MDMA for Co-occurring PTSD and OUD After Childbirth

NCT05219175 | Recruiting Phase 2 FDA Drug

• 1 other identifier: IUSOU1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label study of the use of MDMA Assisted Therapy for postpartum people with co-occurring Post Traumatic Stress Disorder (PTSD) and Opioid Use Disorder (OUD). The study protocol has been adapted from the Phase 3 studies sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS) for PTSD. Due to the high rate of concurrence of PTSD and OUD, people with OUD may experience great benefit from the treatment of their PTSD with MDMA-assisted therapy based on the phase 2 and 3 studies for PTSD. Use of MDMA-assisted therapy in this population has the potential to be of benefit for their OUD and maternal- infant attachment. This study will serve to explore the feasibility and safety of offering MDMA-assisted therapy for treatment of PTSD in postpartum people with opioid use disorder. The CAPs 5 (PTSD) is the primary outcome, the Timeline Follow-Back (TLFB) for opioid use is the secondary outcome and other assessments of opioid use disorder, effects on maternal-infant attachment, social connectedness and other mental health outcomes are exploratory. The study will be conducted at the University of New Mexico Health Sciences Center located in Albuquerque New Mexico. In addition to northern New Mexico being an epicenter of the current opioid use disorder epidemic in the United States there is a long-standing history of multigenerational use of illicit opioids in many communities of northern New Mexico. There are high rates of opioid use disorder on pregnancy and accompanying Neonatal Opioid Use Withdrawal Syndrome (NOWS) in Albuquerque, Santa Fe, and surrounding communities.

Conditions

Stress Disorders, Post-Traumatic; Opioid Use Disorder

Keywords

PTSD; Opioid Use Disorder; Addiction; MDMA; Psychedelic Assisted Therapy; Maternal Infant Bonding

Outcome Measures

Primary Outcomes (1)

• PTSD

  CAPS-5

  4 weeks after 3rd experimental session

Secondary Outcomes (1)

• Opioid Use Disorder

  6 months after 3rd Experimental Sessions

Other Outcomes (1)

• Effect on nonopioid substance use disorders

  1-6 months after 3rd Experimental Session

Study Arms (1)

Co-occurring PTSD and OUD prior and after treatment with MDMA Assisted Therapy

EXPERIMENTAL

The intervention is MDMA Assisted Therapy focused on PTSD and three experiment sessions with the first session using an initial dose of 100 mg MDMA HCL (\~80 mg MDMA) with supplemental dose of 40 mg MDMA HCL (\~35 mg MDMA). Total dose range for the first session is 100 mg MDMA HCL (\~80 mg MDMA) to 140 mg MDMA HCL (\~115 mg MDMA).The second and third sessions may use an initial dose of 120 mg MDMA HCL (\~100 mg MDMA) with a supplemental dose of 60 mg MDMA HCL (\~50 mg MDMA) for a total dose range of 120 mg MDMA HCL (\~100 mg MDMA) to 180 mg MDMA HCL (\~160 mg MDMA) Total cumulative dose range for the three sessions is 340mg MDMA HCL (\~280 mg MDMA) to 500 mg MDMA HCL (\~435 mg MDMA)

Drug: MDMA Assisted Therapy

Interventions

MDMA Assisted Therapy DRUG

The intervention is MDMA Assisted Therapy focused on PTSD and three experiment sessions with the first session using an initial dose of 100 mg MDMA HCL (\~80 mg MDMA) with supplemental dose of 40 mg MDMA HCL (\~35 mg MDMA). Total dose range for the first session is 100 mg MDMA HCL (\~80 mg MDMA) to 140 mg MDMA HCL (\~115 mg MDMA).The second and third sessions may use an initial dose of 120 mg MDMA HCL (\~100 mg MDMA) with a supplemental dose of 60 mg MDMA HCL (\~50 mg MDMA) for a total dose range of 120 mg MDMA HCL (\~100 mg MDMA) to 180 mg MDMA HCL (\~160 mg MDMA) Total cumulative dose range for the three sessions is 340mg MDMA HCL (\~280 mg MDMA) to 500 mg MDMA HCL (\~435 mg MDMA)

Co-occurring PTSD and OUD prior and after treatment with MDMA Assisted Therapy

Eligibility Criteria

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

You may qualify if:

• Potential participants are eligible to enroll in the protocol if they:
• Are at least 18 years old.
• Have opioid use disorder and are using daily oral methadone of 180 mg or less, or sublingual buprenorphine (or buprenorphine with naloxone in 4:1 ratio) of 24 mg or less. Assessed as stable for at least 3 months based upon review of the University of New Mexico Milagro and FOCUS program medical records or direct communication with the participant's buprenorphine or methadone prescriber.
• Are fluent in speaking and reading English. This criteria is needed as the protocol requires two therapists that have specific training and it would be very difficult to identify two therapists fluent in another language
• Are able to swallow pills.
• Agree to have study visits recorded, including Experimental Sessions, Independent Rater assessments by an on-site Independent Rater for CAPS-5, and non-drug therapy sessions.
• Must 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.
• Must agree to inform the investigators within 48 hours of any medical conditions and procedures.
• If able to become pregnant, 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, 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). Not able to become pregnant is defined as permanent sterilization or postmenopausal.
• Agree to the lifestyle modifications described in Section 3.0 above:
• Medical History
• At Screening, meet DSM-5 criteria for current moderate to severe PTSD with a symptom duration of 6 months or longer.
• At Screening, meet DSM-5 criteria for Opioid Use Disorder.
• At Screening, have had PTSD symptoms for at least three months and at least moderate PTSD symptoms in the last month based on PCL-5 total score of 40 or greater.
• 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

You may not qualify if:

• Potential participants are ineligible to enroll in the protocol if they:
• Are not able to give adequate informed consent.
• Prisoners will be excluded
• Are likely, in the investigator's opinion and via observation during the Preparatory Period, to be re-exposed to their index trauma, lack social support, or lack a stable living situation.
• Have any current problem which, in the opinion of the investigator or study physician, might interfere with participation.
• A 12 Lead EKG demonstrates QTc greater than 460 msec at time of screening for any potential participant or for the participants using methadone on an EKG obtained within 72 hours of each MDMA treatment session. An abnormal EKG may be repeated once to confirm the presence of QTc prolongation. 460 msec used as the upper acceptable limit as this study only includes women and the level of QTc that is considered abnormal is 10-20 msec longer for women.
• Psychiatric History
• \. Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment. 8. Have a history of or a current primary psychotic disorder, bipolar disorder 1 assessed via MINI and clinical interview or dissociative identity disorder assessed via structured clinical interview (SCID).
• \. Have a current eating disorder with active purging assessed via MINI and clinical interview.
• \. Have current major depressive disorder with psychotic features assessed via MINI.
• \. Have a current moderate (not in early remission in the 3 months prior to enrollment based on meeting 4 or 5 of 11 diagnostic criteria per DSM-5) or severe alcohol or cannabis use disorder within the 6 months prior to enrollment (meets at least 6 of 11 diagnostic criteria per DSM-5).
• \. Have an active illicit (other than cannabis or opioids) or prescription drug substance use disorder at any severity within 3 months prior to enrollment.
• Medical History
• \. Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate.
• \. Have uncontrolled essential 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).

Sponsors & Collaborators

• University of New Mexico: lead
• Multidisciplinary Association for Psychedelic Studies: collaborator

Study Sites (1)

University of New Mexico Health Sciences

Albuquerque, New Mexico, 87131, United States

RECRUITING

Related Publications (11)

• 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.

  PMID: 33972795 RESULT

• Haight SC, Ko JY, Tong VT, Bohm MK, Callaghan WM. Opioid Use Disorder Documented at Delivery Hospitalization - United States, 1999-2014. MMWR Morb Mortal Wkly Rep. 2018 Aug 10;67(31):845-849. doi: 10.15585/mmwr.mm6731a1.

  PMID: 30091969 RESULT

• Nardou R, Lewis EM, Rothhaas R, Xu R, Yang A, Boyden E, Dolen G. Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Nature. 2019 May;569(7754):116-120. doi: 10.1038/s41586-019-1075-9. Epub 2019 Apr 3.

  PMID: 30944474 RESULT

• Mithoefer MC, Feduccia AA, Jerome L, Mithoefer A, Wagner M, Walsh Z, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019 Sep;236(9):2735-2745. doi: 10.1007/s00213-019-05249-5. Epub 2019 May 7.

  PMID: 31065731 RESULT

• Sessa B, Higbed L, O'Brien S, Durant C, Sakal C, Titheradge D, Williams TM, Rose-Morris A, Brew-Girard E, Burrows S, Wiseman C, Wilson S, Rickard J, Nutt DJ. First study of safety and tolerability of 3,4-methylenedioxymethamphetamine-assisted psychotherapy in patients with alcohol use disorder. J Psychopharmacol. 2021 Apr;35(4):375-383. doi: 10.1177/0269881121991792. Epub 2021 Feb 18.

  PMID: 33601929 RESULT

• Bogenschutz MP, Johnson MW. Classic hallucinogens in the treatment of addictions. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan 4;64:250-8. doi: 10.1016/j.pnpbp.2015.03.002. Epub 2015 Mar 14.

  PMID: 25784600 RESULT

• Reiff CM, Richman EE, Nemeroff CB, Carpenter LL, Widge AS, Rodriguez CI, Kalin NH, McDonald WM; the Work Group on Biomarkers and Novel Treatments, a Division of the American Psychiatric Association Council of Research. Psychedelics and Psychedelic-Assisted Psychotherapy. Am J Psychiatry. 2020 May 1;177(5):391-410. doi: 10.1176/appi.ajp.2019.19010035. Epub 2020 Feb 26.

  PMID: 32098487 RESULT

• Winkelman M. Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, Peyote, Ibogaine and Ayahuasca. Curr Drug Abuse Rev. 2014;7(2):101-16. doi: 10.2174/1874473708666150107120011.

  PMID: 25563446 RESULT

• Meulewaeter F, De Pauw SSW, Vanderplasschen W. Mothering, Substance Use Disorders and Intergenerational Trauma Transmission: An Attachment-Based Perspective. Front Psychiatry. 2019 Oct 18;10:728. doi: 10.3389/fpsyt.2019.00728. eCollection 2019.

  PMID: 31681040 RESULT

• Danovitch I. Post-traumatic stress disorder and opioid use disorder: A narrative review of conceptual models. J Addict Dis. 2016 Jul-Sep;35(3):169-79. doi: 10.1080/10550887.2016.1168212. Epub 2016 Mar 24.

  PMID: 27010975 RESULT

• Mills KL, Lynskey M, Teesson M, Ross J, Darke S. Post-traumatic stress disorder among people with heroin dependence in the Australian treatment outcome study (ATOS): prevalence and correlates. Drug Alcohol Depend. 2005 Mar 7;77(3):243-9. doi: 10.1016/j.drugalcdep.2004.08.016.

  PMID: 15734224 RESULT

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Opioid-Related Disorders; Behavior, Addictive

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Compulsive Behavior; Impulsive Behavior; Behavior

Study Officials

• Hadya Khawaja, MS, CIP

  UNM Health Sciences Human Research Protections Program

  STUDY DIRECTOR

Central Study Contacts

Lawrence M Leeman, MD MPH

CONTACT

5054106990; lleeman@salud.unm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label study comparing outcomes before and after treatment with MDMA Assisted Therapy

Study Record Dates

• First Submitted: January 2, 2022
• First Posted: February 1, 2022
• Study Start: April 16, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)