Michael Mithoefer, M.D.

The study is moving along smoothly and our results continue to be very promising...All the subjects who have received MDMA-assisted therapy thus far have experienced improvement in their PTSD symptoms.

MDMA-Assisted Psychotherapy in the Treatment of Posttraumatic Stress Disorder (PTSD): Seventh Update on Study Progress

Michael Mithoefer, M.D.

Seven years ago I began formal efforts with MAPS to pursue research investigating MDMA-assisted psychotherapy as a treatment for posttraumatic stress disorder (PTSD). As of February 2006, our study has now been underway for two full years. We enrolled the first subject in March 2004, more than three years after receiving Food and Drug Administration (FDA) approval and less than three weeks after approval from the Drug Enforcement Agency (DEA). Here’s where we are at the two-year mark:

• Eleven subjects have completed the study, and the twelfth subject is a month into the study.

• After receiving placebo in the first stage, two subjects have gone on to complete the open-label stage (which includes two MDMA-assisted psychotherapy sessions).

• A third subject who received placebo in Stage 1 is scheduled to return for the open-label stage in early March. • We submitted our annual review report to the Institutional Review Board (IRB) in January 2006. The IRB subsequently granted approval for another year.

• On February 6, 2006 our Data Safety Monitoring Board (DSMB) met to review the records for all six subjects who have enrolled since their last meeting. The DSMB reported that they did not have any concerns about the safety of the study, and recommended that it continue without modification. The DSMB is comprised of an MD, a PsyD, and a PharmD who are not otherwise involved in the study.

• We have completed telephone screening on 87 potential subjects.

• One potential new subject is scheduled for formal screening and two others are considering it.

• We have added newspaper advertising to our recruitment efforts. As required, the text of the newspaper ad was approved by the IRB. We don’t know yet how many new subjects we will enroll as a result of this advertising, which is quite limited because of cost. There are other local, non-MDMA PTSD research studies taking place at the medical school and at private, for-profit, research companies. To some extent, we are competing with their much larger advertising budgets. While I’m sure this competition for subjects has slowed down our recruiting, I’m confident that we will be able to find the additional nine subjects we need.

The study is moving along smoothly and our results continue to be very promising. As we ponder the initial data we have decided to ask the FDA and the IRB for permission to make two protocol changes:

1) To add a supplemental dose of 62.5 mg of MDMA (or placebo) two to two- and-a-half hours after the initial dose of 125 mg.

2) To add a third MDMAassisted psychotherapy session. All the subjects who have received MDMA-assisted therapy thus far have experienced improvement in their PTSD symptoms.

For some this improvement has been quite dramatic and for a few it has been less so. It is our impression that several subjects might have benefited from a supplemental dose of MDMA, and that several might have benefited from a third MDMA-assisted therapy session.

Because this is a small pilot study, we don’t expect to prove a statistical difference between doses or number of sessions, but we think these changes could yield useful information to guide future study design. Because ours was the first Phase II study we were very conservative in only asking for two MDMA-assisted therapy sessions and only a single dose of 125 mg of MDMA for each session. Since our initial protocol was approved, the FDA and relevant IRBs have approved an MDMA study at Harvard that will use a supplemental dose. The MAPS-sponsored MDMA/PTSD studies in Israel and Switzerland will use supplemental doses as well; the latter will also have three MDMA-assisted sessions. It’s gratifying to note that since my last Bulletin update the MDMA studies I refer to above have all received government approval or are on the verge of doing so. Thanks to MAPS’ coordination, I have had the opportunity to meet with all these researchers, as well as other psychedelic researchers from the US and Europe, on a number of occasions. The Harvard and Swiss teams have both come to Charleston to visit us and become familiar with the protocol that we are using to conduct our study. My wife and co-therapist, Annie, and I are also looking forward to a visit from the Israeli team very soon. We greatly value this collaboration with other researchers so geographically separated, but so closely connected in our shared desire to explore the therapeutic potential of MDMA-assisted therapy. •