PTSDPhase 3NCT06189027
Epigenetics and MDMA-Assisted Psychotherapy for PTSD
A Phase 3 study testing MDMA and Psychotherapy in people with PTSD, run by University of Southern California at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- PTSD
- What is being tested?
- MDMA and Psychotherapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Nov 2018to 31 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- (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
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- 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.
Who cannot join
- (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
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- 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.
- Any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgment of the investigator will be excluded; however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behavior, in the judgment of the investigator, will not be enrolled
- Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist
- Require ongoing concomitant therapy with a psychiatric medication with exceptions described in Section 12.0: Concomitant Medications.
- Medical History
- *Have evidence or history of significant (controlled or uncontrolled) hematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal, gastrointestinal, immunocompromising, or neurological disease, including seizure disorder, or any other medical disorder judged by the investigator to significantly increase the risk of MDMA administration (participants with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded). Note: if participants present with a history of glaucoma, enrollment would be allowed only with the approval of their ophthalmologist
- *Have uncontrolled hypertension using the standard criteria of the American Heart Association (values of 140/90 milligrams of Mercury [mmHg] or higher assessed on three separate occasions)
- *Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] corrected by Bazett's formula)
- *Have a history of additional risk factors for Torsade de pointes ( e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
- *Require use of concomitant medications that prolong the QT/QTc interval during Experimental Sessions. Refer to Section 12.0 Concomitant Medications.
- *Have symptomatic liver disease
- *Have history of hyponatremia or hyperthermia
- *Weigh less than 48 kilograms (kg)
- Are pregnant or nursing, or are of childbearing potential and are not practicing an effective means of birth control
Trial locations and contacts
1 site in 1 country.
United States1 site
Univeristy of Southern California
Los Angeles, California, 90089
About this study
Official title: Epigenetic Regulation of Stress-related Genes in Relation to MDMA-Assisted Psychotherapy Treatment for Post-Traumatic Stress Disorder
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.
Read the detailed description
For a detailed description of the parent study see "A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD" (ClinicalTrials.gov Identifier: NCT03537014). The current substudy the site coordinators at participating sites in the multi-site phase 3 clinical trial will collect saliva from research participants in the parent study at the following time points:
- Collect saliva prior to first MDMA (vs placebo) treatment session at the Baseline Visit 3 or Visit 4 for the Phase 3 parent study, prior to the first MDMA (vs placebo) treatment session.
- Collect saliva following final MDMA (vs placebo) treatment session at Primary Outcome Visit 19 or Visit 20 in the Phase 3 parent study, approximately 18 weeks after the first MDMA (vs placebo) treatment session.
The collection of saliva will be accomplished using the Oragene DNA OG-500 salivary DNA kits (https://www.dnagenotek.com/ROW/products/collection-human/oragene-dna/500-series/OG-500.html).
The salivary samples take no more than 2-3 minutes to collect by passive drool into the salivary collection kit.
- Conditions
- PTSD
- Being tested
- MDMA, Psychotherapy
- Keywords
- MDMA, Psychotherapy, PTSD
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MDMADrug
Also called MDMA Assisted Psychotherapy
Adjunctive administration of MDMA to assist psychotherapeutic process
PsychotherapyBehavioural
Psychotherapy aimed at assisting with PTSD symptom reduction
| Study group | Role | What they receive |
|---|---|---|
| MDMA Assisted Psychotherapy | Active comparator | A longitudinal course of psychotherapy with administration of MDMA on two occasions to assist with the psychotherapeutic process Receives: 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 Receives: Behavioral: Psychotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Correlation between PTSD Symptoms and Epigenetic Changes
Correlations between changes in PTSD symptoms and methylation changes in target genes
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2024
- Study start20 Nov 2018
- Primary completion1 Nov 2023
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PTSDStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- Multidisciplinary Association for Psychedelic Studies
- Responsible party
- Principal investigator, Rael Cahn, University of Southern California
- Investigators
- Rael Cahn, MD, PhD, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06189027
- Sponsor's protocol ID
- UP-18-00343
- Status last verified
- Apr 2026
- First submitted
- 30 Oct 2018
- Last updated
- 4 May 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36815187
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epigenetic Regulation of Stress-related Genes in Relation to MDMA-Assisted Psychotherapy Treatment for Post-Traumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT06189027
- Acronym / sponsor ID
- UP-18-00343
- Conditions
- PTSD
- Keywords
- MDMA, Psychotherapy, PTSD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- Multidisciplinary Association for Psychedelic Studies
- Study start
- 20 Nov 2018 (actual)
- Primary completion
- 1 Nov 2023 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 3 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
For a detailed description of the parent study see "A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD" (ClinicalTrials.gov Identifier: NCT03537014). The current substudy the site coordinators at participating sites in the multi-site phase 3 clinical trial will collect saliva from research participants in the parent study at the following time points:
- Collect saliva prior to first MDMA (vs placebo) treatment session at the Baseline Visit 3 or Visit 4 for the Phase 3 parent study, prior to the first MDMA (vs placebo) treatment session.
- Collect saliva following final MDMA (vs placebo) treatment session at Primary Outcome Visit 19 or Visit 20 in the Phase 3 parent study, approximately 18 weeks after the first MDMA (vs placebo) treatment session.
The collection of saliva will be accomplished using the Oragene DNA OG-500 salivary DNA kits (https://www.dnagenotek.com/ROW/products/collection-human/oragene-dna/500-series/OG-500.html).
The salivary samples take no more than 2-3 minutes to collect by passive drool into the salivary collection kit.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MDMA Assisted Psychotherapy | Active comparator | Drug: MDMA, Behavioral: PsychotherapyA longitudinal course of psychotherapy with administration of MDMA on two occasions to assist with the psychotherapeutic process |
| Placebo Assisted Psychotherapy | Placebo comparator | Behavioral: PsychotherapyA longitudinal course of psychotherapy with administration of placebo on two occasions to assist with the psychotherapeutic process |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- (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
Key exclusion criteria (27 listed)
- (As per the parent Phase III Trial - "A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD" (ClinicalTrials.gov Identifier: NCT03537014)).
- *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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MDMAAlso: MDMA Assisted PsychotherapyAdjunctive administration of MDMA to assist psychotherapeutic process | Drug | MDMA Assisted Psychotherapy |
| PsychotherapyPsychotherapy aimed at assisting with PTSD symptom reduction | Behavioural | MDMA Assisted Psychotherapy, Placebo Assisted Psychotherapy |
Primary outcome
Epigenetic regulation of target genes
Time frame: 4 months
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.
Correlation between PTSD Symptoms and Epigenetic Changes
Time frame: 4 months
Correlations between changes in PTSD symptoms and methylation changes in target genes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
- Results publication: PubMed 36815187Lewis 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.
- Link to information on how to enroll in the parent Phase III TrialLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rael Cahn, MD, PhD principal investigator
University of Southern California
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MDMA and Psychotherapy in people with PTSD, run by University of Southern California at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Epigenetic regulation of target genes (time frame: 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06189027, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026; AzTrials last refreshed its copy on 1 Nov 2026.