The Food and Drug Administration is weighing whether to approve the use of MDMA, also known as Ecstasy, for treatment of post-traumatic stress disorder.
But the agency’s independent advisory panel of experts reviewed studies on June 4, and overwhelmingly decided against endorsing the treatment. Although not required, the F.D.A. often follows the recommendations of its advisory committees.
A final decision is expected in mid-August.
Lykos Therapeutics submitted evidence from clinical trials in an effort to obtain agency approval to sell the drug legally to treat people with a combination of MDMA and talk therapy.
Millions of Americans suffer from PTSD, including military veterans who are at high risk of suicide. No new treatment for PTSD has been approved in more than 20 years.
What is MDMA?
Methylenedioxymethamphetamine (MDMA) is a synthetic psychoactive drug first developed by Merck in 1912. After being resynthesized in the mid-1970s by Alexander Shulgin, a psychedelic chemist in the Bay Area, MDMA gained popularity among therapists. Early research suggested significant therapeutic potential for a number of mental health conditions.
MDMA is an entactogen, or empathogen, that fosters self-awareness, feelings of empathy and social connectedness. It is not a classic psychedelic like LSD or psilocybin, drugs that can cause altered realities and hallucinations. Among recreational users, MDMA is commonly known as molly or Ecstasy.
In 1985, as the drug became a staple at dance clubs and raves, the Drug Enforcement Administration classified MDMA as a Schedule I substance, a drug defined as having no accepted medical use and a high potential for abuse.
Are there health risks?
Agency staff of the F.D.A. raised concerns about “significant increases” in blood pressure and pulse rates among some of the participants in the Lykos clinical trials, noting those were risks that could “trigger cardiovascular events.”
Many experts in the field say the drug is generally safe and nonaddictive in its pure form.
Adverse reactions associated with MDMA when taken outside a clinical setting are often caused by adulterants like methamphetamine and synthetic cathinones, often known as bath salts.
Some recreational users report a lower mood in the days after taking MDMA, most likely because of a temporary shortage of serotonin in the brain, but experts say that more research is needed.
What is the framework for approval?
In 2017, F.D.A. granted “breakthrough” status for the MDMA-assisted therapy. The status, an acknowledgment of a drug’s therapeutic promise, aims to shorten the regulatory timeline.
The original application was sponsored by the nonprofit Multidisciplinary Association for Psychedelic Studies, which created a for-profit entity, Lykos Therapeutics, to market MDMA should it win F.D.A. approval.
The application poses an unusual situation for the F.D.A., which does not typically regulate drug treatments that are paired with talk therapy — an essential part of Lykos’s regimen to treat PTSD.
On June 4, the advisory panel of experts examined Lykos’s clinical data, heard from the public and agency staff, who had released an analysis at the end of May. The expert panel rejected the application, citing concerns over effectiveness and safety.
What do the therapy sessions entail?
About 200 patients in the most recent Lykos clinical trial underwent three sessions — eight hours each — where about half were given MDMA and half were given a placebo, according to a report published in Nature Medicine. The sessions were four weeks apart.
Patients also had three appointments to prepare for the therapy and nine more in which they discussed what they learned.
The most recent drug trial found that more than 86 percent of those who received MDMA achieved a measurable reduction in severity of their symptoms. About 71 percent of participants improved enough that they no longer met the criteria for a PTSD diagnosis.
Any approval by the agency would probably be restricted. The drug was studied during sessions attended by a psychotherapist and for safety, by a second therapist, given the vulnerability of patients. The F.D.A. staff analysis proposed some limits upon the drug’s approval, including that it be administered only in certain settings, that patients be monitored and that adverse effects be tracked.
But doctors and therapists could still prescribe MDMA off-label, expanding its potential for treatment of other illnesses like depression or anxiety.
What’s next?
Although the two studies that underpin Lykos’s application suggest that MDMA therapy led to significant improvements for patients with PTSD, an F.D.A. staff report May 31 highlighted shortcomings in the study designs. Most notably, the report flagged the high percentage of participants who were able to determine whether they had been given MDMA or a placebo, a phenomenon common to many drug trials involving psychoactive compounds.
In rejecting the application, the advisory panel members also cited the lack of data on potential abuse of the drug and whether bias among the therapists and facilitators involved in part in the study had influenced participants to report positive outcomes.
Overall, the F.D.A. staff analysis was largely positive, noting that participants “experienced statistically significant and clinically meaningful improvement in their PTSD symptoms, and that improvement appears to be durable for at least several months.”
Lykos Therapeutics said it would continue working with the agency to address the concerns raised by the advisory committee on June 4.
“While we are disappointed in the vote, we are committed to continuing to collaborate with the F.D.A. with their ongoing review,” the company’s chief executive, Amy Emerson, said in a statement. “Today’s discussion made clear that there is an urgent need for new, effective and accessible therapies to address this unmet need for those living with PTSD.”
Are there other uses for MDMA?
There are a number of continuing studies exploring MDMA’s potential to treat a wide range of hard-to-treat mental health challenges, among them obsessive compulsive disorder and major depression.
Dr. Joshua Gordon, director of the National Institute of Mental Health, said that early data on MDMA and other psychedelic compounds has electrified the field of psychiatry, especially research suggesting that they can lead to lasting benefits after just a handful of treatments.
But he cautioned against too much hope. “MDMA therapy has the potential be at least as efficacious as other agents we have, and the effects can last a while,” he said. “But it’s not going to work for everyone. It is not a miracle drug.”