MDMA-assisted Brief Cognitive Behavioral Conjoint Therapy for PTSD

NCT05979844 | Completed Phase 3 FDA Drug

• 1 other identifier: IVAPT2
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this pilot trial is to examine the preliminary effectiveness of MDMA-facilitated bCBCT for improving chronic PTSD and relationship functioning in a sample of veterans and their intimate partners seeking care within the VA San Diego Healthcare System.

Conditions

PTSD; Relational Problems

Keywords

PTSD; Intimate relationships; MDMA

Outcome Measures

Primary Outcomes (1)

• Clinician-rated PTSD symptoms

  Measured using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). The CAPS-5 is a 20-item diagnostic interview that asks about the severity of four PTSD-related symptom clusters: re-experiencing, avoidance, negative alterations in cognition and mood, and alterations in arousal and reactivity. The evaluator rates responses on a 5-point Likert scale (0 = Absent to 4 = Extreme/Incapacitating). Total scores range from 0 to 80 with higher scores indicating greater severity.

  Baseline - 6 months post-treatment

Secondary Outcomes (1)

• Relationship satisfaction

  Baseline - 6 months post-treatment

Other Outcomes (13)

• Suicidality

  Baseline - 6 months post-treatment

• Self-reported PTSD symptoms

  Baseline - 6 months post-treatment

• Emotion regulation

  Baseline - 6 months post-treatment

Study Arms (1)

Non-medicine sessions of bCBCT + Medicine Sessions with 3,4-methylenedioxymethamphetamine (MDMA)

EXPERIMENTAL

bCBCT Non-medicine sessions: 8 sessions MDMA Medicine sessions: Initial Dose 1: 80 mg MDMA HCl (\~68 mg MDMA) Supplementary Dose 1: 40 mg MDMA HCl (\~34 mg MDMA) Initial Dose 2: 100 mg MDMA HCl (\~84 mg MDMA) Supplementary Dose 2: 40 mg MDMA HCl (\~34 mg MDMA)

Drug: 3,4-methylenedioxymethamphetamine (MDMA); Behavioral: Brief Cognitive Behavioral Conjoint Therapy (bCBCT)

Interventions

3,4-methylenedioxymethamphetamine (MDMA) DRUG

2 MDMA sessions; PTSD+ Veteran partner only

Non-medicine sessions of bCBCT + Medicine Sessions with 3,4-methylenedioxymethamphetamine (MDMA)

Brief Cognitive Behavioral Conjoint Therapy (bCBCT) BEHAVIORAL

8 bCBCT sessions; Both partners

Non-medicine sessions of bCBCT + Medicine Sessions with 3,4-methylenedioxymethamphetamine (MDMA)

Eligibility Criteria

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

You may qualify if:

• Be a veteran (age 18 years or older) who meets criteria for PTSD on the CAPS-5 or be an intimate partner (age 18 or older) of a veteran meeting the criteria for PTSD who is willing to participate in the intervention and who does not meet criteria for PTSD on the PCL-5 (i.e., must score a 30 or lower).
• Be in a committed relationship together of at least 12 months, and be cohabiting.
• Be fluent in speaking and reading English.
• Are willing to commit to medication dosing, therapy sessions, follow-up sessions, completing evaluation instruments, and all necessary telephone contact.
• Be able to swallow pills. (PTSD+ veteran only)
• Agree to have study visits recorded, including Experimental MDMA Sessions, and be aware that Independent Rater assessments for bCBCT sessions will occur.
• 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 a participant becoming suicidal or unreachable. (PTSD+ veteran only)
• Agree to inform the investigators within 48 hours of any new medical conditions or procedures.
• If able to become pregnant (i.e., assigned female at birth, fertile, following menarche and until becoming post-menopausal unless permanently sterile), must have a highly sensitive negative pregnancy test at study entry and prior to each Experimental MDMA Session, and must agree to use adequate birth control through 10 days after the last Experimental MDMA Session. Adequate birth control methods include intrauterine device (IUD), injected, implanted, intravaginal, or transdermal hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner, or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e., condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom). (PTSD+ veteran only)
• Agree to the following lifestyle modifications: comply with requirements for fasting and refraining from certain medications prior to Experimental MDMA Sessions. (PTSD+ veteran only)
• Not enroll in any other interventional clinical trials during the duration of the study, and commit to medication dosing, therapy, and study procedures.
• Both partners agree to not begin a new form of mental healthcare during the screening or treatment phases of the trial, without first discussing with the PI in consultation with the study physician.
• It is acceptable for participants to continue ongoing non-PTSD focused or non-couple-based mental healthcare, if it is not increased in frequency or specifically excluded by the study protocol.
• All ongoing therapies should be documented by the site and discussed with the study physician prior to enrollment to avoid confounding treatment effects. In some instances, the study physician may request that the participant delay enrollment until their planned course of therapy is complete, and an integration period has elapsed.
• Participants may continue with PTSD focused and/or couple-based mental health care during the screening period prior to Baseline and following treatment period prior to study termination if they have approval from the study PI and their study provider (as applicable).

You may not qualify if:

• Are not able to give adequate informed consent.
• Are currently engaged in compensation and pension (C\&P) litigation whereby financial gain would be achieved from prolonged symptoms of PTSD or any other psychiatric disorders.
• Are likely, in the investigator's opinion and via assessment period, to be re- exposed to their index trauma or other significant trauma, lack social support, or lack a stable living situation
• Have used Ecstasy (material represented as containing MDMA) more than 10 times within the last 10 years or at least once within 6 months of the first Experimental MDMA Session. (PTSD+ veteran only)
• Have any current problem which, in the opinion of the investigator or study physician, might interfere with participation due to it impacting the patient's safety and/or ability to participate in the protocol
• Have hypersensitivity to any ingredient of the Investigational Medicinal Product (IMP). (PTSD+ veteran only)
• Psychiatric History - both members of dyad unless otherwise noted
• Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment. (PTSD+ veteran only)
• Have a history of or a current primary psychotic disorder assessed via the DIAMOND and clinical interview
• Have a history of or a current Bipolar I disorder, Bipolar 2 disorder, or manic episode assessed via the DIAMOND and clinical interview (PTSD+ veteran only)
• Have a current eating disorder with active purging assessed via DIAMOND and clinical interview. (PTSD+ veteran only)
• Have current major depressive disorder with psychotic features assessed via DIAMOND
• Have current panic disorder assessed via DIAMOND (PTSD+ veteran only)
• Have a current alcohol or substance use disorder other than caffeine or nicotine that the investigators, therapy team, and/or study physician judge to be a safety concern for enrollment in the study or that could interfere with the therapeutic process or with other aspects of study participation. Any participant who is not able to agree or adhere to a plan to reduce use and manage symptoms will not be enrolled
• Suicidal ideation score of 4 or greater within the last 6 months of the assessment at a frequency of once a week or more

Sponsors & Collaborators

• Healing Breakthrough: collaborator
• Lykos Therapeutics: collaborator
• San Diego Veterans Healthcare System: collaborator
• Dr. Leslie Morland: lead

Study Sites (1)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161, United States

Location

Related Publications (1)

• Morland LA, Perivoliotis D, Wachsman TR, Alam A, Knopp K, Khalifian C, Ramanathan D, Chargin BE, Bismark AW, Glynn S, Stauffer C, Wagner AC. MDMA-assisted brief cognitive behavioral conjoint therapy for PTSD: Study protocol for a pilot study. Contemp Clin Trials Commun. 2024 May 24;40:101314. doi: 10.1016/j.conctc.2024.101314. eCollection 2024 Aug.

  PMID: 38994348 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

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

Study Officials

• Leslie Morland

  San Diego Veterans Healthcare System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. Leslie Morland

Model Details: An open label, single site study assessing the preliminary effectiveness, safety, and acceptability of an intervention consisting of MDMA-assisted bCBCT

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 7, 2023
• Study Start: October 6, 2023
• Primary Completion: November 14, 2025
• Study Completion: November 14, 2025
• Last Updated: December 8, 2025

Record last verified: 2025-12

Locations

US (1)