This section of the manual addresses the conditions necessary for MDMA-assisted psychotherapy. MDMA can have profound emotional and physical effects. Its use requires thorough assessment and preparation of the participant. The participant must commit to: comply with dietary and drug restrictions, attend all preparatory therapy and follow-up sessions, and complete the evaluation instruments. The therapists commit to: providing adequate preparation time during non-drug sessions; giving careful attention to the set and setting during MDMA sessions (Metzner, et al, 1988; 2001); and ensuring adequate follow-up therapy. The therapists remain with the participant during MDMA-assisted sessions until the acute emotional and physical effects of the MDMA have worn off, as determined by 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 of the therapy session. The participant commits 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 also commits to daily telephone contact with the therapists for a week after each MDMA session.

2.1 Prerequisites and Contraindications

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, the type of previous psychotherapy must be established as effective, based on a controlled clinical trial. 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 contraindicate 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). People suffering from PTSD experience a high co-morbidity rate of other anxiety and mood disorders (Brady, et al, 1994; Faustman & White, 1989). Within the mood disorder spectrum, those who meet the criteria for Bipolar Affective Disorder Type 1 must be excluded from this therapeutic approach (see exclusion criteria); however those meeting the criteria for other mood and anxiety disorders are eligible to participate.

The next prerequisite is that the participant 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. Generally the participant should 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 cannot safely discontinue medication.

The third prerequisite is that for one week preceding each MDMA session the participant refrain from taking the following:

  1. Herbal supplements
  2. Nonprescription medications (with the exception of non-steroidal anti-inflammatory drugs or acetaminophen), unless with prior approval of the treating therapist.
  3. Prescription medications (except for birth control pills, thyroid hormones, hormone replacement, NSAIDS, or other medications approved by the physician supervising the MDMA-assisted therapy). If the participant is taking any other prescription medications to be discontinued before the session, their personal physician must give permission.
It is also necessary that the participant refrain from taking anything by mouth except alcohol-free liquids after 12 A.M. the evening before an MDMA-assisted session. The participant must also agree to refrain from using any psychoactive drug for 24 hours following the session. These restrictions are carefully reviewed with the participant during and after presentation and signing of the Informed Consent. There are several categories of prospective participants for whom this therapy is contraindicated, including:
  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 appear to be at risk for victimization or self-harm. Participants who have engaged in self-harm within 6 months or have made suicide attempts within 6 months of this study.
  8. Participants who do not meet the appropriate medical criteria.
In all early or pilot research studies, individuals with dissociative identity disorder and borderline personality disorder are to be excluded from treatment. However, in later research studies, individuals with these disorders may be eligible for treatment, if they can remain stable when unmedicated and if careful clinical judgment is exercised.

The above information is gathered during the initial evaluation and introductory sessions. The therapist must carefully follow these guidelines and document compliance with therapy-related guidelines and restrictions. Establishing this context for treatment provides the participant with a sense of safety and comfort and also ensures adequate preparation of the set and setting for therapy. It is an important 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.

2.1 Assessment Protocol − Baseline Measures

2.1.1 Assessment Battery (Two Weeks Before Treatment)
Diagnosis is made by means of structured interviews to enhance diagnostic reliability and interview validity. An assessment battery to establish baseline measures of PTSD symptomatology, mood state and global functioning is performed approximately two weeks before the onset of treatment and consists of the following diagnostic instruments:

1. Structured Clinical Interview for the DSM-IV: SCID-IV (First et al, 1994). The SCID is a semi- structured interview that permits accurate diagnosis of life-time and current psychiatric disorders using DSM-IV criteria. 2. Clinician-Administered PTSD Scale: CAPS (Blake et al, 1990). The CAPS is a structured interview designed specifically for the assessment of PTSD. It assesses the seventeen symptoms of PTSD along with eight associated features. Forms 1 and 2 will be given to measure current and lifetime PTSD diagnosis (CAPS-1); CAPS-2 allows for the assessment of PTSD symptom status over time. 3. Impact of Events Scale: IES (Horowitz et al, 1979). The IES is a 15-item self-report scale designed to measure the extent to which a given stressful life event produces subjective distress. 4. Symptom Checklist 90: This is a standardized instrument used to measure subjective feeling states. 5. NEO Personality Inventory: (Piedmont, 1998). This model of personality structure provides insight as to the internal psychological forces that have resulted in Axis I psychopathology.

2.1.2 Additional Assessments (During and Post-Treatment)
Several additional assessment measures will be used during and post-treatment, as outlined below:
6. Working Alliance Inventory: WAI (Hovrath and Greenburg, 1989). The WAI is a 36-item self- report scale designed to assess the quality of the working alliance existing between participant and therapist. This measure will be administered once during the second introductory session and again during the follow-up therapy session occurring after each MDMA session. 7. Subjective Units of Distress: SUDS. This is a standardized subjective rating scale by which a subject can quickly rate comfort level throughout the session. It will be used to assess subjective distress during the course of each MDMA-assisted session 8. The Repeatable Battery for the Assessment of Neuropsychological Status: RBANS (Randolph, 1997). This assessment measures change in a participant's neuropsychological status over time. The domains assessed include: Immediate Memory, Visuospatial/Constructional, Language, Attention, and Delayed Memory. 9. The Paced Auditory Serial Addition Task: PASAT (Roman et al 1991). This assessment is a sensitive measure of information-processing speed and efficiency, concentration skills, and immediate memory. 10. Rey-Osterrieth Complex Figure: (Mitrushina et al, 1999). This measures visuoperceptual skills, spatial organizational skills, and memory.

In the current study, measures 8, 9 and 10 will be administered as baseline and again after both MDMA-assisted sessions to measure neurocognitive function in specific domains selected to assess memory and attention, two areas found to be affected by regular Ecstasy use (Fox et al, 2001; Gouzoulis-Mayfrank et al, 2000; Morgan, 1999; Rodgers, 2000).