Psilocybin Therapy for Methamphetamine Use Disorder and HIV

NCT07756736 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 1DP2DA066200
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Methamphetamine Use Disorder; Human Immunodeficiency Virus (HIV)

Keywords

methamphetamine use disorder; HIV; methamphetamine; psilocybin; amphetamine-related disorders; stimulant use disorder; people with HIV; psychedelics; psychedelic-assisted therapy

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (1)

• Methamphetamine Use (TLFB)

  Baseline to Visit 9 (approximately 38 days)

Study Arms (2)

High-Dose Psilocybin

EXPERIMENTAL

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; Behavioral: Motivational Support

Low-Dose Psilocybin

ACTIVE COMPARATOR

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 5 mg; Drug: Psilocybin 25 mg; Behavioral: Motivational Support

Interventions

Psilocybin 5 mg DRUG

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.

Low-Dose Psilocybin

Psilocybin 25 mg DRUG

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.

High-Dose Psilocybin; Low-Dose Psilocybin

Motivational Support BEHAVIORAL

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.

Also known as: Motivational Enhancement Therapy (MET)

High-Dose Psilocybin; Low-Dose Psilocybin

Eligibility Criteria

• Age: 25 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nicky Mehtani, MD, MPH: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

UCSF at Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Amphetamine-Related Disorders

Interventions

Psilocybin; Motivational Interviewing

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Directive Counseling; Counseling; Mental Health Services; Behavioral Disciplines and Activities; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Nicky J. Mehtani, MD, MPH

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eliza Banbury, BA

CONTACT

510-985-3522; prism.trial@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: August 11, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: August 11, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)