How MDMA Went From Club Drug to ‘Breakthrough Therapy

As the director of addiction psychiatry at NYU Langone Medical Center, Stephen Ross spends most of his time helping people quit drugs. But early next year, he will begin administering MDMA in his “dosing room,” a chamber in Dr. Ross’s medical research lab that resembles a comfortable living room, with a gong on the wall and ceramic mushrooms decorating the shelves. After ingesting a 125-milligram capsule of the drug, a patient will recline on a brown felt couch as Dr. Ross and a co-therapist conduct an eight-hour talk-therapy session.

MDMA, aka ecstasy, will still be an illegal drug when Dr. Ross begins these sessions. But it’s emerging as one of the most promising treatments for intractable post-traumatic stress disorder. In Phase II clinical trials, which ended in November 2016, more than two-thirds of patients attained “sustained remission” of their PTSD after three MDMA-assisted therapy sessions. Based on those results, the FDA approved plans for Phase III trials, which will be led by 80 licensed therapists around the country, including Dr. Ross.

In August, the agency went a step further, giving MDMA a Breakthrough Therapy Designation, which puts it on a fast track for review and potential approval. The coming Phase III trials are the last step in the drug’s long, quixotic journey to prescription medicine.

If MDMA is medically legalized, it will be more tightly controlled than most pharmaceutical drugs. Unlike opioids and medical marijuana, MDMA won’t be available at a pharmacy. No one will go home with a bottle of ecstacy pills, making resale impossible and reducing the possibility of abuse. The drug will be prescribed only as part of an inpatient therapy program and exclusively for the treatment of PTSD. About 8% of Americans—24.4 million people—suffer from the disorder, but that rate more than doubles for veterans. “This is a very hard-to-treat disorder,” Dr. Ross says. Traditional talk therapy risks retraumatizing the most severe cases, and the only two drugs approved for PTSD treatment—Zoloft and Paxil—alleviate symptoms but don’t treat the underlying condition. They also require daily use for long periods. “That,” Dr. Ross says, “isn’t a fix.”

MDMA was first synthesized in 1912 by the German pharmaceutical giant Merck in an attempt to develop a blood-clotting drug similar to one made by rival Bayer. MDMA failed at that task, and Merck chemists were unable to find another commercially viable application.

In 1976, Alexander Shulgin, an American chemist in Berkeley, Calif., resynthesized the compound, tested it on himself and theorized that its disinhibiting effects would be useful in therapy. Research has shown that MDMA suppresses the amygdala, the brain’s primal fear center, and activates the frontal cortex, where executive function is housed—a combination that allows negative emotions to be processed in a more considered and less painful manner. The therapist George Greer published the first reports of MDMA’s pharmacological effects in 1978. MDMA, he wrote, “has great potential as a tool for human development and consciousness research” and “can enhance psychotherapy and personal growth, and occasionally relieve psychosomatic symptoms, when taken in a supportive setting with an open and willing attitude.” By the early 1980s, hundreds of therapists were providing MDMA to their patients to treat numerous disorders, including depression.

At the same time, the drug found another eager audience: club-goers, who nicknamed it ecstasy. But the feelings of euphoria, energy and emotional warmth that give MDMA its “hug drug” reputation belie serious physical risks. The drug has amphetamine properties and elevates both blood pressure and pulse rate, which are dangerous for people with underlying cardiovascular disease. Deaths from recreational use typically occur when users get dehydrated and overheat. Fatal incidents at all-night raves caught the government’s attention, and in 1985, the Drug Enforcement Administration classified MDMA as a Schedule I drug. Any therapist caught administering it risked loss of license and jail time.

Rick Doblin, 63, has been working for most of his adult life to change that. In 1982, Doblin was a small-time contractor living in Florida. He encountered MDMA for the first time at the Esalen Institute, a retreat center in Big Sur, Calif., and later tried the drug with a girlfriend. “The love and empathy generated by MDMA, along with self-compassion, were qualities that cried out to be studied,” Doblin says. Two years later, he watched a patient suffering from PTSD undergo MDMA-assisted therapy. “That completely persuaded me of its therapeutic potential,” Doblin says.

A police officer holds a MDMA tablet.Photo: Fernando Vergara/Associated Press

In 1985, Doblin learned that the DEA was moving to ban the drug. He abandoned his contracting business and founded a nonprofit—the Multidisciplinary Association for Psychedelic Studies—to fight the prohibition. His attempts failed, but in the process Doblin became a spokesman and an advocate for the use of psychedelics in therapy—giving interviews, lobbying government officials, raising funds and filing petitions.

From 1986 to 1988, MAPS applied five times to conduct human trials using MDMA but was rejected each time by the FDA. Undeterred, Doblin enrolled at Harvard’s Kennedy School of Government in 1988 to learn how to better work inside the federal bureaucracy, and he wrote his thesis on the regulation of the medical uses of psychedelic drugs.

He wanted to create safe, effective clinical trials for MDMA, and in 2000 he met Michael Mithoefer, a therapist specializing in PTSD. Mithoefer had grown frustrated by the available treatments. “What I was seeing is that people either drop out because they can’t tolerate the therapy, or they do it and it doesn’t work,” he says. He wasn’t sure that MDMA was the answer, but anecdotal results from the preprohibition years were encouraging, and Mithoefer was looking to study psychedelics as a component of psychotherapy. He had resigned himself to doing this abroad, possibly in the Caribbean, but Doblin convinced him that they should do further research together in the U.S.

Mithoefer and his wife and co-therapist, Annie, conducted the first MAPS-funded Phase II trial in 2004, which used MDMA to treat PTSD in victims of rape and childhood sexual abuse. These were patients with chronic cases that had proved resistant to other treatment methods. A second group, made up of veterans, firefighters and police officers, followed. A later study focused on survivors of life-threatening illnesses.

One of those survivors was Andy Gold, a corporate lawyer from Oakland, Calif. When Gold got cancer during the biggest case of his life, he powered through the treatments and the trial, suppressing the trauma of his near-death experience to focus on his work. He beat cancer but subsequently lost all enthusiasm for work and life. He describes his MDMA-assisted therapy sessions as a series of bunker-busting bombs that broke away layers of scar tissue around his trauma. “It’s not a magic pill,” he says. “It’s not like an antibiotic that kills and you’re cured. But I do think it has had a lasting benefit. I feel lighter. A fair amount of the malaise is gone.”

Therapists refer to MDMA as an empathogen—something that enables patients to feel empathy not just for others but also for themselves. “They take the MDMA and have this expansiveness,” says Julane Andries, a therapist who treated Gold during Phase II trials. “They’re not feeling fear. They’re not feeling shame. They’re not feeling anger. They can look at themselves and have compassion.”

Of the 90 people who completed the 12-month follow-up after Phase II, 68% of them “did not meet PTSD criteria,” according to the study results MAPS submitted to the FDA. Of the remaining third, many had some reduction in symptoms but were still troubled by the condition.

The physical risks of MDMA—dehydration, overheating—are mitigated during therapy sessions, where patients are monitored and liquids are regularly administered. Patients with uncontrolled hypertension are ineligible for trials, as are those with a history of psychosis or borderline personality disorder. There are subtle psychological risks too. “Like any other deep therapeutic experience, this can stir things up,” Mithoefer says. This concerns Doblin more than the physiological dangers. The worst thing that could happen, he says, is “a bunch of untrained therapists giving [MDMA] out….When patients take MDMA, PTSD emotions that have been suppressed come to the surface, and if people aren’t feeling safe and supported, they could end up feeling worse off. We think the real issue is managing psychological reactions.”

According to Doblin, one group that stands to benefit from MDMA is America’s veterans. The Department of Veterans Affairs estimates that 30% of Vietnam vets suffered from PTSD, and the condition is even more prevalent in those who’ve fought in Iraq and Afghanistan. By Doblin’s estimates, the VA spends $17 billion a year on disability payments for veterans with PTSD, payments that go on indefinitely when the condition doesn’t improve.

Doblin has met with the secretary of the Navy, an assistant secretary of defense and two executive directors at the VA. He found receptive audiences but was unable to persuade the VA or Department of Defense to fund research. (The VA and Pentagon both declined to comment for this article.)

Veterans are free to participate in trials on their own, and they will be a priority of the Phase III studies. Though no VA hospital will officially direct patients to MAPS, therapists affiliated with those hospitals may do so, and Doblin says many veterans are among the 18,000 who have volunteered for Phase III trials on the MAPS website.

The MDMA that MAPS has used so far comes from a single source, a kilogram manufactured in 1985 by Dave Nichols, a DEA-licensed medicinal chemist at Purdue. But with Phase III trials on the horizon, MAPS needed a new source that could produce the drug exactly as it will be made if MDMA is approved as medicine.

After getting bids from more than a dozen factories with licenses to produce Schedule I drugs, Doblin selected Onyx, in Manchester, England. He paid $4,000 for that first kilogram in 1985; the second one will cost $400,000. (Future batches will be less expensive; much of the cost is in testing procedures, analytical measures validations and paperwork for the FDA.) A further $600,000 will be needed for encapsulation at Sharp Packaging in Philadelphia and for testing things like moisture content and particle size.

Doblin predicts that MDMA will be approved by 2021. By that time, he will have spent 35 years and $60 million in donations on the legalization effort. He’s still fundraising for the Phase III trials, an effort which recently took him to Burning Man, the weeklong festival in the Nevada desert. But if MDMA is approved, MAPS can begin to generate revenue by manufacturing and distributing the drug to approved clinics. MDMA is an off-patent compound, meaning MAPS won’t get patent protection in exchange for its research investment. But in certain cases, the FDA grants five years of “data exclusivity” to groups that identify and prove new indications for off-patent drugs. This will give MAPS a five-year monopoly on MDMA manufacturing in the U.S. before anyone else can produce generic versions of the drug.

Unlike opioids, MDMA won’t be available at a pharmacy. No one will go home with a bottle of ecstacy pills.

The revenue from manufacturing MDMA could threaten MAPS’ nonprofit status, so Doblin spun off the clinical research division in 2014 into a public benefit corporation. As a B-Corp, it will pay taxes on income but favor social benefit over profit. Forming a B-Corp, Doblin says, “is another way to reassure regulators that if MDMA becomes a medicine, we’re not going to be like, ‘How do we roll it out as fast as we can?’ ”

If the drug is approved, the rollout will be limited by the number of DEA-certified clinics and licensed therapists who have been trained to conduct MDMA-assisted therapy. Doblin predicts that there will someday be thousands of these clinics, offering not just MDMA but also other psychedelics that were formerly banned substances. Esketamine, a synthetic version of ketamine (aka Special K), was awarded Breakthrough Therapy Designation in 2016 and is now in Phase III trials for the treatment of depression. Psilocybin, the active ingredient in magic mushrooms, isn’t far behind: Several Phase II trials for use as an antidepressant have successfully concluded, and a protocol for Phase III is scheduled to be submitted to the FDA next year.

Dr. Ross, who will conduct the Phase III MDMA trials at NYU Langone Medical Center, was one of the lead investigators for the Phase II psilocybin trials. The “dosing room” in his lab was created to help patients on psilocybin forget that they were in the sterile, fluorescent-lit confines of a hospital.

“Within five years, I would predict that ketamine, MDMA and psilocybin are available,” Dr. Ross says while staring at the couch where he will soon have given two of those three banned substances to patients. “I imagine you’ll have these holistic treatment centers that will treat a whole variety of psychiatric illness, and therapists will have the ability to use what they think fits the clinical situation. I think this could radically change psychiatry.”