Psilocybin and Methylenedioxymethamphetamine (MDMA) for Post-traumatic Stress Disorder (PTSD)

NCT06989957 | Recruiting Phase 1 FDA Drug

• 1 other identifier: IRB00463389
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety and effectiveness of co-administered MDMA and psilocybin in military Veterans with a diagnosis of Posttraumatic Stress Disorder (PTSD). To apply or learn more, please view our website: https://hopkinspsychedelic.org/pamvet

Conditions

Posttraumatic Stress Disorder

Outcome Measures

Primary Outcomes (5)

• Incidence of Adverse Events

  Participants will be asked how the participant has been feeling since the last visit and will be asked about incidence of any adverse events (AEs) since the last visit. In addition to monitoring any spontaneously reported AEs at each study visit, participants will also be queried specifically if the participant has experienced any return of drug-like (i.e., MDMA or psilocybin) effects or other AEs the participant suspects to be drug-related at all meetings occurring after the first dosing session. A serious adverse event (SAE) will be defined as either: a death or a life-threatening occurrence, including hospitalization; incarceration; new onset of a significant medical disorder; or significant exacerbation of an existing medical disorder. All AEs and SAEs will be monitored closely by the study team to guide appropriate follow-up and all AEs and SAEs will be documented and followed to resolution.

  30 weeks

• The Columbia Suicide Severity Rating Scale (C-SSRS)

  The Columbia Suicide Severity Rating Scale (C-SSRS) will be used to assess severity of suicide ideation during every study visit. Suicidal Ideation Intensity scale (0-25 score range summed from five items, with higher scores indicating more severe suicidal ideation).

  33 weeks

• Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual-5 (CAPS-5)

  The CAPS-5 assessment consists of 30 items that are designed to measure the frequency and intensity of PTSD symptoms, covering all 20 Diagnostic and Statistical Manual-5 (DSM-5) PTSD symptoms. Each item is scored on a 5-point scale (0, absent - 4, extreme/incapacitating). Score ranges from 0 to 80 with higher scores indicating higher symptom severity.

  33 weeks

• PTSD Checklist (PCL-5)

  The PTSD Checklist for DSM-5 is a self-report psychometric instrument widely employed in both clinical and research settings to assess the presence and severity of PTSD symptoms as outlined in the DSM-5. The PCL-5's 20 items correspond to the DSM-5 symptom criteria for PTSD. This version of the PCL-5 will assess symptoms within the preceding week. PCL-5 questionnaires will be administered to participants via email (not clinician-administered). It is scored by summing the responses to 20 items, each rated on a 5-point scale (0-4), resulting in a total score ranging from 0 to 80. A higher score indicates greater severity of PTSD symptoms.

  33 weeks

• World Health Organization Quality of Life- Brief version (WHOQOL-BREF)

  The World Health Organization Quality of Life (WHOQOL) Brief version scores on this subscales range from 0-30 with higher scores reflecting better quality of life.

  33 weeks

Secondary Outcomes (3)

• Clinical Global Impression (CGI-I) Scale

  9 weeks

• Patient global impression of improvement (PGI-I)

  9 weeks

• The Sheehan Disability (SDS) Scale

  33 weeks

Study Arms (2)

Experimental MDMA + psilocybin (exact dosage not disclosed)

EXPERIMENTAL

MDMA will be given initially, followed by psilocybin 30 minutes later.

Drug: Psilocybin; Drug: MDMA

Comparator MDMA + psilocybin (exact dosage not disclosed)

ACTIVE COMPARATOR

MDMA will be given initially, followed by psilocybin 30 minutes later.

Drug: Psilocybin; Drug: MDMA

Interventions

Psilocybin DRUG

Experimental Psilocybin (exact dosages not disclosed)

Experimental MDMA + psilocybin (exact dosage not disclosed)

MDMA DRUG

Experimental MDMA (exact dosages not disclosed)

Experimental MDMA + psilocybin (exact dosage not disclosed)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>=21 years old
• Military Veteran
• Have given written informed consent
• Able to swallow pills
• Have a confirmed DSM-5 diagnosis of Post-traumatic Stress Disorder with symptom duration \>= 6 months
• Have a baseline CAPS-5 score of \>=28
• Be judged by study team clinicians to be at low acute risk for suicidality
• Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study.
• Be medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
• Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days.
• Agree to refrain from using any psychoactive drugs, including alcoholic beverages within 24 hours of each drug administration. The exceptions are caffeine and nicotine.
• Agree to refrain from using any caffeine or nicotine within 2 hours of dosing session start.
• Agree not to take any as needed (PRN) medications on the mornings of drug sessions without approval of the treatment team.
• Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.
• Agree to stop taking 5HT2A antagonist medications at least 5 half-lives before dosing.

You may not qualify if:

• Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I or II Disorder
• Current or history within one year of meeting DSM-5 criteria for a moderate or severe alcohol, or other drug use disorder (excluding tobacco, caffeine, and cannabis)
• Current or history within one year of meeting DSM-5 criteria for Borderline Personality Disorder.
• Clinically significant suicidal ideation (e.g. with strong intent or means; C-SSRS \> 3) within past 6 months
• Have a first degree relative with schizophrenia or other psychotic disorders (except substance/medication-induced or due to another medical condition), or bipolar I disorder
• Nicotine dependence that would be incompatible with an individual to be nicotine free for 8-10 hours on a dosing session day
• Medical condition incompatible with MDMA or psilocybin administration (e.g., cardiovascular, drug-induced hyperthermia, hyponatremia).
• Currently taking on a daily basis any medications (including herbal substances and supplements) with a Central Nervous System effect on serotonin (including serotonin-reuptake inhibitors (SRIs), monoamine oxidase inhibitors (MAOIs)), or any medications that affect liver enzyme (2D6) metabolism (e.g., Bupropion)
• Currently taking efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, uridine diphosphate glucuronosyltransferase enzyme (UGT1A9) inhibitors or UGT1A10 inhibitors such as phenytoin, regorafenib, eltrombopag.
• On unstable/changing dose of opioid, benzodiazepine or other psychoactive or pain medication within 4 weeks prior to enrollment and/or unable to abstain from medication on drug administration day
• Current use/positive toxicology for illicit drugs; or positive breath alcohol test at screening and/or prior to each drug administration session
• Lifetime use of any psychedelic drug (e.g., MDMA, psilocybin) at a dosage greater than a level typically defined as 'microdose.'
• Clinically significant transaminitis (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than two times normal value).
• Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing;
• Women who are of child-bearing potential and sexually active agree to use highly effective means of birth control (i.e. implants, injectables, combined oral contraceptives, progestin-containing intrauterine device (IUD) or vasectomised partner) for the duration of this study.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Gracias Family Foundation: collaborator

Study Sites (1)

Johns Hopkins Center for Psychedelic and Consciousness Research

Baltimore, Maryland, 21224, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Psilocybin; N-Methyl-3,4-methylenedioxyamphetamine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Brandon Weiss, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chloe Ford, MSc

CONTACT

410-550-0237; cford36@jh.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The first dosing session will be double-blind; the second dosing session will be single-blind (participant masked).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, active control study comparing a single dose of co-administered MDMA + psilocybin (exact dosages not disclosed) with a single dose of co-administered MDMA active placebo + psilocybin active placebo (exact dosages not disclosed)

Study Record Dates

• First Submitted: May 12, 2025
• First Posted: May 25, 2025
• Study Start: September 17, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)