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.
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.
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 psychopharmacology (Oxford, England)
September 1, 2006
Harry R Sumnall, Jon C Cole, Lisa Jerome
117 citations
The subjective effects of MDMA (ecstasy) vary across different user groups and are shaped by the reasons people give for taking the drug. A 130-item survey was developed and analyzed, revealing six distinct categories of effects: perceptual alterations, entactogenic effects, prosocial effects, aesthetic effects, negative effects, and sexual effects. Heavier users expected fewer negative, perceptual, and aesthetic effects than lighter users, while abstainers expected greater negative, perceptual, aesthetic, and sexual effects. The findings suggest that extra-psychopharmacological factors, such as the function of use, influence the drug experience, and targeting intervention strategies to specific user groups based on their reasons for use may improve effectiveness.
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.
Expert Review of Clinical Pharmacology
June 1, 2020
Kyle T. Greenway, Nicolas Garel, Lisa Jerome et al.
87 citations
Combinations of psychotherapy with antidepressants and psychedelic-assisted psychotherapy both work through complex, interactional mechanisms. A review of therapeutic mechanisms behind conventional and psychedelic paradigms, including the evolution of this knowledge and explanatory frameworks, finds that the contextual model of common factors in psychotherapy provides a powerful perspective on psychotherapy, antidepressants, psychedelics, MDMA, and ketamine. Conventional antidepressants and especially psychedelics may improve psychotherapy's efficacy via neurochemical changes and increased environmental sensitivity. Combined treatments hold significant promise for advancing knowledge and treatment of many forms of psychopathology.
Journal of Psychoactive Drugs
March 15, 2019
Lisa Jerome, Brad Burge, Richard Doblin et al.
87 citations
Psychedelic plants and fungi have been used in indigenous healing for millennia. Modern research began with Albert Hofmann's synthesis of LSD-25 in 1938, and his accidental self-ingestion in 1943. After scientific and cultural exploration in the 1950s and 1960s, research was nearly halted by government restrictions in the 1970s and 1980s, despite evidence of limited medical risks and therapeutic potential. Today, rigorous studies are abundant, including clinical trials with MDMA-assisted therapy for PTSD, alcoholism, and social anxiety, psilocybin studies for depression and addiction, investigations into psychedelics' ability to catalyze spiritual experiences and inspire creativity, and neuroscientific research on their nervous system effects.
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.
Hum Psychopharmacol
March 1, 2014
Rick Doblin, George Greer, Julie Holland et al.
48 citations
This article responds to and critically re-evaluates a prior review of 25 years of empirical research on MDMA (ecstasy). It argues for a more balanced understanding of the drug's effects, emphasizing that controlled therapeutic contexts can yield positive psychological outcomes and beneficial subjective experiences, contrary to earlier conclusions that focused predominantly on harms. The response highlights the need to separate recreational use from clinical applications and calls for nuanced interpretation of prior data to inform mental health research.
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.
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.
Psychopharmacology (Berl)
November 21, 2020
Allison A. Feduccia, Lisa Jerome, Michael C. Mithoefer et al.
39 citations
In four phase 2 trials of MDMA-assisted psychotherapy for PTSD, participants who tapered off antidepressant medications before treatment had worse outcomes than those who did not taper. The non-taper group had significantly lower PTSD symptom scores (mean 45.7 vs. 70.3) and depression scores (mean 12.7 vs. 22.6) at the primary endpoint, and 63.6% no longer met PTSD criteria compared to 25.0% in the taper group. Recent exposure to antidepressants that target reuptake transporters may reduce treatment response to MDMA-assisted psychotherapy.
Current Drug Abuse Reviews
June 1, 2013
Lisa Jerome, Shira Schuster, B. Yazar-Klosinski
36 citations
Psychedelic compounds show promise as treatments for substance abuse disorders. MDMA, which shares features with psychedelics and has reduced PTSD symptoms in assisted psychotherapy, may also help. Early reports indicate some people reduced or stopped substance use after receiving MDMA, especially therapeutically. MDMA releases monoamines, activates 5-HT2A receptors indirectly, and increases prosocial feelings via oxytocin. Heavy lifetime ecstasy use is linked to fewer serotonin transporters and impaired verbal memory. Animal and human studies show moderate abuse liability, but in two recent clinical studies, participants who received MDMA-assisted psychotherapy did not seek ecstasy and tested negative on random drug tests during follow-up. MDMA might directly treat addiction-related neuropharmacological abnormalities or indirectly aid therapy and comorbid conditions.
Science
June 1, 2003
Michael Mithoefer, Lisa Jerome, Richard Doblin et al.
36 citations
This work reviews evidence on whether MDMA (ecstasy) causes neurotoxicity in humans. The authors examine clinical and observational studies assessing the drug's effects on the brain's serotonin system. They conclude that MDMA use is associated with lasting changes in serotonergic function, including reduced serotonin transporter density and altered neurotransmitter activity, suggesting potential neurotoxic effects. However, the review notes limitations in human studies, such as confounding factors and lack of definitive causal evidence. The findings indicate that while MDMA can produce neurobiological alterations, the extent and clinical significance of neurotoxicity remain uncertain.
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.
Frontiers in Psychiatry
January 24, 2022
Tigran Makunts, Lisa Jerome, Ruben Abagyan et al.
19 citations
MDMA, also known as ecstasy, is being studied as a treatment for PTSD and anxiety, with approval expected soon. Although MDMA affects serotonin and could theoretically cause serotonin syndrome—a potentially dangerous condition—no cases have occurred in clinical trials. A review of FDA adverse event reports found 20 cases of serotonin syndrome in people who took MDMA, but all had also used other serotonergic drugs such as amphetamines, stimulants, or opioids. No cases were linked to MDMA alone. These findings suggest that serotonin syndrome from MDMA alone is rare or absent in the available data.
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.