MDMA-Assisted Therapy for Veterans With Moderate to Severe Post Traumatic Stress Disorder

NCT ID: NCT05790239

Last Updated: 2025-03-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-01

Study Completion Date

2026-03-31

Brief Summary

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This randomized, double-blind, single-site phase II 2-arm study will investigate the safety and preliminary efficacy of MDMA-assisted therapy compared with low dose d-amphetamine-assisted therapy on the severity of PTSD symptoms in participants aged 18 years and older with PTSD of at least moderate severity.

Detailed Description

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This randomized, double-blind, single-site phase II 2-arm study will compare MDMA-assisted therapy with low dose d-amphetamine-assisted therapy to treat PTSD symptoms in veteran participants aged 18 years and older with PTSD of at least moderate severity, as measured by the change in CAPS-5 total severity score. The study will be conducted in up to N=40 participants from the Greater Los Angeles VA randomized with a 1:1 allocation to Group 1: MDMA-assisted therapy or Group 2: low dose d-amphetamine assisted therapy.

For each participant, the study will consist of:

* Screening Period: phone screen, informed consent, eligibility assessment, Screening CAPS-5, and Initial Enrollment of eligible participants.
* Preparatory Period: medication tapering, three Preparatory Sessions, baseline assessments (including Baseline CAPS-5), leading to Enrollment Confirmation.
* Treatment Period: three Experimental Sessions, and three Integrative Sessions following each Experimental Session including CAPS-5 assessments.
* Follow-up Period and Study Termination: Primary Outcome CAPS-5 assessment and Study Termination visit.

Conditions

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Post Traumatic Stress Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a randomized study. Participants will be 1:1 randomized to receive either MDMA or d-amphetamine. Stratified randomization will be used, with gender as the stratification variable. Within each of the two strata, the investigators use permuted randomized blocks with a block size of 4.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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MDMA-Assisted Therapy

Participants will receive a flexible divided-dose of MDMA plus therapy at Experimental Sessions.

Group Type EXPERIMENTAL

3,4-methylenedioxymethamphetamine

Intervention Type DRUG

Initial doses per Experimental Session include 68 mg or 100 mg MDMA (equivalent to 80 mg or 120 mg MDMA HCl), followed 1.5 to 2 hours later by a supplemental dose of 34 mg or 50 mg MDMA (equivalent to 40 mg or 60 mg MDMA HCl).

Therapy

Intervention Type BEHAVIORAL

Participants assigned to MDMA and d-amphetamine will undergo a therapeutic approach, which is detailed in the MDMA-Assisted Therapy Treatment Manual and administered by MAPS-trained therapists. In brief, this therapy is guided by the subject's own recollections of traumatic events. The subject and two therapists provide a comfortable and supportive environment and allow the subject to guide the discussion. Subjects are encouraged to experience and express fear, anger, and grief with less likelihood of feeling overwhelmed by these emotions. MDMA seems to engender internal awareness that even painful feelings that arise are an important part of the therapeutic process. In addition, feelings of empathy, love, and deep appreciation often emerge, along with a clearer perspective of the trauma as a past event, a more accurate perspective about its significance, and a heightened awareness of the support and safety that exists in the present.

Low Dose D-Amphetamine Assisted Therapy

Participants will receive a flexible divided dose plus therapy at Experimental Sessions.

Group Type ACTIVE_COMPARATOR

d-amphetamine

Intervention Type DRUG

Initial dose per experimental session will be 5 mg or 10 mg d-amphetamine, followed 1.5 to 2 hours later by supplemental dose of 2.5 mg or 5 mg d-amphetamine.

Therapy

Intervention Type BEHAVIORAL

Participants assigned to MDMA and d-amphetamine will undergo a therapeutic approach, which is detailed in the MDMA-Assisted Therapy Treatment Manual and administered by MAPS-trained therapists. In brief, this therapy is guided by the subject's own recollections of traumatic events. The subject and two therapists provide a comfortable and supportive environment and allow the subject to guide the discussion. Subjects are encouraged to experience and express fear, anger, and grief with less likelihood of feeling overwhelmed by these emotions. MDMA seems to engender internal awareness that even painful feelings that arise are an important part of the therapeutic process. In addition, feelings of empathy, love, and deep appreciation often emerge, along with a clearer perspective of the trauma as a past event, a more accurate perspective about its significance, and a heightened awareness of the support and safety that exists in the present.

Interventions

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3,4-methylenedioxymethamphetamine

Initial doses per Experimental Session include 68 mg or 100 mg MDMA (equivalent to 80 mg or 120 mg MDMA HCl), followed 1.5 to 2 hours later by a supplemental dose of 34 mg or 50 mg MDMA (equivalent to 40 mg or 60 mg MDMA HCl).

Intervention Type DRUG

d-amphetamine

Initial dose per experimental session will be 5 mg or 10 mg d-amphetamine, followed 1.5 to 2 hours later by supplemental dose of 2.5 mg or 5 mg d-amphetamine.

Intervention Type DRUG

Therapy

Participants assigned to MDMA and d-amphetamine will undergo a therapeutic approach, which is detailed in the MDMA-Assisted Therapy Treatment Manual and administered by MAPS-trained therapists. In brief, this therapy is guided by the subject's own recollections of traumatic events. The subject and two therapists provide a comfortable and supportive environment and allow the subject to guide the discussion. Subjects are encouraged to experience and express fear, anger, and grief with less likelihood of feeling overwhelmed by these emotions. MDMA seems to engender internal awareness that even painful feelings that arise are an important part of the therapeutic process. In addition, feelings of empathy, love, and deep appreciation often emerge, along with a clearer perspective of the trauma as a past event, a more accurate perspective about its significance, and a heightened awareness of the support and safety that exists in the present.

Intervention Type BEHAVIORAL

Other Intervention Names

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MDMA

Eligibility Criteria

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Inclusion Criteria

* At Screening, meet DSM-5 criteria for current PTSD with a symptom duration of at least 6 months.
* Fluent in speaking and reading the predominantly used or recognized language of the study site (English).
* Must be a veteran enrolled at a VA Healthcare Center in the Greater Los Angeles area.
* Able to swallow pills.
* Agree to have study visits audiovisually recorded, including Experimental Sessions, IR assessments, and non-drug therapy sessions.
* Able to provide a contact (relative, spouse, close friend, or other support person) who is willing and able to be reached by the investigators in the event of the participant becoming unwell or unreachable.
* Able to identify appropriate support person(s) to stay with the participant on the evenings of Experimental Sessions if needed.
* May have well-controlled hypertension that has been successfully treated with anti-hypertensive medicines, if they pass additional screening to rule out underlying cardiovascular disease.
* May have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed.
* Body weight of at least 45 kilograms (kg). Participants with a body weight of 45-48 kg must also have a body mass index (BMI) within the range of 18 to 30 kg/m2. BMI must be within 18 to 32 kg/m2 (inclusive).
* A person able to be pregnant (PABP) must use a highly effective contraceptive method.

Exclusion Criteria

* Are not able to give adequate informed consent.
* Have evidence or history of significant medical or psychiatric disorders.
* Are abusing illegal drugs.
* Unable or unwilling to safely taper off prohibited psychiatric medication.
* Current enrollment in any other clinical study involving an investigational study treatment or any other type of medical research, unless approved by the study clinician.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stephen Robert Marder

FED

Sponsor Role lead

Responsible Party

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Stephen Robert Marder

Co-Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Stephen Marder, MD

Role: PRINCIPAL_INVESTIGATOR

VA Greater Los Angeles Healthcare System

Stephanie L Taylor, PhD

Role: PRINCIPAL_INVESTIGATOR

VA Greater Los Angeles Healthcare System

Locations

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VA Greater Los Angeles Healthcare System, Westwood campus

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

West Los Angeles Veteran Affairs

Los Angeles, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Stephanie L Taylor, PhD

Role: CONTACT

213-505-1140

Stephen Marder, MD

Role: CONTACT

Facility Contacts

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Sophie M Kennedy

Role: primary

310-478-3711

Gerard De Vera

Role: backup

310-478-3711 ext. 44932

References

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Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, Ot'alora G M, Garas W, Paleos C, Gorman I, Nicholas C, Mithoefer M, Carlin S, Poulter B, Mithoefer A, Quevedo S, Wells G, Klaire SS, van der Kolk B, Tzarfaty K, Amiaz R, Worthy R, Shannon S, Woolley JD, Marta C, Gelfand Y, Hapke E, Amar S, Wallach Y, Brown R, Hamilton S, Wang JB, Coker A, Matthews R, de Boer A, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021 Jun;27(6):1025-1033. doi: 10.1038/s41591-021-01336-3. Epub 2021 May 10.

Reference Type BACKGROUND
PMID: 33972795 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20643699 (View on PubMed)

Grob CS, Poland RE, Chang L, Ernst T. Psychobiologic effects of 3,4-methylenedioxymethamphetamine in humans: methodological considerations and preliminary observations. Behav Brain Res. 1996;73(1-2):103-7. doi: 10.1016/0166-4328(96)00078-2.

Reference Type BACKGROUND
PMID: 8788485 (View on PubMed)

Ponte L, Jerome L, Hamilton S, Mithoefer MC, Yazar-Klosinski BB, Vermetten E, Feduccia AA. Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder. J Trauma Stress. 2021 Aug;34(4):851-863. doi: 10.1002/jts.22696. Epub 2021 Jun 10.

Reference Type BACKGROUND
PMID: 34114250 (View on PubMed)

Other Identifiers

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IVAPT3

Identifier Type: -

Identifier Source: org_study_id

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