Psychedelics and Psychedelic-Inspired Compounds for Substance Use Disorders: Are We Treating the Disease or Opening a Learning Window?

Substance use disorders remain a leading cause of preventable death, and existing care is better described as disease management than as cure. Medications for opioid, alcohol, and tobacco use disorders reduce substance use, and opioid agonist treatment reduces mortality, yet retention is poor and functional recovery is rarely measured. This review asks whether psychedelics treat addiction, or temporarily create a brain state in which treatment, learning, and recovery work differently. By evaluating each pharmacologically unique compound individually, we align cellular mechanisms, animal studies and human trial data across the full spectrum of substance use disorders. Relapse prevention is not a single construct: conditioned place preference, operant reinstatement, extinction learning, and clinical abstinence index different processes, and agreement at one level does not imply agreement at another. Translational concordance is therefore indication- and compound-specific rather than a class property, with the strongest human signals for psilocybin in tobacco and alcohol use disorders, though even the alcohol signal rests on two small randomized trials with discordant results. Risk is compound-specific too: ibogaine is gated by cardiotoxicity, and ketamine carries reinforcing properties and organ toxicity of its own. Plasticity is an opportunity, not an outcome.