MDMA-assisted Cognitive Processing Therapy Versus Cognitive Processing Therapy for Veterans With Severe Posttraumatic Stress Disorder

NCT05837845 | Recruiting Phase 2 FDA Drug

• 1 other identifier: SUP0023APR
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

In partnership with the Veterans Affairs (VA) Palo Alto Health Care System and Stanford University, this study aims to evaluate clinical outcomes, assess implementation feasibility, and health economics of MDMA-assisted Cognitive Processing Therapy (MDMA-aCPT) in the treatment of posttraumatic stress disorder (PTSD). Through a randomized comparison of MDMA-aCPT versus Cognitive Processing Therapy (CPT), a VA gold standard treatment for PTSD, the proposed study will set the stage for understanding the potential use and application of MDMA-aCPT for PTSD within the VA system.

Conditions

PTSD

Keywords

MDMA-assisted Therapy; Cognitive Processing Therapy; Veterans; Posttraumatic stress disorder; Quality of Life

Outcome Measures

Primary Outcomes (1)

• Change in Clinician Administered PTSD Scale (CAPS-5) Total Severity Score

  The Primary Outcome measure will be the change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score from Baseline to 4 months post-baseline assessed by a blinded study staff rater. 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.

  From Baseline to approximately 4 months post-baseline

Secondary Outcomes (1)

• Change in Quality of Life Enjoyment and Satisfaction Questionnaire

  From Baseline to approximately 4 months post-baseline

Study Arms (2)

MDMA-assisted Cognitive Processing Therapy (MDMA-aCPT)

EXPERIMENTAL

This arm consists of 8-15 virtual CPT sessions (average of 12), one 90-minute, non-drug Preparatory Session, three Experimental Sessions with MDMA (\~8 hours), and three 90-minute, non-drug Integration Sessions, occurring over a 9-15-week Treatment Period. Standardized homework is assigned at each CPT session to promote the practice of the skills taught in the session. Participants will receive 80mg MDMA HCl for the first Experimental Session and will have the option of a supplemental dose of 40mg MDMA HCI 1.5-2 hours after the initial dose. For the second and third Experimental Sessions, participants will receive either 80mg or 120mg MDMA HCl as the initial dose, and an optional supplemental dose of 40mg or 60mg MDMA HCl 1.5-2 hours after the initial dose. Participants interested in receiving CPT treatment alone after study completion will have the option to be referred to their local VA PTSD Clinical Team for services 6 months after all study visits are completed.

Drug: MDMA; Behavioral: MDMA-assisted Cognitive Processing Therapy (MDMA-aCPT)

Cognitive processing therapy

EXPERIMENTAL

This arm consists of 8-15 virtual CPT treatment sessions lasting approximately 1-1.5 hours, occurring over a \~12-16-week Treatment Period. These sessions will take place approximately one week apart. Standardized homework is assigned at each session to promote the practice of the skills taught in the session. Participants will have the option to crossover to the MDMA-aCPT arm 6 months after all study visits are completed.

Behavioral: Cognitive Processing Therapy

Interventions

MDMA DRUG

Participants will receive a flexible divided-dose of MDMA HCl plus therapy at three Experimental Sessions, as well as non-drug Preparatory and Integration Sessions

MDMA-assisted Cognitive Processing Therapy (MDMA-aCPT)

Cognitive Processing Therapy BEHAVIORAL

Participants will receive 8-15 (average of 12) sessions of Cognitive Processing Therapy

Cognitive processing therapy

MDMA-assisted Cognitive Processing Therapy (MDMA-aCPT) BEHAVIORAL

Participants assigned to MDMA-aCPT will undergo a therapeutic approach administered by trained therapists. MDMA seems to engender internal awareness that even painful feelings that arise are an important part of the therapeutic process. MDMA can elicit feelings of empathy, love, and deep appreciation, 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. A combined treatment of MDMA and therapy may be especially useful for treating PTSD because MDMA can attenuate the fear response of a perceived threat to one's emotional integrity and decrease defensiveness without blocking access to memories or preventing a deep and genuine experience of emotion.

MDMA-assisted Cognitive Processing Therapy (MDMA-aCPT)

Eligibility Criteria

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

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Are at least 18 years at the time of signing the informed consent
• Are a U.S Military Veteran
• Are receiving services from VA Palo Alto Healthcare System, VA San Francisco Healthcare System, or VA NorCal Healthcare System
• Are fluent in speaking and reading in English
• Agree to have study visits audio and/or video recorded
• If assigned to MDMA-aCPT, able to identify appropriate support person(s) to stay with the participant on the evenings of the MDMA sessions
• Meet DSM-5 criteria for PTSD with a symptom duration of at least 6 months
• Have severe PTSD symptoms in the last month
• Body weight of at least 48 kilograms (kg)
• Is not pregnant, planning to get pregnant, or breastfeeding
• Capable of giving signed informed consent

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Have a history of any medical condition that could make receiving a sympathomimetic drug harmful
• Have current unstable medical illness
• Have cardiac conditions, including uncontrolled hypertension, prolonged QTc interval, and other cardiac conditions
• Have received Electroconvulsive Therapy (ECT), ketamine-assisted therapy, or used ketamine within 12 weeks of enrollment
• Moderate or severe alcohol or cannabis use disorder within the last 12 months
• Active illicit drug (other than cannabis) or prescription drug substance use disorder at any severity within the last 12 months
• Have current serious suicide risk
• Unable or unwilling to stop or safely taper off prohibited medications
• Have used MDMA (ecstasy) ever
• Currently enrolled in any clinical study
• Personal history of primary psychotic disorder, type I bipolar disorder, severe personality disorder, eating disorder with compensatory behaviors, or depressive disorder with psychotic features
• Lack social support, or lack a stable living situation

Sponsors & Collaborators

• Patricia Suppes: lead
• Stanford University: collaborator
• VA Palo Alto Health Care System: collaborator
• Steven & Alexandra Cohen Foundation: collaborator

Study Sites (1)

VA Palo Alto Health Care System / Stanford University

Palo Alto, California, 94304, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

N-Methyl-3,4-methylenedioxyamphetamine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Trisha Suppes, MD, PhD

  VA Palo Alto Healthcare System / Stanford University

  PRINCIPAL INVESTIGATOR

• Shannon Wiltsey Stirman, PhD

  VA Palo Alto Healthcare System / Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Donnelly

CONTACT

650-849-0161; exploratorytherapeuticslab@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: This is a randomized study. Participants will be 1:1 randomized to receive either MDMA-aCPT or CPT.

Study Record Dates

• First Submitted: April 20, 2023
• First Posted: May 1, 2023
• Study Start: February 10, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)