MIAMI — Adding methylenedioxymethamphetamine (MDMA), also known as ecstasy, to intensive psychotherapy appears to relieve posttraumatic stress disorder (PTSD), regardless of the cause, pooled data from six phase 2 studies show.

Dr Allison Feduccia

The pooled data from the trials showed that 53% of patients with chronic PTSD whose condition was resistant to other therapies were free of PTSD symptoms after undergoing MDMA-assisted psychotherapy sessions and that this relief persisted at 12-month follow-up.

"The findings were very remarkable. The treatment is not only durable, but patients continue to improve during the year that followed," Allison Feduccia, PhD, from the Multidisciplinary Association for Psychedelic Studies (MAPS) Public Benefit Corporation, Santa Cruz, California, told Medscape Medical News.

"We think this is because of the healing that has taken place during the psychotherapy sessions. People are able to go back to their jobs or improve their relationships. We see it as not a long-term treatment but more of an intensive psychotherapy, catalyzed by the MDMA, which allows them to overcome PTSD," said Feduccia.

The findings were presented here at the American Society of Clinical Psychopharmacology (ASCP) 2018 annual meeting.

No Hallucinations

The US Food and Drug Administration (FDA) recently granted breakthrough therapy designation to MDMA as an adjunct to psychotherapy for adults with PTSD, as previously reported by Medscape Medical News.

MDMA-assisted psychotherapy consists of three nondrug preparatory sessions that last 90 minutes each. These are followed by two or three all-day (8-hour) psychotherapy sessions in which MDMA is given. The 8-hour MDMA-assisted psychotherapy sessions are spaced a month apart.

"We set up a living room–type space, and patients work with a male and female therapy team for all of the sessions. During these sessions, they go through periods of listening to music with eye shades on, and then they will spend a lot of time speaking with the therapist about whatever is coming up for them related to the traumatic experiences they've had," Feduccia said.

"MDMA doesn't produce hallucinations, like LSD or psilocybin. It works more to release serotonin, dopamine, and norepinephrine, as well as oxytocin, and so it allows people to really experience an opening and a reduction of fear and arousal of the senses around the emotional injury," she said.

Neuroimaging studies in healthy individuals have shown that MDMA decreases activity in the amygdala and increases the connectivity between the hippocampus and the amygdala.

"That really speaks to the idea that it is probably reducing areas in the brain that have become overactive and not allowing someone to process a traumatic memory without a lot of overwhelming fear, so they are able to talk through what happened, gain new insights and perspectives, and there is forgiveness, acceptance. That is the premise of MDMA therapy," Feduccia said.

The sessions are long so people can enter deeply into their trauma with the support of the male and female therapy team, she added.

"It's a nondirective therapy. The therapists offer support. It's not like cognitive-behavioral therapy. It allows the person to access their own healing through going through the therapeutic healing process," Feduccia said.

Low Abuse Potential

The six trials included 107 participants with chronic PTSD. All had total score of 50 on the Clinician Administered PTSD scale (CAPS-4). Patients were randomly assigned to receive either active treatment with MDMA or placebo and psychotherapy.

The pooled data showed a significant reduction in total scores on the CAPS-4 from baseline (P < .001) among patients who received MDMA-assisted psychotherapy.

In the placebo group, which consisted of 31 patients, 23% no longer met PTSD criteria; in the MDMA-assisted group, 72 patients (53%) no longer met PTSD criteria.

In addition, MDMA-treated patients showed significant improvements in depression, as measured by the Beck Depression Inventory–II (P < .05), and sleep quality, as measured by the Pittsburgh Sleep Quality Index (P < .05).

The cause of PTSD, whether war trauma, childhood abuse, or sexual assault, had no bearing on treatment outcomes, Feduccia noted.

"Remarkably, at the 12-month follow-up visit, 68% of participants did not meet criteria for PTSD, demonstrating the long-term durability of this novel treatment," she said.

In addition, the participants reported gains in life outcomes, including enhanced relationships, increased effectiveness at their jobs, or ability to return to work.

MDMA has a very low potential for abuse in this context, Feduccia said.

"Even in a recreational type of setting, MDMA is considered to have low to moderate potential for abuse. Ecstasy tablets have a lot of other substances, not just MDMA. Also, this is given in a clinical setting. I don't know why they call this ecstasy. It involves a lot of hard work on the part of our patients to process what they have been through with the assistance of MDMA," she said.

Receiving FDA breakthrough designation was "huge," Feduccia said.

"We will be starting a phase 3 trial in August of 2018. These will be large-scale studies at 15 sites with about 300 participants. If we are able to replicate the results, then we foresee the treatment being approved by 2021. We are going to be applying for expanded access in about a year," she said.

Feduccia pointed out that there has been no government funding for any of these studies.

"We tried to get government funding but were not successful. We have raised all the money from private donations. We have now reached our fund raising goal for the phase 3 trials, which is $26 million. One of our board of directors gave $5 million dollars, and someone gave an anonymous donation of $4 million in bitcoins, and that put us over the edge."

Exciting Results...With Caveats

"I am certainly excited about these results, but there are many caveats to this excitement," Rebecca Hendrickson, MD, PhD, University of Washington, Seattle, told Medscape Medical News.

Dr Rebecca Hendrickson

"So far, this work has been done by a limited number of researchers who are very invested in this intervention working. The patient sample is small and from a self-selecting population and not necessarily representative of a more general patient population, and it is not yet clear how effective the blinding is likely to have been in these studies. Many interventions have very promising results at this early stage which do not hold up in larger trials, but as early results go, these are among the most exciting results coming out right now, and I very much look forward to seeing the results of larger trials," Hendrickson, who was not part of the study, told Medscape Medical News.

The PTSD field is at an interesting junction right now, Hendrickson noted. There are multiple highly effective treatments, she said.

"I would strongly encourage anyone who is considering seeking treatment for PTSD to do so. So many of my patients comment a few months into treatment that they wish they had sought treatment sooner, now that they realize how effective it is," she said.

On the other hand, she said, treatment does not work for everyone.

"Some people do not tolerate the trauma-focused psychotherapy options. Some people respond to our pharmacotherapy for PTSD, and some do not. And even for those who do respond to treatment, it is not uncommon for some symptoms, especially sleep problems, to linger. So new treatment options are absolutely needed," she said.

The results from these pooled data are particularly exciting for a several reasons, Hendrickson added.

"First, it seems likely that they may reach a population we have struggled to reach with other PTSD therapies. Second, effective pharmacologic augmentation to psychotherapy is an urgently needed area, both treatments that can decrease the initial distress that often accompanies psychotherapy for PTSD, and also treatments that can boost the immediate and long-term efficacy of the therapy.

"Obviously, treatments that can be completed in a limited period of time but provide durable improvement are the ideal we would all like to have available for patients, and I think this combination pharmacopsychotherapy option is one that has the potential to provide this ideal," she said.

Hendrickson emphasized that the results from this research should not be taken to mean that MDMA is safe to use outside of clinical studies.

"When patients ask about these studies, I tell them that these results address outcomes from the use of a carefully controlled amount of MDMA used a small number of times in a carefully controlled environment. These results do not suggest that recreational or casual use of MDMA should be presumed to be a treatment for PTSD."

Dr Feduccia is an employee of MAPS Public Benefit Corporation. Dr Hendrickson has disclosed no relevant financial relationships.

American Society of Clinical Psychopharmacology (ASCP) 2018. Abstract 3001456, presented May 30, 2018.

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