Methamphetamine Use Disorder
Conditions
Keywords
psilocybin, methamphetamine, HEAL Initiative, psychedelic-assisted therapy, substance use disorder
Brief summary
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).
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).
Interventions
DRUGPsilocybin (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.
BEHAVIORALManualized cognitive behavioral therapy platform (2 preparation + 2 integration sessions).
Manualized CBT, adapted from Hendricks et al. (2026; https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2848757)
Sponsors
Peter Hendricks
National Institute on Drug Abuse (NIDA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
statistician(s)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Abstinent Days | Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3). | Percentage of days abstinent from methamphetamine (Timeline Followback, urine-confirmed); possible range is 0% to 100%, with higher scores reflecting more abstinence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Abstinence | Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3) | 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." |
| Methamphetamine Use Disorder in Remission | 30/90-day (UG3), 30/90/180-day (UH3) | 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." |
| Health-related Quality of Life | Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3) | 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. |
| Self-perceived Quality of Life | Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3) | 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. |
| Craving | Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3) | 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. |
| Withdrawal | Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3) | 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. |
| Severity of Dependence | Baseline through 90-day follow-up (UG3) and 180-day follow-up (UH3) | 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). |
| Mystical-type Experience | Day of dosing (≈7 hours) | 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. |
| Challenging Experience | Day of dosing (≈7 hours) | 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 |
| Emotional Breakthrough | Day of dosing (≈7 hours) | 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. |
| Psychological Insight | Day of dosing (≈7 hours) | 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. |
Countries
United States
Contacts
CONTACTSeher Premani, MPH
CONTACTNoah Sweat, BS
PRINCIPAL_INVESTIGATORPeter S Hendricks, PhD
University of Alabama at Birmingham
Outcome results
None listed