MAPS has sponsored six phase 2 trials of MDMA-assisted psychotherapy for PTSD that lasted from April 2004 to March 2017. The safety and efficacy results from these trials were submitted to the FDA, along with a summary of the sertraline and paroxetine data that supported the New Drug Application (NDA) for approval of these drugs for the indication of PTSD. Sertraline and paroxetine summary data was extracted from documents found in the FDA drug database, including the Review and Evaluation of Clinical Data and the drug labels (17–20). Breakthrough therapy designation (BTD) is one of the Food and Drug Administration’s (FDA) expedited drug development pathways. To be eligible How Long Does MDMA Stay in Your System for BTD, a sponsor must demonstrate that the investigational product is intended to treat a serious and life-threatening condition, with preliminary evidence supporting a substantial advantage at a clinically significant endpoint over existing drugs (1).
- Previous research on MDMA for PTSD has suggested that those with a recent history of SSRI treatment may not respond as robustly to MDMA18.
- While MDMA is currently listed as a Schedule I drug, the agency’s review found it has the same abuse potential as a Schedule II stimulant, a category that includes cocaine.
- MDMA provides a feeling of safety, peacefulness, and love, that allows you to revisit both past experiences and parts of yourself that you don’t fully accept.
- Serious suicidal ideation (a score of 4 or 5 on the C-SSRS) was minimal during the study and occurred almost entirely in the placebo arm (Fig. 4).
- Therefore, an inactive placebo was determined in partnership with the FDA as a more conservative statistical comparison, and the study utilized observer-blinded efficacy assessments to minimize bias in efficacy measurements.
- He clarified that in “unusual situations,” MDMA can be taken in the wrong dose, leading to bad outcomes.
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- The capacity for MDMA to increase feelings of empathy and compassion for the self and others may contribute to improved self-awareness and subsequently reduce the denial of alcohol misuse (70).
- Many existing studies on MDMA-AT and P-AT also include small sample sizes and maintain some risk of bias, particularly with lack of randomization and unexpectedly high response to low dose control conditions (59,73,74).
- In the MDMA-AT group, 49 of 52 (94.2%) participants were certain or thought that they received MDMA; one of 52 (1.9%) participants inaccurately thought that they received placebo; and two of 52 (3.8%) participants could not tell (Supplementary Table 6).
- 2021 research suggests that using MDMA in clinical settings may be safe and well-tolerated and may result in significant reductions in PTSD symptoms.
- Undeterred by the political challenges, MDMA clinical research continued, with a MAPS-sponsored clinical study gaining approval in 2000 to look at MDMA for PTSD in Spain.
Researchers included several covariates in the analysis, but it’s possible they didn’t account for some covariates that could have impacted results among certain participants. About 71% of participants who received MDMA did not meet the criteria for PTSD at the follow-up time. However, in July of this year, Australia became the first country to allow psychiatrists to prescribe MDMA for the treatment of certain mental health conditions. MDMA-assisted therapy seemed to work equally well regardless of the severity of a person’s PTSD, and in people at risk of alcohol or substance use disorder, or with a history of childhood trauma. Following a Phase 3 clinical trial completed in 2021, the new study marks the second and final Phase 3 trial that MAPS needs to apply for FDA approval.
General Health
This article examines the current research behind MDMA therapy, its uses, and what the process of MDMA therapy may involve. MDMA was first synthesized in Germany around 1912 by chemists at the pharmaceutical company, Merck. Later in 1914, Merck patented MDMA, guessing it could have pharmaceutical value.
FDA advisors voted against MDMA therapy – researchers are still fighting for it
Although recent research suggests that dissociative subtype PTSD is difficult to treat36, participants with the dissociative subtype who received MDMA-assisted therapy had significant symptom reduction that was at least similar to that of their counterparts with non-dissociative PTSD. Furthermore, given that other treatments for PTSD are not consistently effective for those with the dissociative subtype, these data, if replicated, would indicate an important novel therapeutic niche for MDMA-assisted therapy for typically hard-to-treat populations. Here, we assess the efficacy and safety of MDMA-assisted therapy in individuals with severe PTSD. Participants were given three doses of MDMA or placebo in a controlled clinical environment and in the presence of a trained therapy team.
Systematic reviews of the literature found that most research enrolls people whose lifetime use far exceeds the average (59–61). In contrast, cognitive function in three trials of MDMA-assisted psychotherapy failed to find impairment after any dose of MDMA (48). When asked about ‘ecstasy’ use at 12-month follow-up after participation in a Phase 2 trial, eight participants, six of whom had taken ecstasy prior to enrollment, reported having used it one to three times. This indicates that MDMA given in the context of psychotherapy does not have high abuse liability (41, 43, 44, 47, 62). MDMA is widely considered part of the psychoactive group of substances called entactogens (Greek roots meaning «touching within»).
- If the FDA approves MDMA as a medicine, they will make a recommendation to the Drug Enforcement Administration (DEA) about rescheduling MDMA, which is anticipated to apply only to Lykos Therapeutics’s MDMA product.
- BOther reasons for exclusion could include withdrawal of consent, adverse event or death, discontinuation of treatment by investigator, lack of therapeutic rapport and illness or lost to follow-up.
- Regulated doses in a controlled setting may help improve psychotherapy sessions for certain conditions, such as post-traumatic stress disorder (PTSD).
- Estimating risk of long-term deleterious effects of discrete doses of MDMA in a controlled setting compared to retrospective studies in people reporting ecstasy use is inappropriate for several reasons.
- The de facto estimand assessed the impact of these missing data points in the mITT set.
MAPS recently completed MAPP2, the second of two Phase 3 trials to support FDA approval of this Breakthrough-Designated therapy. With this completion, MDMA-assisted therapy is expected to receive FDA evaluation in 2023. Researchers have recently met resistance from an advisory committee for the FDA, posing new challenges for the advancement of a potentially life-saving intervention.
On 1 July 2023, Australia legalized MDMA-assisted psychotherapy for the treatment of PTSD. On this date, psychiatrists also gained the ability to prescribe psilocybin for treatment-resistant depression. For these specific uses, the Poisons Standard listed MDMA and psilocybin as Schedule 8 drugs. A rejection of MDMA-assisted therapy would also send «a very strong message» that psychedelic trials should focus on the effects of the drug alone rather than on the drug-therapy combination, King says – an approach that «fails millions of people». Another issue the committee raised was the fact that 40% of participants had taken MDMA before – mostly on the order of two to four times in the past 10 years, Emerson says. The committee expressed concerns that people who had sought out the illegal drug likely had a more favourable view of it going into the trial, which could introduce positive bias.
Author Correction: MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial
An association with MDMA was determined based on the relative incidence of TEAEs with at least a twofold difference between the MDMA and placebo groups. The SAP was developed in accordance with FDA requirements and was approved by the European Medicines Agency to meet the requirements for future marketing applications. The primary and secondary efficacy analyses therefore utilized a de jure estimand of the mITT set for assessing treatment efficacy from the CAPS-5 and SDS data while on the study drug. The de jure dataset did not include outcome measurements taken after treatment discontinuation in the analysis of treatment efficacy. Previous research on MDMA for PTSD has suggested that those with a recent history of SSRI treatment may not respond as robustly to MDMA18. Given that 65.5% of participants in the current trial have a lifetime history of SSRI use, it is difficult to separate the ramifications of long-term SSRI treatment from the effects of treatment resistance.
Some had taken part in the MDMA trials and said they found the medication to be transformative. “We noticed a striking lack of abuse-related adverse events,” said Millis, noting that the FDA had advised the study sponsors to collect this type of data. While the study took steps to “blind” study participants, there was considerable discussion around the fact many of those in the study could tell they had received the experimental drug, leading to what’s known as “functional unblinding,” which can ultimately affect the results. A team of two therapists, generally one man and one woman, then guides the patient through the eight-hour MDMA «session.» Later, there’s follow-up talk therapy, without the drug, to help the patient process any feelings, thoughts or impressions that came up while under the influence of the drug.