Psilocybin Therapy for Methamphetamine Use Disorder and HIV (PRISM)

Psilocybin Recovery Intervention for Stopping Methamphetamine Use

The goal of this clinical trial is to learn whether it is possible to use psilocybin in combination with motivational support therapy to treat moderate-to-severe methamphetamine use disorder (MeUD) in people with HIV who are seeking to stop using methamphetamine. The main questions it aims to answer are:

• Do people with HIV and MeUD find psilocybin with motivational support therapy feasible and acceptable as a potential treatment?
• Is psilocybin safe and tolerable among people with HIV and MeUD?

Participants will:

• Be randomly assigned to receive a single monitored dose of either 25 mg (higher dose) or 5 mg (lower dose) psilocybin
• Have 3 preparation and 3 integration motivational support therapy visits before and after the psilocybin dosing session.
• Report their methamphetamine use prior to, during, and up to 3 months following the intervention
• Optionally receive one additional open-label 25 mg psilocybin session after the 4-week assessment, if eligible

Study Overview

• Status: Not yet recruiting
• Conditions: Methamphetamine Use Disorder; Human Immunodeficiency Virus (HIV)
• Intervention / Treatment: Drug: Psilocybin 25 mg; Behavioral: Motivational Support; Drug: Psilocybin 5 mg

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eliza Banbury, BA; Phone Number: 510-985-3522; Email: prism.trial@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • UCSF at Zuckerberg San Francisco General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 25 to 64
• Diagnosed with HIV at least 3 months ago
• Moderate-to-severe methamphetamine use disorder
• Uses methamphetamine regularly and identifies it as their primary drug
• Has a goal of quitting methamphetamine use
• Able and willing to abstain from methamphetamine and other non-prescribed drugs for at least 24 hours prior to and throughout psilocybin dosing sessions
• Currently living indoors with stable housing anticipated for the duration of the study
• Has a text-capable cellphone
• Willing to use highly effective contraception and not donate sperm throughout the study
• Able to participate in study procedures in English

Exclusion Criteria:

• History of any primary psychotic disorder (e.g., schizophrenia or schizoaffective disorder), bipolar I disorder, or certain other psychiatric conditions as determined by study assessment
• Current moderate-to-severe opioid, alcohol, or sedative use disorder (Note: people on stable doses of buprenorphine or methadone may be eligible)
• Currently taking certain medications that may interact with psilocybin
• Recent use of a psychedelic drug
• Certain significant heart, liver, or kidney conditions
• Uncontrolled high blood presure (i.e., >150/90 mmHg)
• History of stroke or seizure in the past year
• Current pregnancy or breastfeeding
• Current involvement in the criminal legal system that would be expected to interfere with study participation
• Current or planned enrollment in a contingency management program or another investigational substance use treatment trial within the past month

Note: Additional eligibility criteria apply. Certain criteria and thresholds are not listed here to preserve the scientific integrity of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Dose Psilocybin; Participants receive a single oral dose of 25 mg psilocybin (PEX010) during a blinded 8-hour dosing visit, delivered within a manualized motivational support framework of 3 preparatory and 3 integration therapy sessions before and after dosing. After 4 weeks following the dosing session, eligible participants may receive a second optional open-label 25 mg psilocybin session with additional preparatory and integration support.	Drug: Psilocybin 25 mg; Single oral 25 mg dose of psilocybin, administered as a capsule under direct clinical observation during a monitored ~8-hour dosing session. Given as the higher dose during the double-blind randomized phase and as the dose used in the optional open-label session.; Behavioral: Motivational Support; Manualized motivational support delivered by trained facilitators, adapted from the NIAAA Project MATCH MET manual. During the double-blind phase, participants attend 3 preparatory talk therapy sessions before dosing and 3 integration talk therapy sessions after dosing; the optional open-label session is accompanied by an additional 1 preparatory and 3 integration talk therapy sessions before and after the second (open-label) dose. Sessions support rapport, intention-setting, psilocybin psychoeducation and safety, and post-session meaning-making.; Other Names: Motivational Enhancement Therapy (MET)
Active Comparator: Low-Dose Psilocybin; Participants receive a single oral dose of 5 mg psilocybin (PEX010) during a blinded 8-hour dosing visit, delivered within a manualized motivational support framework of 3 preparatory and 3 integration therapy sessions before and after dosing. After 4 weeks following the dosing session, eligible participants may receive an optional open-label 25 mg psilocybin session with additional preparatory and integration support.	Drug: Psilocybin 25 mg; Single oral 25 mg dose of psilocybin, administered as a capsule under direct clinical observation during a monitored ~8-hour dosing session. Given as the higher dose during the double-blind randomized phase and as the dose used in the optional open-label session.; Behavioral: Motivational Support; Manualized motivational support delivered by trained facilitators, adapted from the NIAAA Project MATCH MET manual. During the double-blind phase, participants attend 3 preparatory talk therapy sessions before dosing and 3 integration talk therapy sessions after dosing; the optional open-label session is accompanied by an additional 1 preparatory and 3 integration talk therapy sessions before and after the second (open-label) dose. Sessions support rapport, intention-setting, psilocybin psychoeducation and safety, and post-session meaning-making.; Other Names: Motivational Enhancement Therapy (MET); Drug: Psilocybin 5 mg; Single oral 5 mg dose of psilocybin, administered as a capsule under direct observation during a monitored ~8-hour dosing session. Serves as the low-dose active control during the double-blind randomized phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment Efficiency	Proportion of participants who undergo in-person screening who are fully enrolled in the study and initiate treatment.	Screening to Baseline (approximately 35 days)
Dosing Completion	Proportion of enrolled participants who receive psilocybin dosing.	Baseline to Dosing Visit (approximately 10 days)
Retention	Proportion of participants receiving psilocybin who complete the end-of-double-blind-period study visit.	Dosing Visit to Visit 9 (approximately 28 days)
Acceptability	Scores on an end-of-treatment acceptability questionnaire.	Visit 9, approximately 38 days
Adverse Events	Number of participants who experience treatment-emergent adverse events between initial psilocybin dosing and the end-of-double-blind-period visit.	Dosing Visit to Visit 9 (approximately 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Methamphetamine Use (TLFB)	Change from baseline in self-reported past-month days of methamphetamine use, assessed by Timeline Followback (TLFB), at Day 28 post-dose.	Baseline to Visit 9 (approximately 38 days)

Collaborators and Investigators

• Sponsor: Nicky Mehtani, MD, MPH
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Nicky J. Mehtani, MD, MPH, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: August 5, 2026
• First Submitted That Met QC Criteria: August 5, 2026
• First Posted (Actual): August 11, 2026

Study Record Updates

• Last Update Posted (Actual): August 11, 2026
• Last Update Submitted That Met QC Criteria: August 5, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: HIV; psilocybin; methamphetamine; psychedelics; psychedelic-assisted therapy; stimulant use disorder; methamphetamine use disorder; people with HIV; amphetamine-related disorders
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Mental Disorders; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Substance-Related Disorders; Chemically-Induced Disorders; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Amphetamine-Related Disorders; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Health Services; Health Care Facilities Workforce and Services; Behavioral Disciplines and Activities; Indole Alkaloids; Indolizidines; Indolizines; Directive Counseling; Counseling; Mental Health Services; Tryptamines; Psilocybin; Motivational Interviewing
• Other Study ID Numbers: 1DP2DA066200 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No