When I walked into Marcela Ot’alora’s office, I immediately wished I could pack up a small backpack of belongings and move in. With just enough of the underpinnings of your run-of-the-mill therapist’s office — jade plant, box of tissues, framed poster of a bald-headed child that might be a monk or an angel — it also felt like my brother’s Brooklyn studio apartment, with ratty Persian rugs overlaid on one another, a couch that was clean but bore the faint shadows of visiting bodies and a chrome and wooden stereo receiver on a small end table. It was easily the type of place you could imagine friends sitting on the floor, bowls of olives and tumblers of wine snug between tangled legs, having lazy what-does-life-mean conversation into the late hours. Which, I learned, wasn’t a far cry from what actually does happen there, only your friends are trained psychotherapists and the conversation is fueled by 3,4-Methylenedioxymethamphetamine (MDMA).
Ot’alora is the Principal Investigator (PI) of the Boulder Phase 2 pilot study of MDMA-assisted psychotherapy in subjects with chronic, treatment-resistant Post-Traumatic Stress Disorder (PTSD). The results from the experimental sessions held in her office from 2013-15 — and from similar Phase 2 studies in Charleston, South Carolina, Vancouver, Canada, and Israel — had an effect felt not just locally, but beyond. In November, the U.S. Food and Drug Administration (FDA) hosted staff and researchers from the study and gave the green light for application to start Phase 3 trials, the final stage of research needed before the FDA decides whether to approve MDMA-assisted psychotherapy as a prescription treatment for PTSD.
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When local psychiatrist Will Van Derveer was in medical school in the ’90s, he was taught MDMA was a party drug that had no medical use. However, he was curious enough to join the clinical trial as its study physician; only a medical doctor can dispense the Schedule I drug during treatment sessions. He quickly realized that he could gain greater insight into the drug’s potential if he stuck around after it kicked in.
“Administering doses of MDMA to participants is an important but rather dull role, compared with being a psychotherapist in the room with people rapidly resolving long-term traumatic memories,” Van Derveer says. “I did not want to miss out on the opportunity to learn all aspects of this unique method of healing PTSD.”
Traditional treatment of PTSD usually involves both pharmacological and psychological intervention, most often in tandem and most often over a long period of time. However, MDMA-assisted psychotherapy doesn’t operate on a “slow and steady” model but rather uses the administration of MDMA as a pharmacological adjunct to catalyze the psychotherapy during an eight-hour experimental session.
“MDMA creates conditions that are really conducive to treating PTSD,” Ot’alara says. “It lowers the activation in the left amygdala, the brain’s center of fear, so even if someone does feel fear, they also feel ‘OK, I’m afraid, but I can manage it, I can do it.’”
MDMA was patented in 1914 by the German chemical and pharmaceutical company Merck as an intermediate compound in the synthesis of other drugs. Literature shows that a number of psychiatrists and therapists in the U.S. and Europe have used MDMA as an adjunct to psychotherapy since the 1940s. According to an article in the Journal of Psychopharmacology, the drug was reported to “decrease feelings of fear while maintaining a clear-headed alert state of consciousness.” This “state of mind” was optimal for both patients and providers as they tried to sift through difficult subject matter.
Not unlike other psychedelic drugs that moved too quickly from laboratories into the hands of people seeking their own mind-altering experiences, MDMA showed up on the streets, cut with a filler like sugar, caffeine and amphetamines, going by the names Ecstasy or Molly. In 1985, MDMA was classified in the U.S. as a Schedule I controlled substance and since then has — literally — been sitting on the shelf, shrouded in skepticism.
The MDMA used in the Boulder study may have sat around gathering dust, too, were it not for the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit research and educational organization. In 1986, MAPS purchased the MDMA from a lab at Purdue University and since then has been undertaking a roughly $25 million plan to make the drug into an FDA-approved prescription medicine by 2021. MAPS is currently the only organization in the world funding clinical trials of MDMA-assisted psychotherapy for PTSD, and given the frequency of the debilitating condition and the failure of approved methods to treat it, a thorough investigation of its safety and efficacy could result in a more effective and secure treatment option.
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For most people, the patter of footsteps outside their apartment door wouldn’t raise an eyebrow — at most, maybe a lazy curiosity: neighbor, pizza delivery guy, visiting lover? For Allison Heistand-Phelps, they sounded an alarm.
“I’d be hiding in the bathroom for an hour because I wasn’t sure if they’re gonna break in and harm me in some way — even though in my heart I knew they probably weren’t — it was always the ‘what if?’” she says.
For most of her adult life — for all of it until very recently, in fact — Heistand-Phelps suffered from PTSD. It manifested in myriad ways — the hypervigilance associated with hearing someone outside her door being one, debilitating depression, body flashbacks and moodiness among others — that all conspired to derail her life before it had even begun.
The Diagnostic and Statistical Manual of Mental Disorders, used in the United States as the universal authority for psychiatric diagnoses, characterizes PTSD by a combination of three types of symptoms: hyperarousal symptoms such as hypervigilance, anxiety and sleep disturbance; intrusive re-experiencing of traumatic experiences, such as intrusive memories, nightmares or flashbacks; and avoidance symptoms, including emotional numbing and withdrawal.
Trauma itself is the origin of PTSD, but the brain is actually to blame for its insidious grasp on people’s lives. The exaggerated and uncontrolled fear response that characterizes PTSD originates in the amygdala. Once activated, the amygdala stimulates autonomic activity including increased heart rate, blood pressure and blood sugar — the processes responsible for the “fight or flight” response. Fighting or fleeing are good options when faced with real danger, but the body and mind can’t sustain the heightened level of physiologic stress for long periods of time.
Many treatments for PTSD are frequently ineffective because they circumvent this system, which is mostly unconscious, says Van Derveer.
“Most psychotherapies and approved medications such as cognitive therapy and Selective Serotonin Reuptake Inhibitor (SSRI) medication mostly target cortical brain areas that are not where PTSD lives.”
When I met Heistand-Phelps, she explained that living in the clutches of trauma isn’t really living at all.
“I didn’t know how much longer I could hang on,” she says. “It’s really hell on earth. It’s reliving some of the worst things that could happen to a human while trying to live at the same time.”
Heistand-Phelps went to therapy, tried a dozen medications, breathing exercises, “any and every” lifestyle modification, but found she could only manage her symptoms so much. An artist since childhood, the imagery of imprisonment was tattooed on all of her work. It wasn’t until a nurse practitioner suggested the MDMA study and Heistand-Phelps began to read about the treatment’s success that she felt a modicum of hope.
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Heistand-Phelps laughs when she recalls showing up at Ot’alora’s downtown office for her first experimental session with the study.
“I had never taken any drugs, I hadn’t even smoked a joint!” she says. “I had no idea what was about to happen to me, but I also felt like I could trust them because they seemed really caring, and all the interactions I’d had with the study people were very kind and warm.”
Although she couldn’t imagine what would happen once she took MDMA, the architecture of the study ensured that Heistand-Phelps wasn’t walking into the complete unknown. As with any trial, there was a rigorous screening process for participation and, more importantly, volunteers had three 90-minute preparatory sessions with a male/female therapist team before their first experimental session with MDMA.
Interested candidates were first screened via a scripted telephone interview to identify any exclusionary medical or psychiatric conditions (i.e., Borderline Personality Disorder). If they passed, they then moved to an outpatient setting for a comprehensive evaluation by an independent rater and a physician. Whereas volunteers hoped for unremarkable electrocardiograms and serum blood tests within normal limits, they did need one qualifier to be off the charts to be accepted into the study.
The Clinician-Administered PTSD Scale (CAPS) was used as the primary outcome measure in the study. To qualify for the study, volunteers needed a baseline CAPS score greater than 50 (signifying moderate to severe symptoms) following at least 3 months of prior SSRI treatment in addition to at least six months of psychotherapy. Heistand-Phelps’ pre-study CAPS score was 117, one of the highest of any study participant (the scale goes from 1-136).
Right before her first experimental session, Heistand-Phelps says, her “defeatist attitude” kicked in.
“I remember thinking ‘I probably got the placebo, I don’t deserve the real thing’ … and then I started to feel the medicine kicking in. ‘This is way different than anything I’ve ever felt.’”
She had received the “active” dose of MDMA (either 100 or 125 milligrams) versus the active placebo of 40 milligram. Although her dose wasn’t confirmed until both volunteers and therapists were unblinded after the second experimental dose, it seemed unlikely that a placebo could have enveloped Heistand-Phelps in what she describes as “the first true feeling I’d ever had of safety, love and being at peace with myself.”
“It felt like a hug but without the threat of someone harming you,” she says. “Loving, euphoric happiness in a deep way. The first session really got me to feel comfortable in myself and in my body, to feel a sense of safety I’d never felt before.”
MDMA stimulates the release of feel-good neurotransmitters like oxytocin, serotonin and dopamine, the catalysts for Heistand-Phelps’ sense of security. The MDMA, says Van Derveer, “helps people relax and more efficiently work through their traumatic memories in the psychotherapy with far less fear.”
During the experimental session, each participant’s therapist team stays with him/her for eight to 10 hours. Although they work as nurses, social workers and psychiatrists in the outside world, their role in the study is to monitor and respond to the participant’s experience during the session. If someone requests physical touch, like a hug or for their hand to be held, the therapists accommodate. If someone wants to put on headphones and listen to music, that’s encouraged as well. If a participant is spending too much time “inside,” the therapists might nudge them to share a thought. They also monitor each participant’s blood pressure and temperature every 30 minutes for the first four hours and every hour for the last four. When the session is over, the therapists leave, and participants spend the night with a volunteer night attendant. The next morning, the therapists return for a 90 minute integrative session, dissecting the process of “what happened,” says Ot’alora.
As written in the study protocol, the experimental dose is administered three times over a three-month period. Between doses, participants have weekly integrative sessions and daily phone calls. Although every participant noticed marked change after each session, Ot’alora says that no one asked for more MDMA after their participation in the study was complete.
“Participants have felt it’s this that worked — the team, the sessions, the setting,” says Ot’alora. “We’ve had amazing results after one year. People have gotten so much better. They continue to work, to grow, to live their lives so differently. What happens is that MDMA wears off but the feelings and connections don’t. You remember what it felt like to be peaceful, and that you can feel it again. You find a way to bring it back.”
For both those who suffer from the debilitating effects of PTSD, the dearth of effective treatment options isn’t just frustrating, it’s dangerous. According to the U.S. Department of Veterans Affairs, up to 22 veterans commit suicide daily, many of whom are currently receiving treatment for PTSD. Kevin Dryden, a local family medicine physician, feels the frustration from a provider’s perspective.
“The medications I can prescribe are variably helpful, but sometimes they don’t help at all,” he says. “PTSD isn’t depression, it isn’t anxiety, it isn’t a mood disorder, which is what those medications are for. It’s a different animal.”
Dryden is cautiously optimistic that MDMA could address some of the gaps left by traditional PTSD treatment, but he also wants to ensure that its safety is well-documented before it becomes an approved medicine.
“As with any medication, there can be negative side effects,” he says. “I wonder about the things you worry about with other amphetamines, like heart issues, as well as Serotonin Syndrome because it releases serotonin.”
Thus far, there have been no emergencies or adverse events during any of the experimental sessions in any of the Phase 2 studies. Rather, the evidence is mounting that the MDMA-assisted psychotherapy is both safe and effective, with several advantages over currently approved PTSD treatments. First, says Van Derveer, its success rate, in the small trials so far completed, is about three times better. Second, it has fewer side effects: only 7 percent of people drop out of the treatment compared to 30 to 40 percent in studies of medications for PTSD. Finally, people take MDMA three times, versus having to take a currently approved medication with more side effects often for several years. “If the Phase 2 results are replicated in Phase 3,” he says, “then we might soon have a tool for PTSD that is vastly superior to currently approved treatments.”
When the study team met with the FDA in November, they were armed with even more data to warrant further investigation into the treatment.
“After a year, we’ve had an average of 40-point drops in CAPS scores, which is a significant drop,” says Ot’alora. “Right now, out of 26 people, 20 of them no longer meet criteria for PTSD, three of them still meet criteria but had at least a 30-point drop, and the other three stayed around the same. We didn’t have anybody that got worse.”
In April, the study team anticipates formal approval from the FDA to proceed with Phase 3 trials. Starting early this summer, 10-12 sites across the country (Boulder included) will host six therapists to conduct MDMA-assisted psychotherapy with 20 participants per site. Ot’alora hopes that Phase 3 will be complete in two years, which inches the treatment option promisingly close to its anticipated approval date of 2021.
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When I met Heistand-Phelps a year after she completed the MDMA-assisted psychotherapy study, there was little evidence of the person that walked into Ot’alora’s office on the verge of giving up. When I shook her hand, it was warm. For years, her hands were always cold, a symptom her psychiatrist likened to her body’s response of shunting blood from the extremities because her brain was proclaiming threat. As we spoke, she smiled often and apologized for talking too much. In school, she tells me, she was painfully shy, teachers commenting on her report cards that they worried she wasn’t getting the material. And when she showed me her artwork from before and after the treatment, the stark black, white and linear forms of her earlier pieces blossomed into a tumble of color and femininity that characterizes her work today. She corrected me, though, when I wondered if she was unrecognizable to herself.
“It’s not like you’re a new person,” she says, “it’s just that now you’re able to shine through. It’s like having glasses for the first time after you’ve been blind your whole life.”