Dose-Response Study of MDMA-assisted Psychotherapy in People With PTSD

NCT01793610 | Completed Phase 2 Results FDA Drug

• 1 other identifier: MP-12
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if MDMA in combination with therapy is safe and effective in people with chronic, treatment-resistant PTSD. The main questions it aims to answer are:

• Does MDMA-assisted therapy reduce PTSD symptoms?
• Is there a difference in PTSD symptoms between the 40 mg, 100 mg, and 125 mg groups? Researchers will compare two active doses (100 mg and 125 mg) of MDMA-assisted therapy versus a comparator dose of 40 mg MDMA-assisted therapy to determine if there is a reduction in PTSD symptoms. Participants will undergo three non-drug preparatory sessions, three MDMA-assisted therapy sessions and three non-drug integrative therapy sessions after each MDMA-assisted therapy session.

Conditions

Posttraumatic Stress Disorder

Keywords

MDMA; Posttraumatic stress disorder; sleep; Depression; Safety

Outcome Measures

Primary Outcomes (1)

• Change in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) Total Severity Score From Baseline to One Month Post 2nd Experimental Session

  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. It contains symptom subscales, a CAPS-IV 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 Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

Secondary Outcomes (6)

• Change in PTSD Diagnostic Scale (PDS) From Baseline to One Month Post 2nd Experimental Session

  Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

• Change in Beck Depression Inventory II (BDI-II) From Baseline to One Month Post 2nd Experimental Session

  Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

• Change in Global Assessment of Functioning (GAF) Total Score From Baseline to One Month Post 2nd Experimental Session

  Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

• Change in Pittsburgh Sleep Quality Index (PSQI) From Baseline to One Month Post 2nd Experimental Session

  Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

• Change in Dissociative Experiences Scale (DES-II) From Baseline to One Month Post 2nd Experimental Session

  Baseline Enrollment to 1-Month Post 2nd Experimental Session (Stage 1 Primary Endpoint)

Study Arms (3)

Comparator Dose (40 mg) MDMA-assisted therapy

ACTIVE COMPARATOR

Participants receive an initial dose of comparator dose midomafetamine HCl (40 mg) during each of two therapy sessions.

Drug: Comparator Dose (40mg) MDMA HCl; Behavioral: Psychotherapy

Active Dose 2 (100 mg) MDMA-assisted therapy

EXPERIMENTAL

Participants receive an initial dose of Active Dose 2 midomafetamine HCl (100 mg) during each of two therapy sessions.

Drug: Active Dose 2 (100 mg) MDMA HCl; Behavioral: Psychotherapy

Active Dose 1 (125 mg) MDMA-assisted therapy

EXPERIMENTAL

Participants receive an initial dose of Active Dose 1 midomafetamine HCl (125 mg) during each of two therapy sessions.

Drug: Active Dose 1 (125 mg) MDMA HCl; Behavioral: Psychotherapy

Interventions

Comparator Dose (40mg) MDMA HCl DRUG

An initial comparator-dose of 40 mg midomafetamine HCl orally given at the start of two separate psychotherapy sessions scheduled 3 to 5 weeks apart, with the initial dose possibly followed 1.5 to 2.5 hours later by a supplemental dose half the size of the initial dose (20 mg).

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

Comparator Dose (40 mg) MDMA-assisted therapy

Active Dose 2 (100 mg) MDMA HCl DRUG

An initial dose of full-dose 100 mg midomafetamine HCl orally given at the start of two separate psychotherapy sessions scheduled 3 to 5 weeks apart, with the initial dose possibly followed 1.5 to 2.5 hours later by a supplemental dose half the size of the initial dose (50 mg).

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

Active Dose 2 (100 mg) MDMA-assisted therapy

Active Dose 1 (125 mg) MDMA HCl DRUG

An initial dose of full-dose 125 mg midomafetamine HCl orally given at the start of two separate psychotherapy sessions scheduled 3 to 5 weeks apart, with the initial dose possibly followed 1.5 to 2.5 hours later by a supplemental dose half the size of the initial dose (62.5 mg).

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

Active Dose 1 (125 mg) MDMA-assisted therapy

Psychotherapy BEHAVIORAL

Non-directive manualized therapy

Also known as: Manualized MDMA-assisted psychotherapy

Active Dose 1 (125 mg) MDMA-assisted therapy; Active Dose 2 (100 mg) MDMA-assisted therapy; Comparator Dose (40 mg) 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:

• Diagnosed with chronic PTSD for six months or longer.
• Have a CAPS score showing moderate to severe PTSD symptoms.
• 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.
• Are willing to refrain from taking any psychiatric medications during the study period.
• Willing to follow restrictions and guidelines concerning consumption of food, beverages or nicotine the night before and just prior to each MDMA session.
• Willing to remain overnight at the study site.
• Are willing to be driven home after experimental sessions either by a driver they arrange, a taxi, or study personnel.
• Are willing to be contacted via telephone by study personnel.
• If of child-bearing age, must have a negative pregnancy and agree to use an effective form of birth control.
• Must provide a personal contact who is willing to be reached in case of emergency.
• Agree to let the investigators know within 48 hours of any planned medical interventions.
• Are proficient in reading and speaking English.
• Agree to have all psychotherapy sessions recorded.

You may not qualify if:

• Are pregnant or nursing, or if of child-bearing age and do not use an effective means of birth control.
• Weigh less than 48 kg.
• Meet DSM-IV criteria for substance abuse or dependence for any substance in the past 60 days.
• Have used "Ecstasy" (material represented as containing MDMA) more than five times in the last ten years or at least once within 6 months of the MDMA session.
• 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 in the study.

Sponsors & Collaborators

• Lykos Therapeutics: lead

Study Sites (1)

Offices of Marcela d'Otalora

Boulder, Colorado, 80304, United States

Location

Related Publications (6)

• Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM. The development of a Clinician-Administered PTSD Scale. J Trauma Stress. 1995 Jan;8(1):75-90. doi: 10.1007/BF02105408.

  PMID: 7712061 BACKGROUND

• Beck AT, Steer RA. Internal consistencies of the original and revised Beck Depression Inventory. J Clin Psychol. 1984 Nov;40(6):1365-7. doi: 10.1002/1097-4679(198411)40:63.0.co;2-d.

  PMID: 6511949 BACKGROUND

• Beck AT, Steer RA, Ball R, Ranieri W. Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Pers Assess. 1996 Dec;67(3):588-97. doi: 10.1207/s15327752jpa6703_13.

  PMID: 8991972 BACKGROUND

• 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; Depression

Interventions

N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Behavioral Symptoms; Behavior

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

• Marcela d'Otalora, MA, LPC

  Private Practice

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: February 13, 2013
• First Posted: February 15, 2013
• Study Start: May 13, 2013
• Primary Completion: December 3, 2015
• Study Completion: February 1, 2017
• Last Updated: June 5, 2025
• Results First Posted: October 14, 2020

Record last verified: 2025-05

Locations

US (1)