Randomized, Double-blind, Placebo-Controlled Pilot Study of MDMA-assisted Therapy for PTSD

NCT01689740 | Completed Phase 2 Results

• 1 other identifier: MP-9
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people with chronic, treatment-resistant PTSD. The main question it aims to answer is: Is there a reduction in PTSD symptoms in people given a low dose of MDMA with therapy versus a high dose of MDMA with therapy? Researchers will compare two sessions of MDMA-assisted therapy with either 25 mg of MDMA HCl or 125 mg of MDMA HCl in Stage 1. Participants will undergo preparatory therapy sessions without any study drug, followed by two sessions of MDMA-assisted therapy, each followed by integrative therapy sessions without study drug. Participants who received 25 mg during Stage 1 will be given the option to enroll in Stage 2 and complete two additional open-label MDMA-assisted therapy sessions with the full dose of 125 mg MDMA.

Conditions

Posttraumatic Stress Disorder (PTSD)

Keywords

MDMA; Posttraumatic stress disorder; PTSD; Israel; psychotherapy; midomafetamine

Outcome Measures

Primary Outcomes (1)

• Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 1

  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 1-Month Post Experimental Session 2 (End of Stage 1)

Secondary Outcomes (14)

• Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to End of Stage 2

  Baseline to End of Stage 2

• Change in Clinical Administered PTSD Scale (CAPS-IV) Total Score From Baseline to Long-Term Follow-Up

  Baseline to 12 months post-final experimental session

• Change in Beck Depression Inventory (BDI-II) Total Scores From Baseline to End of Stage 1

  Baseline to 1-Month Post Experimental Session 2 (End of Stage 1)

• Change in Beck Depression Inventory (BDI-II) Total Score From Baseline to End of Stage 2

  Baseline to End of Stage 2

• Change in Beck Depression Inventory (BDI-II) Total Scores From Baseline to Long-Term Follow-Up

  Baseline to 12 month post-final experimental session

Study Arms (3)

Lead in: 125 mg MDMA-assisted therapy (Open-Label)

EXPERIMENTAL

Participants receive open-label MDMA with an initial dose of 125 mg midomafetamine HCl, possibly followed by a supplemental dose of 62.5 mg, during two psychotherapy sessions scheduled 3-5 weeks apart.

Drug: Open-Label Full Dose MDMA-assisted therapy (125 mg); Behavioral: Psychotherapy

Active placebo dose MDMA-assisted therapy (25 mg)

PLACEBO COMPARATOR

Participants receive initial dose of 25 mg midomafetamine HCl, possibly followed by a supplemental dose of 12.5 mg, during two psychotherapy sessions scheduled 3-5 weeks apart.

Drug: Active Placebo Dose MDMA-assisted therapy (25 mg); Behavioral: Psychotherapy

Full dose MDMA-assisted therapy (125 mg)

EXPERIMENTAL

Participants receive initial dose of 125 mg midomafetamine HCl, possibly followed by a supplemental dose of 62.5 mg, during two psychotherapy sessions scheduled 3-5 weeks apart.

Drug: Full Dose MDMA-assisted therapy (125 mg); Behavioral: Psychotherapy

Interventions

Active Placebo Dose MDMA-assisted therapy (25 mg) DRUG

Initial dose of 25 mg midomafetamine HCl administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 12.5 mg 1.5 to 2.5 hours later.

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

Active placebo dose MDMA-assisted therapy (25 mg)

Full Dose MDMA-assisted therapy (125 mg) DRUG

Initial dose of 125 mg midomafetamine HCl administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 62.5 mg 1.5 to 2.5 hours later.

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

Full dose MDMA-assisted therapy (125 mg)

Open-Label Full Dose MDMA-assisted therapy (125 mg) DRUG

Initial dose of 125 mg midomafetamine HCl administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 62.5 mg 1.5 to 2.5 hours later.

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

Lead in: 125 mg MDMA-assisted therapy (Open-Label)

Psychotherapy BEHAVIORAL

Non-directive psychotherapy will be conducted throughout the study.

Also known as: Manualized MDMA-assisted psychotherapy

Active placebo dose MDMA-assisted therapy (25 mg); Full dose MDMA-assisted therapy (125 mg); Lead in: 125 mg MDMA-assisted therapy (Open-Label)

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 with a duration of 6 months or longer.
• Have a CAPS score showing moderate to severe symptoms.
• Had at least one unsuccessful attempt at treatment for PTSD, either with talk therapy or with drugs, or stopped treatment because of inability to tolerate psychotherapy or drug therapy.
• Are at least 18 years old.
• 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.
• Agree that, one week before the MDMA session, will refrain from taking all below unless with prior approval of research team: herbal supplements, nonprescription medications (with the exception of nonsteroidal anti-inflammatory drugs or acetaminophen, any prescription medications, with the exception of birth control pills, thyroid hormone, or other medications;
• Are willing to follow restrictions and guidelines concerning consumption of food, beverages. and nicotine the night before and just prior to each experimental session.
• Are willing to remain overnight at the study site.
• 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.
• Agree not to participate in any other clinical trial for the duration of this clinical trial, including the follow-up period.
• Are proficient in speaking and reading Hebrew.
• Agree to have all psychotherapy sessions recorded to audio/video.

You may not qualify if:

• Are pregnant or nursing, or if they can have children and are not practicing an effective means of birth control.
• Weigh less than 48 kg.
• Are abusing illegal drugs.
• Have used "Ecstasy" (material represented as containing MDMA) more than five times 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)

Beer Yaakov Hospital

Be’er Ya‘aqov, 70350, Israel

Location

Related Publications (4)

• 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

• 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

• Moshe Kotler

  Beer Yaakov Hospital

  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: September 7, 2012
• First Posted: September 21, 2012
• Study Start: January 17, 2013
• Primary Completion: April 7, 2016
• Study Completion: July 16, 2017
• Last Updated: June 6, 2025
• Results First Posted: October 30, 2020

Record last verified: 2025-05

Locations

IL (1)