Chronic pain and opioid use disorder (OUD) are two interconnected public health crises that lack effective treatments. This review examines whether psychedelics could serve as novel therapeutics by acting on shared brain mechanisms underlying both conditions. Preclinical and human evidence suggests psychedelics may reverse pain- and opioid-induced neuroadaptations like central sensitization. The authors map how psychedelics could modulate overlapping dimensions of pain (sensory, affective, cognitive) and opioid-related phenomena (craving, withdrawal). They note a scarcity of controlled studies but propose mechanistic insights and methodological guidelines for future clinical trials. The goal is to accelerate development of alternatives to opioids amid the escalating crisis.
Greater childhood trauma is linked to lower aversive effects from higher doses of THC in people being treated with methadone for opioid use disorder. In a placebo-controlled crossover trial with 25 participants, those with more childhood trauma reported fewer negative subjective effects after taking 20 mg of oral THC. This reduced sensitivity to THC's aversive effects may contribute to increased cannabis use among individuals with opioid use disorder. The findings highlight the importance of assessing childhood trauma in opioid use disorder treatment and research.
Psychedelics show promise for treating chronic pain and opioid use disorder (OUD) by acting on shared brain mechanisms that underlie both conditions. Preclinical and human evidence suggests psychedelics may reverse pain- and opioid-induced neuroadaptations such as central sensitization. The review describes how psychedelics could modulate sensory, affective, and cognitive dimensions of pain alongside opioid craving and withdrawal. Despite the clinical need, controlled studies on pain management alternatives for people with OUD or on long-term opioid therapy remain scarce. The authors propose mechanistic insights and methodological considerations for future translational studies and clinical trials to accelerate development of novel therapeutics amid the opioid crisis.