MDMA Therapy: What the FDA Found
MDMA therapy reached the FDA in 2024 as the psychedelic movement’s flagship. The agency’s advisers voted 9 to 2 that the data did not show it works for PTSD and 10 to 1 that its benefits did not outweigh its risks. The FDA rejected it, citing trials no one was blind to, safety data the sponsor had trained therapists not to collect, and misconduct at a trial site that the authors knew about and did not disclose. Two years later the same application is back. Here is what the record says.
Lykos, now Resilient Pharmaceuticals, resubmitted the application in August 2026 without the new phase 3 trial the FDA asked for.
The FDA did not reject MDMA therapy on a technicality
It rejected it because the sponsor could not show the drug works, could not show it is safe, and had run its trials in a way that made both questions unanswerable. These are the FDA’s words, not ours.
“Although we do have two positive studies, these results are in the context of dramatic functional unblinding.”
David Millis, FDA reviewer, to the advisory committee, June 4, 2024
“It seems like there are so many problems with the data. Each one alone might be ok, but when you pile them up on top of each other, when you’ve got unblinding and there are tons of compounds, and the durability data, there’s not enough data on diverse populations or people with severe PTSD.”
Melissa Decker Barone, PsyD, VA Maryland, committee member, June 4, 2024
“The systematic training of not reporting ‘positive’ or ‘favorable’ effects as AEs raises concerns over the reliability of the safety data.”
FDA complete response letter to Lykos Therapeutics, August 8, 2024
“You have not demonstrated that the effect observed with midomafetamine is durable beyond the 18-week end-of-study assessments.”
FDA complete response letter, August 8, 2024
FDPS has no quarrel with a real trial of MDMA for PTSD. The 2024 decision was the system working: career scientists, an independent panel, overwhelming margins, no political motive. What has changed since is not the evidence. It is the people in the chairs, and a presidential order that cuts the review the panel relied on to one or two months. Our position is in Psychedelics policy: science first, no shortcuts.
Two phase 3 trials, 194 people, and almost nobody blind
MAPP1 and MAPP2 compared MDMA plus therapy against placebo plus the same therapy. The headline effects were large. So was everything that undermines them.
Share no longer meeting PTSD criteria at 18 weeks
MDMA plus therapy versus placebo plus therapy
MAPP1: 90 people, effect size d = 0.91. MAPP2: 104 people, d = 0.7. Note the placebo arms: a third to a half of people got better on therapy alone.
Mitchell et al., Nature Medicine, 2021; Mitchell et al., Nature Medicine, 2023
Who knew what they got
MAPP2 participants certain or thinking they knew their assignment
MDMA raises heart rate, blood pressure and body temperature and produces feelings no one mistakes for a sugar pill. The FDA: the studies “are nearly impossible to blind.” An unblinded trial measures hope as much as drug.
What the FDA found in the pooled safety data
The sponsor’s own briefing conceded that subjective drug effects “were not collected in the Sponsor’s Phase 3 program, unless they had been reported as AEs.” Euphoria, the thing that makes MDMA a drug people abuse, was not recorded as an outcome. The FDA: “Midomafetamine effects perceived as positive were not recorded.”
FDA briefing document, NDA 215455; Lykos sponsor briefing document
The complete response letter, in the agency’s words
The FDA signed its rejection on August 8, 2024 and made the letter public in September 2025. It asked for a new randomized, double-blind trial and an independent audit of every study record, including the session recordings.
- Safety data“Based on this failure to collect important information on ‘positive’ or ‘favorable’ events, and the unreported adverse events identified by FDA at the study sites, there are substantial concerns about the reliability of the safety data.”
- Efficacy“Approximately 40% of the enrolled participants reported prior use of midomafetamine, which is much higher than the background use”; together with unblinding, these limitations “preclude the ability to establish substantial evidence of effectiveness.”
- DurabilityNo effect shown “beyond the 18-week end-of-study assessments.”
- The fix“The most informative design would be a randomized, double-blind study,” plus “an independent third-party data audit of all study records and reports, including the recordings of the treatment sessions.”
FDA complete response letter, NDA 215455 (PDF); HCPLive on its public release, September 2025
The therapy the FDA cannot regulate
The product is not a pill. It is a pill plus many hours of a proprietary therapy. The FDA: “FDA does not regulate the practice of psychotherapy, and the Agency is limited in our ability to describe the elements of psychotherapy in product labeling,” and “the contribution of psychotherapy to the overall treatment effect observed in these clinical studies has not been characterized.” Committee member Paul Holtzheimer called the psychological intervention “a bit of a black box.”
The independent review agreed
The Institute for Clinical and Economic Review gave the evidence its lowest rating, “insufficient,” and declined to set a price: “we have substantial concerns about the validity of the results.” Stakeholders told ICER some participants felt pressured to report good outcomes and suppress bad ones. ICER’s David Rind: “the publicly available evidence is insufficient to assess the balance of benefits and harms.”
FDA briefing document; FDA transcript; ICER final evidence report, June 2024; ICER press release
What happened in the trial room
MAPS founder Rick Doblin wrote in his doctoral thesis that “the loving and trusting feelings that can be induced by MDMA can make patients more vulnerable to sexual pressure,” as The Guardian reported. Then it happened, in his organization’s trial.
Vancouver, site MP4
A participant in a MAPS phase 2 trial was treated by a married therapist team. Trial videos, reported by CBC, “show Dryer and Yensen cuddling, spooning, blindfolding and pinning down the clearly distressed woman.” After the trial the relationship with Richard Yensen “became sexual in nature,” in MAPS’s own words. Psychiatrist Donna Dryer resigned her license in 2023 with a formal reprimand for conflict of interest and boundary violations. Yensen was not licensed, so no board could act against him.
Three papers retracted
In August 2024 the journal Psychopharmacology retracted three MAPS MDMA papers: “The authors have subsequently confirmed that they were aware of these violations at the time of submission of this article, but did not disclose this information to the journal or remove data generated by this site from their analysis. Additionally, the authors also did not fully declare a potential competing interest.” Rick Doblin and his co-authors “disagree with this retraction.”
Committee member Elizabeth Joniak-Grant, at the June 2024 meeting: “I have real concerns with the validity of the data and the allegations of misconduct.” Walter Dunn, who voted yes on both questions, still conceded that “the greatest strength of the treatment is also its greatest liability, and that’s the therapists in the room.” When the panel voted no, the industry’s response was not a better trial. It was a public campaign against the panel’s members.
The drug outside the clinic
Approval would not stay in the clinic. It would rebrand ecstasy as medicine for two million Americans who already use it.
What NIDA and the DEA say
MDMA is Schedule I at 21 CFR 1308.11(d). NIDA: “Research suggests MDMA is potentially addictive”; users “can experience a dangerously steep rise in body temperature”; “Long-term MDMA use can also lead to heart problems or liver damage.” The DEA: hyperthermia can result in “liver, kidney, or cardiovascular system failure, swelling of the brain, and even death.”
Deaths, where they are counted
Deaths with ecstasy or MDMA on the certificate, England and Wales. The United States does not code MDMA separately in its death data.
Who uses it
Americans 12 and older used ecstasy in the past year in 2024 (0.7 percent); 22 million have tried it. The FDA’s review also noted illicit-use harms including hyponatremia, rhabdomyolysis, seizures and cases where MDMA “was used to perpetrate sexual assault.” A toxicologist on the panel: “we’re actually managing more and more severe cases of MDMA overdose.”
SAMHSA, 2024 NSDUH detailed tables; FDA briefing document; FDA transcript
An advocacy group that owns the drug company that runs the trials
MAPS was founded in 1986 to legalize psychedelics. Its drug arm took $100 million from investors and renamed itself Lykos. The organization whose mission is legalization also owns the company that produced the evidence.
- January 5, 2024MAPS PBC closes an oversubscribed Series A of “over $100 million,” led by Helena with the Steven and Alexandra Cohen Foundation and others, and becomes Lykos Therapeutics, “transitioning from a development-stage company to one focused on commercialization.” MAPS keeps ten-to-one voting power and six of eight board seats. Lykos release; MAPS
- August 2024The FDA rejects the application. Lykos lays off about 75 percent of its staff; Doblin leaves the board; the CEO resigns weeks later. BioSpace
- August 2025Lykos recapitalizes with $50 million and renames itself Resilient Pharmaceuticals. Doblin on the FDA letter: “There is a changing of the goal posts.” BioSpace
- August 2026Resilient refiles the application “without a new Phase 3 study,” after a 32-person phase 1 trial and an internal audit. Doblin: “We knew the FDA wasn’t saying no, just not yet.” Psychedelic Alpha; MAPS
The price of a course
per patient for MDMA-assisted therapy as delivered in the phase 3 trial, in 2020 dollars, by the sponsor’s own cost study. ICER modeled $23,117 for drug plus therapy.
Marseille et al., PLOS ONE, 2022; ICER, 2024
The stated destination
“It will take 10 years for the culture to really move to the point where we’re ready for a licensed legalization. That will be 2035.”
Rick Doblin, founder of MAPS, GQ, 2021
Doblin has also described a goal of “net-zero trauma by 2070” through “fully globalized access to MDMA-assisted therapy.” Medical approval is the on-ramp, and the founder says so. It is the medical marijuana playbook with a new molecule.
Undoing a 10 to 1 vote without new evidence
- December 2024 and May 2026The VA funds and then launches its first MDMA-assisted therapy trial since the 1960s, about 80 veterans in Providence and West Haven. Secretary Doug Collins: “Clinical use of these therapies outside of research will only be considered by VA once FDA approval is granted.” VA, 2024; VA, 2026
- FY2024 NDAA, Section 723Congress orders the Pentagon to fund trials of MDMA, psilocybin, ibogaine and 5-MeO-DMT in service members with PTSD or TBI, from Rep. Dan Crenshaw’s Douglas “Mike” Day Act. Public Law 118-31
- April 18, 2026Executive Order 14401 creates priority vouchers to cut FDA review of breakthrough psychedelics to one or two months, orders a Right to Try pathway and sets aside $50 million for state programs. Commissioner Makary: approvals grounded in “sound science and rigorous clinical evidence.” White House; Psychiatric Times
- August 2026The rejected application is refiled with no new phase 3 trial.
What FDPS is asking for
Hold the line the FDA drew. A new randomized, double-blind trial and an independent audit, as the complete response letter required. A one-month review cannot answer questions a four-year review could not.
Keep the advisory committee. Career scientists voted 10 to 1. Sidelining them is not a scientific argument.
No Right to Try end run. PTSD is not a terminal illness, and the pathway was never meant to move a drug the FDA just rejected into clinics.
Veterans deserve proven medicine. The VA secretary has it right: research first, clinical use only after FDA approval.
See also Is psilocybin safe?, Ibogaine: what the evidence shows and The Drug Report’s psychedelics coverage.
MDMA therapy and the FDA: common questions
Did the FDA approve MDMA therapy?
No. On August 8, 2024 the FDA issued a complete response letter rejecting Lykos Therapeutics’ application for MDMA-assisted therapy for PTSD and asked for a new randomized, double-blind phase 3 trial and an independent audit of study records. The company, renamed Resilient Pharmaceuticals, refiled in August 2026 without a new phase 3 trial. As of October 2026 MDMA remains a Schedule I drug with no approved use.
Why did the FDA reject MDMA therapy?
Its advisory committee voted 9 to 2 that the data did not show effectiveness and 10 to 1 that benefits did not outweigh risks. The FDA cited functional unblinding (about 94 percent of MDMA participants knew they got the drug), prior MDMA use by about 40 percent of participants, no evidence of durability beyond 18 weeks, incomplete cardiac and liver safety data, therapists trained not to record favorable drug effects as adverse events, and unreported adverse events found at study sites.
Did MDMA therapy work in the trials?
In the two phase 3 trials, 67 and 71 percent of people on MDMA plus therapy no longer met PTSD criteria at 18 weeks, versus 32 and 48 percent on placebo plus the same therapy. The effect sizes were large, but almost every participant knew which arm they were in, 40 percent had used MDMA before, three papers from the program were retracted for undisclosed misconduct, and the independent reviewer ICER rated the evidence “insufficient.”
What are the risks of MDMA?
In the trials, 46 percent of MDMA participants had a blood pressure rise of 20 mm Hg or more during a session, heart rate rose an average of 23 beats per minute, and the FDA found the cardiac profile “not well characterized.” NIDA describes MDMA as potentially addictive and warns of dangerous rises in body temperature, heart problems and liver damage. In England and Wales, 78 deaths in 2024 listed ecstasy or MDMA on the death certificate.
What was the misconduct in the MDMA trials?
At a Vancouver phase 2 site, a married therapist team was recorded cuddling, blindfolding and pinning down a distressed participant, and one therapist later had a sexual relationship with her; the psychiatrist resigned her license with a reprimand in 2023. In August 2024 the journal Psychopharmacology retracted three MAPS papers because the authors knew of the violations when they submitted, did not disclose them, kept the site’s data, and did not fully declare a competing interest.
What does FDPS want?
The new double-blind trial and independent audit the FDA asked for in 2024; the advisory committee process kept intact; no Right to Try end run for a drug the FDA rejected; and, for veterans, the VA’s standard of research first and clinical use only after FDA approval.
Related: Psychedelics hub · The psychedelic hype vs. the evidence · Who opposes psychedelic legalization · Is psilocybin safe? · Ibogaine: what the evidence shows · Arguments against psychedelic legalization · Drug facts
The FDA already answered. Let the answer stand.
Ten of eleven independent experts said the benefits do not outweigh the risks. FDPS is working to keep that judgment from being overturned by politics instead of evidence.
