The U.S. Food and Drug Administration is considering whether to approve the use of MDMA, also known as ecstasy, to treat post-traumatic stress disorder, and an independent advisory committee of experts is scheduled to review studies on Tuesday and vote on whether the treatment is effective and whether its benefits outweigh the risks.
The committee will hear from Lycos Therapeutics, which has submitted evidence of clinical trials to gain regulatory approval to legally sell a drug that combines MDMA and talk therapy to treat patients.
Millions of Americans suffer from PTSD, including military veterans who are at high risk for suicide, and no new treatments for PTSD have been approved for more than 20 years.
What is MDMA?
Methylenedioxymethamphetamine (MDMA) is a synthetic psychoactive drug first developed by Merck in 1912. After being resynthesized by Bay Area psychedelic chemist Alexander Shulgin in the mid-1970s, MDMA gained popularity among therapists, with early studies suggesting significant therapeutic potential for a number of psychiatric disorders.
MDMA is an entactogen or empatogen that fosters self-awareness, empathy, and social connections. It is not a classic hallucinogen like LSD or psilocybin, which alter reality or cause hallucinations. Among recreational users, MDMA is commonly known as Molly or Ecstasy.
In 1985, as the drug became a staple of dance clubs and raves, the Drug Enforcement Administration classified MDMA as a Schedule I substance, meaning it has no accepted medical use and a high potential for abuse.
Are there any health risks?
FDA officials expressed concern about “significant increases” in blood pressure and pulse rate in some participants in Lycos' clinical trials, which they said posed a risk of “leading to cardiovascular events.”
Many experts in the field say the drug is generally safe and non-addictive in its pure form.
Side effects when MDMA is taken outside of a medical setting are often caused by adulterants such as methamphetamine or synthetic cathinones (also known as bath salts).
Some recreational users report feeling depressed for a few days after taking MDMA, possibly due to a temporary lack of serotonin in the brain, but experts say more research is needed.
What is the approval framework?
In 2017, the FDA granted MDMA-assisted therapy “breakthrough” status, a designation that indicates the drug's therapeutic benefits and is intended to shorten regulatory timelines.
The original application was sponsored by the nonprofit Multidisciplinary Association for Psychedelic Research, which earlier this year formed a for-profit entity, Lykos Therapeutics, to sell MDMA if it receives FDA approval.
The application poses an unusual challenge for the FDA, which doesn't typically regulate drug treatments combined with talk therapy, a key part of Lycos's treatment for PTSD.
An expert advisory committee is scheduled to review Lycos' clinical data, public comments, and staff analysis and make a recommendation to the FDA on June 4. The FDA often follows the committee's recommendations, and a final decision is expected in mid-August.
What does a therapy session involve?
According to a report published in the journal Nature Medicine, Lycos' clinical trials involved roughly 200 patients undergoing three eight-hour sessions, about half of whom received MDMA and the other half a placebo. Sessions were spaced 4 weeks apart.
Patients had three consultations to prepare for treatment and nine more to discuss what they had learned.
The latest drug trials found that more than 86 percent of subjects given MDMA experienced a noticeable reduction in the severity of their symptoms, with about 71 percent of subjects' symptoms improving to the point that they no longer met the criteria for a PTSD diagnosis.
Any regulatory approval would likely be limited. The drug was studied in sessions with a psychotherapist present, with a second therapist present for safety, given the patients' vulnerability. An FDA staff analysis suggested several limitations to the drug's approval, including administering it only in certain circumstances, monitoring patients, and tracking side effects.
However, doctors and therapists can still prescribe MDMA off-label, opening up the drug's potential to treat other illnesses such as depression and anxiety.
What are the chances of FDA approval?
While the two studies on which Lycos' application was based suggested that MDMA therapy significantly improved the condition of PTSD patients, an FDA staff report released last week highlighted flaws in the study design. Most notably, the report noted that a high percentage of participants could tell whether they had received MDMA or a placebo, a common phenomenon in many drug trials involving psychoactive compounds.
The Institute for Clinical Economic Review, a nonprofit that researches the costs and effectiveness of medicines, criticized the study, calling its findings “inconclusive.”
Overall, the FDA's analysis was largely positive, noting that participants “experienced statistically significant and clinically meaningful improvements in PTSD symptoms that appeared to persist for at least several months.”
Does MDMA have other uses?
There is a lot of ongoing research exploring MDMA’s potential to treat a variety of hard-to-treat mental illnesses, including obsessive-compulsive disorder and severe depression.
Dr. Joshua Gordon, director of the National Institute of Mental Health, said the early data on MDMA and other hallucinogens has shocked the psychiatric field, especially studies suggesting that lasting effects could be achieved after just a few treatments.
But he warned against getting too excited: “MDMA therapy can be at least as effective as other drugs, and the effects last for a while,” he said, “but it doesn't work for everyone. It's not a miracle drug.”