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).

Study Overview

• Status: Not yet recruiting
• Conditions: Methamphetamine Use Disorder
• Intervention / Treatment: Drug: Psilocybin (single oral capsule administered at one of two dose levels, Dose A or Dose B; specific doses withheld during conduct).; Behavioral: Manualized cognitive behavioral therapy platform (2 preparation + 2 integration sessions).

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Seher Premani, MPH; Phone Number: 205-975-7721; Email: spremani@uab.edu
• Study Contact Backup: Name: Noah Sweat, BS; Phone Number: 205-996-0212; Email: nsweat@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
      • Principal Investigator: Peter S Hendricks, PhD
      • Contact: Seher Premani, MPH; Phone Number: 205-975-7721; Email: spremani@uab.edu
      • Contact: Noah Sweat, BS; Phone Number: 205-996-0212; Email: nsweat@uabmc.edu

Participation Criteria

Eligibility Criteria

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

Description

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

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: Psilocybin, Dose A; Single oral dose during an 8-hour supervised session (Specific dose withheld during conduct).	Drug: Psilocybin (single oral capsule administered at one of two dose levels, Dose A or Dose B; specific doses withheld during conduct).; The specific doses (in mg) are intentionally omitted from this registration during the conduct of the trial to preserve masking and reduce expectancy effects. The doses will be disclosed when results are reported after primary completion, by which point participants have been debriefed.; Behavioral: Manualized cognitive behavioral therapy platform (2 preparation + 2 integration sessions).; Manualized CBT, adapted from Hendricks et al. (2026; https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2848757)
Experimental: Psilocybin, Dose B; Single oral dose during an 8-hour supervised session (Specific dose withheld during conduct).	Drug: Psilocybin (single oral capsule administered at one of two dose levels, Dose A or Dose B; specific doses withheld during conduct).; The specific doses (in mg) are intentionally omitted from this registration during the conduct of the trial to preserve masking and reduce expectancy effects. The doses will be disclosed when results are reported after primary completion, by which point participants have been debriefed.; Behavioral: Manualized cognitive behavioral therapy platform (2 preparation + 2 integration sessions).; Manualized CBT, adapted from Hendricks et al. (2026; https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2848757)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abstinent Days	Percentage of days abstinent from methamphetamine (Timeline Followback, urine-confirmed); possible range is 0% to 100%, with higher scores reflecting more abstinence.	Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Abstinence	Complete abstinence from methamphetamine (Timeline Followback, urine-confirmed); a dichotomous (yes or no) outcome where no use whatsoever during the assessment period is coded as "yes" and any use at all during the assessment period is coded as "no."	Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3)
Methamphetamine Use Disorder in Remission	Modified DSM-5 Methamphetamine Use Disorder in early remission (SCID-5); a dichotomous (yes or no) outcome where those who meet DSM-5 criteria for Methamphetamine Use Disorder in early remission are coded as "yes" and those who do not meet DSM-5 criteria for Methamphetamine Use Disorder in early remission are coded as "no."	30/90-day (UG3), 30/90/180-day (UH3)
Health-related Quality of Life	Health-related quality of life as measured by the RAND-36 self-report measure. The RAND-36 contains 8 primary health scales (Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Social functioning, Emotional well-being [mental health], Energy/fatigue [vitality], Bodily pain, and General health perception) and 2 summary scales (Physical Health Summary and Mental Health Summary) with possible scores for each scale ranging from 0 to 100. Higher scores represent better health states and outcomes.	Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3)
Self-perceived Quality of Life	Self-perceived quality of life as measured by the WHOQOL-BREF self-report measure. This measure includes 4 scales (Physical, Psychological, Social, and Environment), each with a possible range from 0 to 100. Higher scores indicate a better quality of life.	Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3)
Craving	Craving, as measured by the Stimulant Craving Questionnaire-Brief (STCQ-Brief), a 10-item self-report tool measuring present-moment craving for stimulants. A score is calculated by averaging all 10 items, with a possible range of 0 to 6. Higher mean scores reflect more severe craving.	Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3)
Withdrawal	Methamphetamine withdrawal as measured by the Amphetamine Cessation Symptom Assessment (ACSA), a 16-item clinical rating tool used to measure the severity of amphetamine withdrawal symptoms over the preceding 24 hours. Scores range from 0 to 64, with higher scores reflecting more severe withdrawal symptoms.	Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3)
Severity of Dependence	Severity of methamphetamine dependence, as measured by the Stimulant Use Disorder Severity Scale (StUDSS). The StUDSS is a new patient-reported outcome instrument measuring the severity of symptoms for stimulant use disorder. Total symptom severity is based on a sum of all items, with a possible range of 0 to 44. Higher scores reflect more severe dependence. The StUDSS also yields a categorical severity rating based on total criteria count: Mild (2 or 3 criteria), Moderate (4 or 5 criteria), or Severe (6 or more criteria).	Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3)
Mystical-type Experience	Mystical-type experience during the day of dosing as measured by the Mystical Experience Questionnaire (MEQ). The MEQ yields 4 scales: Unity, Positive Mood, Transcendence of Time and Space, and Ineffability. Possible scores for each scale range from 0 to 5 and greater scores reflect higher intensity and greater depth of the mystical experience.	Day of dosing (≈7 hours)
Challenging Experience	Challenging experience during the day of dosing as measured by the Challenging Experience Questionnaire (CEQ). The CEQ yields 7 scales: Fear, Grief, Physical Distress, Insanity, Isolation, Death, and Paranoia. Possible scores range from 0 to 5, with greater scores reflecting higher intensity and more severe degree of psychological or physical distress during the experience	Day of dosing (≈7 hours)
Emotional Breakthrough	Emotional breakthrough on the day of dosing as measured by the Emotional Breakthrough Inventory (EBI). The EBI is a 6-item scale scored using a 0 to 100 Visual Analogue Scale (VAS) for each item. The total overall score is calculated as the sum of all six items, yielding a total summed score ranging from 0 to 600. Greater scores on the EBI reflect a deeper, more complete sense of psychological resolution and catharsis.	Day of dosing (≈7 hours)
Psychological Insight	Psychological insight during the day of dosing as measured by the Psychological Insight Questionnaire (PIQ). The PIQ measure insight on 2 scales: Avoidance and Maladaptive Patterns Insights and Goals and Adaptive Patterns Insights. Scores on the 2 scales range from 0 to 5, with greater scores representing a higher intensity of acute psychological realizations gained during the experience.	Day of dosing (≈7 hours)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Meaning in Life	Meaning in life as measured by the Meaning in Life questionnaire. This questionnaire yields 2 scales: Search for Meaning and Presence of Meaning. Scores range from 1 to 7 for both scales with greater scores reflecting exploration for existential significance (Search for Meaning) and conviction that one's life is rich with purpose (Presence for Meaning).	Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3)
Psychosocial-Spiritual Well-Being	Psychosocial-spiritual well-being as measured by the NIH Healing Experience of All Life Stressors Short Form (NIH-HEALS-SF). The NIH-HEALS-SF yields 3 scales: Deepened Connection, Active Reflection & Introspection, and Profound Trust & Acceptance. Total scores for each scale range from 1 to 5 (if computing a mean) or 3 to 15 (if computing a sum for comparison to published data). Higher scores reflect a stronger capacity for psychological resilience, emotional healing, and spiritual well-being while facing major life stressor.	Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3)

Collaborators and Investigators

• Sponsor: Peter Hendricks
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Peter S Hendricks, PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2027
• Primary Completion (Estimated): February 1, 2032
• Study Completion (Estimated): February 1, 2032

Study Registration Dates

• First Submitted: August 11, 2026
• First Submitted That Met QC Criteria: August 17, 2026
• First Posted (Actual): August 19, 2026

Study Record Updates

• Last Update Posted (Actual): August 19, 2026
• Last Update Submitted That Met QC Criteria: August 17, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: psilocybin; methamphetamine; substance use disorder; psychedelic-assisted therapy; HEAL Initiative
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Technology, Industry, and Agriculture; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Facility Design and Construction; Architecture; Psilocybin; Floors and Floorcoverings
• Other Study ID Numbers: IRB-300017113; IND 121000 (Registry Identifier: FDA); 1UG3DA067126 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data, metadata, and a data dictionary will be shared through an NIH-designated repository accessible via the HEAL Data Ecosystem, consistent with the study's Data Management and Sharing Plan and the HEAL Public Access and Data Sharing Policy.
• IPD Sharing Time Frame: De-identified individual participant data and the supporting documents will become available no later than publication of the primary outcome results or the end of the funding period, whichever comes first, and will remain available indefinitely thereafter through the repository.
• IPD Sharing Access Criteria: Data will be deposited in an NIH-designated repository accessible through the HEAL Data Ecosystem. Qualified researchers may request the de-identified dataset, data dictionary, and supporting documents through the repository's data-access process. Because these are substance use disorder data, access may be controlled or registered under the repository's terms and the Certificate of Confidentiality, and a data use agreement may be required.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

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