Psychiatric Times. Vol. 28 No. 5

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Clinical Psychopharmacology

Does MDMA Have a Role in Clinical Psychiatry?

By Michael C. Mithoefer, MD | May 6, 2011

Dr Mithoefer is in private practice of psychiatry and clinical research in Mount Pleasant, SC. Dr Mithoefer reports that he receives funding from the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit organization for conducting research, protocol development, and training of other researchers, and for acting as medical monitor for other studies.

Risks of MDMA

MDMA administration carries psychological risks, such as increased anxiety, confusion, ruminations, and dissociation.^9,26,45 Our findings suggest that at the doses we used, these risks can be mitigated with proper preparation, a supportive setting during MDMA sessions, and good follow-up to facilitate integration. Some patients in our study had intense anxiety and needed reassurance during MDMA sessions, especially when the drug first took effect. Often in the days after an MDMA session, patients had second thoughts about what they had discussed during the session. With proper support, participants could successfully process these doubts and any accompanying emotions and could come to recognize these challenges as a meaningful part of healing. The fact that this close follow-up was necessary to address psychological difficulties underscores the potential problems that may be associated with MDMA in recreational settings.

In illicit settings, in addition to these psychological risks, the primary acute risks of ecstasy (which may contain varying amounts of MDMA and other substances) involve hyperthermia and dehydration or overhydration, with resulting water intoxication and cerebral edema. These complications are highly unlikely in a controlled research setting. MDMA predictably causes increases in pulse rate and blood pressure that could be dangerous for persons with underlying cardiovascular disease. We excluded patients with any serious medical problems and psychiatric problems such as psychosis, bipolar disorder type 1, and active addiction, and we did not encounter any drug-related serious adverse events.

Some controversy remains about adverse long-term neurocognitive effects in ecstasy users. Following their meta-analysis of cognitive functions of ecstasy users, Rogers and colleagues⁴⁶ cautiously concluded that the drug may significantly affect verbal memory, with a lesser effect on visual memory. However, results from other meta-analyses were somewhat contradictory.^47,48 A definitive conclusion about the adverse effects of MDMA remains elusive because of the considerable methodological challenges involved in studying illicit drug users; however, a very recent study by Halpern and colleagues⁴⁹ that was designed to minimize these methodological problems “found little evidence of decreased cognitive performance in ecstasy users save for poorer strategic self-regulation, possibly reflecting impulsivity … which may have been a pre-morbid attribute of ecstasy users.”

More germane to an assessment of the risks of clinical administration is the fact that there has been no evidence of memory loss or other adverse neuropsychological effects after administration of a few doses of pure MDMA in medical settings in phase 1 or phase 2 studies. In our 20 participants, we measured neurocognitive function before and after 2 doses of MDMA or 2 doses of placebo and found no indication of adverse effects.¹⁶ This is represented by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores shown in Figure 2.

It is important to point out that our safety data should not be taken to imply that there are no psychological and physical risks accompanying the use of ecstasy, or even pure MDMA in other settings, at higher and more frequent doses, and when used in an addictive pattern, which can be highly problematic. Like many of the drugs we use in medicine, MDMA can be dangerous when it is used inappropriately or when it is abused.

The future of MDMA in psychiatry

These early results provide encouragement that MDMA-assisted psychotherapy may prove to be a valuable treatment for PTSD. However, there is still a long way to go from promising phase 2 trials to the demonstration of safety and efficacy in much larger phase 3 studies, which would be required for FDA ap-proval of MDMA as a prescription medicine.

Additional rigorous clinical trials will determine whether interesting early results will evolve into clinical applications. Nevertheless, given the considerable clinical experience with MDMA before it was deemed a schedule 1 substance, the robust results in the first controlled trial, and the intriguing—perhaps unique—qualities of MDMA administered in the context of psychotherapy, it is likely that MDMA may find an important place in the future of psychopharmacology.

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by James OBrien | June 03, 2011 10:56 AM EDT

I think enough data is in on EMDR. How about a study of MDMA vs. Prazosin?

by Michael Mithoefer | May 28, 2011 10:52 AM EDT

I appreciate the comments of Rodrigo Figueroa and Jennifer Fauntleroy. I think a study comparing EMDR with MDMA-assisted psychotherapy would be worthwhile. Currently, the resources available for clinical trials of MDMA-assisted psychotherapy are directed toward the kinds of study designs that will be necessary for the FDA to consider approving MDMA for clinical use. If larger studies do lead to approval, then studies comparing MDMA-assisted psychotherapy to other methods of therapy will be important and will be easier to do. There is not an ethical problem in our current studies because we enroll only treatment-resistant patients who have failed to respond to previous treatments (in some cases previous EMDR), and if a participant is in therapy at the time of enrollment they may continue that same therapy during the study.
Michael Mithoefer

by Rodrigo Figueroa | May 21, 2011 7:17 PM EDT

And what about head to head EMDR plus MDMA vs EMDR plus placebo? MDMA alone could be against ethical standards, leaving sick people without an evidence-based treatment.

by jennifer fauntleroy | May 19, 2011 2:33 PM EDT

How about a head to head EMDR vs, MDMA?

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