Looking back over nearly two years of extensive and exhausting experience with multiple IRBs, we are gratified to be able to report that significant improvements have been made in the protocol design.

These changes include:

1. Participants will be required to spend the night at the offices of Dr. Mithoefer after the end of each experimental (MDMA or placebo) session. They will be driven home after the completion of the non-drug therapy session occurring the day after the experimental session. A private room within the clinic will be provided for each subject after each experimental session. The room will be an office designated for that purpose and will be furnished with comfortable furniture and a sofa-bed. All records pertaining to the study and any other sensitive material will be securely stored in a separate area of the clinic.

2. A registered nurse will serve as an attendant during overnight stays. She or he will be the same gender as the subject and will be trained for the role by Dr. Mithoefer.

3. Near the end of each experimental session and immediately afterwards, the researchers (Michael Mithoefer MD and Ann Mithoefer BSN) will remain with the subject until they have concluded that the participant is emotionally stable. If a participant is extremely agitated or upset or appears to be in imminent danger of harming self or others, then the researchers will hospitalize the participant until he or she is stable.

4. The researchers will maintain daily contact via telephone with each participant for a week after each experimental session. Daily contact will increase the researchers' ability to monitor the mental health status and emotional state of the participant subsequent to each experimental session. 5. There will now be three members of the Data Safety Monitoring Board (DSMB). Dr. Mithoefer will not serve on the board. The DSMB will have scheduled meetings after the first five subjects have completed their first experimental sessions, again after these same subjects have completed their final follow-ups, after subjects 6-10 have completed their final follow-ups, and after subjects 11-15 have completed their final follow-ups.

6. Participants must meet additional qualifications in order to be enrolled in the study. They must not be diagnosed with borderline personality disorder, they must be literate, and they must have a CAPS score equal to or greater than 50. They must have had at least one unsuccessful attempt at treatment with a selective serotonin uptake inhibitor (SSRI) and one unsuccessful treatment with any form of psychotherapy for which there exist a controlled trial indicating efficacy in the treatment of PTSD. This includes cognitive-behavioral therapy (including exposure therapy), stress inoculation training, including anxiety management, and insight-oriented psychotherapy. Treatment with an SSRI must have lasted for at least three months, and psychotherapy must have lasted for six months and included at least twelve sessions.

7. Participants who are also patients of Dr. Mithoefer must have an interview with another psychiatrist not involved in the design or administration of the study before engaging in the informed consent process. This interview is intended to minimize any undue influence the principal investigator may have over the potential participant's decision to take part in the study.

8. Subjects will be stratified prior to randomization according to whether or not they have been Dr. Mithoefer's patients. This will ensure that the proportion of participants receiving MDMA will remain similar for patients of Dr. Mithoefer and for subjects who are not his patients.

9. After reading the consent form, participants will complete a 16-item quiz on information contained within the consent. This will allow the researchers to assess comprehension of study procedures, risks and other study related matters, and will allow the researchers to address any confusion on the part of the participant indicated by an incorrect response. 10. Participants will no longer undergo a blood draw to assess serum sodium at the end of each experimental session. The protocol contained this assessment as a means of detecting potential hyponatremia. However, concerns for participant comfort during the experimental sessions, and recognizing that at least three of the antecedents of hyponatremia will not be present in this controlled setting, we requested and received permission from the FDA and the IRB to omit the routine blood draw. A blood draw will only be taken if a participant shows signs of hyponatremia in the course of an experimental session.

11. During the final research follow-up conducted 3 months after the first experimental session, participants will complete the Reactions to Research Participation-Questionnaire-Short Form. This is a 24-item assessment of participants' experience of study participation, reasons for participation, and perceived costs and benefits of participation. The measure contains items addressing participation due to perceived coercion or undue influence by the investigators.