Peptide & Experimental
MDMA-assisted psychotherapy
Amphetamine derivative with entactogenic effects, studied as an adjunct to psychotherapy for PTSD; narcotic under Schedule I of the German Narcotics Act (BtMG) · MDMA, midomafetamine, MDMA-AT, MDMA-assisted therapy, methylenedioxymethamphetamine, ecstasy, MAPP1, MAPP2
Many people know MDMA as the party drug ecstasy. In research it is given in a few supervised sessions, embedded in psychotherapy for post-traumatic stress disorder (PTSD). Two phase 3 trials were positive, the FDA nevertheless rejected approval in 2024, and Australia has allowed prescribing since 2023.
In short
In two randomized, double-blind phase 3 trials with 90 and 104 people, PTSD symptoms fell considerably more with MDMA plus therapy than with the same therapy and placebo, including in severely affected participants. In August 2024, the FDA nevertheless did not consider this sufficient evidence: many participants recognized whether they had received MDMA, around 40 percent had used it before, the effect was only documented up to week 18, and side effects were recorded incompletely. Australia has allowed specially authorized psychiatrists to prescribe it for PTSD since July 2023. According to MAPS, the application in the US was resubmitted in August 2026; a decision is pending. In Germany, MDMA is a narcotic that cannot be legally traded.
What MDMA is and how it is supposed to work in therapy
MDMA is a derivative of amphetamine. For a few hours, trust, openness and a feeling of closeness increase. In therapy this is meant to help people look at distressing memories without being overwhelmed by fear. In the studies, MDMA is given in three supervised sessions, with preparatory and follow-up conversations. The substance is therefore part of a therapy program, not a medication to be taken daily.
Part of the idea has been measured in humans. In a placebo-controlled crossover study with 30 healthy men, participants under MDMA learned faster to let go of a conditioned fear response and retained this the next day. Oxytocin in the blood rose on average fourfold but was not related to the learning effect. Whether this pathway explains the improvement in PTSD has not been shown.
What is well supported
- Two positive phase 3 trials. In MAPP1 the PTSD scale fell by 24.4 points versus 13.9 with therapy and placebo (d = 0.91), in MAPP2 by 23.7 versus 14.8 points (d = 0.7). Both trials were randomized and double-blind; in MAPP2, blinded independent raters assessed the outcomes.
- Also in severely affected people. Included were people with dissociation, depression, past alcohol or drug problems and childhood trauma. Impairment in everyday life also improved in both trials.
- Confirmed in the meta-analysis. Across 9 randomized studies with 298 participants, there was a large effect on PTSD symptoms (SMD −1.19) and a smaller one on dissociation.
- A measurable learning effect. Unlearning conditioned fear proceeded faster under MDMA in healthy people and lasted until the next day.
What the studies show
MAPP1, Nature Medicine 2021: severe PTSD
90 people with severe PTSD, after discontinuing their psychiatric medication, randomly assigned to MDMA or placebo, each with the same manualized therapy of three preparatory and nine integration sessions. Two months after the last session, the PTSD scale among those who completed treatment fell by 24.4 points with MDMA and by 13.9 points with placebo (d = 0.91). The authors reported no abuse-related side effects, suicidality or QT prolongation.
MAPP2, Nature Medicine 2023: moderate to severe PTSD
104 participants, one third not white, just over a quarter with moderate PTSD. The PTSD scale fell by 23.7 points with MDMA and by 14.8 with placebo (d = 0.7), everyday impairment by 3.3 versus 2.1 points. A severe side effect occurred in 5 of 53 under MDMA and 2 of 51 under placebo; there were no deaths and no events classified as serious.
Meta-analysis 2026: large effect, very low certainty
A preregistered analysis up to August 2025 found 14 studies, 8 of which provided usable data. For PTSD symptoms the result was SMD −1.19 in 298 participants, for dissociation −0.37, for functioning −0.83. For depressive symptoms there was no clear advantage. Most studies had a high risk of bias in measurement, and hardly any had an active control group; the authors rate the certainty of the evidence as very low.
FDA 2024: expert panel and rejection
In June 2024, the FDA advisory committee voted 9 to 2 that the data do not show efficacy and 10 to 1 that the benefits do not outweigh the risks. In its letter of August 8, 2024, the FDA named three main reasons: pleasant or positive effects were not recorded as events, and at at least two sites inspectors found unreported side effects; a lasting effect beyond week 18 was not demonstrated; and around 40 percent of participants had used MDMA before, which favors unblinding and expectation effects. The FDA recommended a new randomized, double-blind trial with blinded long-term follow-up.
Where the data stop
- Blinding. People who get MDMA notice it. With many participants who already knew MDMA, it is hard to separate how much of the effect is expectation.
- Duration of the effect. The effect is documented up to 8 weeks after the last session. The follow-up study consisted of a single visit between 6 months and 2 years and was not enough for the FDA.
- Incomplete safety data. Laboratory values such as liver values and electrolytes, as well as a complete cardiac assessment, were missing from the application.
- Comparison with established therapies. The comparison was with the same therapy plus placebo, not with another effective PTSD treatment.
- Depression. In the meta-analysis, no clear advantage for depressive symptoms.
Status, approval and legal
In Germany, MDMA is listed in Schedule I of the German Narcotics Act (Betäubungsmittelgesetz) and therefore can neither be legally traded nor prescribed. In the EU there is no approved MDMA medicine. In the US, the FDA rejected the application for midomafetamine for PTSD on August 8, 2024. According to a MAPS statement of August 10, 2026, the successor company Resilient Pharmaceuticals, formerly Lykos Therapeutics, has resubmitted the application without a new phase 3 trial. As of October 7, 2026, no decision is known.
Since July 1, 2023, Australia has allowed psychiatrists authorized by the medicines regulator TGA to prescribe MDMA for PTSD; there is no approved finished medicinal product there. In sport, MDMA is prohibited in competition (WADA list 2026, S6).
Safety
There were no deaths in the phase 3 trials. In MAPP2, 9.4 percent under MDMA and 3.9 percent under placebo had a severe side effect. This result applies to the study setting with preselection of participants and supervised sessions.
The FDA advisory committee named as open issues low blood sodium, missing ECG and laboratory data, the risk of boundary violations in therapy, abuse and diversion, and the duration of impairment after a session. For future studies, the FDA requires laboratory values before and after dosing, blood pressure and pulse after each dose, and fixed criteria for discharge after the session. This text is information and does not replace medical advice.
BK-Score Supported, with caveats
| Human evidence | 6 | |
|---|---|---|
| Mechanism | 4 | |
| Safety data | 4 | |
| Hype gap | 3 | |
| Track record of use | 4 |
Evidence 6, because two randomized, double-blind phase 3 trials with 90 and 104 participants show large effects on PTSD symptoms (Mitchell 2021, Mitchell 2023), but the FDA did not consider this sufficient proof of efficacy – because of unblinding, around 40 percent prior experience with MDMA and missing data on durability beyond week 18 – and a 2026 meta-analysis rates the certainty of the evidence as very low (Fares-Otero 2026). Mechanism 4, because faster unlearning of conditioned fear and a fourfold rise in oxytocin have been measured in humans (Vizeli 2022), but the path from there to improvement in PTSD has not been shown. Safety 4, because the studies reported no deaths and few severe side effects, but the FDA criticized incompletely recorded side effects, missing laboratory and ECG data and unreported events at two sites. Hype 3, because MDMA-assisted therapy was promoted as a breakthrough, while the FDA expert panel saw no demonstrated efficacy by 9 votes to 2 and approval was rejected. Use 4, because therapeutic use is limited to studies and, since 2023, to a small number of authorized psychiatrists in Australia. Direction mixed: strong effects in the studies, but unresolved questions about blinding, durability and safety recording.
The score rates the state of knowledge, not the substance. “Safety data 9” means well studied – not harmless. “Track record of use 9” means used long and widely – that is not proof of efficacy.
Subjective assessment by Biohacking Kompakt based on published scoring rules – not a scientific rating and not a medical recommendation. Rules and all ratings (German)
Frequently asked questions about MDMA-assisted psychotherapy
Does MDMA-assisted therapy work for PTSD?
In two phase 3 trials, PTSD symptoms fell by 24.4 and 23.7 points with MDMA plus therapy, and by 13.9 and 14.8 points with therapy and placebo. The difference is large. What is uncertain is how much of it is due to unblinding and expectation and how long it lasts.
Why did the FDA reject MDMA?
In August 2024 the FDA named three main reasons: side effects and pleasant effects were recorded incompletely, the effect was only documented up to week 18, and around 40 percent of participants had used MDMA before. It recommended a new double-blind trial with blinded long-term follow-up.
Where is MDMA therapy allowed?
In Australia, specially authorized psychiatrists have been allowed to prescribe MDMA for PTSD since July 2023. In the US it is not approved; according to MAPS, the application was resubmitted in August 2026. In the EU there is no approved product.
Is MDMA available as a therapy in Germany?
No. MDMA is listed in Schedule I of the German Narcotics Act and therefore can neither be legally traded nor prescribed.
What risks are known?
There were no deaths in the studies; severe side effects were more frequent under MDMA than under placebo. The FDA advisory committee named low blood sodium, missing cardiac and laboratory data, boundary violations in therapy and abuse as open questions.
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Sources
- Mitchell JM et al., Nature Medicine 2021 – MAPP1, MDMA-assisted therapy for severe PTSD, phase 3, 90 participants
- Mitchell JM et al., Nature Medicine 2023 – MAPP2, MDMA-assisted therapy for moderate to severe PTSD, phase 3, 104 participants
- Fares-Otero NE et al., Eur Neuropsychopharmacol 2026 – systematic review and meta-analysis of MDMA-assisted therapy for PTSD
- Vizeli P et al., Front Pharmacol 2022 – MDMA and the extinction of conditioned fear, crossover study in 30 healthy people
- FDA, Psychopharmacologic Drugs Advisory Committee, minutes of the meeting of June 4, 2024 on midomafetamine (NDA 215455)
- FDA, Complete Response Letter on NDA 215455 midomafetamine of August 8, 2024 (published via openFDA)
- MAPS, statement of August 10, 2026 on the resubmission to the FDA
- TGA (Australia), change in the classification of psilocybin and MDMA to enable prescribing by authorized psychiatrists from July 1, 2023
- German Narcotics Act (Betäubungsmittelgesetz), Schedule I – methylenedioxymethamphetamine (MDMA)
- WADA Prohibited List 2026, informational German translation by NADA – S6 stimulants, MDMA prohibited in competition
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Information only, not medical advice and not a usage or dosage recommendation. Prescription-only and unapproved substances belong in the hands of a physician. Last updated: 2026-10-07.