Psilocybin for Methamphetamine Use Disorder

Psilocybin in the Treatment of 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).

Single-site, phased UG3/UH3 randomized, quadruple-masked, parallel-group controlled trial (target N = 42). Participants are randomized 1:1 to a single administration of psilocybin at one of two dose levels, each delivered with a manualized platform of two preparation and two integration sessions. The specific doses are withheld in this registration during the conduct of the trial to preserve masking and reduce expectancy effects, and will be reported with results. The UG3 phase (n = 12) establishes feasibility and safety; the UH3 phase (n = 30) expands enrollment with longer follow-up. Support is provided 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