The times they are a-changinā over at the Drug Enforcement Agency. After 50-odd years of clamping down on hallucinogenics like LSD, the DEA is quietly okaying the release of MDMA, another psychoactive schedule-I drug (street-named Ecstasy or Molly) for Food and Drug Administrationāapproved psychotherapeutic trials.
For decades, legalization advocates and healers have trumpeted the therapeutic benefits of the prosocial, fear-reducing MDMAāwhich, with its stimulation of hormones and neurotransmitters like oxytocin and dopamine, is known as āthe love drug.ā But psychopharmacologists were on the fence about its clinical benefits until a few years ago, when studies of the MDMA-assisted psychotherapeutic work of Michael Mithoefer were released.
Mithoefer, a clinical faculty member at the Medical University of South Carolina, has demonstrated remarkable early results using MDMA as a therapist-supervised treatment for chronic PTSD. His work is being approved by the FDA and could eventually clear a path for MDMA treatment clinics specializing in trauma. We caught up with Mithoefer between research trials to learn more.
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RH: How did you get interested in psychedelic treatment? Was it part of your clinical training?
MITHOEFER: I didnāt have any psychedelic training in my residency, but during that time Stanislav and Christina Grof trained me in Holotropic Breathwork, a meditative practice that uses breathing and music to activate natural inner healing and shift consciousness. It introduced me to the healing potential of nonordinary states of consciousness.
RH: The focus was on altered states of conscious, not necessarily with medication intervention?
MITHOEFER: Yes. In fact, my wife and I used this method of breathwork for 10 years with people before we started working on the first MDMA protocol in 2000.
RH: What tipped you off that MDMA might be a worthwhile treatment approach?
MITHOEFER: Several thousand psychiatrists and psychologists and other therapists were using MDMA in conjunction with therapy in the late ā70s, until it became illegal in 1985. I was aware of the controlled research and case reports from that time. Iād met with some of the psychiatrists whoād used it back then. Also, my wife and I had experienced it a few times ourselves in therapy, back when it was legal.
We knew it could be helpful in alleviating peopleās suffering, and saw how it could help them communicate with less defensiveness and more openness. I was treating a lot of people with PTSD, and we wanted to study its usefulness as a catalyst to psychotherapy. So unlike most drug studies, weāre not just looking at the effect of the drug: itās the experience in the therapy that we think is such an important part of the healing that MDMA can catalyze.
RH: Is MDMA the same thing as Ecstasy and Molly?
MITHOEFER: Ecstasy and Molly are supposed to be MDMA, but theyāre often not. I read one report from the Drug Enforcement Agency a year or so ago that said something like less than 20 percent of the Molly and Ecstasy confiscated on the street had any MDMA in it at all.
RH: Why is MDMA so helpful with communication?
MITHOEFER: Well, we know it causes a release of serotonin as well as other neurotransmitters, like dopamine and norepinephrine. It also causes increased levels of various hormones, including oxytocin, which is known to increase affiliation in animal models, and helps humans experience others in a less negative way. It makes sense then that MDMA could make it easier to communicate if people werenāt as sensitive to interpreting someone elseās expression as being threatening.
RH: Youāre saying the impact on the neurotransmitters can kind of smooth out communication and make things seem less fearful and threatening?
MITHOEFER: Thatās right. We also know that MDMA decreases activity in the amygdala. Thatās the fear center, and it increases activity in the prefrontal cortex, which is the higher processing center. In people with PTSD, thereās an increase in activity in the amygdala and decreased activity in the prefrontal cortex. MDMA has the opposite effect.
RH: So it allows people with PTSD to process trauma without the overwhelming emotional response?
MITHOEFER: Yes. Thereās also a concept in psychotherapy called the optimal arousal zoneāthe space between hypo- and hyper-arousal where the brain is alert but not threatened. It seems that MDMA gives people a period of time in a more optimal arousal zone, with less likelihood of being overwhelmed by fear. Theyāre also not dissociated or cut off from their emotions. They have a sense of connecting emotionally with what theyāre talking about, but without being overwhelmed by the emotion.
RH: Wow, that sounds pretty ideal: decreased fear, a relaxed amygdala, and prefrontal cortex firing. Why wouldnāt I want to be in that state of mind all the time? Whatās the downside?
MITHOEFER: This is not a daily drug at all. We give it only at three different times, a month apart. People usually feel physically tired afterward, as it takes a bit of a toll on the body. Most people need a day or so to recuperate and get their energy back. Itās not the kind of thing youād want to take all the time.
RH: What does the treatment look like?
MITHOEFER: First thereās careful medical, psychiatric, and psychological screening, which is done by outside psychologists. An independent rater does the measures; the clinician administered PTSD scale (CAPS) is our primary outcome measure. Thereās another outside physician who does some medical screening that involves lab work and an EKG to rule out people who have serious medical problems, especially cardiovascular disease, because MDMA does increase pulse and blood pressure. Then we have three preparatory therapy sessions to get to know people and prepare them for what the focus of the sessions will be. The sessions themselves last for eight hours. People arrive at 9:30 a.m., we speak to them a little bit first, and then we give them the MDMA or a placebo.
RH: It is a research study after all.
MITHOEFER: Yes. Our trials are all double-blind. And they all involve people who havenāt responded to prior treatment for PTSD. During that eight hours, there are always two therapists presentāmale and female. In our studies, itās myself and my wife. The therapists spend the whole day with a person, and we encourage alternating periods of inner focus, with periods of talking to the therapists when it feels right.
After we give people MDMA, weāll encourage them to focus inward. Often they use eye shades and headphones with music, if theyāre comfortable with those things. They spend time just focusing on their inner experience and then periodically coming out and talking to us. We check in with them every hour if they havenāt talked to us. Usually it ends up being about half the time talking to the therapist, and half the time focusing inward, in alternating periods. And we think itās the personās own inner healing intelligence that guides the process. So itās quite a nondirective approach.
If people are stuck, the therapists respond to whatās coming up. Iām trained in Richard Schwartzās Internal Family Systems (IFS) approach, so we may use elements of that. In fact, I did a substudy that showed that in a very high percentage of people, parts work comes up spontaneously, without having it introduced by the therapist. But generally, we try to see what each individualās process is and then support that.
RH: Youāre saying that the MDMA seems to allow the parts work to flow a bit more naturally?
MITHOEFER: People tend to start talking about their parts and have a lot of āSelf energy,ā in IFS terms. Theyāre able to unblend from troublesome parts and have more self-compassion. It seems to be very helpful for parts work.
RH: Are you trying to nudge the person into certain therapeutic directions?
MITHOEFER: We never say, āNow itās time to talk about your trauma.ā At some point, people just start talking about their trauma. Sometimes they spontaneously talk about psychodynamic issues, and other times they recognize cognitive distortions and do spontaneous cognitive-behavioral work. Sometimes itās parts work. We support whatever is coming up for that person.
RH: Your treatment varies from exposure therapy to people working through transference issues. Youāre kind of bridging the divide between the CBT world and the dynamic world with this work.
MITHOEFER: Thatās why we think itās good not to be too directive, because if we just recommend that people do imaginal exposure, for instance, we might miss other important things that come up. And you know, the luxury of having all that time is helpful.
RH: How do you conclude the eight-hour session?
MMITHOEFER: We focus on wrapping up and making sure people are in an okay place. We donāt necessarily summarize, because quite often people feel like they just want to be quiet and let the process continue to percolate. But they donāt go home: they stay in the clinic overnight with a night attendant. Thatās so they can have that time to let the process continue to unfold.
By 5:30 p.m., when the night attendant arrives, most of the MDMA effect has worn off, but people are still very connected to their experiences, so itās kind of nice that they donāt have to go home and talk to a lot of people. They can be pretty quiet. They rest. And the therapists come back and meet with them the next morning for an hour and a half before they go home.
RH: Any more follow up?
MITHOEFER: We talk to them every day on the phone for a week just to check in. And then we meet with them twice more for 90-minute integration sessions over the next several weeks, before the next MDMA session a month later. Our primary endpoint is actually after two MDMA sessions, and we get good results with that. But thereās some additional improvement after three sessions. So we do a total of three in most studies.
RH: Iād imagine even people in the placebo group, after spending eight hours of intense introspection and reflection, probably show some benefit.
MITHOEFER: Yes, they do. In our first study, we used an active placebo. The mean CAPS score was just under 80 at the beginning, at baseline, and the placebo group, after two eight-hour placebo sessions, had a 22 point drop in the CAPS. Thatās statistically significant. They were certainly better, but they still had severe PTSD. They still had a CAPS score of almost 60.
RH: How did that compare with the MDMA group?
MITHOEFER: The MDMA group had a CAPS drop of 55 points, compared to 22 with all the same therapy but without MDMA. In other words, MDMA-assisted treatment resulted in a reduction of PTSD symptoms two and a half times as much as that experienced in nonmedicated treatment.
Afterward, people whoād gotten the placebo could cross over and get MDMA with the same therapy. After a 22-point drop originally with just the therapy, that group received MDMA and had an over 30-point drop. So they ended up basically in the same place once they got MDMA, with the total of about a 55-point drop. And 83 percent no longer met criteria for PTSD in the MDMA group, compared to 25 percent for the therapy-only group.
RH: Some trauma treatment experts, like Bessel van der Kolk, say these results are comparable with all the best current treatments, like EMDR and trauma-focused CBT.
MITHOEFER: Yes, Besselās pretty enthusiastic about it. One thing we find is that people continue to improve with this treatment. That optimal arousal condition, given the therapy and the experience, continues to unfold. Itās not that people stay in that state all the time, but what weāve seen is that people can continue work with the process and follow up. We have three follow-up sessions after each MDMA session. Itās pretty interesting that the effect of the medicine wears off, but the effect of the therapeutic experience actually continues to grow. Weāve found many people have even lower CAPS scores at one year than they did at two months after their last session.
RH: Since itās an illegal or controlled substance, how can you conduct the research?
MITHOEFER: There are extra steps to doing research with a schedule-I drugāwhich means we not only need FDA and IRB approval, but DEA approval as well. Itās quite a major process to get all of the approvals, but it can be done.
RH: So whatās next for your research?
MITHOEFER: We sent all of our data to the FDA in November, and they gave us clearance to proceed to phase-III multicentered trialsāwhich is the last step before you can apply for a drug to become a legal medicine. Right now, weāve trained therapy teams for 14 sites for phase III, which will start early next year: 11 sites in the US, two in Canada, and one in Israel.
RH: If it becomes fully approved, this will be something thatās administered only by MDs, people who can already prescribe psychoactive drugs?
MITHOEFER: Any physician who can prescribe controlled substances will be able to prescribe the MDMA. But they wonāt have to be the only ones doing the therapy. Weāre talking to the FDA about this. What we recommend is to have it be limited to licensed MDMA clinics.
At one time, any physician could form a methadone clinic and get a license. So we think itās going to be like that: a place where theyāre set up to do it, with people who have the proper training to facilitate. It could be mostly nonphysician therapists, with a physician whoās responsible for the MDMA administration. Weāre predicting approval, possibly by 2021.
RH: Have you started training therapists?
MITHOEFER: We have an organized training program with an online component and then two in-person trainings: one for six days and the other for five. A lot of that is watching and discussing videos of sessions, with some self-study in between, followed by a period of supervision and feedback. Weāve trained more than a hundred therapists. Weāre going to need a lot more, so weāre always happy if people register their interest for the future trainings.
RH: What are you hearing from the traumatized people whoāve gone through these trials?
MITHOEFER: Many people have said they think it saved their lives, that they wouldnāt have survived much longer without it. They often say it changed their relationship to their emotions. So itās not that people never get anxious afterward, but theyāve had the experience of being able to process their emotions without being overwhelmedāwhich is an experience that many of them hadnāt had for a long time. Once theyāve had that with the MDMA, they felt it was a possibility to continue to have it. And they noticed that even though it wasnāt easy once the MDMA had worn off, it changed their feeling about being able to be present with their emotions in a very helpful way. One person said, āOne thing the medicine does is help your mind get relaxed and get out of the way, because the mind is so protective of that trauma.ā Thatās a pretty good description of what tends to happen.
RH: Anything else we should know?
MITHOEFER: A number of people have said they donāt know why they call this Ecstasy. Itās important to let people know that you donāt just get blissed out and everythingās fine. Even with the MDMA, like any therapy, when you process a trauma, itās painful. MDMA makes it possible to look at the trauma when it hasnāt been possible before. But it still can be painful.
RH: Thatās why a therapistās support is important.
MITHOEFER: Like any deep therapy, it can stir things up. People need to be prepared for that and have proper support to integrate all that comes up afterward. So the therapy is a very important component of it, including the follow-up sessions.
RH: Whatās the most important thing for general therapists to know about MDMA treatment?
MITHOEFER: Part of the challenge is educating people about this rather strange treatment. Once people are informed about it, and see the outcomes, it actually makes a lot of sense.
Ryan Howes
Ryan Howes, Ph.D., ABPP is a Pasadena, California-based psychologist, musician, and author of the āMental Health Journal for Men.ā Learn more at ryanhowes.net.