Study Comparing Three Doses of MDMA Along With Therapy in Veterans With Posttraumatic Stress Disorder

NCT01211405 | Completed Phase 2 Results

• 1 other identifier: MP-8
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective and reducing PTSD symptoms in veterans with chronic PTSD. The main question it aims to answer is: Do three doses of MDMA reduce PTSD symptoms? Researchers will compare 30, 75, and 125 mg of MDMA HCl with therapy to see which dose best reduces PTSD symptoms. Participants will undergo three preparatory non-drug therapy sessions with a male and female co-therapist team, then undergo three day-long MDMA-assisted therapy sessions after receiving an initial dose of 30, 75, or 125 mg MDMA HCl. After each MDMA-assisted therapy session, participants will undergo three integrative therapy sessions.

Conditions

Posttraumatic Stress Disorder

Keywords

MDMA; Therapy; Veterans; Posttraumatic Stress Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Clinician-Administered PTSD Scale (CAPS-IV) From Baseline to Primary Endpoint

  The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.

  Baseline to one month after second experimental session

Secondary Outcomes (5)

• Change in Global Assessment of Function (GAF) From Baseline to Primary Endpoint

  Baseline to one month after second experimental session

• Change in Posttraumatic Growth Inventory (PTGI) From Baseline to Primary Endpoint

  Baseline to one month after second experimental session

• Change in Beck Depression Inventory (BDI-II) From Baseline to Primary Endpoint

  Baseline to one month after second experimental session

• Change in Dissociative Experience Scale (DES-II) From Baseline to Primary Endpoint

  Baseline to one month after second experimental session

• Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to Primary Endpoint

  Baseline to one month after second experimental session

Study Arms (3)

Low dose MDMA-assisted therapy

ACTIVE COMPARATOR

Participants will receive 30 mg midomafetamine HCl (MDMA) with therapy during each of two blinded experimental sessions.

Drug: Low dose MDMA-assisted therapy; Behavioral: Therapy

Medium dose MDMA-assisted therapy

ACTIVE COMPARATOR

Participants will receive 75 mg midomafetamine HCl (MDMA) with therapy on each of two blinded experimental sessions.

Drug: Medium dose MDMA-assisted therapy; Behavioral: Therapy

Full dose MDMA-assisted therapy

EXPERIMENTAL

Participants will receive 125 mg midomafetamine HCl (MDMA) with therapy during each of two blinded experimental sessions, followed by a third open label session.

Drug: Full dose MDMA-assisted therapy; Behavioral: Therapy

Interventions

Low dose MDMA-assisted therapy DRUG

30 mg midomafetamine HCl administered p.o. once at start of an experimental session. Upon mutual agreement, this may be followed by a supplemental dose of 15 mg 1.5 to 2 hours later

Also known as: MDMA, 3,4-methylenedioxymethamphetamine, midomafetamine

Low dose MDMA-assisted therapy

Medium dose MDMA-assisted therapy DRUG

75 mg midomafetamine HCl administered p.o. once at start of an experimental session. Upon mutual agreement, this may be followed by a supplemental dose of 37.5 mg 1.5 to 2 hours later

Also known as: MDMA, 3,4-methylenedioxymethamphetamine, midomafetamine

Medium dose MDMA-assisted therapy

Full dose MDMA-assisted therapy DRUG

125 mg midomafetamine HCl administered p.o. once at start of an experimental session. Upon mutual agreement, this may be followed by a supplemental dose of 62.5 mg 1.5 to 2 hours later

Also known as: MDMA, 3,4-methylenedioxymethamphetamine, midomafetamine

Full dose MDMA-assisted therapy

Therapy BEHAVIORAL

Non-directive therapy during each session

Full dose MDMA-assisted therapy; Low dose MDMA-assisted therapy; Medium dose MDMA-assisted therapy

Eligibility Criteria

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

You may qualify if:

• Be diagnosed with chronic PTSD, duration of 6 months or longer resulting from traumatic experience during military service;
• Have a CAPS score showing moderate to severe PTSD symptoms;
• Have had at least one unsuccessful attempt at treatment for PTSD either with talk therapy or with drugs, or discontinuing treatment because of inability to tolerate psychotherapy or drug therapy.
• Are at least 18 years old;
• Must be generally healthy;
• Must sign a medical release for the investigators to communicate directly with their therapist and doctors;
• Are willing to refrain from taking any psychiatric medications during the study period;
• Willing to follow restrictions and guidelines concerning consumption of food, beverages, and nicotine the night before and just prior to each experimental session;
• Willing to remain overnight at the study site;
• Agree to have transportation other than driving themselves home or to where they are staying after the integrative session on the day after the MDMA session;
• Are willing to be contacted via telephone for all necessary telephone contacts;
• Must have a negative pregnancy test if able to bear children, and agree to use an effective form of birth control;
• Must provide a contact in the event of a participant becoming suicidal;
• Are proficient in speaking and reading English;
• Agree to have all clinic visit sessions recorded to audio and video

You may not qualify if:

• Are pregnant or nursing, or if a woman who can have children, those who are not practicing an effective means of birth control;
• Weigh less than 48 kg;
• Are abusing illegal drugs;
• Have used ecstasy (material representing itself as MDMA) more than 5 times or at least once in the last 6 months;
• Are unable to give adequate informed consent;
• Upon review of medical or psychiatric history must not have any current or past diagnosis that would be considered a risk to participation.

Sponsors & Collaborators

• Lykos Therapeutics: lead

Study Sites (1)

Offices of Michael Mithoefer

Mt. Pleasant, South Carolina, 29464-4345, United States

Location

Related Publications (4)

• Mithoefer MC, Mithoefer AT, Feduccia AA, Jerome L, Wagner M, Wymer J, Holland J, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry. 2018 Jun;5(6):486-497. doi: 10.1016/S2215-0366(18)30135-4. Epub 2018 May 1.

  PMID: 29728331 RESULT

• Jerome L, Feduccia AA, Wang JB, Hamilton S, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl). 2020 Aug;237(8):2485-2497. doi: 10.1007/s00213-020-05548-2. Epub 2020 Jun 4.

  PMID: 32500209 DERIVED

• Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Front Psychiatry. 2019 Sep 12;10:650. doi: 10.3389/fpsyt.2019.00650. eCollection 2019.

  PMID: 31572236 DERIVED

• Mithoefer MC, Feduccia AA, Jerome L, Mithoefer A, Wagner M, Walsh Z, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019 Sep;236(9):2735-2745. doi: 10.1007/s00213-019-05249-5. Epub 2019 May 7.

  PMID: 31065731 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

N-Methyl-3,4-methylenedioxyamphetamine; Therapeutics

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Lykos Therapeutics

trialdata@lykospbc.com

877-627-7722

Study Officials

• Michael Mithoefer, MD

  Private Practice

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2010
• First Posted: September 29, 2010
• Study Start: November 10, 2010
• Primary Completion: June 4, 2015
• Study Completion: August 2, 2016
• Last Updated: June 5, 2025
• Results First Posted: February 2, 2022

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data and study-related documents will be available following primary publication of outcomes.
• Access Criteria: Interested persons should correspond with the central contact for the study.

Locations

US (1)