Nature medicine
June 1, 2021
Jennifer M Mitchell, Michael 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.
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.
Nature medicine
October 1, 2023
Jennifer M. Mitchell, Marcela Ot’alora G., Bessel Van der Kolk et al.
400 citations
In a phase 3 trial, MDMA-assisted therapy reduced PTSD symptoms and functional impairment more than placebo with therapy in 104 participants with moderate to severe PTSD. The average decrease in PTSD symptom severity was 23.7 points with MDMA-assisted therapy versus 14.8 points with placebo, and functional disability improved by 3.3 versus 2.1 points. Participants were ethnoracially diverse, with 27% identifying as Hispanic/Latino and 34% as other than White. Severe side effects occurred in 9.4% of the MDMA group and 3.9% of the placebo group; no deaths or serious adverse events were reported. The treatment was generally well tolerated.
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.
Psychopharmacology
November 1, 2018
Alicia L Danforth, Charles S Grob, Christopher Struble et al.
284 citations
Autistic adults with severe social anxiety who received MDMA-assisted psychotherapy showed significantly greater improvement in social anxiety symptoms compared to those given an inactive placebo. The improvement was rapid and durable, with effects still present at a six-month follow-up. The study used two eight-hour psychotherapy sessions with either MDMA (75–125 mg) or placebo, plus three non-drug sessions after each. The effect size was very large at the primary endpoint and remained large at follow-up. Social anxiety stayed the same or continued to improve for most in the MDMA group after treatment ended. Initial safety and efficacy support larger studies.
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.
Frontiers in Psychiatry
September 12, 2019
Allison A. Feduccia, Lisa Jerome, Berra Yazar‐klosinski et al.
172 citations
MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) shows a large effect size in pooled analyses, substantially improving safety and efficacy over approved medications paroxetine and sertraline, which have only small to moderate effects. The treatment involves up to three monthly 8-hour sessions with MDMA administered under direct observation, plus preparatory and integrative psychotherapy. Dropout rates are lower than in medication trials, and risks of diversion, overdose, or withdrawal are minimal. Breakthrough Therapy Designation from the FDA has accelerated phase 3 trials, with a planned submission for approval in 2021.
Scientific Reports
November 24, 2020
Julane Andries, Lisa Jerome, Evan Sola et al.
170 citations
A randomized controlled trial tested MDMA-assisted psychotherapy for anxiety in people with life-threatening illnesses. Participants received either MDMA (125 mg) or placebo during two 8-hour psychotherapy sessions. At one month after the second session, the MDMA group showed a greater average reduction in anxiety scores (23.5 points) compared to the placebo group (8.8 points), but the difference did not reach statistical significance. The treatment was well tolerated. After the trial, all participants received open-label MDMA sessions. These preliminary results suggest MDMA-assisted psychotherapy may be a promising approach, but larger trials are needed to confirm its effectiveness.
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.
PLoS ONE
March 17, 2021
Marcel O. Bonn‐Miller, Sue Sisley, Paula Riggs et al.
129 citations
A randomized placebo-controlled trial tested three concentrations of smoked cannabis (high THC, high CBD, THC+CBD) against placebo in military veterans with PTSD. Over three weeks, all groups including placebo showed significant improvements in PTSD symptom severity, but none of the active cannabis concentrations outperformed placebo statistically. The treatments were generally well tolerated. This preliminary trial did not find evidence that smoked cannabis is more effective than placebo for PTSD symptoms in the short term, highlighting the need for further well-powered studies.
Focus (American Psychiatric Publishing)
July 1, 2023
Jennifer M Mitchell, Michael 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.
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.
Journal of psychiatric research
May 1, 2022
Timothy D Brewerton, Julie B Wang, Adele Lafrance et al.
81 citations
Among 89 individuals with severe PTSD enrolled in a placebo-controlled trial of MDMA-assisted therapy, 15% had eating disorder symptoms in the clinical range and 31.5% in the high-risk range at baseline, despite no active purging or low weight. After treatment, participants who received MDMA-assisted therapy showed significantly greater reductions in eating disorder symptoms compared to those who received placebo, especially among women with elevated baseline scores. The findings suggest that eating disorder psychopathology is common in severe PTSD and that MDMA-assisted therapy may reduce these co-occurring symptoms.
Journal of psychoactive drugs
January 1, 2014
Amy Emerson, Linnae Ponté, Lisa Jerome et al.
64 citations
The Multidisciplinary Association for Psychedelic Studies (MAPS) was founded in 1986 as a nonprofit psychedelic pharmaceutical company in response to the 1985 scheduling of MDMA. MAPS developed the first double-blind, placebo-controlled trial of MDMA-assisted psychotherapy for PTSD and plans for FDA prescription approval in 2021. Its research expanded to include LSD-assisted psychotherapy for anxiety from life-threatening illness, observational studies of ibogaine for addiction, and MDMA for social anxiety in people with autism. MAPS' harm-reduction efforts aim to avoid backlash and build a post-prohibition world by helping non-medical users transform difficult psychedelic experiences into growth opportunities.
PLoS ONE
January 10, 2024
Rachel Yehuda, Leah Bedrosian, Charlotte Harrison et al.
52 citations
In a randomized, double-blind, placebo-controlled Phase 3 trial of 90 participants with severe PTSD, MDMA-assisted therapy produced significantly greater improvements than therapy with placebo on measures of emotional coping and self-experience. Participants receiving MDMA showed larger gains on the Toronto Alexithymia Scale, the Self-Compassion Scale, and most factors of the Inventory of Altered Self-Capacities, including affect regulation and interpersonal functioning, with identity diffusion being the only exception. Most participants had histories of developmental trauma and multiple traumas. These findings suggest that MDMA-assisted therapy enhances psychological capacities that are often linked to poor treatment outcomes, offering insight into how psychedelic agents may reduce PTSD symptoms.
Journal of Traumatic Stress
February 19, 2020
Ingmar Gorman, Alexander Belser, Lisa Jerome et al.
43 citations
MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) not only reduces symptoms but also promotes posttraumatic growth (PTG)—positive changes in self-perception, relationships, and life philosophy. Pooled data from three phase 2 clinical trials with 60 participants showed that those receiving active MDMA (75–125 mg) had significantly more PTG and larger reductions in PTSD symptom severity at the primary endpoint compared to the control group (0–40 mg MDMA). At 12-month follow-up, PTG remained higher, symptom severity lower, and two-thirds of participants no longer met PTSD criteria. These large-magnitude effects suggest PTG may be a new mechanism of action for this treatment.
Frontiers in psychiatry
January 1, 2022
S Parker Singleton, Julie B Wang, Michael Mithoefer et al.
36 citations
In nine veterans and first-responders with chronic PTSD, MDMA-assisted therapy (MDMA-AT) did not significantly increase amygdala-hippocampus resting-state functional connectivity as hypothesized, showing only a trend. After treatment, brain activation during trauma memory recall decreased in the cuneus. Recovery from PTSD correlated with changes in four functional connections during autobiographical memory recall: left amygdala with left and right posterior cingulate cortex and left insula, and left isthmus cingulate with left posterior hippocampus. These findings suggest that amygdala, hippocampus, and insula functional connectivity may be a target of MDMA-AT, highlighting regions involved in memory processes.
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 Humanistic Psychology
June 23, 2021
Julie B. Wang, Jessica Lin, Leah Bedrosian et al.
22 citations
MDMA-assisted therapy (MDMA-AT) can be scaled across multiple clinic sites while maintaining high treatment fidelity. In an open-label study across 14 North American sites, cotherapist dyads were trained in a manualized protocol and administered three experimental sessions to participants with severe PTSD. Adherence to the therapy protocol was high across both dyads and sites. PTSD symptom severity, measured by the CAPS-5, decreased substantially after three sessions at 18 weeks. MDMA was well tolerated. These results indicate that the benefits of MDMA-AT for PTSD can be achieved in a multi-site, real-world clinical setting.
Psychopharmacology (Berl)
November 1, 2024
Lisa Jerome, Allison A. Feduccia, Julie B. Wang et al.
10 citations
This is a retraction note for a previously published article on the long-term outcomes of MDMA-assisted psychotherapy for PTSD. The original article reported a longitudinal pooled analysis of six phase 2 trials, but it has been retracted. The retraction does not provide any findings or data about the treatment's efficacy or long-term effects.
Psychopharmacology (Berl)
November 1, 2024
Michael C. Mithoefer, Allison A. Feduccia, Lisa Jerome et al.
9 citations
This is a retraction note for a previously published article about MDMA-assisted psychotherapy for PTSD. The original article described the design and rationale for phase 3 trials, which were based on a pooled analysis of six phase 2 randomized controlled trials. The retraction indicates that the original article should not be relied upon, but the note itself does not provide any findings or data about the treatment's effectiveness.
medRxiv Preprint Server
May 25, 2022
S. Parker Singleton, Julie B. Wang, Michael Mithoefer et al.
9 citations
preprint
In nine veterans and first-responders with chronic PTSD, MDMA-assisted therapy did not significantly increase amygdala-hippocampus resting-state functional connectivity as hypothesized, only showing a trend. After treatment, activation in the cuneus decreased when recalling traumatic versus neutral memories. The amount of PTSD recovery correlated with changes in four functional connections during autobiographical memory recall: left amygdala with left and right posterior cingulate cortex and left insula, and left isthmus cingulate with left posterior hippocampus. These findings suggest that MDMA-AT may alter functional connectivity in brain regions involved in memory and fear processing, but more research is needed to determine if these effects are specific to MDMA-AT compared to other PTSD treatments.
medRxiv Preprint Server
January 3, 2023
Bessel A. van der Kolk, Julie B. Wang, Rachel Yehuda et al.
2 citations
preprint
A Phase 3 clinical trial tested MDMA-assisted therapy (MDMA-AT) against placebo with therapy for severe PTSD. 85% of participants reported early childhood trauma, linked to deficits in emotional coping. MDMA-AT significantly improved alexithymia, self-compassion, and altered self-capacities compared to therapy alone. These changes address transdiagnostic mental processes that often hinder treatment response.