Looking to the Future of MDMA-Assisted Psychotherapy

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CONFERENCE REPORTER

“There’s more to trauma than physicality,” Rachel Yehuda, PhD told attendees at the 2021 American Psychiatric Association (APA) Annual Meeting. “For decades we have been talking about how to integrate pharmacotherapy with psychotherapy. But we haven’t understood how to do it.”

For patients with posttraumatic stress disorder (PTSD), one possibility is combining therapy and mind-altering drugs, like 3,4-methyl​enedioxy​methamphetamine (MDMA), panelists explained.

Mark Bates, PhD, former branch chief for Psychological Health Promotion in the Department of Defense’ Psychological Health Center of Excellence, presented findings from 6 phase 2 trials of combined MDMA and psychotherapy in the treatment of PTSD.¹ The studies included 103 participants who had experienced treatment-resistant PTSD symptoms on average for more than 15 years.¹

Participants progressed through several types of sessions in all of the studies. First, participants and clinicians conducted an initial, 90-minute interview, preparing the participants for the MDMA-assisted sessions and discussing their PTSD. Then participants underwent 8-hour MDMA-assisted or placebo sessions. During this time, participants wore eyeshades and listened to music, and had the option of discussing their troubling experiences.

The participants who received MDMA experienced an altered mental state, which was believed to make the discussion easier on them as compared with those in the placebo group. “One of the most important features,” Bates said, “is this reduced fear response in combination with increased empathy, trust, and closeness. In the words of one participant, ‘it’s like being in a box full of puppies.’ You can actually feel safe to bring up things that were otherwise very uncomfortable.”

Participants and therapists debriefed for 90 minutes the day after the MDMA session. Integration, Bates explained, helps “the patients retrieve and consolidate much of what happened during the dosing session and integrate it into their daily lives.”

The results of the studies were encouraging, he reported. Among participants who received MDMA, 56% no longer met PTSD criteria by the end of the study and, at a 12-month follow-up, that number rose to 67%.¹ Mean change on participants’ Clinician Administered PTSD Scale (CAPS-IV) fell around 45 points. Meanwhile, 23% of participants who received the placebo did not meet criteria for PTSD by the end of the study.

Robert Koffman, MD, dug deeper into the science behind MDMA’s potential effects. “We really don’t know how it is that MDMA actually works,” admitted Koffman, first senior consultant for integrative medicine and behavioral health at the National Intrepid Center of Excellence. He noted research indicates that MDMA seems to create the exact opposite effects of PTSD: Whereas PTSD is associated with increases in amygdalar activity, heightened fear responses, decreased hippocampal activity, emotional numbness and distrustful hypervigilance, MDMA is associated with reduced amygdalar activity, increased hippocampal activity, reductions in fear and defensiveness, and higher feelings of safety and trust.² It may also allow for memory reconsolidation.³ In short, Koffman said, “MDMA increases access to these traumatic memories without the kind of flooding and emotional numbing characterized by the speechless terrors” that usually accompany PTSD.

However, Koffman noted the altered mental state induced by MDMA is not enough to achieve positive results. “What we are really discussing in this talk,” he said, “is the relationship between the drug and the therapy.” In addition, the therapy involves additional training to be successful, he cautioned. A therapist should not try to understand the patients’ problems rationally and then use specific techniques to change their situation; instead, he explained, therapist’ goal should be to mediate their patient’s access to deep states of their psyches and facilitate “a powerful transformational experience of a transcendental nature.”⁴

During the Q and A session Yehuda, who is director of the Center for Psychedelic Psychotherapy and Trauma Research at Mount Sinai School of Medicine, said that psychedelic-assisted psychotherapy raised important questions about the nature of psychiatric healing. “This is almost treasonous for a psychiatry meeting,” she admitted, “but the actual molecule and neurochemical effects are probably a lot less important to the healing than the fact that you have provided an opportunity to look at something that [the patient] couldn’t see, because it was either too painful or it was blocked.”

“The future is here,” Koffman concluded. Although MDMA is currently a Schedule 1 drug, the Multidisciplinary Association for Psychedelic Studies “fully expects MDMA to be rescheduled by 2023, possibly even by next year.”

In fact, MDMA treatments are about to pass another important milestone. Next month Nature Medicine will publish results of a phase 3 trial in which 67% of participants no longer met criteria for PTSD after 2 months of treatment with MDMA combined with thereapy.⁵

“We are so comfortable with our molecules and our neurochemistry,” said Yehuda. “But I know enough to know that the answers are not just in the molecule. It has to do with the entire healing process. The good news is that makes clinicians really important.”

References

1. Jerome L, Feduccia AA, Wang JB, et al. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl). 2020;237(8):2485-2497.

2. Mithoefer MC, Wagner MT, Mithoefer AT, et al. The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol. 2011;25(4):439-452.

3. Feduccia AA, Mithoefer MC. MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? Prog Neuropsychopharmacol Biol Psychiatry. 2018;84(Pt A):221-228.

4. Mithoefer, MD. A manual for MDMA-assisted psychotherapy in the treatment of posttraumatic stress disorder. Multidisciplinary Association for Psychedelic Studies. August 19, 2015. Accessed May 5, 2021.

5. Nuwer R. A psychedelic drug passes a big test for PTSD treatment. The New York Times. May 3, 2021. Accessed May 5, 2021.