Psilocybin for Methamphetamine Use Disorder

This trial tests whether psilocybin-assisted treatment can help adults stop using methamphetamine. Participants receive a single oral dose of psilocybin during a supervised session, paired with brief cognitive behavioral therapy, and are followed for up to six months. The study is supported by the HEAL Initiative (https://www.nih.gov/heal).

Inclusion Criteria: * Age 18+ * DSM-5 moderate or severe Methamphetamine Use Disorder * Severity of Dependence Scale score ≥ 4 * Methamphetamine use on more than 7 of the past 30 days and more than one positive urine test before randomization * A goal of complete abstinence on the Thoughts About Abstinence questionnaire * Able to read, write, and speak English * A friend or family member available for post-session release * Good general health by history and physical * Confirmed pre-dose abstinence of at least 24 hours (clinically assessed) Exclusion Criteria: * Pregnancy or breastfeeding, or not using effective contraception * Current psychiatric diagnoses other than a mild substance use disorder or tobacco/nicotine use disorder * Current hypertension (\>140/90 at rest) * Regular use of centrally acting serotonergic medications or MAO inhibitors (washout/re-screen permitted) * Personal history of any psychotic or bipolar I/II disorder, or a first- or second-degree relative with such * Current suicidal or homicidal ideation * Plan to relocate within 6 months * Psychedelic use in the past 3 years, more than 3 lifetime psychedelic occasions, more than 3 lifetime ketamine or MDMA occasions, or any prior 5-MeO-DMT or ibogaine use