Michael Mithoefer, M.D.

Michael Mithoefer, M.D.

PROGRESS CONTINUES to be slow but steady. Since the last update (MAPS Bulletin, Autumn 2006), three more subjects have been enrolled, so we only need three more to reach our target of twenty. One potential subject is currently in the screening process and another is scheduled for screening in early November.

We now have final outcome data on the first person to complete a third MDMA-assisted session since the option for that session has been added to the protocol. She had a marked decrease in symptoms following three open-label MDMA sessions, after receiving placebo on two occasions during the double-blind stage of the protocol with little response. The second person to participate in a third session will have her final symptom measures in November. It is our impression that the third session was helpful for her as well. All results thus far are still preliminary, because the study is ongoing.

As allowed in the revised protocol, we have continued to administer a supplemental dose of 62.5 mg. of MDMA approximately two hours after the initial dose. There have been no adverse events resulting from this additional dose, and the fact that it extends the period of MDMA’s strongest effects seems to be helpful, though we do not yet have enough data to analyze whether that effect makes a difference in outcome.

We are nearing completion of this pilot protocol and are beginning to plan for the possibility of moving into FDA Phase 3 trials.

There has now been a second subject who had a strong response to placebo. She elected not to continue to the optional open-label MDMA Stage. We expected that the all-day intensive therapy sessions accompanying placebo administration along with all the non-drug follow-up therapy sessions would lead to significant response in some people in the placebo group. Preliminary data indicate, though, that our placebo response rate is within the general range seen in most psychiatric drug treatment research.

We have still not succeeded in recruiting any veterans with war-related PTSD, despite our Institutional Review Board (IRB)-approved postings to online veterans’ support groups. A volunteer recently offered to help us design and implement more sophisticated internet marketing, using a website linked to the MAPS home page. Once this is designed, we will need to get IRB approval to use it. In the hope of studying at least a few veterans, we are considering applying to the FDA and IRB to add a continuation of the study with five more slots open only to people with war-related PTSD. If this is granted, we will still consider the current pilot study to be completed when 20 subjects have finished, and will move forward with data analysis and publication of the results.

On October 19 we submitted a request to the IRB to do long-term followup research on people who complete the existing protocol. Currently, our final measure of PTSD symptoms occurs two months after the last MDMA-assisted therapy session. We are now proposing to re-administer the Clinician Administered PTSD Scale (CAPS) one year (or longer for subjects who have already completed the study) after the last MDMA-assisted psychotherapy session. This project will be conducted over the phone by Mark Wagner, Ph.D., the psychologist who conducts all of our screening and followup testing. We will also ask people to fill out a questionnaire to gather additional information about their experience following participation in the study.

In conjunction with this request to do long term follow-up, we also asked the IRB for a modification and clarification of their media policy regarding our study. Thus far, in keeping with the requirements of the IRB, we have asked subjects not to speak to the media until the entire study is over. We think it would be sufficient, and more reasonable, to ask subjects to refrain from speaking to the media only while their own active participation in the study is in process, rather than having to wait until the entire study is completed. This will be especially true if we extend the study by adding long-term follow-up.

The study’s Data Safety Monitoring Board (DSMB) will have its final meeting in December or early January, after the 15th subject has completed the final follow-up outcome measure, which takes place two months after the final experimental session. The function of the DSMB is to review partial data at various points of completion and to determine whether the study should continue as designed, continue in a modified fashion, or be halted due to safety concerns. The DSMB has already met four times-after two subjects had been enrolled into the study, after five subjects had been enrolled, and also following completion of the study by the 5th and 10th subjects. These previous reviews found no safety concerns and recommended that the study continue to recruit subjects.

It’s gratifying that, two and a half years after enrolling our first subject, we are nearing completion of this pilot protocol and are beginning to plan for the possibility of moving into FDA Phase 3 trials. It’s also exciting that para-llel MAPS-sponsored Phase 2 studies investigating MDMA-assisted psychotherapy for PTSD are moving forward on two other continents, in Switzerland and Israel. •