NCT00090064

Brief Summary

The goal of this clinical trial is to compare MDMA-assisted therapy to placebo with therapy in people with chronic, treatment-resistant posttraumatic stress disorder (PTSD). The main question it aims to answer is: Is there a reduction in PTSD symptoms among people given MDMA-assisted therapy compared to placebo with therapy? 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 psychotherapy sessions and non-drug integrative sessions. The study will test whether MDMA-assisted therapy can be safely given to participants. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Mar 2004

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 12, 2004

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

August 24, 2004

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 25, 2004

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 2, 2008

Completed
2.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 21, 2010

Completed
11.4 years until next milestone

Results Posted

Study results publicly available

October 25, 2021

Completed
Last Updated

June 6, 2025

Status Verified

May 1, 2025

Enrollment Period

4.1 years

First QC Date

August 24, 2004

Results QC Date

August 25, 2021

Last Update Submit

May 23, 2025

Conditions

Posttraumatic Stress Disorder

Keywords

MDMAMethylenedioxymethamphetaminePTSDpsychotherapymidomafetamine

Outcome Measures

Primary Outcomes (1)

  • Change in Clinician-Administered PTSD Scale (CAPS-IV) From Baseline to 2-month Follow-up

    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 2 months post second experimental session

Secondary Outcomes (1)

  • Change in Impact of Events Scale Revised (IES-R) From Baseline to 2-month Follow-up

    Baseline to 2 months post second experimental session

Study Arms (2)

MDMA-assisted therapy (125 mg)

EXPERIMENTAL

Participants will receive an initial dose of 125 mg midomafetamine HCl orally followed 2 to 2.5 hours later by a second dose of 62.5 mg midomafetamine HCl during two 8-hour long blinded therapy sessions.

Drug: Midomafetamine HClBehavioral: Therapy

Placebo with therapy

PLACEBO COMPARATOR

Participants will receive an initial dose of 125 mg placebo orally followed 2 to 2.5 hours later by a second dose of 62.5 mg placebo during two 8-hour long blinded therapy sessions.

Drug: Lactose placebo pillBehavioral: Therapy

Interventions

Midomafetamine HClDRUG

125 mg of midomafetamine HCl followed by a supplemental half-dose of 62.5 mg of midomafetamine HCl

Also known as: MDMA HCl, 3,4-methylenedioxymethamphetamine, MDMA, Midomafetamine
MDMA-assisted therapy (125 mg)
Lactose placebo pillDRUG

125 mg followed by a supplemental half-dose of 62.5 mg

Also known as: Placebo
Placebo with therapy
TherapyBEHAVIORAL

Non-directive therapy provided by a team of two co-therapists

MDMA-assisted therapy (125 mg)Placebo with therapy

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Have current PTSD (within the past 6 months) in response to crime victimization, including childhood sexual or physical abuse, or meet criteria for PTSD in response to combat;
  • Have a CAPS score showing moderate to severe PTSD symptoms;
  • They must either:
  • Have had at least one unsuccessful attempt at treatment for PTSD with a SSRI and psychotherapy;
  • Be a veteran with PTSD symptoms that have endured for no less than one year but no more than five years
  • Be at least 18 years old;
  • Must be generally healthy;
  • Willing to remain overnight at the study site;
  • Agree to have transportation home the morning 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 reading English;

You may not qualify if:

  • Are pregnant or nursing, or are able to bear children and are not practicing an effective means of birth control;
  • Weigh less than 50 kg or more than 105 kg;
  • Are unable to give adequate informed consent;
  • Prior use of "Ecstasy" (illicit drug preparations purported to contain MDMA) more than 5 times or at any time within the previous 6 months;
  • Have a history of certain excluded medical disorders.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Offices of Michael Mithoefer MD

Mt. Pleasant, South Carolina, 29464, United States

Location

Related Publications (6)

  • Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R. The safety and efficacy of +/-3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol. 2011 Apr;25(4):439-52. doi: 10.1177/0269881110378371. Epub 2010 Jul 19.

    PMID: 20643699RESULT

  • Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Martin SF, Yazar-Klosinski B, Michel Y, Brewerton TD, Doblin R. Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. J Psychopharmacol. 2013 Jan;27(1):28-39. doi: 10.1177/0269881112456611. Epub 2012 Nov 20.

    PMID: 23172889RESULT

  • Zeifman RJ, Kettner H, Ross S, Weiss B, Mithoefer MC, Mithoefer AT, Wagner AC. Preliminary evidence for the importance of therapeutic alliance in MDMA-assisted psychotherapy for posttraumatic stress disorder. Eur J Psychotraumatol. 2024;15(1):2297536. doi: 10.1080/20008066.2023.2297536. Epub 2024 Jan 4.

    PMID: 38174611DERIVED

  • 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: 32500209DERIVED

  • 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: 31572236DERIVED

  • 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: 31065731DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

N-Methyl-3,4-methylenedioxyamphetamineTherapeutics

Condition Hierarchy (Ancestors)

Stress Disorders, TraumaticTrauma and Stressor Related DisordersMental Disorders

Intervention Hierarchy (Ancestors)

AmphetaminesPhenethylaminesEthylaminesAminesOrganic 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
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 24, 2004

First Posted

August 25, 2004

Study Start

March 12, 2004

Primary Completion

May 2, 2008

Study Completion

June 21, 2010

Last Updated

June 6, 2025

Results First Posted

October 25, 2021

Record last verified: 2025-05

Locations

US(1)