Psilocybin-assisted psychotherapy for methamphetamine use disorder: A pilot open-label safety and feasibility study

Background & Aims There are few effective treatments for methamphetamine use disorder, despite increasing global demand. Here, we assessed the safety and feasibility of outpatient psilocybin‐assisted psychotherapy for methamphetamine use disorder.

Design

Single arm, open label pilot study.

Setting

Outpatient public stimulant treatment program at St. Vincent's Hospital, Sydney, Australia.

Participants

We recruited 15 participants that were ≥25 years old, seeking treatment for methamphetamine use, using methamphetamine ≥4 days/month at screening, and without serious mental illness or contraindicated medical conditions or medications.

Intervention

Participants received three preparatory psychotherapy sessions over two weeks before a single psilocybin dosing session (25 mg oral), followed by two integration psychotherapy sessions over one week. Psychotherapy included elements of motivational enhancement and acceptance and commitment therapy. Participants were followed for 90 days post psilocybin‐assisted psychotherapy session.

Measurements

Primary endpoints were safety (as measured by adverse events over the trial and vital signs during psilocybin dosing) and feasibility (as measured by enrolment and dropout rates), and secondary endpoints included measuring self‐reported methamphetamine and other illicit drug use, drug craving, depression, anxiety, stress and quality of life measures.

Findings

Of 56 participants pre‐screened, 15 were eligible and enrolled, 14 completed the intervention and 13 completed 90‐day post‐dose follow‐up.”. No serious adverse events (AEs) occurred, and the seven treatment related AEs were self‐limiting and mild to moderate in severity. AEs included hypertension during the dosing session and headache (n = 4), nausea (n = 1) and noise sensitivity (n = 1) within the week following the dose. Methamphetamine use (over the prior 28 days) was observed to be higher at screening (median 12 days, IQR 7–16, n = 15) relative to day 28 (median 0 days, IQR 0–2, n = 13) and 90 (median 2 days, IQR 1–4, n = 14) post psilocybin. [Correction added on 20 November 2025, after first online publication: In the preceding sentence, ‘lower’ has been changed to 'higher' in this version.] Methamphetamine craving was also observed to be lower while quality of life, depression, anxiety, and stress were observed to be higher at days 28 and 90 follow‐up relative to baseline.

Conclusions

Psilocybin assisted psychotherapy for methamphetamine use disorder was feasible to implement in an outpatient setting and did not appear to generate safety concerns. A larger randomised controlled trial is required to confirm efficacy and safety.