Randomized, Double-blind, Controlled of MDMA-assisted Psychotherapy in 12 Subjects With PTSD

NCT01958593 | Terminated Phase 2 Results

• 1 other identifier: MP-4
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare full dose MDMA-assisted therapy to placebo with therapy in participants with chronic, treatment-resistant PTSD. The main question it aims to answer is: Does MDMA-assisted therapy versus placebo with therapy reduce PTSD symptoms? Participants will receive either MDMA-assisted therapy or placebo with therapy during two blinded experimental sessions spaced three to five weeks apart. During experimental sessions, participants receive an initial dose of 125 mg of MDMA HCl, or placebo, followed by a dose of 62.5 mg of MDMA HCl, or placebo. During this treatment period, participants will also undergo non-drug preparatory therapy sessions and non-drug integration sessions. Researchers will compare PTSD symptoms in the MDMA-assisted therapy group to the placebo with therapy group to see if there is a reduction in symptoms after the treatment period. Safety measures will also be assessed between groups.

Conditions

Posttraumatic Stress Disorder

Keywords

PTSD; Posttraumatic stress disorder; MDMA; psychotherapy; therapy

Outcome Measures

Primary Outcomes (1)

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

  Clinician-administered and scored assessment of PTSD symptoms via structured interview, including global symptom severity, dichotomous diagnostic score and subscale scores. The Clinician-Administered PTSD Scale for DSM-4 (CAPS-4) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-4. It contains symptom subscales, a CAPS-4 total severity score, and a diagnostic score. 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 Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)

Secondary Outcomes (6)

• Change in PTSD Diagnostic Scale (PDS) Total Severity Score From Baseline to Primary Endpoint

  Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)

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

  Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)

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

  Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)

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

  Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)

• Change in Dissociation Experiences Scale II (DES-II) Total Score From Baseline to Primary Endpoint

  Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)

Study Arms (2)

Placebo with therapy

PLACEBO COMPARATOR

Participants will receive placebo with therapy during each of two experimental sessions.

Drug: Placebo; Behavioral: Psychotherapy

MDMA-assisted therapy

EXPERIMENTAL

Participants will receive MDMA (initial dose of 125 mg midomafetamine HCl followed by a supplemental dose of 62.5 mg midomafetamine HCl) with therapy during each of two experimental sessions.

Drug: Midomafetamine HCl; Behavioral: Psychotherapy

Interventions

Placebo DRUG

Placebo with therapy administered in two blinded experimental sessions. Participants in this group in Stage 1 may take part in Stage 2.

Also known as: Inactive placebo

Placebo with therapy

Midomafetamine HCl DRUG

Participants will receive MDMA-assisted therapy during two blinded experimental sessions. After unblinding, may receive a third session of open-label MDMA-assisted therapy.

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

MDMA-assisted therapy

Psychotherapy BEHAVIORAL

Psychotherapy before and after experimental sessions.

MDMA-assisted therapy; Placebo with therapy

Eligibility Criteria

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

You may qualify if:

• Diagnosed with moderate to severe PTSD;
• Have chronic PTSD, defined as persisting for longer than 6 months;
• Have treatment-resistant PTSD, meaning unable to achieve remission despite previous therapy or medication or discontinued treatment due to inability to tolerate previous therapy or medication;
• Are willing to refrain from taking any psychiatric medications during the study period;
• Willing to remain overnight at the study site;
• Agree to have transportation home after experimental sessions;
• 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;
• Are proficient in speaking and reading English;
• Agree not to participate in any other interventional clinical trials during the duration of this study.

You may not qualify if:

• Are pregnant or nursing, or if of child bearing potential, are not practicing an effective means of birth control;
• Weigh less than 48 kg;
• Are unable to give adequate informed consent;
• Have used "Ecstasy" (illicit drug preparations purported to contain MDMA) more than five times in the last 10 years or at least once within six months of enrollment;
• Upon review of medical or psychiatric history must not have any current or past diagnosis that would be considered a risk to participation in the study.

Sponsors & Collaborators

• Lykos Therapeutics: lead

Study Sites (1)

Offices of Dr. Ingrid Pacey MBBS FRCP[C]

Vancouver, British Columbia, V6R 1N6, Canada

Location

Related Publications (3)

• 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; Psychotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Study Director
• Organization: Lykos Therapeutics

trialdata@lykospbc.com

877-627-7722

Study Officials

• Ingrid Pacey, MBBS FRCP[C]

  University of Victoria

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 7, 2013
• First Posted: October 9, 2013
• Study Start: October 14, 2014
• Primary Completion: September 10, 2015
• Study Completion: October 17, 2016
• Last Updated: June 5, 2025
• Results First Posted: August 2, 2021

Record last verified: 2025-05

Locations

CA (1)