Nature Medicine
June 1, 2021
Jennifer Mitchell, Michael P. Bogenschutz, Alia Lilienstein et al.
965 citations
A phase 3 clinical trial tested MDMA-assisted therapy against placebo for severe PTSD. Participants received manualized therapy with either MDMA or placebo alongside preparatory and integrative sessions. At two months after the last session, the MDMA group showed a significantly greater reduction in PTSD symptoms (average 24.4-point drop on the CAPS-5 scale) compared to the placebo group (13.9-point drop), with a large effect size. Functional impairment also improved more with MDMA. No serious safety issues such as abuse potential, suicidality, or heart rhythm problems were observed. The findings suggest MDMA-assisted therapy is highly effective and safe for severe PTSD, including in people with common co-occurring conditions.
J Psychopharmacol
July 19, 2010
Michael C Mithoefer, Mark T Wagner, Ann T Mithoefer et al.
672 citations
In a pilot randomized controlled trial, MDMA-assisted psychotherapy reduced PTSD symptoms more than placebo therapy in people with chronic, treatment-resistant posttraumatic stress disorder. The treatment was well tolerated, with no serious adverse events. These results suggest that MDMA-assisted psychotherapy may be a safe and effective intervention for this difficult-to-treat population, warranting further investigation.
Lancet Psychiatry
May 1, 2018
Michael C Mithoefer, Ann T Mithoefer, Allison A. Feduccia et al.
443 citations
A randomized, double-blind, phase 2 clinical trial tested MDMA-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers. Participants were randomly assigned to receive different doses of MDMA during psychotherapy sessions. The findings revealed that the active dose of MDMA led to significant and lasting reductions in PTSD symptoms compared to the lower dose, indicating that this innovative therapeutic approach can effectively treat this condition and provide significant relief for individuals with profound trauma.
Journal of psychopharmacology (Oxford, England)
January 1, 2013
Michael C Mithoefer, Mark T Wagner, Ann T Mithoefer et al.
377 citations
In a long-term follow-up of the first completed trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD, all 19 original participants took part, and 16 completed all outcome measures 17 to 74 months after their final MDMA session (average 45.4 months). The mean CAPS score at follow-up (23.7) was nearly identical to the mean score at study exit (24.6), indicating that the substantial symptom relief achieved during the trial was maintained over time. Although two participants relapsed, the majority sustained clinically significant improvements, and no one reported harm from participation.
Journal of psychopharmacology (Oxford, England)
August 1, 2017
Mark T Wagner, Michael C Mithoefer, Ann T Mithoefer et al.
163 citations
Traumatic events can lead to lasting personality changes, especially increased neuroticism. In a randomized trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD, changes in openness—but not neuroticism—moderated the link between reduced PTSD symptoms and the treatment. Patients showed increased openness and decreased neuroticism from baseline to long-term follow-up. These preliminary findings suggest MDMA-assisted psychotherapy may alter personality structure beyond just relieving PTSD symptoms, leading to enduring personality change.
Focus (American Psychiatric Publishing)
July 1, 2023
Jennifer Mitchell, Michael P. Bogenschutz, Alia Lilienstein et al.
97 citations
A phase 3 clinical trial tested MDMA-assisted therapy for severe PTSD. In 90 participants randomized to receive either MDMA or placebo alongside therapy, those receiving MDMA showed a significantly larger reduction in PTSD symptoms, with an average decrease of 24.4 points on the CAPS-5 scale compared to 13.9 points in the placebo group. Functional impairment also improved more with MDMA. No serious safety issues like abuse potential or suicidality were observed. The treatment was effective even for patients with common co-occurring conditions such as depression or substance use history. The authors conclude MDMA-assisted therapy is a safe and highly effective treatment for severe PTSD.
Journal of Psychoactive Drugs
January 1, 2019
Anne C Wagner, Michael C Mithoefer, Ann T Mithoefer et al.
92 citations
Combining Cognitive Behavioral Conjoint Therapy for PTSD (CBCT) with MDMA-assisted psychotherapy in a small pilot trial can reduce PTSD symptoms and improve relationship satisfaction. A case study of one couple with a severe trauma history, representative of the trial participants, details the integrated methodology and the couple's treatment experience. The article describes how these two therapeutic modalities were merged and demonstrates that the combination produces positive outcomes, including symptom reduction and enhanced relationship functioning.
European Journal of Psychotraumatology
December 7, 2020
Candice M Monson, Anne C Wagner, Ann T Mithoefer et al.
90 citations
A small pilot study tested whether adding MDMA to cognitive-behavioural conjoint therapy (CBCT) for PTSD is safe and effective. Six couples, where one partner had PTSD, completed a condensed 7-week CBCT protocol that included two sessions where both partners received MDMA. No serious side effects occurred. PTSD symptoms improved substantially, as rated by clinicians, patients, and partners (effect sizes d = 1.85–3.59). Patients also showed improvements in depression, sleep, emotion regulation, and trauma-related beliefs. Relationship adjustment and happiness improved for both patients and partners (d = 0.64–2.79). MDMA may enhance CBCT's benefits for individuals with PTSD and their partners.
Frontiers in Psychiatry
January 1, 2021
Anne C Wagner, Rachel E Liebman, Ann T Mithoefer et al.
40 citations
Healing from trauma happens in relationships, and PTSD affects more than just the diagnosed individual. In a pilot trial of Cognitive Behavioral Conjoint Therapy (CBCT) for PTSD combined with two MDMA psychotherapy sessions, six romantic couples where one partner had PTSD showed improvements across multiple areas. Both partners reported increases in post-traumatic growth, relational support, and social intimacy. Partners also reported less behavioral accommodation and conflict, while patients with PTSD reported better psychosocial functioning and empathic concern. These gains lasted through a 6-month follow-up. The findings suggest that combining CBCT with MDMA can improve relational and growth outcomes, supporting a dyadic approach to holistic trauma recovery.
European Journal of Psychotraumatology
January 1, 2024
Richard J. Zeifman, Hannes Kettner, Stephen Ross et al.
34 citations
Therapeutic alliance—the quality of the relationship between therapist and client—predicts improvement in PTSD symptoms after MDMA-assisted psychotherapy. Among 22 adults with chronic PTSD who received MDMA during a clinical trial, stronger therapeutic alliance measured at sessions 4 and 9 (but not before the third session) was associated with lower clinician-assessed PTSD severity after treatment, even after accounting for initial symptom severity. Self-reported PTSD severity was also predicted by alliance at baseline, session 4, and session 9, though the baseline finding did not survive correction for multiple comparisons. These results provide initial evidence that common psychotherapeutic factors like alliance contribute to outcomes in MDMA-assisted therapy.
Archives of Clinical Neuropsychology
August 31, 2016
Michael Wagner, Michael C Mithoefer, Ann T Mithoefer et al.
1 citation
In a Phase II clinical trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD, increases in Openness and decreases in Neuroticism personality traits were linked to greater symptom reduction, regardless of treatment condition. Participants receiving MDMA showed the largest gains in Openness, which predicted lower PTSD severity. The authors propose that MDMA, combined with psychotherapy, may facilitate a reorganization of mental experience through altered brain pathways, rather than through psychological learning alone.
Frontiers in Psychology
January 1, 2024
Kelley C O'Donnell, Lauren Okano, Michael Alpert et al.
A conceptual framework for MDMA-Assisted Therapy for PTSD centers on the participant's inner healing intelligence as the primary agent of change, with the therapeutic relationship as the core facilitative condition. This inner-directed, holistic, self-directed, relational, and trauma-informed approach includes a non-pathologizing stance toward embodied experiences, such as intense emotional expression, multiplicity, suicidal ideation, and transpersonal experiences. Therapists bring psychodynamic, somatic, and transpersonal awareness, empathic attunement, relational skillfulness, and cultural humility. MDMA with this psychotherapy outperformed placebo with psychotherapy in Phase 2 and 3 trials, though significant symptom reduction also occurred in the placebo group, supporting the psychotherapy model itself.
Kelley C O'Donnell, Michael Alpert, Lauren Okano et al.
preprint
MDMA-Assisted Therapy for PTSD uses a short-term, intensive psychotherapy model that includes three sessions facilitated by MDMA along with non-drug therapy sessions. The MDMA helps recall and process traumatic memories and enhances learning in social contexts, integrating top-down and bottom-up trauma care. This paper describes the psychotherapeutic concepts and theories behind this approach, centering on the participant's inner healing intelligence as the main agent of change, with the therapeutic relationship as a core facilitative condition. Phase 2 and 3 trials showed MDMA with therapy outperformed placebo with therapy in reducing PTSD symptoms, though significant symptom reduction also occurred in participants who received only therapy.