tetrahydrocannabinol (THC)—improved Insomnia Severity Index scores after 2 weeks of treatment (adjusted difference − 3.25 [95% CI − 5.26 to − 1.24]) and resulted in a more restful sleep as a sub-measure of the Leeds Sleep Evaluation Questionnaire (LSEQ) (difference 0.48 [95% CI 0.01–0.95]) but with no effect on overall sleep quality as measured by the LSEQ. In a single ascending-dose RCT (n = 9), THC reduced sleep-onset latency compared with placebo at 10 mg, 20 mg and 30 mg doses (mean difference − 43.00 min [95% CI − 82.76 to − 3.24], − 62.00 [95% CI − 103.60 to − 20.40] and − 54.00 [95% CI − 103.93 to − 4.07], respectively). All the included studies were as
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