Summary: Connecticut Magazine reports on the MAPS-sponsored Phase 3 trials of MDMA-assisted psychotherapy, honing in on the UConn Health site where Dr.Monnica Williams is leading the only clinical trial actively recruiting participants who experience race-based trauma. Dr. Williams elaborates on the importance of recognizing diversity within clinical trials, stating, “Therapy is very context specific — your participant or client, you understand them within the context of their culture, and because cultures are so different, there are a lot of different ways that people need to be understood.”
Originally appearing here.
This is “where the patients receive the MDMA,” Sara Reed says as she and UConn psychologist Monnica Williams lead me into a room in the main building at UConn Health in Farmington.
Here UConn researchers are conducting part of a phase 3 Food and Drug Administration clinical trial looking at a promising new treatment for post-traumaatic stress disorder. The treatment combines traditional therapy sessions with guided therapeutic sessions using MDMA, a psychoactive drug better known as ecstasy or molly. It has previously been shown to be effective in more than half of participants.
As I take a seat on the couch that patients use during treatments at UConn Health, Williams, the principal investigator in the trial, and Reed, study coordinator for the research, explain that this site is one of 15 spread across the U.S., Canada and Israel. At these sites a combined total of 200-300 people will participate in a double-blind study that is the largest ever to look at the potential for MDMA-assisted therapy treatments for PTSD. Participants will be given 12 non-drug therapy sessions, plus three full-day MDMA-assisted sessions.
Previously, phase 2 trials looked at 107 participants. After treatment with MDMA-assisted psychotherapy, 56 percent of participants no longer showed signs of PTSD when measured two months after treatment. One year later, that number had risen to 68 percent.
The phase 3 trial is expected to be concluded by 2020. If the study goes smoothly, MDMA treatments could be approved as early as 2021, a shocking prospect for a once-controversial area of medicine.
Until recently, MDMA studies and others involving drugs associated with recreational use and abuse were often casualties of the War on Drugs. Researchers, even at prestigious universities, risked ridicule and struggled to secure funding, doing largely unheralded work on shoestring budgets. But the past few decades have seen a tectonic shift in the acceptance of these treatments, and they may be on the way to becoming a part of mainstream science and culture.
Michael Pollan’s new book How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence was released in May and quickly became a bestseller. Though that work focused on hallucinogens such as LSD, it helped shine a national spotlight on the potential of various drugs traditionally associated with recreation. Elsewhere in Connecticut, researchers at Yale are studying ketamine, known as the street drug Special K, for its potential in treating depression.
A few years ago, Williams was among those skeptical of psychedelic treatments.
The research is sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit pharmaceutical company that studies psychedelic medical treatments. Williams was contacted by MAPS because members of the organization wanted help diversifying their study participants. One of Williams’ specialties is race-based trauma, and while she applauded the organization’s effort to work with diverse participants, she was wary of the treatment. “I didn’t know anything about it and it sounded pretty dubious when it was first explained to me,” she recalls.
Even so, Williams was curious. She read studies published in respected peer-review journals and learned that some of the top experts in PTSD treatment believed in MDMA’s potential. When she watched videos of real MDMA therapy sessions with real patients, her skepticism subsided.
“What impressed me more than even just the speed of their improvement was the treatment seemed very humane compared to a lot of the empirically supported treatments that we do now,” she says. These traditional therapy-based treatments include prolonged exposure therapy where PTSD is treated by having patients re-experience the traumatic event by remembering and engaging with it. “That treatment is very difficult because the clients have to recount their trauma in excruciating detail over and over again and then listen to those on tape every day. I imagined that I was going to see therapy for prolonged exposure with participants while they were under the influence of MDMA, but when I saw the videos, there was no prolonged exposure going on — it seemed like they were getting better on their own, and it seemed a little magical to me.”
MDMA’s potential in a therapeutic setting should perhaps be less surprising than it is. After all, before it was dubbed ecstasy and became a part of party culture, it was spread across America by psychologists.
MDMA was first synthesized and patented in 1912 by the pharmaceutical company Merck. The German company studied it on animals in 1927 and again in the ’50s, but concluded it had no potential medical benefit. That could well have been the end of the substance’s history if it wasn’t for Alexander Shulgin.
Equal parts mad scientist and shaman, Shulgin was a California biochemist whose fascination with mind-altering substances began in the 1960s. An acquaintance of Humphry Osmond, a British psychiatrist who coined the term “psychedelic,” Shulgin created one of the world’s first biodegradable pesticides for Dow Chemical. In exchange for the patent, Dow gave Shulgin leeway to experiment with mind-altering substances, though company officials eventually grew uncomfortable with the relationship and severed ties.
Later known by a variety of nicknames, among them Dr. X, Dr. Ecstasy and the “godfather of psychedelics,” Shulgin, who died in 2014, mostly operated within the law, if occasionally on its outermost edges. During his career, he created a dizzying array of compounds — close to 200, by his count — capable of dramatically altering human perception. These included “stimulants, depressants, aphrodisiacs, ‘empathogens,’ convulsants, drugs that alter hearing, drugs that slow one’s sense of time, drugs that speed it up, drugs that trigger violent outbursts, drugs that deaden emotion — in short a veritable lexicon of tactile and emotional experience,” The New York Times Magazine wrote in 2005.
The most famous compound of all was, of course, MDMA, which he rediscovered in 1976. After experimenting with it on himself, he thought it could be useful in reducing anxiety and have other therapeutic effects. He shared this idea with colleagues working in mental health and its use was initially spread by psychiatrists and psychologists, who reported it had benefits when used in conjunction with therapy.
MAPS founder Rick Doblin learned about the drug’s use as an adjunct to therapy in 1982, but by that point the drug had made its way outside the therapist’s office and onto the party scene. The compoun
d was criminalized by the Drug Enforcement Adminstration in 1985. A year later Doblin formed MAPS to continue the study of MDMA in an FDA-approved clinical setting.
Progress for the drug’s clinical use was slow but steady. Safety studies were conducted in the late ’80s, the first phase 1 study on humans began in 1996. Eight years later, the FDA and DEA approved the first U.S. clinical trial of MDMA in humans as an Investigational New Drug for the treatment of PTSD. That study’s positive results led to the phase 3 study in which UConn Health is participating.
Study participants in Connecticut and elsewhere are given MDMA in pill form. About 45 minutes after they receive the drug they start to feel its effects. Two therapists oversee the procedure, but the patient is not engaged with them for the whole 8-hour session. “We invite them to lay down and they put on eye shades and listen to music; we have headphones,” Williams says. “On average, participants may spend half of their time sort of quietly processing their experiences on their own and half of the time talking with the therapists.”
Often during treatments, patients are very emotional, sometimes crying, other times overcome with happiness. Videos of sessions released by MAPS show this. In one, a woman is crying tears of joy and seems euphoric as she describes her fears “dancing” between her and her therapist. In another session, an Iraq war veteran is calm but deeply reflective as he describes feeling more at peace. “Even if I try to think of Iraq and everything, I somehow feel, like, really peaceful about the fact that that’s my journey,” he says.
Members of the U.S. military have been watching the progress of the study with great interest, as PTSD is a major issue for soldiers. Some research sponsored by MAPS has looked specifically at veterans with PTSD. In addition, MAPS is also sponsoring research into ways MDMA might be used along with therapy to help adults with autism reduce anxiety. The organization also sponsors unrelated research looking at LSD-assisted psychotherapy and other forms of psychedelics and their potential in assisted therapy. Other researchers have begun looking into MDMA as a potential treatment for depression, the most common mental health disorder in the U.S.
Brad Burge, MAPS director of strategic communications, says it’s unclear exactly why MDMA seems to help in the treatment of PTSD, but there are various theories.
MDMA prompts the release of serotonin and dopamine in the brain, which together can help patients remember trauma and keep them motivated through long therapy sessions. MDMA also prompts the release of hormones associated with trust, bonding and intimacy. “MDMA, when it’s used in recreational contexts, is sometimes referred to as the ‘love drug’ and this is why,” Burge says. “It creates these feelings of intimacy, of love and trust in the people around you when you’re under its influence. In the context of therapy, it may help people feel more trusting of the therapist they’re working with.”
Finally, MDMA acts in the amygdala, a primal part of the brain associated with fear and the fight-or-flight response. “People with PTSD have a hyperactive amygdala on average,” Burge says. “MDMA actually turns down the volume of the amygdala. It directly reduces activity in the amygdala, we can see that in brain-imaging studies. … People can talk about the most terrifying experiences of their lives in a relatively calm and articulate way.”
UConn Health is the only site involved in the phase 3 studies where the staff is actively recruiting and looking at people of color.
“People of color are often very underrepresented in clinical research,” Reed says. The team at UConn is dedicated to changing that with this research, an important step to make sure the treatment works for people of various backgrounds.
Williams says, “If a treatment has been developed by white people and tested on white people, then we really don’t know whether or not it’s going to be appropriate or acceptable or useful or effective with people from a different worldview, different cultural experiences and different outlooks.” She adds, “Therapy is very context specific — your participant or client, you understand them within the context of their culture, and because cultures are so different, there are a lot of different ways that people need to be understood.”