James Casey recalls having a fondness for fireworks while growing up on the outskirts of small towns in rural Louisiana and North Carolina. That was before his 2011 deployment as a U.S. Army medic to Kandahar, Afghanistan, where he was steadily exposed to the trauma of modern warfare. After he returned to the U.S. a year later at age 19, the sound of fireworks and similar blasts of noise produced ghastly images of the lifeless Kandahar patients who proved beyond his medical aid, mangled bodies that at times covered his entire field of view.
Like nearly 30 percent of Afghanistan and Iraq War veterans, Casey was diagnosed with post traumatic stress disorder, which he sought to quell with everything from medication to group therapy to hypnosis. Nothing worked. After 18 months Casey was ready to accept his PTSD as a life sentence, he says. Then he read about upcoming trials of MDMA-assisted psychotherapy for PTSD patients in Boulder, Colorado, where he was headed to study molecular biology.
“It gave me my life back,” he says, recalling the phase II trial organized in 2015 by the Multidisciplinary Association for Psychedelic Studies, or MAPS, in which Casey underwent three MDMA-assisted psychotherapy sessions over five weeks. “I did a year and a half of therapy before MDMA,” he says. “But with MDMA it was like a year and a half of the previous therapy in one day.”
On supporting science journalism
If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.
The speed and effectiveness of the psychedelic experience Casey describes has caught the attention of the Food and Drug Administration, despite the Drug Enforcement Administration’s 1985 classification of MDMA as a Schedule I substance—the murderer’s row of illicit drugs that include heroin and are deemed to have no medical value. This past August the FDA granted MDMA “breakthrough therapy” status in the treatment of PTSD, meaning it may provide a substantial improvement over existing therapies. The agency will work closely with MAPS—a privately funded research institute founded in Florida 31 years ago and based in Santa Cruz, California—to design and conduct phase III trials starting next spring. This marks the first time psychedelic-assisted psychotherapy will be monitored in phase III trials for possible prescription use.
The German pharmaceutical company Merck first developed MDMA (methylenedioxymethamphetamine) in 1912, during its search for a drug to control blood clotting. But the company soon abandoned the project. MDMA sat dormant until Alexander Shulgin, a research scientist for Dow Chemical, synthesized the psychedelic again in 1965. Shulgin soon began using the drug in self-trials, and concluded it was a powerful psychoactive with potential use for psychotherapy. By the mid-1970s a small network of psychiatrists was using MDMA informally in treatment. But the drug, known recreationally as ecstasy or Molly, was also turning into a staple of the global rave and club scene, and the DEA outlawed its use in 1985 amid the Reagan administration’s “Just Say No” to drugs campaign. It is just in the last few years that MDMA has witnessed a scientific resurgence, as academic institutions increasingly reevaluate the therapeutic potential of MDMA and other psychedelics including LSD and psilocybin.
Previous MDMA-assisted psychotherapy studies have shown great promise. A 2010 trial conducted in Charleston, South Carolina, with veterans, firefighters and police officers—a previously treatment-resistant group of people who had suffered PTSD for an average of 17 years—found that 83 percent of participants no longer met the criteria for PTSD after four months of the experimental treatment. MAPS-organized phase II studies showed similar results, with 68 percent of participants no longer meeting the PTSD criteria one year after the therapy.
“In terms of effectiveness, there is nothing else like it,” says Mark Haden, the psychedelic program officer at the British Columbia Center on Substance Use in Vancouver, Canada, who is helping design phase III trials for MAPS. Two medications often prescribed for PTSD—paroxetine and sertraline—have proved ineffective for many patients according to the National Academies. And the most common psychotherapy approach—prolonged exposure therapy, which gradually recreates the trauma so patients can confront it—takes years and suffers from high dropout rates. “MDMA-assisted psychotherapy is probably going to be the next standard of treatment for PTSD,” Haden says.
Other experts express more caution. Empirical evidence for MDMA therapy’s effectiveness is scarce and treatment guidelines remain experimental, they note, adding that the drug's safety also remains to be firmly established. “The work of Michael Mithoefer has been very impressive,” says Charles Grob, a psychiatry and behavioral studies professor at University of California Los Angeles, referring to the PTSD therapist who directed MAPS’ first phase II trials in 2004. “He’s demonstrated fairly impressive efficacy and reduction of PTSD symptoms, and even amelioration of the disturbance." Grob, who is not involved in MAPS research or trials, adds: “Time will tell whether it bears out in regards to maintaining strong safety parameters and demonstrating efficacy, but the preliminary evidence is quite good."
Little is certain about MDMA’s pharmacological mechanisms—a lack of information blamed largely on decades of DEA restrictions on research. The drug affects the brain by increasing the activity of neurotransmitters including serotonin, which helps regulate mood. It also increases levels of the neurohormone oxytocin, which scientists believe helps increase trust and reduce reactions to traumatic memories. Neuroscientists also think MDMA may reduce activity in the amygdala, the “fight-or-flight” response center of the brain, so people can confront traumatic memories—and talk through them in detail with a therapist—without feeling danger.
These scientific hunches may help explain Casey’s reaction to MDMA. “It was like this armor that I could put over myself. I could dive into the darkness of my traumatic experience and come out unscathed,” he says. “It really allowed me to wade through my subconscious and figure out the root causes for some of the problems in my life.”
Whereas phase II trials were about confirming MDMA’s effectiveness on a small group of patients, phase III will focus on reproducing those results on a larger sample size—between 200 and 300 participants—says Shannon Clare Carlin, manager of MAPS’ MDMA therapy training program. Phase III will also focus on collecting safety data in search of rare health risks that have not shown up in previous trials, such as potential adverse effects on a certain blood type or people with a rare gene. “The quality of the data and statistical significance from phase III is pretty much the main factor the FDA is going to look at to see if this therapy can be made into a legal medicine,” Carlin says, adding that MAPS has raised a little over $18 million of the $25 million needed to finance phase III trials.
In recent years MDMA has added to a renaissance of psychedelic research to treat a range of medical conditions. In a 2011 study researchers at the Johns Hopkins University School of Medicine found that psilocybin, the psychoactive compound found in some species of mushroom, had “life-changing” health benefits with minimal negative effects. Other studies have highlighted psilocybin as an overwhelmingly safe, effective treatment against tobacco and alcohol addiction. Carlin says that the MAPS trials have also shown MDMA to be fairly safe, and that MAPS is working to mitigate side effects such as jaw clenching and nausea in some participants.
Along with the drug’s physiological and psychoactive effects, Carlin and Casey both underline the importance of the psychotherapist’s role in MDMA therapy. Participants dictate the direction of the MDMA-assisted sessions, with the two psychotherapists on hand taking cues from each subject’s sensations, moods and speech. The therapists say they do not follow a strict agenda, and instead try to create the ideal environment and facilitate emotional processing so participants can achieve their own healing. Casey likens the effect to going through the depths of a dark cave. The MDMA is a “headlamp” that provides him with a limited view of the cave, he says, while the psychotherapists—who are more familiar with the psychedelic landscape—accompany him on his journey.
MAPS encourages therapists to undergo an MDMA session as part of their preparation for sitting with the patients. This FDA-approved training involves one placebo and one MDMA session, something MAPS finds invaluable to the training. “It’s interesting to do research and drug development with the FDA because it really doesn’t care how the drug works. They just care that it works,” Carlin says. “The FDA is looking for good science. If somebody shows them good data, that something works, they will seriously consider it.”