The goals of this manual are 1) to delineate the core elements of MDMA-assisted psychotherapy in the psychotherapeutic treatment of PTSD and, 2) to educate therapists about the phases and steps involved in conducting this therapy. This manual will assist in the process of standardizing and validating this treatment in the context of controlled clinical trials and will provide therapists with appropriate strategies for preparing the patient for MDMA-assisted sessions, conducting the MDMA sessions, and facilitating follow-up sessions designed to expand and integrate the therapeutic process.

The foundation of this treatment is the theoretical assumption that the medicine, MDMA, is not in itself the therapy. Rather, MDMA is considered a powerful ally for both clinician and participant.

The adjunctive position of MDMA in the therapeutic process is based partly on its ability to induce a heightened state of empathic rapport along with its ability to facilitate the therapeutic process (Grob & Poland, 1997). The treatment paradigm rests on hypotheses concerning the benefits of increased rapport combined with a willingness to explore the trauma and its consequences in an atmosphere of hope, reassurance, and encouragement that enables the subject to develop alternative cognitive structures and change the meaning of his/her suffering. These effects are hypothesized to enhance the rate of recovery from PTSD.

The successful use of MDMA in therapy is dependent on "the sensitivity and talent of the therapist who employs (it)" (Grinspoon & Doblin, 2001, p. 693). With this understanding, the therapist carefully works with the participant to establish a sense of safety, security, trust, and openness, and to delineate the intended goals of the therapy prior to the MDMA-assisted session[s]. As Greer and Tolbert (1998) noted, "The relationship should be oriented toward a general healing for the client, who should feel safe enough in the therapists' presence to open fully to new and challenging experiences" (p. 372). This requires that the therapists carefully set the parameters of treatment and prepare the participant for the process prior to each MDMA-assisted session. The post-session integrative aspect of the therapy is aimed at bringing the lessons gained in a non-ordinary state of consciousness across the bridge to the ordinary state of mind where these lessons can translate into advances in the participant's level of functioning. These strategies are introduced at the beginning of therapy and emphasized throughout the process.

Additionally, this manual will outline the inclusion and exclusion criteria, the assessment protocol and other specifics of our current research study of MDMA-assisted therapy for PTSD. Conditions for the use of MDMA ­ assisted Psychotherapy with PTSD This section of the manual will address the conditions for the use of MDMA-assisted psychotherapy. MDMA can have profound emotional and physical effects. Its use requires thorough assessment and preparation of the participant. The participant must be committed to compliance with dietary and drug restrictions, preparatory therapy and follow-up sessions, and completing evaluation instruments.

The therapists must be committed to providing adequate preparation time during non-drug sessions and to giving careful attention to the set and setting during MDMA sessions (Metzner, et al, 1988; 2001), and to providing adequate follow-up therapy. The therapists must remain with the participant during MDMA-assisted sessions until the acute emotional and physical effects of the MDMA have worn off as assessed through examining physiological signs, degree of self-reported distress (Subjective Units of Distress, SUDS, must be at or below baseline) and clinical judgment concerning stability. The therapists and participant must all agree that the participant is in a safe and stable condition at the end the therapy session. The participant must agree to an overnight stay in the treatment facility, accompanied by an attendant, and he or she must also agree to find a friend, relative or partner who will provide transport home from the psychotherapy session following the MDMA session. The participant must also agree to daily telephone contact with the therapists for a week after each MDMA session.

The first prerequisite for conducting MDMA-assisted psychotherapy with PTSD is that the participant must meet the DSM ­ IV criteria for current PTSD. In early pilot studies, a CAPS score of 50 or above is used as an indicator of PTSD. The participant must have experienced at least one unsuccessful attempt at treatment with medications and/or psychotherapy, including a trial treatment with a selective serotonin re-uptake inhibitor (SSRI). In early and pilot research studies, only individuals who continue to meet the diagnostic criteria for PTSD after receiving an SSRI for three months or more and after receiving at least 12 sessions of psychotherapy for six months or more will be enrolled in the study. With respect to the current study, previous psychotherapy must be one for which a controlled clinical trial indicating efficacy. This includes cognitive-behavioral therapy (including exposure therapy), stress inoculation training, including anxiety management, and insight-oriented psychotherapy (Foa et al. 2003; Jaycox et al. 2002; Krupnik 2002; Resick and Schenk 1992). The participant must also have a medical history and physical examination to rule out any medical condition that would require exclusion from this form of therapy. These conditions may include major cardiovascular, cerebrovascular, or other medical disorders judged by the examining physician or the principal investigator (PI) to be significant (see below for other medical exclusionary criteria).

There is a high co-morbidity rate of other anxiety and mood disorders with PTSD (Brady, et al, 1994; Faustman & White, 1989). Within the mood disorder spectrum, those who meet the criteria for Bipolar Affective Disorder Type 1 would be excluded from this therapeutic approach (see exclusion criteria); however those meeting the criteria for other mood and anxiety disorders would be eligible for participation.

The next prerequisite for inclusion is that the participant must be willing to refrain from taking any psychiatric medications from the outset of therapy until two months following the final MDMA session. If a participant is currently taking psychiatric medication, then agreement to suspend medication must be approved and in writing by the participant's prescribing physician and this discontinuation must be monitored appropriately. In general, it is recommended that the participant be medication-free for at least 5 times a particular drug's half life. Careful clinical judgment must be used to exclude any participant who could not safely discontinue medication.

The third prerequisite is that for one week preceding each MDMA session the participant adheres to the following:

1. Refrain from taking any herbal supplement.
2. Refrain from taking any nonprescription medications (with the exception of non- steroidal anti-inflammatory drugs or acetaminophen unless with prior approval of the treating therapist).
3. With the permission of their physician they will not take any prescription medications (with the exception of birth control pills, thyroid hormones, hormone replacement, NSAIDS, or other medications approved by the physician supervising the MDMA- assisted therapy).

There are several categories of prospective participants for whom this therapy is contraindicated. These include:

1. Pregnant or nursing women and women who are of child-bearing potential and not practicing an effective means of birth control.
2. Participants with a history of primary psychotic disorder or bipolar affective disorder type 1.
3. Participants with an eating disorder with active purging.
4. Participants who weigh less than 50 kg or more than 105 kg.
5. Participants with substance abuse or dependency within the past three months.
6. Participants who present a suicide risk or who are at risk for hospitalization.
7. Participants who do not meet the appropriate medical criteria.
8. Participants who appear to be at risk for victimization or self-harm. Patients who have engaged in self-harm within 6 months or have made suicide attempts within 6 months of this study.

This information is given and obtained during the initial evaluation and introductory sessions. The therapist is required to stringently follow these guidelines and to document compliance with therapy-related guidelines and restrictions. Knowing that this context for his/her treatment is reliably in place provides the participant with a sense of safety and comfort. It also establishes a foundation for adequate preparation of the set and setting for therapy. It is an opportunity for the therapists to facilitate development of a therapeutic alliance, identify the participant's concerns, respond to questions and prepare the participant for MDMA-assisted treatment sessions.