Psychedelic drug MDMA faces questions as FDA considers approval for PTSD

WASHINGTON — Federal health regulators are questioning the safety and evidence behind the first bid to use MDMA, the mind-altering club drug, as a treatment for PTSD, part of a decadeslong effort by advocates to move psychedelic drugs into the medical mainstream.

The Food and Drug Administration posted its initial review of the drug Friday, ahead of a meeting of outside advisers who could help decide whether MDMA — currently illegal under federal law — becomes the first drug of its kind to win U.S. approval as a medication.

In their assessment, FDA scientists said that patients who received MDMA and talk therapy showed “rapid, clinically meaningful, durable improvements in their PTSD symptoms." But they also called the research “challenging to interpret,” and questioned how long the benefits might last.

They said it’s difficult to know how much of the improvement came from MDMA versus simply undergoing intensive therapy, and also raised several safety concerns, including MDMA's heart risks and potential for abuse.

The outside experts will take a nonbinding vote on the drug’s overall benefits and risks during Tuesday's meeting. The FDA will make the final decision, likely in August.

Antidepressants are now the only FDA-approved drugs for post-traumatic stress disorder, which is closely linked to depression, anxiety and suicidal thinking and is more prevalent among women and veterans.

If approved, MDMA would be reclassified as a prescription medicine and made available to specially certified doctors and therapists. Currently, the drug is in the same ultra-restrictive category as heroin and other substances the federal government deems prone to abuse and devoid of any medical use.

MDMA, also known as ecstasy or molly, is the first in a series of psychedelics that are expected to be reviewed by the FDA in coming years. It’s part of a resurgence of research into the potential of psychedelics for hard-to-treat conditions like depression, addiction and anxiety. MDMA's main effect is triggering feelings of intimacy, connection and euphoria.

Companies are studying MDMA, psilocybin, LSD and other mind-expanding drugs for numerous mental health problems.

Until recently, psychedelic research was mainly funded by a handful of nonprofit advocacy groups, including Multidisciplinary Association for Psychedelic Studies, or MAPS. The company seeking approval for MDMA, Lykos Therapeutics, is essentially a corporate spinoff of MAPS, which conducted all the studies submitted for FDA review.

In two studies, patients received MDMA as part of an intensive, four-month course of talk therapy lasting more than a dozen sessions, only three of which involved taking the drug. The drug is thought to help patients come to terms with their trauma and let go of disturbing thoughts and memories.

The approach was studied in nearly 195 adults with moderate-to-severe PTSD who were randomly assigned to undergo the therapy with MDMA or with a dummy pill. Following treatment, patients who received MDMA had significantly lower PTSD scores and were more likely to be in remission.

But FDA reviewers noted that the vast majority of patients correctly guessed whether they had received MDMA or a dummy pill, making it “nearly impossible” to maintain the so-called “blinded” objectivity considered essential for high-quality drug research. The agency also questioned how long the drug's benefits might last. The studies tracked some patients for up to two years, but reviewers noted that about a quarter of patients quickly dropped out of the follow-up study, limiting the usefulness of the results.

The most common side effects of MDMA included headache, nausea, muscle tightness and decreased appetite. More serious issues included heart palpitations and elevated blood pressure, which FDA reviewers said had the “potential to trigger” life-threatening heart problems.

They also raised concerns about the potential for patients to abuse MDMA, which functions similarly to amphetamines and other stimulants.

While MDMA would be a first-of-a-kind approval, U.S. doctors and the FDA itself have already laid some of the groundwork for working with drugs that can cause intense, psychological experiences.

Hundreds of clinics across the U.S. already offer ketamine — the powerful anesthetic sometimes used as a party drug — to treat a host of ailments, including depression, anxiety, chronic pain and PTSD. The FDA has only formally approved the drug for use during surgery, but its availability allows doctors to prescribe it “off-label” for various mental and physical ailments.

In 2019, the FDA approved Johnson & Johnson’s proprietary form of the drug, Spravato, a nasal spray that treats severe depression. Similar to ketamine, the drug is offered at doctor’s offices and clinics where patients usually spend several hours reclining in a chair.