MAY 2011
CLINICAL PSYCHOPHARMACOLOGY
pist. The participants reported benefits such as “enhanced self-understanding [and] insight into personal patterns or problems, greater selfconfidence or self-acceptance, lowered defenses [while] undergoing a therapeutic emotional process,” and “less negative thoughts or feelings.”
A study of MDMA We recently published the first completed phase 2 pilot study of MDMA as a therapeutic agent.16 This was a double-blind placebo-controlled pilot study of MDMA-assisted psychotherapy in 20 patients with chronic, treatment-resistant PTSD. MDMA was administered to carefully screened participants under direct supervision during two 8-hour psychotherapy sessions with male and female cotherapists, using a nondirective method of therapy that is currently being manualized.17 Nondrug psychotherapy sessions prepared participants for the MDMA sessions, and follow-up psychotherapy sessions helped them integrate their experiences.
sion. All had a similar improvement. This was a pilot study with a small total number of participants designed to test proof of concept and safety in a patient population. Despite this low power, the results did reach statistical significance. The results of a recently completed long-term follow-up showed that 2 patients experienced symptom relapse. However, most maintained symptomatic improvement for a mean of 3.5 years.18 This study was not designed to determine the mechanism of action of MDMA-assisted psychotherapy; however, our clinical observations, as well as our formal results, can be partially explained on the basis of the current understanding of the pharmacology of MDMA. Although we observed a wide range of individual variation in the nature of participants’ experiences during and following MDMA sessions, much of the beneficial effect fell into 1 of 2 categories, both of which were experienced at various times by most patients.
What is already known about MDMA (3,4-methylenedioxymethamphetamine) and its role in clinical psychiatry? Anecdotal reports of clinical use before it was placed in Schedule 1 have suggested that MDMA may have clinical utility.
What new information does this article add? This article discusses the promising results of the first completed clinical trial of MDMA as a potential psychiatric treatment.
What are the implications for psychiatric practice? Pending further research, MDMA may have a role as an adjunct to psychotherapy for posttraumatic stress disorder and other psychiatric disorders.
Standard outcome measures of PTSD symptoms—the ClinicianAdministered PTSD Scale (CAPS) was the primary measure—showed that the MDMA group had statistically clinically significant improvement compared with the placebo group, which had received the same psychotherapy (CAPS improvement, P = .015; clinical improvement, greater than 30%; CAPS reduction of 83% in MDMA group vs 25% in placebo group). Figure 1 shows the CAPS results at 2-month follow-up. Seven of the 8 placebo recipients elected to enter an open-label crossover continuation phase in which they received MDMA on 2 occasions with the same schedule of psychotherapy before and after each ses-
Overcoming obstacles to therapeutic processing of trauma. MDMA appeared to lower fear levels while increasing access to emotions in general—including painful emotions. This created an opportunity for patients to process painful, traumatic experiences while avoiding the extremes of either being overwhelmed by emotions or experiencing emotional numbing (both common features of PTSD). One of our study participants said: Without the study I don’t think I could have ever dug down deep, I was so afraid of the fear. In the sessions there was just no fear; that builds your confidence. When I tried in therapy before, it would send me into a tailspin.
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After an MDMA-assisted session, another participant told us: It’s like night and day for me compared to other methods of therapy. Without MDMA, I didn’t even know where I needed to go. Maybe one of the things the drug does is let your mind relax and get out of the way because the mind is so protective about the injury. Corrective positive experiences. During MDMA sessions, the experiences of the participants were often emotionally challenging, but in addition to these challenging, painful experiences, most participants, at other times in the sessions, also had positive, affirming experiences. They often experienced a sense of comfort and joy that they may not have felt for years, and they were frequently left with a more positive perspective about the world. Consequently, the cognitive distortions and unrealistic fears that had accompanied PTSD were corrected. For example, one man who had been sexually abused as a child told us that he had spent his adult life observing that other people were having an experience that he presumed must be what they called “happiness”—something he had not experienced and had always assumed he was incapable of experiencing. During his MDMA session, he felt happy for the first time in memory. Hopelessness was replaced by the conviction that happiness was no longer beyond his reach, and indeed, he then discovered the ability to feel happiness without MDMA. Many other participants felt this way as well. One woman said: I feel like I’m walking in a place I’ve needed to go for so long and just didn’t know how to get there. I feel like I know myself better than I ever have before. Now I know I’m a normal person. I’ve been through some bad stuff, but . . . those are things that happened to me, not who I am. . . . This is me, the medicine helps, but this is in me.
Possible mechanisms While the format of MDMA-assisted psychotherapy and the nondirective therapeutic approach we used are (Please see MDMA, page 38)