The therapeutic effects of psychedelics for opioid use disorder: A systematic review of clinical studies

Opioid-related overdose deaths have reached record high levels, and novel treatments for opioid use disorder (OUD) are needed. The three United States Food and Drug Administration (FDA)-approved medications for OUD function primarily at the mu-opioid receptor. While these remain the gold-standard treatment for OUD, they have shortcomings and treatment options separate from the opioid receptor system deserve attention. Preclinical, clinical, and naturalistic studies of psychedelics have shown some evidence that they may reduce opioid and other substance use. Here, we present the results of a systematic review of clinical studies investigating the therapeutic applications of psychedelics for OUD to describe the current state of the literature and guide future clinical study design in this area. Findings indicate few studies completed using serotonergic psychedelics, with most investigating ibogaine or ketamine. In addition, findings are limited by many studies of weak design focused on opioid withdrawal, and few double-blind or placebo-controlled trials with considerable methodological heterogeneity making comparisons difficult across compounds. Most studies were found to have a high risk of bias mostly related to lack of randomization, blinding, and blinding of assessment outcomes. We outline these limitations and steps towards improving the quality of future studies of psychedelics for OUD.