MDMA-assisted therapy for PTSD: what the two phase 3 trials reported, why the FDA declined approval in August 2024, and where it is lawfully prescribed.
MDMA-assisted therapy is psychotherapy in which MDMA is given alongside psychotherapy in supervised sessions, studied mainly for PTSD. In the United States the FDA declined to approve it in August 2024 and MDMA is Schedule I. The documents we reviewed describe US access only through clinical trials. In Australia, psychiatrists approved as Authorised Prescribers have been able to prescribe it for PTSD since July 1, 2023.
At The Psychedelic Journal, we reviewed the two published phase 3 trial papers, the FDA's complete response letter document, a Drug Topics report, the Code of Federal Regulations (CFR) and a New South Wales (NSW) Health page on October 20, 2026. This is a desk review of published documents, and nobody on this site has tested, handled or sourced MDMA. The legal status described here is as of October 20, 2026.
MDMA-assisted therapy is manualized psychotherapy delivered with MDMA in a clinical trial setting, and in the United States the FDA declined to approve it in August 2024. In the phase 3 trials, the comparison group received the same psychotherapy with a placebo. MDMA on its own is not the therapy, and the published papers describe both studies as randomized, double-blind, placebo-controlled phase 3 trials.
MDMA is listed in Schedule I, paragraph (d)(11), of 21 CFR 1308.11, and federal law does not recognize an accepted medical use for Schedule I substances. In August 2024 the FDA issued a complete response letter on Lykos Therapeutics' new drug application for MDMA capsules for PTSD. According to Drug Topics, the FDA said it could not approve the application based on the data submitted.
Since July 1, 2023, MDMA has been a Schedule 8 controlled drug in Australia when used for PTSD. Only psychiatrists approved under the Authorised Prescriber scheme may prescribe it there. If you are in the United States, you can search for a study with our clinical trial finder.
The documents we reviewed record FDA action only through August 2024. Check current FDA status on the FDA website. Our MDMA guide covers MDMA more broadly.
The phase 3 trials compared manualized psychotherapy given with MDMA against the same psychotherapy given with placebo. Both trials were published in Nature Medicine, the first in 2021 and the second in 2023. Mitchell and colleagues led both papers.
The first trial assigned 90 people: 46 to MDMA with therapy and 44 to placebo with therapy. The second trial randomized 104 people: 53 to MDMA-assisted therapy and 51 to placebo with therapy. By their titles, the first trial studied severe PTSD and the second studied moderate to severe PTSD.
Both trials measured symptoms on the CAPS-5, a clinician-rated PTSD scale, and counted how many participants no longer met PTSD diagnostic criteria. No dose or session schedule is given here.
If you are comparing MDMA-assisted therapy with other psychedelic research on this condition, read our psychedelic therapy for PTSD guide.
The first phase 3 trial, known as MAPP1, reported that more people in the MDMA group than in the placebo group no longer met PTSD diagnostic criteria at the 18-week assessment. Among people who completed that assessment, 28 of 42 (67%) in the MDMA group and 12 of 37 (32%) in the placebo group no longer met the criteria. That is a gap of 35 percentage points, measured in completer groups smaller than the 46 and 44 people first assigned.
On the CAPS-5, the mean change was -24.4 points in the MDMA group and -13.9 points in the placebo group. That is a difference of 10.5 points. The paper reports an effect size (Cohen's d) of 0.91, and the full text is on PubMed Central.
The paper reports that adverse events more common with MDMA were mostly transient and mild to moderate, including muscle tightness, decreased appetite, nausea, sweating and feeling cold. It recorded no increase in suicidality-related adverse events and no abuse-potential events in either group. This was a sponsored trial of 90 people, and the FDA advisory committee's concern about functional unblinding applies to this kind of design.
The second phase 3 trial, known as MAPP2, reported a larger drop in PTSD symptom scores with MDMA-assisted therapy than with placebo plus therapy. The CAPS-5 least-squares mean change was -23.7 with MDMA and -14.8 with placebo (P < 0.001), a difference of 8.9 points. The 2023 paper reports an effect size of d = 0.7.
By the end of the study, 71.2% (37 of 52) of the MDMA group and 47.6% (20 of 42) of the placebo group no longer met PTSD criteria. That gap is 23.6 percentage points, compared with 35 points in the first trial.
The authors report that common adverse events included muscle tightness, nausea, decreased appetite and sweating, similar to earlier studies. The trial excluded people at high suicide risk, people with comorbid personality disorders and people with underlying cardiovascular disease. The authors also noted that the superiority of MDMA-assisted therapy over selective serotonin reuptake inhibitors (SSRIs) cannot be assumed without a direct comparison. The full text is on PubMed Central.
The FDA declined to approve Lykos Therapeutics' new drug application for MDMA capsules for PTSD in August 2024, issuing a complete response letter. Drug Topics, reporting on August 9, 2024, said the FDA could not approve the application based on the data submitted. It also said the FDA asked for an additional phase 3 trial to further study safety and efficacy. The FDA hosts the August 2024 letter document.
Drug Topics also reported that the FDA's Psychopharmacologic Drugs Advisory Committee met in June 2024 and rejected the therapy. According to that report, committee members raised concerns about functional unblinding, adverse events (particularly cardiovascular effects) and the lack of data on abuse potential.
Lykos's chief executive, Amy Emerson, called the decision "deeply disappointing" and said many of the FDA's requests could be addressed with existing data, post-approval requirements or the scientific literature. We did not read the letter's full text, so none of its wording is quoted here. The account above comes from the Drug Topics report.
Our reviewed documents stop at 2024, so check current status on the FDA website before you rely on this page. An FDA approval would change the US answer on this page, so read the August 2024 decision as the latest event these sources record.
MDMA is a Schedule I substance under federal law in the United States, listed at paragraph (d)(11) of 21 CFR 1308.11 among the Schedule I hallucinogenic substances. Federal law does not recognize an accepted medical use for Schedule I substances. Our guides on whether MDMA is legal in the US and on how federal scheduling applies to psychedelics cover the federal framework in more detail.
In Australia, the Therapeutic Goods Administration (TGA) made MDMA a Schedule 8 (controlled drug) substance from July 1, 2023, when used for PTSD. The same change covered psilocybine for treatment-resistant depression. For any other use, both remain Schedule 9 and are limited to medical and scientific research, including clinical trials.
NSW Health says only psychiatrists authorised under the Authorised Prescriber scheme may prescribe them. A registered psychiatrist needs approval from a Human Research Ethics Committee, then from the TGA, and a separate NSW approval to prescribe and supply. None of the documents we reviewed says how many patients have been treated. They describe no pathway for people outside Australia.
For other countries, our guide on where MDMA is legal sets out the status country by country.
The phase 3 evidence for MDMA-assisted therapy comes from two sponsored trials with small samples of 90 and 104 people. The second trial excluded people at high suicide risk, people with comorbid personality disorders and people with underlying cardiovascular disease. Its authors noted that MDMA-assisted therapy cannot be assumed superior to SSRIs without a direct comparison.
Both papers list muscle tightness, nausea, decreased appetite and sweating among the adverse events seen with MDMA, and the first also lists feeling cold. The FDA advisory committee, as reported by Drug Topics, named cardiovascular effects and missing abuse-potential data among its concerns.
Combining MDMA with serotonergic medicines such as antidepressants is a recognized interaction concern. If you take an antidepressant, leave every decision about it to your prescribing clinician. Our MDMA and SSRI guide explains the interaction. The psychedelic medication safety guide covers other medicines.
MDMA is not to be taken outside an authorized channel; the sources reviewed describe a clinical trial in the United States and an Authorised Prescriber in Australia. None of the documents we reviewed gives a dose, preparation guidance or a safety record for use outside trials. If you are looking for a trial, start with our clinical trial finder.
MDMA-assisted therapy is psychotherapy in which MDMA is given alongside psychotherapy in supervised sessions, studied mainly for PTSD. In the phase 3 trials it meant manualized psychotherapy delivered with MDMA, compared with the same psychotherapy delivered with placebo. MDMA on its own is not the therapy.
In the sources reviewed, MDMA-assisted therapy is not an approved treatment in the United States (the FDA declined in August 2024), and MDMA is a Schedule I substance under 21 CFR 1308.11. Federal law does not recognize an accepted medical use for Schedule I substances. The documents we reviewed describe US access only through clinical trials.
No FDA approval appears in the sources reviewed, which run through August 2024. In August 2024 the FDA issued a complete response letter on Lykos Therapeutics' application for MDMA capsules for PTSD and, as reported by Drug Topics, asked for an additional phase 3 trial.
In Australia, MDMA has been a Schedule 8 controlled drug for PTSD since July 1, 2023, and psychiatrists approved under the Authorised Prescriber scheme may prescribe it. For other uses in Australia it remains Schedule 9, limited to research including clinical trials. The site's guide on where MDMA is legal covers other countries.
In the first trial, 67% of MDMA-group completers and 32% of placebo-group completers no longer met PTSD criteria at 18 weeks. In the second trial, the figures were 71.2% and 47.6% by the end of the study. Both were sponsored trials with small samples, and the FDA advisory committee raised concerns about functional unblinding.
The documents we reviewed describe US access only through clinical trials. If you are looking for one, the site's clinical trial finder tool is a starting point. The second phase 3 trial excluded people at high suicide risk, people with comorbid personality disorders and people with underlying cardiovascular disease. The sources reviewed describe no US access pathway outside a trial.
Combining MDMA with serotonergic medicines such as antidepressants is a recognized interaction concern. If you take an antidepressant, every decision about it belongs with your prescribing clinician. Do not change a medicine without that clinician. MDMA is not to be taken outside an authorized channel, and the site's MDMA and SSRI guide covers the interaction.
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