Role of Melatonin in the Management of Substance Addiction: A Systematic Review

Recent evidence links melatonin hormone and its receptor to the etiology and behavioral manifestation of addiction. The role of exogenous melatonin in addiction treatment is still inconsistent and unclear. The present study aimed to review the literature on randomized clinical trials that evaluated the role of melatonin supplementation, compared to placebo, in the treatment of various substance addictions. The literature searches of relevant articles published in the English language in MEDLINE and Google Scholar databases were performed from inception up to May 2021. We included only randomized clinical trials investigating the effect of melatonin treatment, compared to placebo, on substance addiction-related parameters. Non-randomized clinical trials, observation studies, and animal studies were excluded. The risk of bias-2 was used to assess the quality of the studies. Of 537 articles, 12 randomized control trials (RCT) met our inclusion criteria. Studies have been conducted on substances of addiction including benzodiazepine (BZD), alcohol, nicotine, and opioids. Our results indicated that melatonin treatment had mixed results in improving sleep quality and was not found beneficial in BDZ cessation/discontinuation rate among patients with BDZ dependence. Sleep quality and mental health had improved by melatonin supplements in opioid addiction. In nicotine addiction, melatonin treatment showed effectiveness only on mood changes but not in performance tests. In patients with alcohol use disorder (AUD), melatonin treatment did not show any improvement in sleep quality. We found that the use of exogenous melatonin in substance addiction has mixed results which do not provide sufficient evidence, relative to randomized clinical trials, to establish its role.