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.
Psychopharmacology
September 1, 2019
Michael C Mithoefer, Allison A Feduccia, Lisa Jerome et al.
364 citations
A pooled analysis of six phase 2 trials found that MDMA-assisted psychotherapy significantly reduced PTSD symptoms in adults. Participants receiving active MDMA (75-125 mg) during manualized therapy sessions showed a large treatment effect (Cohen's d = 0.8) compared to those receiving placebo or low doses (0-40 mg). After two sessions, 54.2% of the active group no longer met PTSD diagnostic criteria versus 22.6% of the control group. Depression symptoms also improved more in the active group, though this difference was not statistically significant. MDMA was well tolerated with expected side effects. These findings supported advancement to phase 3 trials and FDA Breakthrough Therapy designation.
Lancet Psychiatry
April 5, 2016
Michael C Mithoefer, Charles S Grob, Timothy D Brewerton
237 citations
Psilocybin and MDMA are emerging as novel psychopharmacological therapies for psychiatric disorders, offering potential alternatives to conventional treatments. These substances are being investigated for their ability to facilitate therapeutic breakthroughs in conditions such as depression and post-traumatic stress disorder. The text outlines their mechanisms, clinical applications, and the growing interest in their use within mental healthcare. It highlights the need for further research to establish safety and efficacy, while acknowledging the promise these therapies hold for addressing treatment-resistant psychiatric conditions.
Journal of psychopharmacology (Oxford, England)
December 1, 2018
Marcela Ot'Alora G, Jim Grigsby, Bruce Poulter et al.
232 citations
MDMA-assisted psychotherapy reduces posttraumatic stress disorder symptoms more than a low dose, with effects lasting at least 12 months. In a double-blind trial, 28 people with chronic PTSD received either 100 mg, 125 mg, or 40 mg of MDMA during psychotherapy sessions. The active dose groups showed larger reductions in Clinician-Administered PTSD Scale scores one month after two sessions, with mean changes of -26.3 for 125 mg, -24.4 for 100 mg, and -11.5 for 40 mg. At 12-month follow-up, 76% no longer met PTSD criteria. No serious adverse events occurred, and the treatment was well-tolerated.
Psychopharmacology
August 1, 2020
Lisa Jerome, Allison A Feduccia, Julie B Wang et al.
163 citations
PTSD symptoms significantly decreased after MDMA-assisted psychotherapy, and the improvement continued for at least 12 months after the final MDMA session. Participants received two to three doses of MDMA (75-125 mg) during psychotherapy sessions. The average reduction in PTSD symptom scores from before treatment to 1-2 months after the last MDMA session was 44.8 points on the CAPS-IV scale, a large effect. Symptoms further decreased slightly over the following year. The proportion of participants who no longer met PTSD diagnostic criteria rose from 56% at treatment exit to 67% at long-term follow-up. Most participants reported benefits such as improved relationships and well-being, while a minority reported harms.
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.
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.
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)
January 1, 2021
Alvaro V Jardim, Dora V Jardim, Bruno Rasmussen Chaves et al.
54 citations
In Brazil's first clinical trial of MDMA-assisted psychotherapy for post-traumatic stress disorder (PTSD), three patients with PTSD from sexual abuse completed treatment. The protocol involved 15 weekly therapy sessions, with three sessions including orally administered MDMA combined with psychotherapy and music, spaced about a month apart. Two months after the final MDMA session, all three patients showed clinically significant improvement, with CAPS-4 scores dropping by more than 30% from baseline. Final scores were 61, 27, and 8, down from 90, 78, and 72. No serious adverse events occurred; common side effects were somatic pains and anguish. Secondary outcomes also improved. MDMA-assisted psychotherapy could become a viable PTSD treatment in Brazil.
Journal of traumatic stress
August 1, 2021
Linnae Ponté, Lisa Jerome, Scott Hamilton et al.
42 citations
Sleep disturbances are common and hard to treat in PTSD. In four randomized controlled double-blind studies, 63 participants received either active MDMA (75-125 mg) or placebo/control MDMA (0-40 mg) during psychotherapy sessions. At the primary endpoint 1-2 months after sessions, PTSD symptoms dropped more with active MDMA than placebo (CAPS-IV score change -34.0 vs. -12.4). Sleep quality also improved more with active MDMA (PSQI score change -3.5 vs. +0.6). Sleep quality continued to improve from treatment exit to 12-month follow-up. These data provide evidence that MDMA-assisted psychotherapy benefits sleep disturbances in PTSD.
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.
Medical hypotheses
January 1, 2021
Timothy D Brewerton, Adele Lafrance, Michael C Mithoefer
28 citations
Eating disorders remain difficult to treat, especially when accompanied by posttraumatic stress disorder. MDMA-assisted psychotherapy for treatment-resistant PTSD shows promise, with two-thirds of participants achieving full remission at one year or more follow-up. The authors hypothesize this therapy will be effective for both eating disorder and PTSD symptoms in people with both conditions. MDMA's effects—reduced fear, enhanced wellbeing, increased sociability, reduced self-criticism, increased compassion, interpersonal trust, and alert consciousness—may counteract avoidance and hyperarousal in therapy. Other features like body image distortion, cognitive rigidity, and socio-emotional difficulties may also improve. Personal accounts describe benefit, but risks and challenges are noted.
Focus (American Psychiatric Publishing)
July 1, 2023
Allison A Feduccia, Lisa Jerome, Berra Yazar-Klosinski et al.
24 citations
Two FDA-approved medications for PTSD, paroxetine and sertraline, show only small to moderate effects over placebo. Pooled analyses of Phase 2 studies indicate that MDMA-assisted psychotherapy—combining the drug with three monthly 8-hour therapy sessions plus preparatory and integrative sessions—produces a large effect size and lower dropout rates than the approved medications. The treatment also carries minimal risk of diversion, overdose, or withdrawal because MDMA is administered under direct observation. This review describes the data that earned MDMA-assisted psychotherapy Breakthrough Therapy Designation from the FDA, which has accelerated Phase 3 trials toward a planned 2021 submission for FDA approval.
Journal of psychopharmacology (Oxford, England)
June 10, 2025
Torsten Passie, Anja Loizaga-Velder, Alicia Danforth et al.
4 citations
A consensus-based model curriculum for education and training in substance-assisted psychotherapy (SAP) covers theoretical topics and practical components including apprenticeship observation, ongoing clinical supervision, and self-experience for trainees. The model, developed by authors with extensive SAP experience, also addresses peer and conventional supervision, respect for intercultural differences, and teachings about indigenous use of related substances. It is largely adapted to western industrialized countries with established graduate-level psychotherapy training. The curriculum may be valuable for psychedelic researchers, those training therapists for research studies, and those preparing for clinical work outside research settings.