Epigenetics and MDMA-Assisted Psychotherapy for PTSD

NCT06189027 | Completed Phase 3 FDA Drug

• 1 other identifier: UP-18-00343
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This is an add-on substudy to an already-approved clinical trial "A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD" (ClinicalTrials.gov Identifier: NCT03537014) which is to be a phase 3 clinical trial studying the efficacy of MDMA-Assisted Psychotherapy for Post Traumatic Stress Disorder. The parent study has been approved by Copernicus Group IRB and is being run by the MAPS Public Benefit Corporation, and is a randomized controlled trial comparing the clinical efficacy of MDMA-assisted psychotherapy to Placebo-assisted psychotherapy. The parent study will recruit participants with Post Traumatic Stress Disorder and involves 20 total study visits over the course of 18 weeks including 3 preparatory psychotherapy visits plus 3 separate treatment sessions involving psychotherapy plus the administration of MDMA vs. placebo and 3 follow up psychotherapy visits after each treatment session. This substudy adds on the collection of saliva in a salivary DNA collection kit at baseline and after treatment to the parent study clinical trail so as to assess whether the MDMA-Assisted Psychotherapy exerts influence on the epigenetic regulation of stress-associated genes as assessed in the salivary epithelial and white blood cells of the research participants. We aim to further assess whether any such changes are correlated with improvements in PTSD symptoms.

Conditions

PTSD

Keywords

MDMA; Psychotherapy; PTSD

Outcome Measures

Primary Outcomes (2)

• Epigenetic regulation of target genes

  Quantify changes in methylation of glucocorticoid receptor NR3C1, the associated gene FKBP5, and Brain Derived Neurotrophic Factor (BDNF) as compared to placebo, in participants with PTSD.

  4 months

• Correlation between PTSD Symptoms and Epigenetic Changes

  Correlations between changes in PTSD symptoms and methylation changes in target genes

  4 months

Study Arms (2)

MDMA Assisted Psychotherapy

ACTIVE COMPARATOR

A longitudinal course of psychotherapy with administration of MDMA on two occasions to assist with the psychotherapeutic process

Drug: MDMA; Behavioral: Psychotherapy

Placebo Assisted Psychotherapy

PLACEBO COMPARATOR

A longitudinal course of psychotherapy with administration of placebo on two occasions to assist with the psychotherapeutic process

Behavioral: Psychotherapy

Interventions

MDMA DRUG

Adjunctive administration of MDMA to assist psychotherapeutic process

Also known as: MDMA Assisted Psychotherapy

MDMA Assisted Psychotherapy

Psychotherapy BEHAVIORAL

Psychotherapy aimed at assisting with PTSD symptom reduction

MDMA Assisted Psychotherapy; Placebo Assisted Psychotherapy

Eligibility Criteria

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

You may qualify if:

• (As per the parent Phase III Trial - "A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD" (ClinicalTrials.gov Identifier: NCT03537014)).
• \*Are at least 18 years old
• \*Are fluent in speaking an d reading the predominantly used or recognized language of the study site
• \*Are able to swallow pills
• Agree to have study visits recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions
• Must provide a contact (relative, spouse, close friend or other support person) who is willing and able to be reached
• Must agree to inform the investigators within 48 hours of any medical conditions and procedures
• If of childbearing potential, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session. Adequate birth control methods include intrauterine device (IUD), injected or implanted 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). Not of childbearing potential is defined as permanent sterilization, postmenopausal, or assigned male at birth.
• Agree to the following lifestyle modifications (described in more detail in Section 4.3 Lifestyle Modifications): comply with requirements for fasting and refraining from certain medications prior to Experimental Sessions, not participate in any other interventional clinical trials during the duration of the study, remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures Medical History
• \*At Screening, meet DSM-5 criteria for current PTSD with a symptom duration of 6 months or longer
• \*At Screening, have at least severe PTSD symptoms in the last month based on PCL-5 total score of 50 or greater
• \*At Screening, 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
• \*At Screening, may have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed
• At Baseline, have at least severe PTSD per CAPS-5 and symptoms in the last month constituting a CAPS-5 Total Severity Score of 35 or greater.

You may not qualify if:

• (As per the parent Phase III Trial - "A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD" (ClinicalTrials.gov Identifier: NCT03537014)).
• Potential participants are ineligible to enroll in the protocol if they:
• \*Are not able to give adequate informed consent
• Are currently engaged in compensation 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 observation during the Preparatory 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 Session; or have previously participated in a MAPS-sponsored MDMA clinical trial
• Have any current problem which, in the opinion of the investigator or Medical Monitor, might interfere with participation
• Psychiatric History
• \*Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment
• \*Have a history of or a current primary psychotic disorder, bipolar affective disorder type 1 assessed via MINI and confirmed via clinical interview or dissociative identity disorder assessed via DDIS and confirmed via clinical interview
• \*Have a current eating disorder with active purging assessed via MINI and confirmed via clinical interview
• \*Have current major depressive disorder with psychotic features assessed via MINI
• \*Meet DSM-5 criteria for active substance use disorder for any substance other than caffeine or nicotine assessed via combination of clinical judgment, MINI, AUDIT, DUDIT, drug test, and blood %carbohydrate-deficient transferrin (%CDT)
• Have current Personality Disorders Cluster A (paranoid, schizoid, schizotypal), Cluster B (antisocial, borderline, histrionic, narcissistic), or Cluster C (avoidant, dependent, obsessive-compulsive) assessed via SCID-5-PD.
• Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist

Sponsors & Collaborators

• University of Southern California: lead
• Multidisciplinary Association for Psychedelic Studies: collaborator

Study Sites (1)

Univeristy of Southern California

Los Angeles, California, 90089, United States

Location

Related Publications (1)

• Lewis CR, Tafur J, Spencer S, Green JM, Harrison C, Kelmendi B, Rabin DM, Yehuda R, Yazar-Klosinski B, Cahn BR. Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSD. Front Psychiatry. 2023 Feb 6;14:959590. doi: 10.3389/fpsyt.2023.959590. eCollection 2023.

  PMID: 36815187 RESULT

Related Links

• Link to information on how to enroll in the parent Phase III Trial

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

Study Officials

• Rael Cahn, MD, PhD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: January 3, 2024
• Study Start: November 20, 2018
• Primary Completion: November 1, 2023
• Study Completion: December 31, 2024
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)