MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial

This open-label study (n=12, 6 couples) describes the safety, tolerability, and efficacy of MDMA (75-100mg) in combination with cognitive-behavioural conjoint therapy (CBCT) where one half of the couple was battling with PTSD.


Cognitive-behavioural conjoint therapy (CBCT) for PTSD has been shown to improve PTSD, relationship adjustment, and the health and well-being of partners. MDMA (3,4-methylenedioxymethamphetamine) has been used to facilitate an individual therapy for PTSD. This study was an initial test of the safety, tolerability, and efficacy of MDMAfacilitated CBCT. Six couples with varying levels of baseline relationship satisfaction in which one partner was diagnosed with PTSD participated in a condensed version of the 15-session CBCT protocol delivered over 7 weeks. There were two sessions in which both members of the couple were administered MDMA. All couples completed the treatment protocol, and there were no serious adverse events in either partner. There were significant improvements in clinician-assessed, patient-rated, and partner-rated PTSD symptoms (pre- to post-treatment/follow-up effect sizes ranged from d = 1.85–3.59), as well as patient depression, sleep, emotion regulation, and trauma-related beliefs. In addition, there were significant improvements in patient and partner-rated relationship adjustment and happiness (d =.64–2.79). These results are contextualized in relation to prior results from individual MDMA-facilitated psychotherapy and CBCT for PTSD alone. MDMA holds promise as a facilitator of CBCT to achieve more robust and broad effects on individual and relational functioning in those with PTSD and their partners.

Authors: Candice M. Monson, Anne C. Wagner, Ann T. Mithoefer, Rachel E. Liebman, Allison A. Feduccia, Lisa Jerome, Berra Yazar-Klosinski, Amy Emerson, Rick Doblin & Michael C. Mithoefer


This paper is the first recent study on MDMA-assisted psychotherapy for couples. Although this type of therapy has been practised before (1960s, and later underground), no double-blind placebo-controlled studies have been done. This study lays the groundwork for such studies.

“The effect sizes for improvements in PTSD and common co-occurring conditions in this pilot study were greater than those found with individually delivered MDMA-facilitated psychotherapy for PTSD. In addition, the effects on PTSD, other symptoms, and relationship outcomes in this study were on par with, or greater than, those previously achieved with CBCT alone.”

Wagner and colleagues (2021) analysed the secondary measures of this study.


A condensed version of a 15-session CBCT protocol was delivered over 7 weeks to six couples, and MDMA was used to facilitate two sessions. There were significant improvements in clinician-assessed, patient-rated, and partner-rated PTSD symptoms, as well as patient depression, sleep, emotion regulation, and trauma-related beliefs.

A manualized psychotherapy for PTSD using MDMA has been shown to improve PTSD symptoms, relationship functioning, and intimate partner well-being. MDMA has not yet been tested alongside a stand-alone, empirically-supported psychotherapy for PTSD.

MDMA-facilitated CBCT was tested in an uncontrolled trial of six couples with a range of baseline relationship satisfaction in which one member was diagnosed with PTSD resulting from a range of traumas. The trial revealed significant improvements in clinician- and patient-rated PTSD severity, comorbid conditions, and relationship improvements.

1.1. Participants

Inclusion criteria for the study were that one partner had a current PTSD diagnosis, that they were at least 18 years old, generally healthy, proficient in speaking and reading English, and that they were willing to refrain from taking any psychiatric medications during the study period.

All participants were heterosexual couples, average age 47 years, with a history of multiple traumatic events and comorbid diagnoses. Two patients were relationally distressed and three partners were relationally distressed according to cut points on the Couples Satisfaction Index.

1.2. Treatment

Participants received all of the session content comprising CBCT, and MDMA sessions were timed to synergize with the CBCT interventions. The treatment lasted 7 weeks and included psychoeducation about trauma and relationships, increasing relational safety, communication skills, tools for behavioural approach, and dyadic cognitive intervention related to problematic trauma-related and relationship cognitions.

Participants were given 75 mg MDMA in the first MDMA session and 100 mg MDMA in the second MDMA session. Adverse events were monitored at 3-month and 6-month follow-up.

1.3. Assessment

Each member of the couple completed assessments at pre-treatment, mid-treatment, post-treatment, and 3- and 6-month follow-ups. There was no missing clinician interview for PTSD data.

Participants were assessed using the Structured Clinical Interview for DSM-5 (SCID-5), the Clinician-Administered PTSD Scale-5 (CAPS-5), and the PTSD Checklist (PCL-5) and Couples Satisfaction Index (CSI) at baseline and at each visit.

Secondary outcome measures included the Beck Depression Inventory (BDI-II), the Pittsburgh Sleep Quality Questionnaire, the Emotion Regulation Questionnaire, and the Traumatic and Attachment Beliefs Scale.

1.4. Analyses

Analyses were conducted in SPSS Version 26 (2018) and growth curve models were used to analyse outcomes at each assessment. Within-group effect sizes were calculated on estimated means and raw pooled standard deviations.

2.1. PTSD and patient comorbid outcomes

Growth curve modelling revealed significant improvements in clinician-assessed PTSD, self- and partner-rated PTSD, depression, sleep, emotion regulation, and overall trauma-related beliefs at post-treatment and follow-ups.

2.2. Intimate relationship outcomes

Growth curve modelling revealed significant improvements in both patient and partner relationship satisfaction across treatment and follow-ups. One patient who was relationally distressed at baseline was relationally satisfied at posttreatment and follow-ups.

  1. Discussion

This study used MDMA to facilitate couple therapy for PTSD, and found that it was safe, did not interfere with treatment, and may have potential to achieve broader relational outcomes not fully realized with individual evidence-based treatment for PTSD.

The effect sizes for PTSD, co-occurring conditions, and relationship outcomes in this pilot study were greater than those found with MDMA-facilitated psychotherapy for PTSD. Additionally, the effects were generally largest at 6-month follow-up, suggesting that MDMA facilitation may confer ongoing benefits.

There are several limitations to the current study, including the lack of a control condition and expert therapists. A Phase 2 randomized controlled trial is currently being conducted to examine the safety and efficacy of MDMA-facilitated CBCT.

Although there are recommended therapies for PTSD, there is still a need to innovate treatment approaches. MDMA-facilitated CBCT may be one avenue of facilitating psychotherapy to improve lives of those who suffer from PTSD.

Study details

Compounds studied

Topics studied

Study characteristics
Original Open-Label

12 Humans


Authors associated with this publication with profiles on Blossom

Anne Wagner
Anne Wagner is the Founder of Remedy, a clinical psychologist and treatment development researcher based in Toronto.

Rick Doblin
Rick Doblin Ph.D. is the founder of MAPS. His persistent work since 1986 has been one of the main drivers behind why psychedelics (including MDMA) are now coming back to therapy.

Michael Mithoefer
Michael Mithoefer is a psychiatrist and a Clinical Investigator and acting Medical Director of MAPS Public Benefit Corporation.


Institutes associated with this publication

MAPS stands for Multidisciplinary Association for Psychedelic Studies, it's the front runner in making psychedelics a legal way to use (and improve) in therapy.

Toronto Metropolitan University
The Toronto Metropolitan University (previously Ryerson University) is associated with psychedelic research but doesn't have a full profile yet.

Compound Details

The psychedelics given at which dose and how many times

MDMA 75 - 100
mg | 2x

Linked Research Papers

Notable research papers that build on or are influenced by this paper

Relational and Growth Outcomes Following Couples Therapy With MDMA for PTSD
This open-label study (n=12, 6 couples) examines the secondary outcomes (up to 6 months later) of Cognitive Behavioral Conjoint Therapy (CBCT) where one partner was suffering from PTSD. There were improvements for both partners on post-traumatic growth, relational support, social intimacy, empathic concern, and less conflict.

Linked Clinical Trial

MDMA-Assisted Cognitive-Behavioral Conjoint Therapy (CBCT) in Dyads in Which 1 Member Has Chronic PTSD
This Phase 1/2 open-label study will combine methods for conducting MDMA-assisted therapy with methods from the CBCT for PTSD in order to treat 10 participants with chronic PTSD and their partners (intimate or non-intimate significant other who does not have a current diagnosis of PTSD) in order to explore whether combined treatment is effective. Each therapy team will have one therapist trained and experienced in MDMA assisted psychotherapy and one therapist trained and experienced in CBCT.

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