Clinical trial NCT01458327
Conditions: Posttraumatic Stress Disorder
Keywords: MDMA PTSD therapy
Sponsor: Lykos Therapeutics
Start date: 2010-12-15; Completion date: 2014-06-27
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study will consist of a single session of MDMA-assisted therapy with a full dose of MDMA for people who took part in a study of MDMA-assisted therapy in people with posttraumatic stress disorder (PTSD) whose PTSD symptoms returned to higher levels at least a year after the first MDMA sessions. The single session will be performed by the same pair of therapists who performed the sessions in the first study. People will have a preparatory session, the MDMA-assisted session and three non-drug sessions afterward. Their PTSD symptoms and symptoms of depression will be measured at the start of this study and two and 12 months after the session.

Detailed description:
This study will investigate the effects of an additional 3,4-methylenedioxymethamine (MDMA)-assisted therapy session in up to three participants with PTSD who relapsed after their PTSD symptoms had significantly decreased during MAPS' initial U.S. Phase 2 trial testing the use of MDMA-assisted therapy in subjects with chronic, treatment-resistant posttraumatic stress disorder PTSD). This new protocol will consist of a single, full-dose open-label session of MDMA-assisted therapy, along with associated non-drug preparation and integrative therapy sessions.

MDMA is an investigational drug that was studied in a randomized, placebo-controlled study in 21 participants, and it included a final evaluation of symptoms at least one year after taking part in the study. While PTSD symptoms in most study subjects stayed at the same levels from when they completed the study, symptoms had returned in a few people. This open-label study is intended to see if an additional MDMA-assisted session conducted at least 14 months after the first sessions can help reduce PTSD symptoms.

The MDMA-assisted therapy session will be conducted by a male and female co-therapist team, one a psychiatrist and the other a psychiatric nurse. Vital signs (blood pressure, pulse and body temperature) and psychological distress will be measured throughout the experimental session. After the experimental session they will spend the night in the clinic with an attendant on duty, and complete a measure of alterations in consciousness, the States of Consciousness Questionnaire (SCQ) on the evening or day following the experimental session. Participants will meet with the investigators the next morning for an integrative therapy session before leaving the clinic. During integrative therapy sessions they will receive support in integrating their experiences and insights from the MDMA-assisted therapy session. There will be daily phone contact with one of the investigators for 7 days after the experimental session. Symptoms of PTSD, depression and general function will be assessed two months after the experimental session. There will be a long-term follow up with repeated outcome measures 12 months after the experimental session

Arms: arm 1: One experimental session of MDMA-assisted therapy
Interventions: intervention 1: Midomafetamine intervention 2: Therapy
Intervention descriptions: intervention 1: 125 mg MDMA followed by 62.5 mg MDMA 1.5 to 2.5 hours later intervention 2: Non-directive therapy

Protocol documents:
Prot_SAP_001.pdf: 
PROTOCOL MP1-E2 
 
IND #63,384 
 
April 29, 2011 
 
An Open-Label Proof-of-Principle Study Testing the Use of an Additional MDMA-
Assisted Psychotherapy Session in People who Relapsed after Participating in a Phase 2 
Clinical Trial of MDMA-Assisted Psychotherapy to Treat Chronic, Treatment-Resistant 
Posttraumatic Stress Disorder (PTSD)  
 
SPONSOR 
Multidisciplinary Association for Psychedelic 
Studies (MAPS) 
309 Cedar Street, #2323 
Santa Cruz, CA 95060 
SPONSOR DESIGNEE 
Rick Doblin, Ph.D. 
 
CLINICAL INVESTIGATOR 
Michael C. Mithoefer, M.D.  
 
MEDICAL MONITOR 
Julie Holland MD  
 
 
 


MAPS Study # MP1-E2                                                                                         Original Protocol Version 1  
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Table of Contents 
 
1.0 LIST OF ABBREVIATIONS .................................................................................................................4 
2.0 INTRODUCTION, BACKGROUND AND RATIONALE .................................................................6 
2.1 INTRODUCTION ......................................................................................................................................6 
2.2 BACKGROUND .......................................................................................................................................6 
2.3 PROTOCOL PURPOSE ............................................................................................................................ 10 
2.4 RATIONALE OF DOSE SELECTION ......................................................................................................... 11 
3.0 PROTOCOL OBJECTIVES ................................................................................................................ 11 
3.1 PRIMARY OBJECTIVE ........................................................................................................................... 11 
3.2 SECONDARY OBJECTIVES .................................................................................................................... 11 
3.3 SAFETY OBJECTIVES ............................................................................................................................ 12 
4.0 PROTOCOL DESIGN .......................................................................................................................... 12 
4.1 PLANNED DURATION OF STUDY .......................................................................................................... 12 
4.2 RECRUITMENT AND SUBJECT POPULATION .......................................................................................... 15 
5.0 METHODS ............................................................................................................................................. 17 
5.1 MEASURES ........................................................................................................................................... 17 
5.2 STUDY PROCEDURES AND VISIT DESCRIPTIONS .................................................................................. 20 
5.3 RANDOMIZATION AND SUBJECT NUMBERING ...................................................................................... 27 
5.4 REMOVAL OR WITHDRAWAL OF SUBJECTS FROM THE STUDY ............................................................. 27 
5.5 PREMATURE DISCONTINUATION OF THE STUDY .................................................................................. 28 
6.0 INVESTIGATIONAL PRODUCT ...................................................................................................... 28 
6.1 DESCRIPTION ....................................................................................................................................... 28 
6.2 ADMINISTRATION ................................................................................................................................ 28 
6.3 DRUG ACCOUNTABILITY ..................................................................................................................... 29 
6.4 DRUG STORAGE AND HANDLING ......................................................................................................... 29 
6.5 MDMA STABILITY .............................................................................................................................. 30 
7.0 RISKS OF PARTICIPATION ............................................................................................................. 30 
7.1 RISKS AND DISCOMFORTS ASSOCIATED WITH NON-DRUG AND EXPERIMENTAL PSYCHOTHERAPY 
SESSIONS AND ASSESSMENT OF MEASURES .............................................................................................. 30 
7.2 RISKS OF RECEIVING MDMA .............................................................................................................. 31 
7.3 ABUSE LIABILITY ................................................................................................................................ 36 
8.0 ADVERSE EVENTS ............................................................................................................................. 36 
8.1 ADVERSE EVENTS ................................................................................................................................ 36 
8.2 SPONTANEOUSLY REPORTED REACTIONS ............................................................................................ 38 
8.3 SERIOUS ADVERSE EVENTS ................................................................................................................. 38 
8.4 MEDICAL EMERGENCIES ...................................................................................................................... 39 
8.5 ADVERSE EVENT COLLECTION ............................................................................................................ 39 
9.0 CONCOMITANT MEDICATIONS AND TAPERING INSTRUCTIONS ..................................... 40 
10.0 CLINICAL LABORATORY ASSESSMENTS ................................................................................ 41 
11.0 STUDY MONITORING, AUDITING AND DOCUMENTATION ................................................ 41 
12.0 DATA ANALYSIS ............................................................................................................................... 42 
12.1 STATISTICAL POWER ......................................................................................................................... 42 
13.0 ETHICS ................................................................................................................................................ 43 


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14.0 INFORMED CONSENT ..................................................................................................................... 43 
15.0 CONFIDENTIALITY ......................................................................................................................... 44 
16.0 COSTS TO PARTICIPANTS ............................................................................................................ 44 
17.0 TREATMENT AND COMPENSATION FOR STUDY RELATED INJURY .............................. 45 
18.0 RECORD RETENTION ..................................................................................................................... 45 
19.0 REFERENCES .................................................................................................................................... 46 
 
 
 


MAPS Study # MP1-E2                                                                                         Original Protocol Version 1  
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1.0 List of Abbreviations 
ACLS  
Advanced Cardiac Life Support  
AE(s)  
Adverse Event(s) 
AED    
Automated external defibrillator  
AMI   
Acute Myocardial Infarction 
BDI-II  
Beck Depression Inventory II 
BLS 
 
Basic Life Support 
BP 
 
Blood pressure 
BT                   Body temperature 
C 
 
Celsius 
CAPS  
Clinician Administered PTSD Scale 
CI 
 
Clinical Investigator (e.g. therapists, co-investigators) 
CPK  
Creatine Phosphokinase 
CRA  
Clinical Research Associate 
CRF(s) 
Case Report Form(s) 
C-SSRS 
Columbia Suicide Severity Rating Scale 
DEA  
Drug Enforcement Agency 
ECG/EKG 
Electrocardiogram 
EMS  
Emergency Medical Services  
FDA  
Food and Drug Administration  
GAF   
Global Assessment of Functioning 
GCP  
Good Clinical Practice 
HCl 
 
Hydrochloride 
HIPAA  
Health Insurance Portability and Accountability Act 
HPLC  
High Performance Liquid Chromatography 
ICF 
 
Informed Consent Form 
ICH 
 
International Conference on Harmonization 
IND 
 
Investigational New Drug  
IRB 
 
Institutional Review Board 
ISF 
 
Investigator Site File 
IV 
 
intra-venous 
LSD 
 
d-lysergic acid diethylamide 
MAOI  
Monoamine oxidase inhibitor 
MAPS  
Multidisciplinary Association for Psychedelic Studies 
MCH  
Mean Corpuscular Hemoglobin 
MDMA 
3,4-methylenedioxymethamine 
MP-1  
MAPS’ first clinical trial of MDMA-assisted psychotherapy for PTSD 
PDS 
 
Posttraumatic Diagnostic Scale 
PTSD  
Posttraumatic Stress Disorder 
PRN  
As needed 
PTSD  
Posttraumatic Stress Disorder 
PTT 
 
Partial Thromboplastin Time 
RRPQ  
Reactions to Research Participation Questionnaire 
SAE(s) 
Serious Adverse Event(s) 
SCID  
Structured Clinical Interview for Diagnoses 


MAPS Study # MP1-E2                                                                                         Original Protocol Version 1  
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SL 
 
Sublingual 
SNRI  
Selective Serotonin and Norepinephrine Uptake Inhibitor 
SSRI  
Selective Serotonin Reuptake Inhibitor  
SUD   
Subjective Units of Distress 
U.S. 
 
United States of America 


MAPS Study # MP1-E2                                                                                         Original Protocol Version 1  
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2.0 Introduction, Background and Rationale 
2.1 Introduction 
 
This protocol is a Multidisciplinary Association for Psychedelic Studies (MAPS)-
sponsored proof-of-principle Phase 2 clinical study. It will investigate the effects of an 
additional 3,4-methylenedioxymethamine (MDMA)-assisted psychotherapy session in up 
to three participants with PTSD who relapsed after their PTSD symptoms had 
significantly decreased during MAPS’ initial U.S. Phase 2 trial testing the use of MDMA-
assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress 
disorder (PTSD). This new protocol will consist of a single, full-dose open-label session 
of MDMA-assisted psychotherapy, along with associated non-drug preparation and 
integrative psychotherapy sessions. 
 
MAPS is a U.S.-based IRS-approved non-profit research and educational organization 
that sponsors research into the therapeutic potential of MDMA, other psychedelic 
compounds, and marijuana. MAPS’ top priority project is working to obtain approval for 
the prescription use of MDMA-assisted psychotherapy in patients with posttraumatic 
stress disorder (PTSD). MAPS is currently sponsoring a Phase 2 study in the U.S. in 
veterans with chronic, treatment-resistant, war-related PTSD. 
 
MAPS’ initial U.S, MDMA/PTSD study has been completed, with promising results 
published in the Journal of Psychopharmacology [2]. Findings from the long-term follow-
up portion of the study, evaluating subjects at an average of 41 months post-treatment, 
suggest that the therapeutic benefits were sustained as measured by the Clinician 
Administered PTSD Scale (CAPS). Upon completion of the treatment portion of the 
study, average CAPS scores two months after two sessions of MDMA-assisted 
psychotherapy were 28.47 +/- 21.33 (n = 19). This is slightly higher than the average 
CAPS scores of 23.69 +/- 22.77 (n = 16) at the long-term follow-up, with scores at both 
timepoints under the cut-off of 50 points for study inclusion. While most of the subjects’ 
symptoms continued to improve or stayed roughly the same from the two-month follow-
up to the long-term follow-up, two subjects had relapsed. These results are being 
prepared for submission to FDA and publication in a peer-reviewed journal. 
  
MAPS U.S. studies are part of an international series of Phase 2 studies designed to 
evaluate safety and efficacy of MDMA-assisted psychotherapy in treating chronic, 
treatment-resistant PTSD for possible use as an approved prescription medication in the 
U.S., Europe and Israel [1].  MAPS’ Swiss pilot study was completed in early 2011, with 
the data currently being prepared for publication. MDMA was administered without 
evidence of harm and generated promising data about efficacy. Additional pilot studies 
are in the approval process in Canada, Jordan and Israel. 
 
2.2 Background 
 
2.2.1 Posttraumatic Stress Disorder (PTSD)    
 


MAPS Study # MP1-E2                                                                                         Original Protocol Version 1  
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PTSD is a debilitating psychiatric disorder arising after a traumatic life event. PTSD 
severely reduces quality of life and may directly or indirectly lead to or exacerbate other 
psychiatric and medical problems. The DSM-IV[3]  criteria for PTSD include:  
 
A. Exposure to a significant traumatic event accompanied by an intense acute 
emotional response.   
B. Persistent re-experiencing of the event or aspects of the experience.   
C. Persistent avoidance of stimuli associated with the event, and/or withdrawal from 
some aspects of life.   
D. Persistent symptoms of increased arousal.   
E. The above symptoms must last for more than one month for Acute PTSD and 
more than three months for Chronic PTSD.  
 
PTSD is a worldwide public health problem for which a wider array of effective 
treatments is needed. The lifetime prevalence of PTSD in the U.S. general population is 
between 6 and 10% [4-8], but it is common in other countries as well [5, 9-12]. 
According to some estimates, PTSD appears to be less prevalent in the general population 
of Europe at 1.9% [13]. In U.S. soldiers returning from combat in the Iraq war, the 
incidence of PTSD is as high as 18% [14], and it is estimated that the number of service 
members returning home with PTSD will ultimately be between 75,000 and 225,000 [15]. 
In countries with endemic armed conflict, the incidence of PTSD in civilians is often far 
greater [16-18].  
 
The search for novel and more effective treatments is of major public health and 
economic significance. PTSD is typically a chronic illness [6, 19] associated with high 
rates of psychiatric and medical comorbidity, disability, suffering, and suicide [5-8]. 
People with PTSD face challenges in relationships and work productivity [20]. In the 
U.S. National Comorbidity Study, the median time to remission for PTSD was 36 months 
with treatment and 64 months without treatment. In both subgroups, more than a third of 
the patients still had symptoms several times per week after 10 years [4].  Forty to 60% of 
PTSD patients were found to be resistant to treatment in this study. In a comparison of 
two types of psychotherapy for women with PTSD after sexual assault in 2002, 47% of 
each treatment group was still diagnosed with PTSD after treatment, based on high 
Clinician Administered PTSD Scale (CAPS) scores [21].  
 
Despite the sheer number of individuals suffering from PTSD and its devastating effects, 
questions remain concerning the best possible treatments [22]. PTSD treatment goals 
include alleviating symptoms and correcting stress-induced neurochemical abnormalities 
associated with the condition. Two selective serotonin reuptake inhibitors (SSRI), 
sertraline and paroxetine, are currently marketed as PTSD medications in the U.S. These 
drugs are known to affect the serotonergic components of PTSD, but it is not known 
whether they can arrest and reverse the hippocampal atrophy found in individuals with 
PTSD [34]. In addition, SSRIs affect PTSD symptoms in a dosage dependent manner and 
they must be used every day in order to be effective [23]. 
 


MAPS Study # MP1-E2                                                                                         Original Protocol Version 1  
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Another treatment approach is to develop drugs and/or psychotherapeutic treatments that 
may indirectly decrease or eliminate the neurochemical pathologies underlying the 
chronic hyperarousal associated with PTSD. Cognitive behavioral therapies, particularly 
prolonged exposure and cognitive processing therapy, are considered among the most 
effective psychotherapies. Other methods such as psychodynamic therapy and eye 
movement desensitization and reprocessing (EMDR) have also proven to be effective in 
treating some symptoms of PTSD [28], although some patients may need more than one 
treatment to reduce or resolve those symptoms [20]. A recent meta-analysis concluded 
that all “bona fide” psychotherapies, including those listed above, are similarly effective 
with PTSD [29].  
  
At least a third of PTSD patients fail to respond to established PTSD psychotherapies or 
respond in a way that falls outside of clinical significance [24-26]. At least one study of 
paroxetine indicated that men with PTSD did not respond to this drug [27], and another 
randomized, double-blind study found no difference between sertraline and placebo in the 
treatment of PTSD [28]. These findings suggest that there is still a substantial need for 
innovative treatments for PTSD. In recent years, there has been a growing amount of 
research into drugs and other methods that may augment the effectiveness of 
psychotherapy for PTSD (see [29] for a review).  Examples of this are virtual reality-
assisted exposure therapy [30, 31] and D-cycloserine-assisted psychotherapy [32]. 
MDMA-assisted psychotherapy is another example of such emergent treatments. 
 
2.2.2 MDMA 
 
MDMA is a ring-substituted phenylisopropylamine derivative invented by the Merck 
pharmaceutical company in 1912 that bears structural and pharmacological similarities to 
both the stimulant amphetamine and the psychedelic drug mescaline. It was initially 
patented by Merck as an intermediary product and then rediscovered by chemist 
Alexander Shulgin in the 1970s [33, 34]. In the United States, MDMA was used as an 
adjunct to psychotherapy by a considerable number of psychiatrists and other therapists 
before it was placed in Schedule 1 in 1985 as a result of extensive non-medical use [35-
37]. Placement in Schedule 1 prohibited it for use except in a federally approved research 
setting.  
 
Prior to scheduling, MDMA in combination with psychotherapy was used in the 
treatment of neuroses, relationship problems and PTSD [38-42]. Case reports and 
narrative accounts of MDMA-assisted therapy suggest that the treatment was often 
successful.  Based on these experiences, assertions have been made that MDMA, used in 
the proper therapeutic setting, can act in several beneficial ways. Specifically, MDMA 
can “reduce or somehow eliminate fear of a perceived threat to one’s emotional integrity” 
[39]. Elimination of these “conditioned fear responses” can lead to more open and 
comfortable communication about past traumatic events, greater access to information 
about them, and a more accurate perspective about their significance in the present. Some 
clinicians and researchers have asserted that MDMA may increase empathy or 
compassion for self and others, decrease defensiveness and help to strengthen a 
therapeutic alliance with psychotherapists, and that the above factors taken together can 


MAPS Study # MP1-E2                                                                                         Original Protocol Version 1  
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Page 9 of 51 
provide the opportunity for a corrective emotional experience [39].  Some investigators 
suggest that MDMA should be categorized as part of a new class of psychotropic agents 
referred to as entactogens [43]. The term refers to MDMA and similar substances that 
produce increased sensitivity to emotions, increased insights about the self, especially in 
the context of interpersonal relationships, and increased feelings of closeness to others.    
 
2.2.3 Previous Clinical Experience with MDMA 
 
Classification as a Schedule 1 drug hampered research into the medical uses of MDMA. 
In recent years, clinical investigation of the safety and efficacy of MDMA-assisted 
psychotherapy has become more feasible [1, 44, 45]. The first double-blind, placebo 
controlled U.S. Phase 1 study sanctioned by the FDA was conducted in 1994, with 
findings that suggested that MDMA caused a significant increase in body temperature 
and heart rate in some healthy volunteers [46]. However, these increases were found to be 
transient and generally tolerable in a controlled clinical setting [46]. Subsequent trials 
confirmed that MDMA produced significant increases in heart rate and blood pressure 
that were likely to be well-tolerated by healthy individuals [47].  
 
The potentially therapeutic effects of MDMA were initially investigated starting in 2000 
in a MAPS-sponsored dose-response pilot study in Spain in women survivors of sexual 
assault with treatment-resistant PTSD [48, 49]. Unfortunately, the study in Spain was 
halted in 2002 due to political pressure from the Madrid Anti-Drug Authority.  Prior to its 
suspension, six women were enrolled and treated in this study without any adverse events 
or signs of deteriorating mental health, and with some mild signs of improvement, with 
single doses ranging from 50 to 75 mg [49].  
 
As of 2011, MDMA has been administered to approximately 510  research participants, 
in both Phase 1 and Phase 2 studies, without any occurrences of drug-related Serious 
Adverse Events (SAEs) [50-68]. In the context of psychotherapy, MDMA has been noted 
to reduce defensiveness and fear of emotional injury while enhancing communication and 
capacity for introspection [35]. 
 
MAPS recently completed its first U.S. study of MDMA-assisted psychotherapy for the 
treatment of PTSD, known as MP-1. This study employed the CAPS as a primary 
outcome measure, with PTSD symptoms measured by a blinded independent rater at 
baseline, 3 to 5 days after each experimental (MDMA or placebo) session, and two 
months after the final experimental session. All participants in this study tolerated 
MDMA well, and MP-1 data suggests that MDMA is associated with significantly greater 
improvement in PTSD than placebo [2]. Findings from the long-term follow-up 
evaluating the US subjects at an average of 41 months post-treatment, suggests that the 
therapeutic benefits have been sustained over time [69]. The sponsor has also supported a 
randomized, double-blind study of MDMA-assisted psychotherapy in twelve subjects 
with PTSD in Switzerland.  
 


MAPS Study # MP1-E2                                                                                         Original Protocol Version 1  
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2.2.4 MDMA-assisted Psychotherapy for PTSD 
 
MDMA-assisted psychotherapy is an innovative mode of treatment that combines 
psychotherapeutic techniques with the administration of MDMA, a pharmacological 
adjunct that may enhance or amplify certain aspects of psychotherapy. MDMA possesses 
unique pharmacological properties that may make it especially well suited for use as an 
adjunct to psychotherapy in PTSD patients [37, 39-41]. In contrast to daily 
administrations of SSRIs, this treatment consists of several sessions of MDMA-assisted 
psychotherapy within the context of a moderate course of non-drug psychotherapy.  
 
Treatment goals of MDMA-assisted psychotherapy for PTSD include alleviating 
symptoms and interrupting the stress-induced neurochemical abnormalities produced by 
the condition. Reports of past experience with MDMA-assisted psychotherapy suggest 
that it may also counteract the effects of PTSD. In fact, the biologic and 
psychotherapeutic approaches overlap and reinforce each other. Knowledge about the 
connections between the neurobiological and the therapeutic effects of MDMA is far 
from complete, but it has been observed that MDMA acutely decreases activity in the left 
amygdala [70]. This action is compatible with its reported reduction in fear or 
defensiveness, and is in contrast to the stimulation of the amygdala observed in animal 
models of conditioned fear, a state similar to PTSD [71, 72]. MDMA also elevates 
oxytocin and changes brain activity in response to fearful and happy faces [51, 73]. 
 
A comprehensive review of MDMA research is included in the Investigator’s Brochure 
supplied by the Sponsor. This document should be reviewed prior to initiating the 
protocol. 
 
2.3 Protocol Purpose 
 
This proof-of-principal Phase 2 open-label study will investigate the effects of a single 
session of MDMA-assisted psychotherapy in up to three subjects who relapsed after their 
PTSD symptom severity had significantly decreased following treatment with MDMA-
assisted psychotherapy in the course of the MAPS sponsored MP-1 study. Up to three 
subjects, who either had a global CAPS severity score of  50 at a long-term follow-up (1 
year or more) after completing MP-1, or who spontaneously contacted the clinical 
investigator to report the worsening symptoms and were subsequently found to have a 
CAPS score of  50, will be enrolled in the study. All participants will receive a full dose 
of MDMA (125 mg possibly followed by 62.5 mg of MDMA) used as an adjunct to 
manualized psychotherapy. Participants will have one preparatory session prior to the 
MDMA-assisted session and three integrative sessions afterwards. The extent of PTSD 
symptoms, as well as depression symptoms and general psychological well-being, will be 
assessed at baseline, and at 2 month and 12 month follow-ups by a clinician and through 
the use of self-report measures. The study will investigate whether a single additional 
session of MDMA-assisted therapy can ameliorate relapse of PTSD in the study subjects.    


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2.4 Rationale of Dose Selection 
 
The study subjects will be administered the full dose of MDMA, consisting of 125 mg 
given initially, possibly followed one and a half to two and a half hours later by 62.5 mg, 
unless contraindicated based on safety measures.  
 
Table 1. Dose Regimen 
 
Initial  
Dose 
Supplemental Dose 
Cumulative  
Dose 
Full MDMA Dose 
125 mg 
62.5 mg 
187.5 mg 
 
The full MDMA dose to be used in this study is identical to those used in previous 
MAPS-sponsored studies in the U.S., Switzerland and Israel. Previous researchers had 
also used doses within this range [46, 47, 53, 60, 74-79]. Prior to the scheduling of 
MDMA, similar doses and regimens were used in psychotherapy [35, 37, 41]. The initial 
full dose is expected to produce all the commonly reported effects of MDMA. The 
supplemental dose will prolong subjective drug effects without producing physiological 
effects any greater than peak effects occurring after the initial dose.  All subjects in this 
study will have previously tolerated a dose of at least 125 mg  during their participation 
in the original Phase 2 trial. 
 
3.0 Protocol Objectives 
The objective of this study is to investigate whether a single session of MDMA-assisted 
psychotherapy can ameliorate the relapse of PTSD in those subjects who had improved 
during participation in a Phase 2 clinical trial evaluating the safety and efficacy of 
MDMA-assisted psychotherapy but whose PTSD symptoms worsened over time during 
the follow-up period or after the initial study.  
 
3.1 Primary Objective 
 Assess changes in PTSD symptoms in relapsed subjects receiving a single session 
of MDMA-assisted psychotherapy as measured via CAPS score at baseline and at 
2 months and 12 months after the session.  
 
3.2 Secondary Objectives 
 Assess changes in self-reported PTSD symptoms in relapsed subjects receiving a 
single session of MDMA-assisted psychotherapy as measured via Posttraumatic 
Diagnostic Scale (PDS) score at baseline, at 2 months and 12 months after the 
experimental session. 
 Assess depression symptoms via the Beck Depression Inventory-II (BDI-II) at 
baseline and at 2 months and 12 months after the experimental session. 
 Assess quality of life via the Global Assessment of Functioning  (GAF) at 
baseline and at 2 months and 12 months after the experimental session. 


MAPS Study # MP1-E2                                                                                         Original Protocol Version 1  
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 Explore self-reported changes in consciousness, as those associated with a 
transformational or mystical experience via the States of Consciousness 
Questionnaire (SOCQ). 
 Assess the participant’s experience as a research subject, perceived reasons for 
consenting to be a research participant and perceived freedom to take part in the 
study via the Reactions to Research Participation Questionnaire (RRPQ). 
 Assess long-term benefits and harms of study participation by completing the 
long-term follow-up questionnaire. 
3.3 Safety Objectives 
The safety objectives of the study are to monitor and assure safety of subjects during and 
after the experimental session by assessing physiological effects, psychological distress, 
adverse events, spontaneously reported reactions and suicidality.   
 
Suicidality will be assessed with the Columbia Suicide Severity Rating Scale (C-
SSRS) at screening, twice during the experimental session, and several times after 
the experimental session. 
 
Vital signs including blood pressure, heart rate and temperature, and the degree of 
psychological distress will be assessed periodically during the experimental 
session. 
 
Serious adverse events, adverse events and spontaneously reported reactions will 
be collected during the study according to Section 8.5. 
4.0 Protocol Design 
This open-label proof-of-principle study will examine the effects of a single session of 
MDMA-assisted psychotherapy in up to three subjects with current PTSD who relapsed 
after the initial improvement they had experienced during the Phase 2 clinical trial testing 
MDMA in conjunction with psychotherapy. The study will include one MDMA-assisted 
psychotherapy session, referred to as an experimental session, with a male/female co-
therapist team. Subjects will meet with their therapist team for one preparatory session, 
conducted prior to the experimental session. Participants will complete the SOCQ after 
the experimental session. The experimental session will be followed by an overnight stay 
at the clinic, an integrative psychotherapy session the next day and two additional 
integrative sessions.  
Symptoms will be assessed by an independent rater as well as using self-report measures. 
The independent rater will assess PTSD symptoms with the CAPS, quality of life with the 
GAF, and subjects will complete the BDI-II to measure symptoms of depression. The 
subjects will complete the PDS, a self-report measure of their PTSD symptoms, to assess 
symptoms via a self-report measure developed to assess the same diagnostic criteria as 
the primary outcome measure. Baseline assessments will be compared with the 
assessments made at the follow-ups. (See Table 2 Time and Events).  
At each visit with the investigators, suicidality will be assessed with the Columbia 
Suicide Severity Rating Scale (C-SSRS), in addition to general well being.  Adverse 
Events and Concomitant Medications will be collected as described in Section 8.5 and 9.0 
of the protocol. 
4.1 Planned Duration of Study 
The duration of the study for each subject will be approximately 12.5 months after 
enrollment. 


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Table 2. Time & Events   
Screen/Baseline 
Preparatory 
Experimental 
Session  
Integrative 
Session 1 
Integrative 
Session 2 
Integrative 
Session 3 
2 Month 
Follow-Up 
12 Month 
Follow-Up 
Visit # 
Prior to  Enrollment 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
Type of Visit 
Baseline Screening 
may take place over 
more than one day up 
to one month prior to 
Visit 2 
Preparatory Session 
Experimental 
Session  
Integrative 
Session 
Integrative 
Session 
Integrative 
Session 
Follow-up & 
Outcome 
Follow-up & 
Outcome  
Visit Timing or Study day or Window 
May be completed during 
screening 
After V1 
Next day after 
V2 
After V3 before 
V5 
After V4 
before V6 
2 months after 
V2 
12 months after 
V2 
Informed Consent 
X 
 
 
 
 
 
 
 
View Medical Records 
X 
 
 
 
 
 
 
 
Consult physician or therapist 
X 
 
 
 
 
 
 
 
Collect Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Medication Taper (if applicable) 
 
 
XA 
 
 
 
 
 
Drug Screen 
X 
 
X 
 
 
 
 
 
Pregnancy Screen (if applicable) 
X 
 
X 
 
 
 
 
 
CAPS, GAF, BDI-II, PDS (with Ind. Rater) 
X  
 
 
 
 
 
X 
X 
Study Enrollment after meeting I/E 
 
 
X A 
 
 
 
 
 
Record to Audio/Video 
 
X 
X 
X 
X 
X 
 
 
General Well-Being 
 
X 
X B 
XF 
X 
X 
X 
X 
C-SSRS 
X 
X 
X B, C, D 
X I 
X  
X  
X 
X 
Administer IP Drug + Therapy 
 
 
X 
 
 
 
 
 
Monitoring of BP, Pulse and Temp.  
 
 
X 
 
 
 
 
 
SUD 
 
 
X C, E 
 
 
 
 
 
SOCQ 
 
 
X H 
 
 
 
 
 
Overnight Stay 
 
 
X H 
 
 
 
 
 
Integrative Therapy Session 
 
 
 
X 
X 
X 
 
 
7 days Integrative Telephone Contact 
 
 
 
X F 
 
 
 
 
AEs Requiring Medical Attention 
 
 
X 
X 
X 
X 
X 
 
Spontaneously Reported Reactions and all AEs  
 
 
XG 
XF, G 
XG 
XG 
 
 
AEs related to changes in psychiatric status or 
withdrawal 
 
X 
X 
X 
X 
X 
X 
X 
Serious Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
RRPQ  
 
 
 
 
 
 
X 
 
Long-term follow-up questionnaire 
 
 
 
 
 
 
 
X 
Termination 
 
 
 
 
 
 
 
X 
 A = Prior to V2 after medical records are received   B =Approximately 6 hours post MDMA   C =At the beginning of the session   D = As needed   E =Approximately every 60-90 minutes F = For 7 days post 
Exp. Session, G = Spontaneously reported reactions will be collected on the day of MDMA administration and for seven days after the Exp. Session  H = After the Exp. Session I= During V3 and Day 2 and Day 
7 of calls post Experimental Session  


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4.2 Recruitment and Subject Population 
 
Participants may be up to three men or women who completed MAPS Phase 2 clinical 
trial MP-1, the initial pilot study of MDMA-assisted psychotherapy, and who in the 
course of long-term evaluation or spontaneously indicated to the clinical investigator the 
relapse of PTSD symptoms. Participants should have a confirmed diagnosis of current 
PTSD at screening with a CAPS score equal to or greater than 50, and must meet all the 
inclusion criteria and none of the exclusion criteria. Participants must be in good physical 
health and without major medical disorders that might affect the safety or tolerability of 
MDMA.  
 
4.2.1 Inclusion Criteria 
 
Summarized Criteria for Posting 
Inclusion Criteria:  
1. Be diagnosed with chronic PTSD; 
2. Have a CAPS score showing moderate to severe PTSD symptoms; 
3. Have participated in MP-1; 
4. Are at least 18 years old; 
5. Must be generally healthy; 
6. Must sign a medical release for the investigators to communicate directly with 
their therapist and doctors; 
7. Are willing to refrain from taking any psychiatric medications during the study 
period; 
8. Willing to follow restrictions and guidelines concerning consumption of food, 
beverages, and nicotine the night before and just prior to each experimental 
session; 
9. Willing to remain overnight at the study site; 
10. Agree to have transportation other than driving themselves home or to where they 
are staying after the integrative session on the day after the MDMA session; 
11. are willing to be contacted via telephone for all necessary telephone contacts; 
12. Must have a negative pregnancy test if able to bear children, and agree to use an 
effective form of birth control; 
13. must provide a contact in the event of a participant becoming suicidal; 
14. Are proficient in speaking and reading English; 
15. agree to have all clinic visit sessions recorded to audio and video 
16. Agree not to participate in any other interventional clinical trials during the 
duration of this study. 
 
 
4.2.2 Exclusion Criteria 
 
Individuals not eligible to be enrolled into this protocol are those who: 
1. Are pregnant or nursing, or if a woman who can have children, those who are not 
practicing an effective means of birth control; 
2. Weigh less than 48 kg; 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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3. Are abusing illegal drugs; 
4. Are unable to give adequate informed consent; 
5. Upon review of past and current drugs/medication must not be on or have taken a 
medication that is exclusionary.  
6.  Upon review of medical or psychiatric history must not have any current or past 
diagnosis that would be considered a risk to participation in the study. 
 
5.0 Methods 
5.1 Measures 
 
The following outcome and safety measures will be used in this research study: 
 
5.1.1 Outcome Measures 
 
The primary outcome measure will be the CAPS, a clinician-scored measure for PTSD 
diagnosis and symptom intensity and severity. A qualified, blinded independent rater will 
perform the CAPS. The independent rater will not be present during the subject’s 
experimental session and will not have any information regarding the experimental 
session. The CAPS provides a standardized method to evaluate the frequency and 
intensity dimensions of each symptom, impact of symptoms on the subject's social and 
occupational functioning, overall severity of the symptom complex and global 
improvement since baseline, and the validity of the ratings obtained. The CAPS interview 
takes approximately one hour to complete. The CAPS has been determined to have good 
internal consistency, concurrent validity, and test/retest reliability [80, 81]. An 
independent rater will assess all subjects according to the Time and Events table. 
 
The secondary measure of PTSD symptoms will be the PDS, a self-report measure 
designed to follow DSM IV criteria for assessing PTSD. The measure is derived from the 
Posttraumatic Symptom Scale – Self Report (PSS-SR), a measure also intended to tap 
into diagnostic criteria for PTSD. The PDS contains 49 items, with responses made on a 
four-point scale, ranging from 0 (“not at all”) to 3 (“five or more times a week”). The 
PDS consists of a list of 12 potential traumatic events, 12 items addressing elements of 
the traumatic event, 17 symptom items, and 9 items assessing impact on areas of life 
function [82]. Items addressing elements of the traumatic event and life function are 
answered as either present or not present (Yes or No). The seventeen symptom items are 
summed to create a symptom severity scale. Cronbach’s alpha for the symptom severity 
scale is 0.92. The PDS has test-retest reliability of 0.74 after a two-week and one-month 
interval, and subscales are inter-correlated, with correlations ranging from 0.73 to 0.82, 
and PDS scores have a moderate to good correlation with SCID diagnosis, with kappa = 
0.65 [82]. Subjects will complete the PDS at the same times as the CAPS.  
 
 
The Beck Depression Inventory-II (BDI-II) is a 1996 revision of the BDI, a 21-item self-
report measure [83, 84], that will serve as a measure of depression according to DSM-IV 
criteria [85]. The BDI-II has been validated, has high internal consistency and good 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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test/re-test reliability and is not overly sensitive to daily variations in mood. It takes five 
to ten minutes to complete [85]. Subjects will complete the BDI-II at the same times as 
the CAPS.  
 
The Global Assessment of Functioning (GAF) is a measure of quality of life and general 
function made through observations. The GAF consists of a single score on the scale 
from 0 to 100, with 100 reflecting superior function and zero reflecting serious risk of 
causing harm to the self or others. The GAF is a reliable, validated measure of social 
functioning [86]. Subjects will complete the GAF at the same time as the CAPS. 
 
The States of Consciousness Questionnaire (SOCQ) is a 100-item questionnaire based on 
the “Peak Experience Profile” designed by Pahnke and colleagues [87, 88]. Participants 
respond to the SOCQ using a five-point Likert-type scale anchored at 0=none at all and 
5=extreme (“more than ever before in my life”). It has seven subscale scores: internal 
unity, external unity, transcendence of time and space, ineffability and paradoxicality 
(claim of difficulty in describing the experience in words), sense of sacredness, noetic 
quality, and deeply felt positive mood. The measure is a self-report instrument and takes 
approximately 20 to 30 minutes to complete. Participants will complete the SOCQ as a 
process measure once after the experimental session in the interval between the end of an 
experimental session and prior to leaving the treatment facility the next day. 
 
The Reactions to Research Participation Questionnaire (RRPQ) [89] is an assessment of 
causes for taking part in research and responses to the experience of being a research 
subject. Subjects will complete this measure during their final study visit. The RRPQ is a 
process measure intended to assess the subject’s experience as a research subject, 
perceived reasons for consenting to be a research subject and perceived freedom to take 
part in the study, and is not an outcome measure. 
 
A long-term follow-up questionnaire that has been developed internally by the Sponsor to 
assess long-term benefits and harms of MDMA-assisted psychotherapy will be completed 
by the study subjects at the 12 month follow-up visit. It contains questions on benefits 
and harms from taking part in the study, questions concerning psychotherapy and 
medications within the period between the two month and 12 month follow up, and 
substance use during this time period. It takes between five and ten minutes to complete. 
 
All psychotherapy sessions, including the experimental session, will be recorded to audio 
and video, with all recordings preserved for research and training purposes. 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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5.1.2 Safety Measures 
 
Safety measures, vital signs and a measurement of psychological distress will be assessed 
during the experimental session.  
 
Subjects will rate their current degree of subjective distress with the SUD scale, a single-
item, self-report scale, repeatedly during the experimental session, with the degree of 
distress marked along a seven point Likert scale.  
 
The C-SSRS is a measure of suicidal behavior devised to detect potential suicidal 
thoughts or behaviors during the clinical trial [90]. It consists of a “Baseline” form that 
assesses lifetime suicidal ideation, ideation intensity and behavior, and a form for 
assessing current suicidal ideation and behavior. The C-SSRS consists of a series of 
questions, and can be administered during a face-to-face interview or over the telephone. 
The investigators will assess suicidality at baseline, twice during the experimental 
session, once during each integrative session, during the second and seventh day of the 
telephone contact, and once during the 2-month and 12-month follow-ups.. The C-SSRS 
data will be reported on Case Report Forms (CRFs) for all administrations except for the 
second integrative session, unless an increase in suicidality is observed by the 
investigators. C-SSRS data from the second integrative session will be kept with the 
subject’s source record. 
 
The investigators will assess general wellbeing during the preparatory session, on each 
integrative session and integrative telephone calls for seven days, and at 2-month and 12-
month follow-ups.  
 
Blood pressure and heart rate will be assessed periodically during the experimental 
session. Blood pressure and pulse will be measured at the outset of the experimental 
session, and once approximately every 30 minutes during the experimental session. More 
frequent measures will be taken if the investigators judge them to be medically indicated. 
Participants with controlled hypertension will have blood pressure and pulse assessed 
every 15 minutes for the first five hours and every 30 minutes for the next three hours. 
Blood pressure will also be measured more frequently if there are clinical symptoms, 
such as chest pain, shortness of breath or neurological symptoms that may be indicative 
of hypertension. The investigators will measure the subject’s body temperature 
approximately every 60 to 90 minutes. The timing of these measurements will be 
adjusted so that they do not interfere with the therapeutic process.  
 
All AEs and spontaneously reported reactions will be collected as described in section 
8.5. Adverse events and spontaneously reported reactions may be collected during face to 
face visits or over the telephone. Common spontaneously reported reactions will be 
collected for seven days after the experimental session on a separate CRF page and will 
be categorized as mild, moderate or severe. 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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5.2 Study Procedures and Visit Descriptions 
 
5.2.1 Prescreening, Screening and Baseline Evaluation (Pre-study) 
 
All individuals who enter screening, as defined in this section, should be assigned a 
screening number and recorded on the “subject screening log” where information on the 
selection of potential subjects in the trial should be collected. The subject screening 
number should also be recorded on the subject’s informed consent form. If a subject is 
enrolled, the study staff should record the enrollment date and assign a subject number. If 
a subject is not enrolled, an explanation should be recorded on the screening log. A CRF 
will not be completed for subjects who are not enrolled. These subjects will only be 
documented on the screening log and source records.  It is the responsibility of the 
investigator to file the screening log in the investigator site file (ISF) to be readily 
available for on-site monitoring and/or inspection by relevant authorities. Screening may 
take place over more than one day and up to one month prior to Visit 2. If, after 
reviewing all information, the investigator concludes that the subject is eligible, the 
subject will be enrolled in the study. Visits will be scheduled consecutively as described 
in the Time and Events Table.  
 
a. Explain and obtain written informed consent from the subject. Written informed 
consent must be obtained prior to performing any tests or evaluations for the study.  
b. Assign the subject a screening number. Complete the screening log.  
c. Conduct a clinical interview about any changes the subject may have had in medical 
or psychiatric history since participation in MP-1 study. 
d. Request the review of the subject’s records to screen for any conditions listed in the 
eligibility criteria of this research protocol and contact the subject’s treating 
physicians to obtain additional information as needed. 
e. If there is evidence of liver disease by history, physical examination or laboratory 
testing, hepatitis serology will be performed. If there is evidence of significant hepatic 
disease other than Hepatitis C, the person will not be eligible for enrollment, and will 
be advised to see their personal physician for further evaluation. If Hepatitis C 
serology is positive and the potential subject has not already been evaluated for 
possible treatment of Hepatitis C, he or she will be referred to a physician with 
expertise in evaluating and treating liver disease. After this evaluation and after 
completion of any recommended treatment, if the Hepatitis C is judged by this 
physician to be relatively stable and of mild severity, the person may be enrolled if 
there are no other contraindications.   
f. If the potential subject has well-controlled hypertension and no other evidence of 
cardiovascular or cerebrovascular disease by history, physical exam or ECG, and if 
the investigator judges their overall health and other cardiovascular risk factors to be 
acceptable (family history, smoking, lipid levels, body weight, level of physical 
activity), they will be referred for exercise testing by a cardiologist and for carotid 
ultrasound.  If these tests fail to reveal evidence of significant vascular disease or 
other cardiac disease, the person may be enrolled if there are no other 
contraindications. Participants taking one or more antihypertensives may be enrolled 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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in the study. The investigators will record and review medications used to control 
hypertension prior to enrollment. 
g. Review the ability of females of childbearing potential to become pregnant and their 
commitment to practice appropriate birth control as determined by the investigator for 
the total duration of the study. 
h. Administer the following tests: 
 Urine-dip pregnancy test on females with childbearing potential  
 Urine drug screen 
 C-SSRS to assess suicide risk  
 
An independent rater who will not be present during any of the therapy sessions will 
administer:  
 CAPS to assess PTSD symptoms and determine eligibility 
 PDS to assess self-reported PTSD symptoms 
 BDI-II to assess depression symptoms 
 GAF to assess general psychological function 
 
5.2.2 Preparatory Psychotherapy Session (Visit 1) 
 
The preparatory session may take place before enrollment.  
 
a. Record preparatory sessions to audio and video.  Subjects may receive copies of 
audio or video recordings from the preparatory session upon request.  
b. AEs and medications will be recorded as described in Sections 8.5 and 9.0 of the 
protocol. 
c. Assess the subject’s general wellbeing. 
d. Administer the C-SSRS. 
e. The subject will undergo a preparatory session, lasting 60-90 minutes, with a male 
and female co-therapist team. The investigators will work with the subject to prepare 
him or her for the experimental session. The investigators will seek to form a strong 
therapeutic alliance with the subject and will help the subject prepare for the 
upcoming experimental session. The preparatory session will promote a safe setting 
for confronting trauma-related memories, emotions and thoughts.   
f. The subject and the investigators will discuss goals for the experimental session and 
will review what will happen during the experimental session, following standard 
procedures and techniques discussed in the Sponsor’s treatment manual.  
g. During the preparatory session the investigators will introduce the subject to the 
attendant that will remain with the subject during the overnight stay after the MDMA-
assisted psychotherapy session. The attendant will be an individual with previous 
training in managing psychological distress.  
h. If a subject would like another individual present during or after the experimental 
session, a meeting between the investigators and that individual will be scheduled 
prior to the experimental session. There must be mutual agreement between the 
subject and the investigators concerning the presence of the support individual. 
i. The investigators will give the Subject Information Sheet to the subject, which 
includes instructions and restrictions for conduct 24 hours prior to receiving the 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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MDMA, including restrictions on food and alcohol consumption. Subjects must agree 
to take: 
 Nothing by mouth except alcohol-free liquids after 24:00 (midnight) the evening 
before the experimental session.  
 Subjects must also refrain from the use of any psychoactive drugs, with the 
exception of caffeine or nicotine, within 24 hours of each experimental session. 
 Subjects must not use caffeine or nicotine for 2 hours before and 6 hours after 
ingesting the drug, or until investigators deem it safe to do so. 
  
5.2.3 Experimental Session (Visit 2) 
 
Subjects who do not complete all screening activities will not be enrolled. If all inclusion 
criteria and no exclusion criteria are met, eligibility will be confirmed with the subject prior 
to Visit 2. After eligibility is confirmed, the subject will be enrolled prior to Visit 2 and 
issued a subject number.  
 
In consultation with their prescribing physician, any individuals taking psychiatric 
medications will start tapering off these medicines, allowing for a washout period of 5 times 
the half life of each medicine before Visit 2.  
 
Subjects will receive a single open-label experimental session of MDMA-assisted 
psychotherapy with the full dose of MDMA. Procedures for MDMA-assisted psychotherapy 
will be as follows:  
 
a. On the day of the experimental session, the subject will arrive approximately 1-1.5 
hours prior to drug administration.  
b. Confirm continuing eligibility by reviewing inclusion/exclusion criteria. 
c. Perform a urine drug screen. A positive drug screen will be reviewed by the 
investigator and may cause delaying drug administration to a later time, rescheduling 
the session to a later date, or withdrawing the subject from the study. 
d. If the subject is a female of childbearing potential, perform a urine pregnancy test. A 
positive pregnancy screen is a cause for withdrawal from the study. 
e. If the subject continues to meet the study criteria and reports that he/she followed 
appropriate rules and restrictions, the session will proceed. 
f. Review procedures for the experimental session with the subject. 
g. Record the entire session to video and audio. Subjects may receive a copy of audio or 
video recordings of their experimental session upon request. 
h. The session will last for approximately eight hours or longer, followed by an 
overnight stay at the study site. 
i. Administer the C-SSRS approximately one hour to a half hour prior to drug 
administration. 
 
 
 
 
 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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Table 4. Schedule of procedures and measures for the experimental session 
 
 
j. Before drug administration, discuss and review the subject’s goals, intentions and 
concerns and some of the commonly experienced effects of MDMA. 
k. Confirm that the subject has not used caffeine or nicotine 2 hours before and 6 hours 
after the drug administration. 
l. The subject’s body temperature will be measured approximately 15 minutes prior to 
initial dose administration and approximately every 60 to 90 minutes after that. The 
investigators may take more frequent measurements if the body temperature exceeds 
more than 1oC above baseline. 
m. Subjects will complete the SUD prior to initial dose administration.  Subjects will 
complete the SUD every 60 to 90 minutes after that, until the session is over, 
allowing a window of up to 30 minutes to fit into the psychotherapy process where a 
natural break occurs. If necessary, the investigators can make a greater number of 
measurements as their clinical judgment dictates. 
n. Measure blood pressure and pulse prior to the experimental session, and once every 
half-hour throughout the experimental session. More frequent measures will be taken 
if the investigators judge them to be medically indicated. Participants with controlled 
hypertension will have blood pressure and pulse assessed every 15 minutes for the 
first five hours and every 30 minutes for the next three hours. Blood pressure will also 
be measured more frequently if clinically significant symptoms are observed, such as 
chest pain, shortness of breath or neurological symptoms. 
o. At approximately 10:00 in the morning, subjects will receive the initial dose of drug 
Approximate Time 
 
Procedure or Action 
9:00  
Urine drug screen and pregnancy test. Subject gets acclimated to the 
environment, C-SSRS 
 9:45  
Baseline BP, Pulse, Subjective Units of Distress Rating (SUD), Body 
Temperature (BT) 
10:00  
MDMA Administration, begin recording to audio and video 
10:30  
BP, Pulse 
11:00  
BP, Pulse, SUD, BT 
11:30  
BP, Pulse; Can administer optional supplemental dose starting 
now 
12:00  
BP, Pulse, BT 
12:30  
BP, Pulse, SUD 
13:00  
BP, Pulse 
13:30  
BP, Pulse, BT 
14:00  
BP, Pulse, SUD 
Every half-hour, and 
as needed 
BP, Pulse 
Every 60-90 minutes 
SUD, BT 
Approximately 6 
hours after drug 
administration 
C-SSRS, General Wellbeing 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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along with a glass of water.  
p. The subject will sit or recline on comfortable furnishings. Eyeshades and a program 
of music will be provided if the subject wishes to use them.  Subjects will listen to a 
program of music designed to support their experience by initially aiding relaxation 
and later evoking and supporting deep emotions and the emergence of unconscious 
material [91-93]. Subjects may speak to the investigators whenever they wish, and the 
investigators will provide guidance and support as needed.  
q. After the first hour, if the subject has not spoken spontaneously, check in with 
him/her about the nature of their experience. For the rest of the experience, as 
appropriate, the investigators will support and encourage the subject in emotional 
processing and resolution of whatever psychological material is emerging. 
r. Record any spontaneously reported reactions during the session. 
s. Provide water and electrolyte containing fluids throughout the session but not to 
exceed 3 L overall. 
t. A supplemental dose half the size of the initial dose may be administered 
approximately 1.5 to 2.5 hours after the initial dose unless contraindicated by safety 
measures. 
u. Provide food during the latter part of the session.  
v. If there is a support individual who has previously been asked and has agreed to be 
present during part or all of the MDMA session, that person may arrive during the 
session at whatever time has been agreed upon, but will wait in the waiting room until 
brought back to the session room by one of the investigators. The support person may 
arrive after the session has ended. 
w. If it is appropriate to do so, initiate the first question of the C-SSRS at any point in the 
session if the subject is experiencing significant psychological distress that does not 
respond readily to processing with the investigators according to the methods 
described in the MDMA-assisted psychotherapy treatment manual. 
x. End the session if all medical and psychiatric parameters are acceptable and the 
subject is alert, ambulatory and emotionally stable. 
y. The subject will complete the SOCQ in the interval after the end of the experimental 
session and prior to leaving the treatment facility the next day.  
z. The investigators will depart the site when they have concluded that the subject is 
emotionally and medically stable. Investigators shall remain available to subjects 
during the experimental session and for one week after via 24-hour cellular phone. 
aa. Spontaneously reported reactions, AEs and medications will be collected as described 
in Sections 8.5 and 9.0 of the protocol.  
  
Subjects will remain overnight in an appropriately furnished room at the study site.  With 
the approval of the investigators, a companion may accompany the subject during the 
overnight stay. An attendant will check in periodically on the subject during the overnight 
stay, even if a companion is present. The attendant will be an individual with some 
previous training in managing psychological distress.  If there is an emergency or the 
subject needs additional support, the attendant can contact the investigators. The subject 
and a companion (if applicable) will receive information that will allow them to contact 
the investigators during the overnight stay in the case of an emergency or request for 
additional support. Subjects will be encouraged to use much of the time during their 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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overnight stay for rest and for a period of reflection and integration in a quiet atmosphere. 
 
Benzodiazepines or zolpidem may be used if needed after the experimental session, as 
approved by the investigator.  
 
5.2.4 Integrative Session 24 Hours after Experimental (Visits 3) 
 
a. On the morning after the experimental session, both of the investigators from the 
subject’s team will meet with the subject during a 90-minute integrative therapy 
session.  
b. The entire integrative psychotherapy session will be recorded to audio and video. 
Subjects may receive copies of this session upon request. 
c. Administer the C-SSRS just prior to beginning of the integrative session.  
d. Discuss and review events that occurred with the subject during the experimental 
session, including thoughts, feelings and memories. If necessary, the investigators 
will help the subject to reduce any residual psychological distress he or she is 
experiencing. The investigators will also encourage the transfer of states of 
acceptance, feelings of intimacy, closeness and reduced fear experienced in the 
experimental session to emotionally threatening everyday situations. The 
investigators will be supportive, validating the experience and facilitating 
understanding and emotional clearing.  
e. The investigators will remain accessible any time the subject needs support 
outside the scheduled integrative session.  
f. Assess the subject’s mental health and the presence of any remaining reactions 
during integrative psychotherapy immediately after the experimental session.  
g. The integrative psychotherapy session can also serve as an opportunity for the 
investigators to gather information about the effects of the drug on the subject in 
an unstructured manner.  
h. After the integrative psychotherapy session, a person previously selected by the 
subject will provide a ride home to the subject. If the subject is unable to locate an 
individual willing or able to take him or her home, or if the designated person is 
unable to assist the subject due to unforeseen events, the investigators will assist 
the subject in finding an alternative means of returning home. 
i. Spontaneously reported reactions, Adverse Events and Medications will be 
collected as described in Sections 8.5 and 9.0 of the protocol.  
j. Remind the subjects that they will have a daily contact with a therapist for the 
next 7 days. 
 
5.2.5 Daily Telephone Contact for Seven days after the Experimental Session 
 
a. Starting on the day of the integrative psychotherapy session following the 
experimental session, one of the investigators will contact the subject via 
telephone or in person on a daily basis for one week.  
b. The integrative contact will be for a brief check-in lasting 5 to 15 minutes, or as 
long as necessary to address any of the subject’s concerns and to assess the 
subject’s well-being. Additional telephone contact can be initiated at the request 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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of the investigators or the subject. 
c. On the second and the seventh day of contact after the experimental session, the 
subject will complete the C-SSRS. 
d. General wellbeing will be assessed at each phone call. 
e. Spontaneously reported reactions, AEs and medications will be collected as 
described in Sections 8.5 and 9.0 of the protocol. 
 
5.2.6 Additional Integrative Psychotherapy Sessions (Visits 4 and 5) 
 
a. The subject will have two additional integrative psychotherapy sessions lasting 
approximately 90 minutes with both of the investigators from the subject’s 
therapist team. The investigators may conduct more sessions if they and the 
subject deem it necessary.  
b. Record each integrative session to audio and video. Subjects may receive a copy 
of one or more integrative sessions upon request. 
c. The C-SSRS will be administered just prior to beginning of each integrative 
session.  
d. General wellbeing will be assessed at each integrative session. 
e. The subject and investigators will continue to work on supporting the subject as 
she or he considers his or her experiences during the experimental session.  
f. The investigators will use clinical judgment to assess the subject’s psychological 
wellbeing during this period of time. If there are any indications of continuing 
anxiety or distress, the investigators may arrange to work on reducing the distress 
at a specially scheduled integrative therapy session, through continuing contact, or 
at the next regularly scheduled integrative therapy session. The subject may also 
initiate contact with the investigators at any time throughout the study.  
g. AEs and medications will be collected as described in Sections 8.5 and 9.0 of the 
protocol. 
h. If an integrative session falls within the period of telephone contact and additional 
phone call is not required that day, all things normally collected during the 
telephone call will be completed in person. 
 
5.2.7 Evaluation Two Months after the Experimental Session (Visit 6) 
 
This visit will consist of two meetings that may be completed on separate days, one with 
the independent rater and the other with the investigators at the study site. 
 
a. Subjects will meet the independent rater for approximately an hour and a half. 
b. The independent rater will administer:  
 CAPS to assess PTSD symptoms 
 PDS to assess self-reported PTSD symptoms 
 BDI-II to assess depression symptoms 
 GAF to assess general psychological function 
c. After completing all assessments and measures with the independent rater, the 
subject will meet with the investigators for approximately 60-90 minutes. 
d. The investigators will assess suicidality with the C-SSRS. 


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e. General wellbeing will be assessed. 
f. Subjects will complete the Responses to Research Participation Questionnaire 
(RRPQ). 
g. Subjects will receive a memory aid card for use between this visit and the 12-
month follow up. Subjects will use this card to record any AEs related to their 
psychiatric status, any changes in their psychiatric status and any medications 
taken to treat these AEs during the follow-up period. Subjects will be asked about 
these at the termination visit. Memory aids will not be collected. 
h. AEs and medications will be collected as described in Sections 8.5 and 9.0 of the 
protocol. 
 
5.2.8 Long-Term Follow-up at Twelve Months 
 
The subjects will be evaluated for long-term effects 12 months after their MDMA-
assisted psychotherapy session. This visit will consist of two meetings, one with the 
independent rater and the other with the investigators. The meetings may take place at the 
study site or over the telephone. 
a. The independent rater will administer the CAPS, PDS, BDI-II and GAF. 
b. Subjects will have a final meeting with at least one of the investigators to review 
specified AEs and medications since the last visit. Subjects should bring the 
memory aid cards to this visit, to be used as aids in recollection.  These cards will 
not be collected. Information on AEs and medications will be collected as 
described in Sections 8.5 and 9.0 of the protocol. 
c. The investigators will assess suicidality with the C-SSRS.  
d. General wellbeing will be assessed. 
e. Subjects will complete a questionnaire assessing positive and negative long-term 
effects of the study.   
f. Subjects will complete the termination visit at this time. 
 
5.3 Subject Numbering 
 
Prior to enrollment, subjects will be tracked with their initials and a screening number 
assigned sequentially starting at "01". Subjects who meet all inclusion and no exclusion 
criteria will be enrolled into the study and will be assigned a five-digit subject number.  
The first two digits will be “E2” to identify the protocol number. The last two digits will 
identify the subject within the site and will be assigned sequentially, with 01 
corresponding to the first subject enrolled, e.g. the first enrolled subject will be E201, the 
second E202, etc. In total, up to three subjects will be enrolled into the study.  
 
5.4 Removal or Withdrawal of Subjects from the Study 
 
Subjects can withdraw consent at any time without prejudice.  The investigators can 
withdraw a subject if, in his or her clinical judgment, it is in the best interest of the 
subject or if the subject cannot comply with elements of the experimental session and 
related visits that are critical for safety.  If the investigators withdraw a subject from the 
session, the investigators will explain the reason for withdrawing the subject.  


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If a subject develops any exclusion criteria that, in the opinion of the Medical Monitor, 
affect the safety of the subject, including psychiatric diagnosis, pregnancy or excluded 
medications, the subject may be removed from the study. Subjects who withdraw from 
the study will not be replaced. 
 
Subjects will be clinically monitored after withdrawal by at least one of the investigators, 
the cause of which will be recorded in the subject’s source records and CRF.  Whenever 
possible, the tests and evaluations listed for the termination and evaluation visits will be 
carried out.  Efforts will be made to obtain information about AE outcomes, if deemed 
necessary by the therapist and/or the Sponsor. 
 
5.5 Premature Discontinuation of the Study 
 
The Sponsor or the clinical investigator (following a consultation with the Sponsor) has 
the right to discontinue this study at any time.  If the study is prematurely terminated, the 
investigator should promptly inform the study subjects and assure appropriate therapy 
and follow-up. All procedures and requirements pertaining to retention and storage of 
documents will be observed. All other study materials will be returned to the Sponsor and 
will be treated in accordance with federal and local regulations. 
 
6.0 Investigational Product 
6.1 Description 
 
The investigational product to be used in this research protocol is MDMA. This ring-
substituted phenylisopropylamine has a complex pharmacology, but it acts most 
prominently as a monoamine releaser and uptake inhibitor [94-96].  Its direct actions on 
serotonergic, adrenergic and other receptors are considerably lower.  
 
6.2 Administration 
 
The study will consist of an open-label administration of a full dose of MDMA (125 mg) 
possibly followed by a supplemental dose of 62.5 mg, unless contraindicated based on 
safety measures.  
 
 
 
6.2.1 Preparation 
 
The investigational product that will be used in this study is MDMA HCl manufactured 
by David Nichols, Ph.D., Dept. of Medicinal Chemistry and Pharmacology, Purdue 
University in 1985.  MDMA in bulk will be sent by Dr. David Nichols Ph.D. or his 
representatives at Purdue University, in West Lafayette IN, to the Clinical Investigator, 
who has been issued the Schedule 1 license by the Drug Enforcement Agency (DEA). 
MDMA will be compounded by the appropriate pharmacist, weighed, and placed into 
gelatin capsules of 125 mg for the initial dose and 62.5 mg for the supplemental dose.  


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6.2.2 Labeling 
 
During compounding, each dose of MDMA will be placed into a holding box (See 
sample holding box label).  
 
The initial and supplemental doses of MDMA for a single subject to complete the 
experimental session will be stored in an envelope labeled with the protocol number, drug 
name, lot number, unique envelope number, Sponsor name and a statement that the drug 
is for clinical trial use only (see envelope label). Each dose of MDMA will be labeled and 
stored in the individual container within the envelope (see container labels for each 
session and dose).  Labels will be provided by the Sponsor and applied by the pharmacist. 
All drug labels will comply with federal, state and local regulations. 
 
 
 
 
 
 
 
 
 
 
 
 
    
 
 
 
   
Each dose will consist of the specified amount of racemic MDMA. Initial doses will be 
distinguished from supplemental doses through labeling “Dose: 125mg” and “Dose: 62.5 
mg” to ensure that the correct dose is administered at the scheduled time. Each dose of 
MDMA will be administered along with a glass of water or electrolyte-containing fluid.  
 
6.3 Drug Accountability 
 
Forms will be provided to track drug accountability and administration throughout the 
study. Drug accountability will be reviewed during routine monitoring visits. 
 
6.4 Drug Storage and Handling  
 
Holding Box Label 
MAPS Study # MP1-E2 
Investigational Product: MDMA  
Initial Dose: 125mg 
Lot #: 5810-09 
Administer as per protocol 
Caution-Limited by Law to Investigational Use Only 
Envelope Label 
MAPS Study # MP1-E2 
Investigational Product: MDMA  
Dose: 125 mg, 62.5 mg 
Lot #: 5810-09 
Envelope #: XXXX 
Subject #_____________ 
Administer as per protocol 
Caution-Limited by Law to Investigational Use Only 
Container label 
MAPS Study # MP1-E2 
Lot #: 5810-09 
Dose: 125 mg MDMA 
Envelope #: XXXX 
Subject #____________  
Administer as per protocol  
Investigational Use Only   
  
Container label 
MAPS Study # MP1-E2 
Lot #: 5810-09 
Dose: 62.5 mg MDMA 
Envelope #: XXXX 
Subject #____________  
Administer as per protocol  
Investigational Use Only   


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MDMA is a Schedule 1 compound and will be stored and handled in compliance with all 
relevant local and federal regulations. In accordance with the DEA requirements, the 
Clinical Investigator will be responsible for storing and dispensing the MDMA.  It will be 
stored in a safe mounted to the floor that has been inspected and approved by the DEA 
for this purpose. Only the Clinical Investigator with the Schedule 1 license will know the 
combination to the safe. The room in which the safe is mounted has an alarm system and 
will be locked whenever the investigator or his staff are not present.   
  
Investigational product will only be removed from the safe for one subject at a time at the 
time of the session, and the MDMA will not leave the premises. All doses administered 
will be recorded on the appropriate accountability logs. 
 
Records pertaining to the use of this Schedule 1 compound will be maintained in 
accordance with relevant federal and state regulations. They will be kept separately from 
other records and will be maintained in a locked cabinet in a locked office with an alarm 
system. 
 
 
6.5 MDMA Stability 
 
As described in Section 6.2.1, MDMA used in this study was prepared for human 
consumption in 1985 by David Nichols, Ph.D., Dept. of Medicinal Chemistry and 
Pharmacology, Purdue University.  Complete details on the chemistry, manufacturing and 
control of the MDMA to be used are described in Drug Master File (DMF) # 6293. The 
identity and purity of this MDMA was confirmed using High Performance Liquid 
Chromatography (HPLC) in 1997 as described in DMF # 6293 and was found to be 
99.87% pure. On August 12, 2002, Chemic Laboratories reanalyzed the MDMA at the 
request of the sponsor prior to starting MAPS’ first U.S. pilot study of MDMA-assisted 
psychotherapy in people with PTSD. The analysis found the MDMA to be more than 
99.7% pure. A more recent analysis performed by Nichols at the request of researcher Dr. 
Carl Hart on February, 2006, continued to find a high degree of purity. This analysis 
found the MDMA in question to be 99.9% pure.  This MDMA was used in an 
investigation of MDMA-assisted psychotherapy that took place in the U.S. with drug 
administration ending in 2008, and it was also used in non-sponsor supported study in 
2006 [97]. 
 
7.0 Risks of Participation 
 
7.1 Risks and Discomforts Associated with Non-drug and Experimental Psychotherapy 
Sessions and Assessment of Measures 
 
During screening, non-drug and drug-assisted psychotherapy sessions and assessment of 
study measures, subjects will be asked to think about and discuss their thoughts and 
emotions relating to the traumatic event or events.  They may experience intense 
emotional responses to recalling and speaking about this material.  Even in a therapeutic 
context, thinking about and discussing the trauma, symptoms related to the trauma or the 


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effects of PTSD on life function can produce distress during and immediately after non-
drug psychotherapy, experimental and open label sessions.  Psychotherapy is conducted 
as part of the research study, including the experimental intervention, and people 
undergoing psychotherapy are expected to confront unpleasant thoughts, feelings and 
memories in the process of therapy. Because psychotherapy is an integral part of the 
research study design, the potential distress arising from psychotherapy is unavoidable.   
 
All psychotherapy sessions will be recorded to audio and video. Subjects may feel 
uncomfortable with having their sessions recorded. Subjects may have access to 
recordings if they request them. The recordings are necessary for developing the 
experimental treatment. Subjects will receive information on who will have access to any 
of their recordings and will have control over any presentation of this material beyond 
viewing by researchers or regulatory agencies. 
 
7.2 Risks of Receiving MDMA 
 
Spontaneously reported reactions and common adverse effects of MDMA are known to 
be modest and have generally not been associated with serious discomfort by healthy 
volunteers in previous studies. Spontaneously reported reactions are compiled from 
previously published literature and include anxiety, diarrhea, difficulty concentrating, 
dizziness, drowsiness, dry mouth, fatigue, headache, impaired gait/balance, increased 
irritability, rumination (increased private worries), insomnia, jaw clenching, tight jaw, 
lack of appetite, low mood, muscle tension, nausea, nystagmus, parasthesias, 
perspiration, restlessness, sensitivity to cold, thirst and weakness. In MAPS study MP-1 
(N=23), comparing MDMA-assisted psychotherapy to inactive placebo, anxiety, 
headache, fatigue, insomnia and lack of appetite were spontaneously reported by 40% to 
80% of participants in both the MDMA and placebo conditions. However, tight jaw, 
nausea, impaired gait/balance, and sensitivity to cold were more often reported by 
participants in the MDMA than the placebo condition, and irritability was slightly more 
likely to be reported in the placebo condition. Additionally, participants in the MDMA 
condition were more likely to report muscle tension in various body parts and diarrhea.  
These effects are transient and diminish as drug effects wane. Sub-acute effects that may 
either continue for the next 24 hours or appear later include insomnia, fatigue, needing 
more sleep, weakness, heavy legs, dry mouth, low mood or irritability. Sub-acute effects 
are reported less often than acute effects. More information on spontaneously reported 
reactions is described in the Investigator's Brochure.  
 
MDMA may produce mild alterations in sensory perception and altered perception of 
time [52, 74, 98].  Women may be more sensitive to these effects [75].  MDMA acutely 
affects attention, information processing and memory. MDMA acutely impairs verbal 
memory and recall for object location without affecting recall of scene change while 
driving [58]. For this reason, subjects will stay at the site overnight and will not be 
permitted to drive after experimental sessions.  
 
MDMA may produce modest changes in immune functioning, lasting up to 48 hours. 
Because of their limited duration, these changes are not likely to have clinical 


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significance beyond several days of possible increased risk of viral upper respiratory 
infection or similar illness.  
 
Further information on the risks associated with MDMA, including information drawn 
from case reports and studies of Ecstasy users, can be found in the Investigator’s 
Brochure.  
 
7.2.1 Cardiovascular and Sympathomimetic Effects 
 
The full dose of 125 mg, followed by a supplemental dose of 62.5 mg after 1.5 to 2.5 
hours, is expected to produce significant but transient, self-limited increases in blood 
pressure and heart rate. These changes should last no more than six hours. In less than 5% 
of volunteers in Phase 1 studies, increases in blood pressure were higher than 140/90 
mmHg. Clinical intervention was not required in any of these cases. Nonetheless, careful 
monitoring of participants and predefined contingency plans will allow the researchers to 
rapidly identify and manage any related toxicity. For more information, see the 
Investigator’s Brochure. 
 
Risks posed by elevated blood pressure will be addressed by excluding people with 
hypertension, unless it is well-controlled, as described in Exclusion criteria section 4.2.2, 
and by monitoring blood pressure and pulse as described in Safety Measures section 
5.1.2. During the experimental session the investigators will continually evaluate the 
patient for increasing blood pressure and signs or symptoms of a developing hypertensive 
or another cardiovascular emergency. Subjects reporting chest pain, shortness of breath 
or neurological symptoms or other potential indicators of hypertension that may need 
intervention will have more frequent measurements.  
 
Reasons for moving a patient to an emergency department or ICU would include, but not 
be limited to, severe headache in the setting of hypertension, angina or neurological 
deficits regardless of blood pressure.  In case of an emergency, intravenous anti-
hypertensive agents will be available in addition to the usual resuscitation drugs and 
equipment. The investigators may, at any time, make a clinical judgment to transfer the 
patient to the ICU for closer monitoring and additional treatment.  
 
The investigators will be prepared to respond to rare complications of cardiovascular 
effects, such as stroke or myocardial infarction. The investigators will attend to any signs 
or symptoms of neurological deficit or confusion that is more extensive than might be 
expected from MDMA or from psychological distress. If any participant has neurological 
deficits, whether or not they are associated with hypertensive crisis, he or she will receive 
oxygen and an IV and will be monitored as described above. He or she will be 
transported to the emergency department at East Cooper Medical Center, the nearest 
hospital, for a head CT scan and further management. If evaluation at the hospital reveals 
a nonhemorrhagic stroke, there will be time to administer recombinant tissue 
plasminogen within the 3 hour time frame recommended in the American Academy of 
Neurology/American Heart Association guidelines [99, 100]. 
 


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The investigators will observe the participant and note any complaints of chest pain. If a 
participant experiences ischemic type chest pain, whether or not it is associated with 
hypertensive crisis, he or she will undergo a stat ECG, receive oxygen and an IV and will 
be monitored as described above. If necessary, he or she will be transported to ICU or a 
location in the hospital where appropriate care can be given. He or she will be given 
nitroglycerin 0.4 mg SL q 5 minutes PRN chest pain pending transport to the hospital. If 
further evaluation at the hospital reveals that the participant has had an acute myocardial 
infarction (AMI), he or she will be well within the time frame required for definitive 
therapy. The American College of Cardiology/American Heart Association guidelines for 
the treatment of AMI recommend percutaneous transluminal coronary angioplasty 
(PTCA) as the treatment of choice when it can be performed within 90 minutes of arrival 
at the hospital in patients who present within 12 hours of an episode of chest pain lasting 
more than 30 minutes and who have ECG evidence of AMI [101]. 
 
7.2.2 Psychological Distress 
 
Mild anxiety and depressed mood are occasionally reported 1–3 days after the MDMA  
administration [47, 75, and see the IB]. Psychological distress from MDMA could arise 
from the first indications of drug effects until the last effects have dissipated 
(approximately 3 to 5 hours after drug administration). Anxiety or distress during the 
experimental session may last for as little as 15 minutes or for as long as 5 hours.  In 
addition, psychological distress could arise following the MDMA session as a result of 
subjects having difficulty integrating their experience after the MDMA effect has 
subsided.  In previous Phase 1 and Phase 2 studies, these symptoms have been modest 
and self-limiting, and have responded well to reassurance from the investigators, with 
occasional use of benzodiazepines for anxiety. In this study, subjects will have the 
intention of confronting and working through traumatic experiences. Hence signs of 
psychological distress, panic or other unpleasant psychological reactions are to be 
expected and may be considered an element of the psychotherapeutic process.  
 
Proper preparation and follow-up support will reduce the difficulties subjects might have 
with acute or sub-acute reactions. All study participants will have undergone previous 
MDMA-assisted psychotherapy sessions and will be familiar with the experience. The 
potential for destabilizing psychological distress will be minimized by: 
 excluding people who might be more vulnerable to it (such as people diagnosed 
with bipolar affective disorder - 1 or with psychotic disorders) 
 a preparatory non-drug psychotherapy session before the experimental session 
 creating an atmosphere of trust during the experimental session 
 close monitoring 
 daily contact with subjects for the period of a week after the experimental session 
 providing non-drug integrative psychotherapy sessions   
 Subjects will remain at the study site for the night after the experimental session 
to further reduce psychological distress. Qualified personnel will be available 
during the overnight stay to respond to the needs of the subject. Attendants will be 
instructed to contact the investigators upon request or at the appearance of signs 
of a potential serious adverse event.  


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During the preparatory session, subjects will be made aware of the fact that difficult 
emotions, including grief, rage and fear or panic, may arise during the experimental 
session.  Every effort will be made to help subjects resolve difficult symptoms and to 
arrive at a more comfortable and relaxed state by the conclusion of the experimental 
session, including empathic listening on the part of the investigators and performance of 
diaphragmatic breathing by subjects.  
 
At the end of the 6–8 hour experimental session, if the subject is still severely agitated or 
experiencing any other severe psychological distress, the following measures will be 
taken:  
 If the subject is anxious, agitated, in danger of any self-harm or is suicidal at the 
end of the experimental session, the investigators will remain with the subject for 
at least two more hours.  During this time, the investigators will employ affect 
management techniques, will talk with the subject to help him or her gain 
cognitive perspective of their experiences, and will help them implement the self- 
soothing and stress inoculation techniques presented during the preparatory 
session. If this situation should occur during an integrative therapy session, at 
least one of the investigators will be available to stay with the subject for at least 
two additional hours. 
 If a subject remains severely anxious, agitated or in danger of self-harm or 
suicide, or is otherwise psychologically unstable at the end of this two-hour  
stabilization period, the clinical investigator will decide between the following  
options: 
1. A psychiatric nurse, therapeutic assistant or therapist will stay with the 
subject until the time of his or her appointment with the investigators 
the next day.  The investigators will then meet with the subject daily 
until the period of destabilization has passed.  
2. If a subject experiences severe, persisting emotional distress, such as 
panic attacks, severe generalized anxiety or insomnia following an 
MDMA session, the investigators may prescribe a benzodiazepine or 
zolpidem as a “rescue medication.”  This medication will be captured 
on the concomitant medications CRF page. Investigators should not 
prescribe an SSRI, SNRI or MAOI in this context. Residual symptoms 
will be addressed during the frequent follow-up psychotherapy visits 
with the investigators. 
3. Hospitalization for stabilization. Should a subject remain 
psychiatrically unstable despite the above measures he or she will be 
transferred to a psychiatric inpatient unit. 
 
Subjects hospitalized after becoming psychiatrically unstable will be suspended from the 
protocol until after recovery or stabilization, at which time the investigator will carefully 
evaluate the subject’s emotional status.   
 


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For those subjects engaged in an ongoing therapeutic relationship with a psychotherapist 
or psychiatrist, the subject’s outside therapists will be involved in the management of any 
psychiatric complications.   
 
7.2.3 Body Temperature 
 
MDMA administered in a controlled setting produces only a slight increase in body 
temperature [75], and ambient temperature does not enhance or attenuate this slight 
elevation in humans.   
 
If temperature rises more than 1° C, attempts will be made to lower it by removing 
blankets and layers of clothing, decreasing the ambient temperature and, if necessary, 
directing a fan toward the participant.  If at any time the temperature rises more than 1.5° 
C above baseline despite these efforts, ice packs will be used, blood will be drawn for stat 
CBC, electrolytes, BUN/creatinine, glucose, CPK, PT, PTT, platelets and liver enzymes, 
and urine will be collected for urinalysis.   
 
7.2.4 Reproductive and Developmental Risks 
 
Risks posed by MDMA to pregnant women are not known.  One of two studies of 
Ecstasy users suggests that use of Ecstasy (often used along with other drugs) during 
pregnancy may be associated with some abnormalities at birth while the other failed to 
find this association [102, 103], as discussed in the Investigator’s Brochure.   
 
Pregnant and lactating women will be excluded from participation in the study, and 
women who are able to become pregnant must have a negative pregnancy screen before 
undergoing the experimental session and must agree to use birth control for the duration 
of the study. 
 
7.2.5 Potential Neurotoxicity Associated with Ecstasy Use 
 
Some researchers believe that MDMA is neurotoxic in humans even at doses used in 
clinical trials [104].  However, they are basing their case on studies that employed 
inappropriately high doses of MDMA utilized in animal studies, and on human studies 
comparing the effects of repeated use of ecstasy, often along with other drugs. We have 
carefully considered the risks of such neurotoxicity and concluded that they are minimal 
in the proposed study. This conclusion is supported by empirical and toxicokinetic 
evidence and is consistent with the lack of toxicity reported in previous clinical MDMA 
studies. More information on the potential neurotoxicity of MDMA can be found in the 
Investigator’s Brochure.  
 
7.2.6 Risk Mitigation 
 
Prior to participating in the current study, all study subjects will have undergone the 
Sponsor initiated MP-1 study, which included two to three MDMA-assisted 
psychotherapy sessions, and are known to have tolerated MDMA well. Careful review of 


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medical records and screening data will be utilized to exclude potential participants with 
preexisting exclusionary medical conditions from the study. Study procedures have been 
developed to mitigate the risks of receiving MDMA described in detail in the 
Investigator’s Brochure. Ambient temperature will be kept at a comfortable level during 
the experimental session. Subjects will not be allowed to drink more than 3L of fluids 
over the course of the experimental session, and fluid intake will be spread out 
appropriately during the session. Fluids administered will include electrolytes.  
7.3 Abuse Liability 
 
Findings in humans and nonhuman animals suggests that MDMA possesses moderate 
abuse potential that is higher than that reported for “classic hallucinogens” like 
psilocybin, but lower than that reported for psychostimulants such as cocaine or 
methamphetamine. More information on abuse liability is provided in the Investigator’s 
Brochure 
 
Whether or not MDMA's abuse potential will negatively affect people with PTSD 
exposed to MDMA when given along with psychotherapy is an open question for which 
there is of yet no direct data. Mithoefer and colleagues are in the process of analyzing 
data from a long-term follow-up of participants in their study of MDMA-assisted 
psychotherapy. Only one of 20 participants took Ecstasy on one occasion after 
completing the study and failed to reproduce the experience she had had with the 
therapists during the study, and a number of participants volunteered that they would 
never seek out Ecstasy outside a legal, controlled therapeutic setting.  
 
Diversion is not an issue in this protocol because MDMA will only be administered a few 
times under the supervision of the clinical investigator and no take-home doses will be 
permitted.  MDMA will be handled following all regulations pertaining to the handling 
and dispensing of controlled substances within research studies. 
 
8.0 Adverse Events 
8.1 Adverse Events 
 
An adverse event (AE) is defined as any untoward or unfavorable medical occurrence in 
a clinical research study participant, including any abnormal sign (e.g. abnormal physical 
exam or laboratory finding), symptom, or disease, temporally associated with the 
participants' involvement in the research, whether or not considered related to 
participation in the research. This definition includes concurrent illnesses or injuries and 
exacerbation of pre-existing conditions.  
 
An unexpected adverse event is one that is not listed in the current Investigator’s 
Brochure or an event that is by nature more specific or more severe than a listed event. 
 
All AEs will be monitored by the investigators until resolution or, if the AE becomes 
chronic, a cause identified.  If an AE is unresolved at the conclusion of the protocol, a 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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clinical assessment will be made by the investigator and/or Medical Monitor as to 
whether continued follow-up of the AE is warranted. 
 
The severity of events reported on the “Adverse Events” CRF will be determined by the 
investigator as: 
 
· 
Mild: No limitation in normal daily activity 
· 
Moderate: Some limitation in normal daily activity 
· 
Severe: Unable to perform normal daily activity 
 
The relationship of the study treatment to an AE will be determined by the investigator 
based on the following definitions: 
 
1. Not Related 
 
The AE is not related if exposure to the investigational product has not occurred, or the 
occurrence of the AE is not reasonably related in time, or the AE is considered unlikely 
to be related to use of the investigational product, i.e. there are no facts (evidence) or 
arguments to suggest a causal relationship, or the AE is more likely related to the 
subject’s pre-existing condition. 
 
2. Possibly Related 
 
The administration of the investigational product and AE are considered reasonably  
related in time and the AE could be explained by causes other than exposure to the  
investigational product. 
 
3. Probably Related 
 
Exposure to the investigational product and AE are reasonably related in time and the  
investigational product is more likely than other causes to be responsible for the AE, or is 
the most likely cause of the AE. 
 
The relationship of the study treatment to an AE will be determined by the investigator. 
 


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8.2 Spontaneously Reported Reactions  
 
Commonly expected spontaneously reported reactions are collected on a separate CRF 
page and will be categorized as mild, moderate or severe. Spontaneously reported 
reactions are compiled from previously published literature and sponsor-supported 
investigations and include anxiety, diarrhea, difficulty concentrating, dizziness, 
drowsiness, dry mouth, fatigue, headache, impaired gait/balance, increased irritability, 
rumination (increased private worries), insomnia, jaw clenching, tight jaw, lack of 
appetite, low mood, muscle tension, nausea, nystagmus, parasthesias, perspiration, 
restlessness, sensitivity to cold, thirst and weakness. Spontaneously reported reactions 
will be collected during the experimental session and the seven days of telephone contact 
following the integrative session that occurs on the day after the experimental session.  
 
8.3 Serious Adverse Events 
 
An SAE is defined as any untoward medical occurrence that at any dose: 
 
 Results in death 
 Is life-threatening (i.e., the subject was, in the opinion of the investigator, at 
immediate risk of death from the event as it occurred); it does not refer to an event 
which hypothetically might have caused death if it were more severe 
 Requires or prolongs inpatient hospitalization 
 Results in persistent or significant disability/incapacity (i.e., the event causes 
substantial disruption of a person’s ability to conduct normal life functions) 
 Results in a congenital anomaly/birth defect 
 Requires intervention to prevent permanent impairment or damage 
 Is an important and significant medical event that may not be immediately life-
threatening or resulting in death or hospitalization, but based upon appropriate 
medical judgment, may jeopardize the patient/subject or may require intervention 
to prevent one of the other outcomes listed above. 
 
AEs which do not fall into these categories are defined as non-serious.  It should be noted 
that a severe adverse event need not be serious in nature and that a SAE need not, by  
definition, be severe. 
 
In addition, a pre-existing event or condition that results in hospitalization should be 
recorded on the medical history.  The hospitalization would not result in the event or  
condition being reported as a study-related SAE unless, in the view of the investigator,  
hospitalization was prolonged as a result of participation in the clinical trial or was  
necessary due to a worsening of the pre-existing condition.  This is because the onset of 
the event (the reason for the procedure) occurred before the subject was entered in the 
trial.  Hospitalization for cosmetics, non-emergency prophylaxis or abortion does not  
result in an SAE report unless, in the view of the investigator, hospitalization for these 
procedures was prolonged as a result of participation in the clinical trial. 
 


MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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8.4 Medical Emergencies 
 
The preparatory session, MDMA session and integrative sessions will be conducted in 
the psychiatric offices of the investigators.  The offices are located 2.6 miles from the 
nearest emergency room.  The office will be equipped with a "crash cart" containing the 
emergency medications and equipment necessary to respond to any complications.  
Intravenous fluids, antiarrhythmic drugs, antihypertensive drugs (such as nitroprusside 
and labetalol), injectable epinephrine and other pressor agents, and other standard 
emergency drugs and equipment will be available on-site as a means of treating any 
potential allergic reactions or other medical emergencies. In addition to drugs, the crash 
cart will contain a defibrillator (with rhythm monitoring capability), an oxygen tank, a 
suction device, a pulse oximeter, an IVAC pump and intubation equipment (including 
laryngoscope, and endotracheal tubes).  As is now common practice in emergency 
departments, an automatic blood pressure cuff will be used in place of intraarterial blood 
pressure monitoring equipment. In the unlikely event of cardiac arrest, the investigators 
will follow the American Heart Association guidelines for 2-person BLS for Healthcare 
Providers (including defibrillation with an automated external defibrillator (AED) until 
the arrival of Emergency Medical Services (EMS), at which time Advanced Cardiac Life 
Support (ACLS) procedures will be instituted. With these personnel and equipment, the 
researchers, in conjunction with EMS if necessary, would be able to begin treatment in 
the office and then transport the participant by ambulance, if hospital admission were 
required, to the emergency department or ICU at East Cooper Medical Center, the nearest 
hospital.  
 
8.5 Adverse Event Collection 
 
All SAEs will be collected for the duration of the protocol.  All SAEs, which occur 
during the course of the trial, whether considered to be associated with the study drug or 
not, have to be reported to the Sponsor within 24 hours of the investigator’s awareness of 
their occurrence.  All SAE reports should be faxed to the Sponsor.  A fax number will be 
provided to the site in separate site-specific instruction for SAE reporting. In addition to 
the fax, the Clinical Investigator (CI) or designee should call the CRA during normal 
working hours and verbally inform the CRA of the SAE.  During off hours or if medical 
advice is needed immediately, please call the Sponsor Medical Monitor.  Instructions for  
SAE reporting with all contact numbers will be provided to the site prior to study start.   
 
Medical Monitor  
 
Julie Holland MD  
NYU School of Medicine 
200 East 33rd Street, Suite 16H 
New York, NY 10016 
Voice mail: 212-358-5808 
 
Study Monitor contact information will be provided in a separate contact list. 
 


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Adverse events that will be collected for the duration of the protocol are: 
 
 All SAEs will be collected through termination. 
 All Adverse Events and spontaneously reported reactions will be collected on the 
day of drug administration and for seven days after the experimental session. 
 Events requiring medical attention will be collected from the experimental session 
through the 12-month follow up. 
 Events related to planned treatments or physician visits for baseline conditions 
collected in the Medical History will not be collected unless there is an 
exacerbation of the condition. 
 Any Adverse Event leading to withdrawal from the protocol will be collected 
throughout the study. 
 All AEs related to changes in psychiatric status will be collected throughout the 
study. 
 
As described in Section 5.2.7, subjects will receive a memory aid card for use between 
the 2-month and 12-month follow-up visits to record any AEs related to their psychiatric 
status during this follow-up period.  
 
9.0 Concomitant Medications and Tapering Instructions 
Concomitant medications will be recorded during screening. If the subject is being 
treated with psychiatric drugs at the time he or she is recruited into the study, the 
prospective subject will be encouraged to discuss any medication tapering necessary with 
his or her outside treating physician, and will be required to give the investigators 
permission to do so as well. The drugs will then be tapered off in an appropriate fashion 
to avoid withdrawal effects. They will be discontinued long enough before the first 
MDMA session to avoid the possibility of any drug-drug interaction (the interval will be 
at least 5 times the particular drug's half-life).  
 
The investigators will request information about any changes in medication just prior to 
the experimental session. All medications, over the counter (OTC) and prescription, will 
be collected from screening through 7 days after the MDMA session.  From 7 days after 
the MDMA session through study termination only prescription or OTC medications 
taken to treat AEs, as specified in Section 8.5, and all changes including discontinuations 
or additions to psychiatric medications will be collected. Medications will be recorded on 
the concomitant medications CRF.   
 
Subjects must be willing to refrain from taking any psychiatric medications, including 
stimulants, from 5 half-lives before the MDMA session until 10 days after the MDMA 
session, with the exception of gabapentin when prescribed for pain control. After that 
subjects may resume taking psychiatric medications taken at baseline at the discretion of 
the prescribing physician, but no new psychiatric medications may be added until after 
the 2 month follow-up.    
 


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Subjects may receive a designated rescue medication that may be administered in the 
event of symptoms that require it during or after the experimental session (e.g. insomnia 
or severe anxiety that does not respond to other management outlined in the treatment 
manual). Rescue medications may be benzodiazepines, as lorazapam, or zolpidem. 
SSRIs, SNRIs and MAOIs should not be used as rescue medications. 
 
Subjects must agree that, for one week preceding the MDMA session: 
a. They will refrain from taking any herbal supplements (except with prior approval 
of the research team).  
b. They will refrain from taking any prescription or nonprescription medications 
(with the exception of non-steroidal anti-inflammatory drugs, acetaminophen, 
birth control pills, thyroid hormones, or other medications approved by the 
research team).  
 
As described in Section 5.2.7, subjects will receive a memory aid card for use between 
the 2-month and 12-month follow-up visits to record any changes in medications used to 
treat AEs related to their psychiatric status during this follow-up period. 
 
10.0 Clinical Laboratory Assessments 
The clinical investigator or the study staff will examine laboratory assessments gathered 
as a part of screening for assessing participant eligibility.  The following laboratory 
assessments will be performed at screening and immediately before the experimental 
session: 
 
 A urine-dip pregnancy test for females of childbearing potential 
 Urine drug screening test 
 
The urinary pregnancy tests and drug tests will be performed at the study site.  
Hepatitis serology or other additional clinical tests may be conducted as indicated to 
determine the subject’s eligibility for the study. 
 
11.0 Study Monitoring, Auditing and Documentation 
The clinical investigators and the study staff will be trained prior to the start of the study.  
The study site will be monitored by site visits and telephone calls to the investigator by 
representatives of the Sponsor. The site will be monitored as appropriate for the rate of 
enrollment in order to comply with GCP guidelines and to ensure validity of the study 
data. During each monitoring visit, source data verification will be performed to ensure 
compliance, including accurate and complete recording of data on CRFs, source 
documents, and drug accountability records. A CRF collation supplied by the Sponsor 
will be completed for each subject enrolled.   
 
During or after the study, the regulatory authorities, the IRB, and/or representatives of the 
Sponsor may request access to all source documents, CRFs and other protocol 
documentation for on-site audit or inspection. 


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12.0 Data Analysis  
The sponsor will collect outcome and safety measures from all subjects who enroll in and 
complete this study. This will include CAPS subscale, global and diagnostic scores, PDS 
severity scores, BDI-II scores, and GAF scores. The sponsor will also collect SOCQ 
subscale scores, vital signs, SUD scores and spontaneously reported reactions.  Data will 
be examined informally and descriptive statistics will be computed. Simple tests of 
differences between baseline and follow up medians or means will be employed as 
described below. 
 
The sponsor will compute difference scores for Global CAPS, PDS severity, BDI-II and 
GAF scores at baseline (upon enrollment in this study) and two months after the 
experimental session, and scores at baseline and at 12-month follow up. After difference 
scores are computed, the sponsor will observe the degree to which scores are greater than 
zero, indicating improvement at the second time point, 
 
The Sponsor will correlate each SOCQ score with CAPS at 2-month and at 12-month 
follow-up to determine whether one or more facet of the experience during the MDMA-
assisted session was related to symptomatic reduction.  
 
There is no expectation that conditions will differ in composition by gender, race or 
ethnicity, duration of PTSD diagnosis or presence versus absence of other permitted 
psychiatric disorders, such as depression. Also, participants in this study will all be 
Caucasian and are likely to be female given that the majority of the original sample were 
women. However, owing to a small sample size, such variations may arise by chance. 
 
The investigators will record average baseline and post-drug peak blood pressure, heart 
rate and body temperature for participants during the experimental session. The 
investigators will also record spontaneously reported reactions and AEs as described in 
section 8.5. Descriptive statistics will be computed for vital signs and subjective distress 
during the experimental session. Frequency tables will be produced on prevalence of 
spontaneously reported reactions and AEs. 
 
12.1 Statistical Power 
 
This is a proof-of-principle study. The study is underpowered for detection of differences 
within subjects over time of a small or moderate effect size, and it may detect differences 
if the effect size is large. Although a power analysis has been provided, such analyses are 
generally performed for tests where formal analyses will be applied to the data.  
 
Analyses of MAPS’ completed U.S. study of MDMA-assisted psychotherapy in 20 
people with PTSD found an effect size of 1.24 for treatment efficacy, as represented by 
changes in CAPS score [2]. The effect size was for a between-subjects study. The 
estimated effect size for this study may be lower as a result of a small sample size. Also, 
participants are selected on the basis of increasing PTSD symptoms. Using Lenth’s 
software [105] and assuming that there will be data from three subjects, the paired t-test 
was used to calculate the effect size. If the true difference between the previous measure 


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of PTSD and the next is 0.7, then power = 0.12, and if the difference is 1, then power 
may be 0.18.   
 
13.0 Ethics 
This clinical study was designed and shall be implemented and reported in accordance 
with applicable regulations (including US Code of Federal Regulations Title 21 and the 
ICH Harmonized Guidelines for Good Clinical Practice) and with the ethical principles 
laid down in the Declaration of Helsinki.  
 
The protocol and the proposed informed consent form (ICF) must be reviewed and 
approved by an Independent Review Board (IRB) before the study start. Signed and dated 
documentation that the protocol and informed consent have been approved by the IRB 
must be provided to the Sponsor. Prior to study start, the Clinical Investigator is required 
to sign a protocol signature page confirming his/her agreement to conduct the study in 
accordance with these documents and all of the instructions and procedures found in this 
protocol and to give access to all relevant data and records to the Sponsor. 
 
14.0 Informed Consent 
The investigators are responsible for obtaining informed consent in adherence to Good 
Clinical Practices (GCP) and according to applicable regulations prior to entering the 
subject into the trial. Eligible subjects may only be included in the study after providing 
written (witnessed, where required by law or regulation), IRB approved informed 
consent. Informed consent must be obtained before conducting any study-specific 
procedures (i.e. all of the procedures described in the protocol). The informed consent 
should include access to original medical records and processing of coded personal 
information. The informed consent discussion must be conducted by a person who is 
qualified according to applicable local regulations. The subject should have the 
opportunity to inquire about details of the MDMA session and to consider participation. 
 
The process of obtaining informed consent should be documented in the subject source 
documents. 
The investigators will provide a copy of the signed ICF to the subject, and will maintain 
the original in the investigator site file (ISF). 
The written ICF and any other written information to be provided to subjects should be 
revised whenever important new information becomes available that may be relevant to 
the subject's consent.  Any revised written ICFs and other written information should 
receive approval from the IRB before use. 
 
The subject should be informed in a timely manner if new information becomes available 
that may affect the decision to take part in the study. The communication of this 
information should be documented.  
 


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Participants can withdraw consent for participation in the study at any time without 
prejudice.  If a subject withdraws consent but does not revoke the Health Insurance 
Portability and Accountability Act (HIPAA) authorization, MAPS will have full access to 
the subject’s medical records, including termination visit information.  If a participant 
revokes only the HIPAA authorization, MAPS will have full access to all of the 
participant’s medical records prior to the date and time of revocation. 
 
15.0 Confidentiality 
Every effort will be made to strictly safeguard the confidentiality of study participants in 
their role as research subjects.  Despite this, absolute privacy cannot be guaranteed. Data 
collected from each subject will be identified only by the subject's initials and by a 
subject number on the source documents. All study measures, records, and audio and 
video recordings will be kept in a locked file drawer in a locked office. Access to study 
measures will be limited to regulatory agencies, researchers assessing the subject for 
changes in symptoms, Sponsor representatives, and individuals analyzing data. 
Researchers with access to data will not be provided with any information that would 
identify subjects by name or by other means.  
 
Removing identifying information from data and restricting access to researchers directly 
involved in assessing the subjects should prevent the dissemination of confidential data, 
with or without identifying information. Maintaining data in a secure environment will 
prevent the accidental or deliberate examination or removal of data.  
 
All psychotherapy sessions will be recorded to video and audio. These recordings will be 
used for the treatment manual development and potentially for training therapists to 
perform MDMA-assisted therapy. They are intended to record the events occurring 
during therapy, and will not serve as outcome measures. Confidentiality of subject names 
and addresses will be maintained in these recordings. Full names and addresses will not 
appear in these recordings. 
 
16.0 Costs to Participants 
The Sponsor of this study will cover the costs that are directly related to this study. This 
includes the costs for all psychotherapy sessions, for the psychological and laboratory 
testing, for the study drug and for any rescue medications used during the study. The 
subject and their health insurance (if any) will not be charged for any procedures done 
solely for the purpose of the study. 
 
The subject or their health insurance remains responsible for the ongoing treatment 
unrelated to the study. The Sponsor will not cover medical expenses related to injuries, 
which occur during the study period that are not directly related to study procedures. 


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17.0 Treatment and Compensation for Study Related Injury 
In the event of a study-related injury, the Sponsor will cover any costs that arise from 
treating the injury. The Sponsor has an insurance policy to cover the subjects from any 
disabilities resulting from the study procedures.  The subject will be compensated 
according to the level of disability arising from medication or procedures used in the 
study. This insurance coverage protects the Sponsor, the institution and the investigators 
from any legal actions pursued against them.  
 
18.0 Record Retention 
Investigators must retain all study records required by the Sponsor and the applicable 
regulations in a secure and safe facility. The investigator must consult a representative of 
the Sponsor before disposal of any study records. “Essential documents” are defined as 
documents that individually and collectively permit evaluation of the conduct of a trial 
and the quality of the data produced. These documents will be filed according to the 
applicable regulations in the ISF. It is the responsibility of the Sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.  
 


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MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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MAPS Study # MP-1 E2                                                                                        Original Protocol Version 1  
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actual driving during intoxication and withdrawal. Addiction, 2006. 101(11): p. 
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Ramaekers, J.G., et al., Involvement of Inferior Parietal Lobules in Prospective 
Memory Impairment during Acute MDMA (Ecstasy) Intoxication: An Event-
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Marrone, G.F., et al., Amphetamine analogs methamphetamine and 3,4-
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Randall, S., et al., Effects of acute 3,4-methylenedioxymethamphetamine on sleep 
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Yubero-Lahoz, S., et al., Sex Differences in 3,4-Methylenedioxymethamphetamine 
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Gamma, A., et al., 3,4-Methylenedioxymethamphetamine (MDMA) modulates 
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Rasmusson, A.M. and D.S. Charney, Animal models of relevance to PTSD. Ann 
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Davis, M. and C. Shi, The extended amygdala: are the central nucleus of the 
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Dumont, G.J., et al., Increased oxytocin concentrations and prosocial feelings in 
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Liechti, M.E., A. Gamma, and F.X. Vollenweider, Gender differences in the 
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de la Torre, R., et al., Non-linear pharmacokinetics of MDMA ('ecstasy') in 
humans. Br J Clin Pharmacol, 2000. 49(2): p. 104-9. 
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Grob, C., Unpublished data on human study of psychological and physiological 
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Blake, D.D., et al., A clinician rating scale for assessing current and lifetime 
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Verrico, C.D., G.M. Miller, and B.K. Madras, MDMA (Ecstasy) and human 
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Vollenweider, F.X., et al., Psychological and cardiovascular effects and short-
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http://www.stat.uiowa.edu/~rlenth/Power]. Available from: 
http://www.stat.uiowa.edu/~rlenth/Power. 
 
 
 
 

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PURPOSE AND BACKGROUND 
This exploratory (“proof-of-principle”) study is designed to provide information on whether an 
additional session of psychotherapy (“talk therapy”) combined with the drug MDMA 
(methylenedioxymethamphetamine) is safe and helpful for people with posttraumatic stress 
disorder (PTSD) whose symptoms had improved after receiving MDMA-assisted therapy 
sessions, but relapsed over time.  The researchers plan to use the results of this study to design 
further studies. 
 
MDMA is an experimental drug, which means that it has not been approved by the United States 
Food and Drug Administration (FDA) for medical use except in research studies.  MDMA is also 
a controlled drug (illegal to use outside of research) and is sometimes known as “Ecstasy” 
(which is supposed to contain MDMA but often contains other drugs instead of or in addition to 
MDMA).  MDMA has already been used legally in research and illegally in uncontrolled 
environments, such as nightclubs.  While much is known about MDMA and its risks, a lot still 
remains unknown about this drug. 
 
The study is sponsored by a U.S.-based non-profit organization, the Multidisciplinary 
Association for Psychedelic Studies (MAPS, www.maps.org).  You have participated in MAPS’ 
first small study of MDMA-assisted psychotherapy in people with PTSD.  MAPS has other 
MDMA/PTSD pilot studies underway in the U.S. and Switzerland and is planning new studies in 
Israel, Canada and Jordan. 
 
Before it became illegal in 1985, some psychologists and psychiatrists combined MDMA with 
psychotherapy to help people with psychological problems, including PTSD.  Though we do not 
know why it may help people with PTSD, we know that MDMA increases positive mood and 
changes the way we see and think about the world around us, making it easier to think about and 
recall things that happened to us that are upsetting.  People say they feel caring and forgiving 
toward themselves and others during the MDMA experience.  It is possible that these drug 
effects, when combined with psychotherapy, help people work through thoughts, memories and 
emotions related to PTSD.  
 
This study will investigate whether an additional MDMA-assisted psychotherapy session with a 
full dose of MDMA, 125 mg, possibly followed by a second dose half the size of the first dose, 
can help with relapsed PTSD symptoms.  
 
LENGTH OF STUDY 
This study will take about 12.5 months after enrollment.  
 
TYPE OF STUDY 
This is an open-label study, meaning that both you and the study therapists will know that you 
have received MDMA and the dose of MDMA that you got.  There will be up to three subjects in 
this study. 
 
 
 
 
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STUDY PROCEDURES/WHAT WILL HAPPEN TO YOU 
 
SCREENING/EVALUATION AND BEGINNING OF STUDY 
If you agree to take part in this study, you will first sign this Subject Information and Consent Form 
before any study-related procedures are performed.  Before you can be in the study, the study 
therapists must first make sure that you qualify for the study and that you are generally physically 
healthy.  The screening process will take approximately 1-1.5 hours.  The study therapists will 
request to review your medical records and may ask your permission to contact your treating doctor 
or psychotherapist to get additional information about your medical history if necessary.  They will 
need to do this so that they will know if you can participate in the study or not.  
 
You will also need to complete the following: 
 
• Two questionnaires about your PTSD symptoms and how you deal with them in your 
everyday life.   
• Discussion with the study doctor about any changes that may have happened in your medical 
or psychiatric condition since your participation in the MP-1 study.  The study doctor will 
rate how well you are doing in general. 
• A questionnaire about feelings of depression or other symptoms or feelings you might experience. 
• A questionnaire about thoughts or feelings you might have about hurting or killing yourself. 
• A questionnaire about your quality of life. 
• A urine test for drugs of abuse.  Your urine drug screen must be negative to take part in the study. 
• A urine pregnancy test if you are a woman and are able to get pregnant.  Your urine 
pregnancy test must be negative for you to take part in the study. 
 
You may need to have extra medical tests done to make sure you can be in the study.  
People who control their high blood pressure with medications may have to see a cardiologist 
(heart doctor) for more tests, and people with a liver disease called hepatitis C may have to visit 
a liver specialist.  If you have hepatitis C, you will have to complete the treatment that the liver 
specialist or your doctor prescribes. 
 
PREPARATORY SESSION  
• You will have a preparatory psychotherapy session with the study therapists.  During the 
session, you will talk about the traumatic incidents that led to your PTSD, how your PTSD 
symptoms have changed since your participation in MP-1 study, the ways PTSD symptoms are 
affecting your life, and what you would like to achieve during this study.  This session will be 
recorded to audio and video, and you may request copies of these recordings.  You will be 
asked questions about thoughts or feelings you might have about hurting or killing yourself.  
• You will be introduced to the attendant who will remain with you during the overnight stay 
after the MDMA-assisted psychotherapy session. 
• If you would like another individual present during or after the experimental session, a 
meeting between the study therapists and that individual will be scheduled prior to the 
experimental session.  There must be mutual agreement between the subject and the study 
therapists concerning the presence of this support individual. 
• You will be given the Subject Information Sheet, which includes instructions and restrictions 
for conduct 24 hours prior to the experimental session. 
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BEGINNING OF STUDY 
If you were taking any psychiatric medicines before the study, including stimulants, you will 
have to gradually stop taking them.  The study doctor (who is one of the two therapists), in 
consultation with your prescribing physician, will help you do this if necessary.  
 
You will have to give the study therapists the name and contact information (such as home phone 
number, cell phone number or email) of a spouse, relative or close friend to contact in case of 
medical emergency; for example, when you might be at risk of hurting yourself or someone else, 
so they can reach that person to let them know what is going on. 
 
SCHEDULE OF EVENTS  
Below is the schedule of events from the screening until the final study visit, which is 12 months 
after the MDMA-assisted psychotherapy session.  
 
 
 
Screening 
Preparation 
MDMA and Non-Drug Therapy 
Sessions 
2 Month 
Follow-up 
12 Month 
Follow-up 
Study Visit # 
 
1 
2 
3 
4 
5 
6 
7 
Screening 
X 
 
 
 
 
 
 
 
Assessment of 
PTSD symptoms 
X 
 
 
 
 
 
X 
X 
Psychotherapy  
 
X 
 
X 
X 
X 
 
 
Psychotherapy  
With MDMA 
 
 
X 
 
 
 
 
 
EXPERIMENTAL SESSION 
There will be one day-long experimental session when you will receive MDMA (125 mg, 
possibly followed by 62.5 mg) and psychotherapy.  The experimental session will occur after 
you enroll in the study. 
 
One week before the experimental session you will need to avoid taking: 
 
• any herbal supplements, except with prior permission from the study doctor;  
• any nonprescription medications, unless you have permission from the study doctor (with 
the exception of non-steroidal anti-inflammatory drugs or acetaminophen [Tylenol]); 
• any prescription medications, with the exception of birth control pills, thyroid hormones 
or other medications approved by the study doctor. 
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You must not eat or drink any alcohol after midnight on the night before the MDMA session, 
though you can drink non-alcoholic liquids during this time, such as water or juice.  You cannot 
use any psychoactive drugs, with the exception of caffeine or nicotine, within 24 hours of the 
MDMA session.  You cannot use nicotine or caffeine for two hours before and six hours after a 
dose of MDMA. 
 
First, you and the study therapists will discuss your goals for the experimental session, and the 
study therapists will answer any questions you may have.   
 
Immediately before the experimental session: 
 
• Your urine will be tested for drugs of abuse, including stimulants, sedatives, opiates and cannabis. 
• If you are a woman who can become pregnant, you will take a urine pregnancy test. 
 
Throughout the experimental session: 
 
• Your blood pressure and pulse will be measured periodically (every 30 minutes). 
• Your temperature will be measured every 60 to 90 minutes. 
• You will also complete a very brief, simple test of how comfortable or distressed you feel at that 
moment.  You will complete it every 60 to 90 minutes throughout the experimental session.  
• About an hour before receiving the drug and about six hours afterward, you will complete the 
questionnaire about thoughts you may have about hurting or killing yourself. 
• The study therapists will check in on you every hour or so to see how you are doing. 
 
The experimental session will be recorded to audio and video, so that the study therapists can have 
accurate records of the session and so that they can gather more information about drug-assisted 
psychotherapy sessions.  The study therapists can give you copies of these recordings if you want. 
 
After test results come back and if they are negative, you will receive a capsule containing 125 
mg of MDMA.  After taking the capsule, you will relax in an environment that is meant to bring 
out thoughts and feelings, including thoughts and feelings about the trauma.  Both study 
therapists will remain with you, and they will help you if you need them to do so.  There will be 
beverages available including water, juices and Gatorade or similar sports drinks, and you will be 
encouraged to drink an adequate amount of fluid.  You can drink it whenever you wish to do so, 
within the limits of the amount that is safe for your body.  Later on, food will also be provided. 
 
Approximately one and a half to two and a half hours after you took the first capsule, you may 
receive the second dose of MDMA, unless the study doctor notices any problems after the first 
dose.  The second dose will contain half the amount MDMA of the first dose.  
 
The study therapists will measure your blood pressure, pulse and temperature, and will watch for 
any unwanted effects or health problems.  If any do occur, they will be treated, and the study 
therapists will explain to you what they are going to do. 
 
The therapists will stay with you until you have fully recovered.  If the therapists think you are at 
risk of hurting yourself or others, they will either remain with you all night or have you admitted 
to a hospital until you are no longer at risk of hurting yourself or others.  The therapists will ask 
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you about thoughts of killing or harming yourself before and after MDMA administration.  You 
will also be asked to complete a questionnaire about what you experienced during the 
experimental session.  You can complete this questionnaire at any time between the end of the 
experimental session and the time you leave the study site the next day. 
 
If you request and the study therapists agree to it, you can have a person of your choice stay with 
you during some or all of the experimental session, starting at an agreed-upon time, or when you 
stay at the office of the study therapists after the session.  When he or she arrives, this person will 
stay in the waiting room until he/she is brought into the session by one of the study therapists. 
 
You will be spending the night in a room in the offices of 
 with an attendant who 
will be staying in another room nearby.  If you need to talk with the therapists or are having any 
problems and need to contact the therapists, the attendant will contact them immediately. 
 
On the next day, you will have a regular (non-drug) therapy session with the study therapists.  
You will need to have someone drive you to wherever you are staying (home, hotel or another 
location) from the non-drug therapy session on that day because we do not know how MDMA 
will affect your ability to drive, and because some people report feeling tired, less alert or having 
trouble concentrating the day after having taken MDMA.  If you cannot find anyone to take you 
home, the study therapists will find someone to drive you. 
 
Starting on the day you return from the non-drug therapy session, the therapists will telephone you 
every day for a week to inquire about how you are feeling and determine whether you should see 
them before your next visit.  On the second and the seventh day of the phone contact, the therapists 
will ask you about thoughts or feelings you might have of killing or harming yourself.  These 
telephone calls will take approximately 5 to 15 minutes, though they can be as long as you need 
them to be.  You may schedule additional meetings or telephone calls with the study therapists 
besides those that are scheduled as part of the study.  You can contact the study therapists at any 
time yourself, and they will be reachable by telephone 24 hours a day throughout the study, except 
on occasions when they are out of town.  At those times, another psychiatrist familiar with the study 
will be on call and can be reached by his/her phone number, which will be given to you as well. 
 
You will be given a card with telephone numbers for reaching 
 and the Copernicus 
Group Independent Review Board (IRB) that reviews the study.  You can keep this card in your 
wallet to make it easier for you to make these contacts if you need to do so.   
 
If you were taking any psychiatric medications before the start of the study, you can resume 
taking them 10 days after the MDMA session.  However, you cannot start any new medications 
until two months after the experimental session.  You agree to contact the study doctor if any of 
the following things happen: you have an increase in symptoms for which you previously took 
medicines, you need to contact your outside therapist other than for the usual appointments, 
and/or you start taking the prescribed psychiatric medicines earlier than 10 days after the MDMA 
session.  You should also contact the study doctor if you have a strong and lasting negative 
reaction (unwanted effect or health problem) after the experimental session. 
 
 
 
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PSYCHOTHERAPY AFTER THE EXPERIMENTAL SESSION 
You will have three regular (non-drug) psychotherapy sessions to help you express, understand, 
bring together and connect any thoughts or feelings you may be having about your symptoms 
and their causes and to think and talk about your experiences during the experimental session.  
You will have psychotherapy with the study therapists on the morning after the experimental 
session, followed by two more psychotherapy sessions.  These visits will last 60 to 90 minutes.  
You and the study therapists will also discuss how to use what you learned to help you work on 
your PTSD, how to face and solve difficulties you may have faced during the experimental 
session, and how to gain maximum benefit and understanding from the experimental session.  
The study therapists will also ask you about thoughts of killing or harming yourself during each 
session.  Each regular psychotherapy session will be recorded to audio and video, and you can 
ask for a copy of these recordings. 
 
FOLLOW-UP 2 MONTHS AFTER THE EXPERIMENTAL SESSION 
During this visit, you will meet with the study therapists and a study researcher who is not one of 
the study therapists.  The study researcher will ask you questions about your PTSD symptoms.  
You will also complete one more PTSD questionnaire, a questionnaire on feelings of depression 
or other symptoms you might have, and a questionnaire on your quality of life.  The study 
therapists will ask if you had any thoughts about hurting or killing yourself during that time and 
assess your general wellbeing.  The tests will help the study therapists tell if your symptoms have 
changed or stayed the same over time.  This visit should last up to two hours.  
 
At the end of the visit, the therapists will give you a memory aid card.  This card is to help you to 
remember any problems related to your mental health that can occur between this visit and your 
last visit, 12 months after the MDMA session.  On this card you will record any new important 
mental health problems, hospitalizations related to you mental health problems and medications 
used to treat these problems.  You will be asked about these problems during your last visit. 
 
LONG-TERM FOLLOW-UP 12 MONTHS AFTER THE EXPERIMENTAL SESSION 
This visit will take place either in person or over the telephone approximately 12 months after 
the MDMA-assisted psychotherapy session.  The same study researcher who asked you about 
your PTSD symptoms at 2 month follow-up will do so again.  
 
The study therapists will ask if you had any thoughts about hurting or killing yourself during the 
time since the previous visit and assess your general wellbeing.  The therapists will ask you 
about any changes in medications or your psychiatric health, including any benefits or harms, 
during the follow-up period between your previous visit and the 12-month follow-up visit. 
 
You will complete another PTSD questionnaire, a questionnaire about feelings of depression you 
may have and a questionnaire about your quality of life.  You will also complete a questionnaire 
containing questions about the good and bad points of MDMA-assisted therapy, and any 
medications or therapy you needed since the last visit.  There are no right or wrong answers to 
these questions.  All these questionnaires will be mailed to you for you to fill out.  They will 
come with an envelope that is already stamped and has only the researchers’ address on it.  Do 
not put your name on the questionnaire. 
 
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The researchers will use your answers to these questionnaires to see if there are any long-lasting 
effects on your PTSD symptoms or other life events from participating in this research study, 
and, specifically, if your PTSD symptoms have improved after receiving an additional MDMA-
assisted psychotherapy session. 
 
POSSIBLE RISKS OR DISCOMFORTS 
MDMA has not been widely tested in humans, but as of 2011 approximately 540 people have 
received MDMA in clinical research settings without any serious problems happening.  
 
There may be unknown side effects or risks from the use of MDMA.  Possible known risks of 
MDMA include the following: 
 
Serious problems:  There have been some serious problems, and even deaths, associated with the 
use of Ecstasy outside of controlled clinical or laboratory settings.  These problems include high 
fever, brain swelling associated with drinking too much liquid, convulsions, and liver damage.  
Some recreational users of Ecstasy became severely anxious, depressed or paranoid (thinking 
that other people are out to get them).  Since you will be receiving moderate amounts of 
uncontaminated MDMA in a controlled setting with trained therapists who will be closely 
monitoring your physical and psychological reactions, these problems are not expected to occur 
either during or after the experimental session.  While this does not guarantee that they will not 
occur, it does mean that if they do occur, the study therapists are prepared to respond to these in 
a safe and professional manner. 
 
Changes in vision, hearing or other senses:  In previous studies in which MDMA was given to 
volunteers (including a total of about 494 healthy people without emotional disorders and 46 
with PTSD), most subjects reported experiencing temporary and minor changes in vision and 
hearing, such as sounds seeming closer or farther away than usual or objects seeming brighter 
than usual.  These changes typically lasted 2 to 3 hours.  Between 12% and 33% of people who 
took MDMA reported unusual feelings in their bodies, such as tingling or numbness. 
 
Blood pressure and heart rate:  The effects of MDMA usually last 4 to 6 hours.  With the dose 
used in this study, the increases in blood pressure and heart rate are likely to be moderate.  
Average increase in systolic blood pressure is 35 mmHg (measurement unit for blood pressure) 
and average diastolic blood pressure increase is 20 mmHg.  Heart rate may increase by 
approximately 30 beats per minute (BPM). 
 
In previous studies, blood pressure rose well above normal levels in a few subjects (a little less 
than 5% of subjects) after receiving MDMA, but these subjects did not report any discomfort and 
did not require any treatment.  Although these increases in blood pressure are similar to what 
happens after heavy exercise, they could cause serious problems in individuals with pre-existing 
heart or vessel conditions.  These serious problems could include heart attack or stroke.  We will 
screen all potential subjects for preexisting heart problems before they are allowed to be in this 
study.  While this does not guarantee that no heart problems will occur, it does reduce the risk of 
this happening. 
 
Do not participate if you know you have pre-existing heart or blood vessel problems. 
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Anxious or jittery feeling:  Some subjects in previous studies (16%) reported feeling over-
stimulated or anxious during the MDMA session.  These feelings usually lasted less than 30 
minutes.  Letting yourself accept and feel these emotions deeply can be part of the 
psychotherapy.  If you are not able to deal with these experiences in a way that helps you, the 
study therapists will work with you to deal with these feelings.  It is possible that if such periods 
of heightened emotion do not clear up or grow weaker during the session, you could be at 
increased risk for suicide or other self-harm afterwards.  You will be encouraged to ask the 
attendant, who will be staying with you after the experimental session, to call the study therapists 
immediately if you have any thoughts about hurting or killing yourself so they can help you 
resolve them safely.  If necessary, they may prescribe an anti-anxiety medication or medication 
for sleep.  If you are in immediate danger of hurting or killing yourself or hurting someone else, 
then the study doctor may require you to be admitted to a hospital.   
 
Insomnia & drowsiness:  In previous studies, between 17% and 23% of subjects have reported 
insomnia (difficulty sleeping) or feeling tired, irritable, or drowsy for as long as 3 days after 
receiving MDMA.  If you have difficulty sleeping, the study doctor may prescribe you a 
medication for sleep. 
 
Mood:  Some after-effects of MDMA may be noticeable up to 2 or 3 days later.  While some subjects 
felt that their mood was better during this period; other subjects (about 14%) felt that it was worse. 
 
Immune System:  You may have a less active immune system for 2 or 3 days after receiving MDMA.  
This may make you more likely to become sick with a cold or other infection during this time.  The 
study describing this finding did not report how many people in the study showed these changes. 
 
Addiction:  There is a small chance that you will become dependent on (addicted to) MDMA.  
One study found that up to 6% of people using Ecstasy for recreational purposes were dependent 
on it.  However, a study of people who received MDMA for the first time in a legal laboratory 
setting found that they did not want to try MDMA again outside of the laboratory. 
 
People who have recently (in the last 6 months) had problems with drug abuse should not take 
part in this study. 
 
Possible Brain Damage:  Experiments in rats and monkeys show that high and repeated doses of 
MDMA can change certain brain cells that release a chemical called serotonin; in mice (though 
not in humans), the affected cells release dopamine.  The changes include loss of the parts of the 
cells (called “axons”) that connect different brain areas.  Rodents given repeated, high doses of 
MDMA are less sensitive to a later dose of MDMA, are more likely to become overheated when 
placed in a warm room, and some studies found that they performed worse in difficult memory 
tests.  Recent studies in monkeys and rodents suggest that the doses used in these studies are far 
higher than those typically taken by humans in either recreational or laboratory settings.   
 
Many studies found that people who had used Ecstasy (which may or may not contain MDMA) 
many times in recreational contexts were not able to recall words, pictures or patterns as well as 
people who did not use Ecstasy, and performed less well on tests of planning and impulse 
control.  These differences are not great, but they lasted for at least a year after people had 
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stopped taking Ecstasy.  Not all studies have found Ecstasy users to have difficulty recalling 
words or pictures or to have impulse control problems.  Studies comparing people before and 
after they had taken a few tablets of Ecstasy in a recreational setting with people who did not 
take them found less improvement in memory when tested about 18 months after they were 
tested the first time in the people who took Ecstasy, and no other changes in thinking or 
planning.  When compared with people who do not use Ecstasy, studies found Ecstasy users 
were more likely to report feeling generally anxious or depressed.  Many of these studies found 
that using alcohol or other drugs was also associated with feeling anxious or depressed.  At least 
two studies found that people who are anxious, depressed or have psychological problems before 
taking any drugs are more likely to take Ecstasy than people without these problems, but there is 
no proof that MDMA might not cause these problems in some people.  Studies of people 
receiving one or two doses of MDMA in a laboratory setting have not found any lasting changes 
in memory or planning.  It is believed that the amount of MDMA you will receive will not 
produce any lasting changes in memory or planning, though this cannot be guaranteed. 
 
Only one study has looked at brain scans of people before they got MDMA and then again after 
they have received one or two moderate doses of MDMA.  This study did not show any changes 
in the brain following MDMA, though it is possible that there were changes that were too small 
to notice.  Other studies looked at people before and after they had taken a few tablets of Ecstasy 
in a recreational setting, and found one small change in the amount of blood flow in a specific 
part of the brain, but did not show signs of brain injury.  The decrease in blood volume might be 
from a temporary decrease in a type of brain receptor or it might be a sign of reduced function in 
this area.  Findings from these studies suggest that the amount of MDMA you will receive in this 
study will not produce any lasting changes in your brain, though this is not guaranteed.   
 
Other Risks: 
 
You should not drive or use machinery after the experimental session (up to 24 hours 
afterwards).  This is because the study drug may cause drowsiness, lack of co-ordination or 
slower reaction time. 
 
If you are tested for drugs of abuse within three days of the experimental session, you may test 
positive.  The study doctor will provide you with an information card in case you are tested for 
drugs of abuse, and if you are tested for drugs of abuse while you are in this study, you can have 
the person(s) testing you call the study doctor to verify that you are in this study.  
 
The interviews you have during the study involve no specific risks or discomforts beyond those 
of a standard clinical interview situation.  You may feel upset at the review of your emotional 
experiences, or you may feel boredom or fatigue.  Answering questions about thoughts you 
might have of hurting or killing yourself may be upsetting.  
 
It is possible that after you stop taking psychiatric medicine (as for depression or anxiety) as part 
of the study, you may start to have symptoms again.  If this happens, you should talk with your 
outside therapist and 
.  If you have to start taking these medicines again before or 
within 10 days after the MDMA session, then the study doctor will have to take you out of the 
study. 
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REPRODUCTIVE RISKS 
Effects of MDMA on the growth and development of an unborn baby are not known.  Birth defects 
could include physical deformities, mental retardation and premature birth; therefore, you will not 
be allowed to enter the study if you are pregnant.  If you incidentally become pregnant after you 
have had the experimental session, the study doctor and the Sponsor (MAPS) will ask you about 
and keep track of your pregnancy and will need to know about the outcome of the pregnancy.  
 
Women who are able to become pregnant must use one of the allowed birth control methods, such as 
birth-control pills or shots, intrauterine devices (IUDs), or diaphragms used along with spermicide 
and with partner using condoms, or sexual abstinence during the first 2 months of the study.  The 
study doctor will explain these methods to you and will help you decide which might be best for 
you, and they can suggest to you where you can get more information and advice about it. 
 
If you are a woman of childbearing potential, you will be tested at the start of the study, and again 
before the MDMA session, to see if you are pregnant.  If, at any time during the study, you think that 
you may be pregnant or are worried that you may become pregnant, you must inform 
 
immediately.  If you should become pregnant during the study, the study doctor will help you get 
proper advice and help you and your unborn baby get proper care while you are pregnant. 
 
NEW FINDINGS 
If any new information becomes available about MDMA while you are taking part in this study, the 
study therapists will tell you about it as soon as possible.  You may contact the study doctor at any time 
after your participation ends to find out if any new information about this study has become available. 
 
POSSIBLE BENEFITS 
Your symptoms of PTSD may improve while participating in this study.  There is no guarantee 
that you will benefit from taking part in this research study.  However, information obtained 
from this study may help doctors and researchers to improve treatment for PTSD in future.  
 
COSTS 
The Sponsor of this study, Multidisciplinary Association for Psychedelic Studies (MAPS), will 
cover the costs that are directly related to this study.  This includes the costs for all 
psychotherapy sessions that are a part of this study, for the psychological and laboratory testing, 
including any extra tests you might need to do solely to see if you can be in the study, and for the 
study drug.  You, your private medical insurance (if any) or the public health insurance plan (if 
any) will not be charged for any procedures done solely for the purpose of the study.  You or 
your insurance company will remain responsible for on-going treatment unrelated to the study. 
 
PAYMENT FOR PARTICIPATION 
The Sponsor, MAPS, will reimburse you for travel-related expenses as follows: 
 
Subjects who drive to the study site: 
If you must drive more than 50 miles round trip for visits, you will be reimbursed at a rate of 
$0.25 per mile.  If you live far enough away that it is not practical or desirable to make the round 
trip in one day, MAPS will pay up to $150.00 a night for all motel bills and up to $50.00 per day 
for meals in advance.   
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Subjects who fly to the study site: 
MAPS will pay for all travel expenses in advance.  MAPS will pay up to $150.00 a night for all 
motel bills and up to $50.00 per day for meals. 
 
If you must pay for parking, MAPS will pay for the costs of parking.  
 
ALTERNATIVES 
One alternative to being in this study is to decide not to participate.  You may decide to try other 
treatments for PTSD.  There are antidepressants, such as Paxil (paroxetine) or Zoloft (sertraline) 
and anti-anxiety medications such as Xanax (alprazolam) and other forms of psychotherapy that 
you can try.  If you are currently having psychotherapy and/or taking medicines, you could 
continue with those for a longer period of time.  The study doctor can discuss the alternatives and 
their potential risks and benefits with you. 
 
CONFIDENTIALITY 
To ensure confidentiality, only your subject number and initials will be provided to the study 
Sponsor.  When not in use, your information will be stored in a locked office.  Absolute 
confidentiality cannot be guaranteed. 
 
Some people need access to the information to monitor the study.  Medical records, including 
audiotapes and videotapes, which identify you and the consent form signed by you will be 
looked at and/or copied for research or regulatory purposes.  Before that any information that 
could directly identify you will be removed.  Medical records may be looked at by: 
 
• the Sponsor (MAPS); 
• the FDA; 
• the Department of Health and Human Services (DHHS) agencies; and/or 
• the Copernicus Group Independent Review Board (IRB). 
 
The results of this research study may be presented in meetings or in publications.  Your identity 
will not be disclosed there. 
 
All records in 
 are subject to subpoena by a court of law. 
 
Audiotapes and videotapes:  The study therapists will listen to or watch these recordings, as well 
as MAPS staff and other researchers seeking to better understand the principles of MDMA-assisted 
psychotherapy.  No identifying information will be written on or otherwise attached to the tape 
recordings.  You may listen to or watch these recordings if you wish, but you do not have to.  You 
will not automatically receive a copy of the recordings, but if you request, you will get it. 
 
You have the right to check your study records and ask for changes if the information is not 
correct. 
 
By signing this Subject Information and Consent Form, you consent to the collection, access, use 
and disclosure of your information as described above. 
 
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TREATMENT AND COMPENSATION FOR INJURY 
In the event of a study-related injury, the physician who treats you will bill your insurance 
company.  If your insurance company denies coverage or if the insurance is not available, then 
MAPS will pay for any costs that arise from treating a study-related injury, including 
hospitalization.  Neither the Sponsor nor the study doctor has a program in place to provide 
additional compensation in the event of an injury.   
 
Your health insurance may not be willing to pay for the costs of treating a study-related 
emergency.  The study Sponsor (MAPS) will pay for any study-related procedure that your 
insurance will not cover. 
 
LEGAL RIGHTS 
The above section does not restrict your right to seek legal assistance.  You do not waive any 
legal rights by signing this Subject Information and Consent Form.  
 
VOLUNTARY PARTICIPATION 
Your decision to take part in this research study is completely voluntary.  There will not be any 
penalty or loss of benefits to you if you decide not to take part. 
 
In addition, you may withdraw from (leave, stop being in) the study at any time for any reason.  
There will be no penalty if you decide to withdraw from the research study.  Before withdrawing 
from this study, notify your study doctor that you wish to withdraw.  This notice will allow your 
study doctor to inform you if there are any potential medical risks of withdrawal.  You may be 
asked to complete some final questionnaires.  If you decide you do not want to continue in the 
study during the experimental session, you will still have to stay in the office until the study 
doctor thinks that you are well enough to leave and that all the effects of the drug have worn off.  
 
WITHDRAWAL 
Your study doctor, the sponsor company, or the FDA have the right to stop your participation in 
the study at any time, with or without your consent, for any of the following reasons: if you have 
an adverse effect from the study drug; if you need a treatment not allowed in this study or for a 
part of the study duration, such as restarting medication for depression or anxiety; if you do not 
keep appointments; if you do not take the study drug as instructed; if you become pregnant; or if 
the study is canceled by the FDA or the sponsor company.  If the study doctor decides to take 
you out of the study, he will let you know that he is doing this and the reason for doing this.  If 
you are taken out of the study, you may be asked you to complete some final questionnaires.  
 
QUESTIONS 
If you have any questions about this study, its procedures, risks, benefits or your alternatives or 
rights, or if at any time you feel you have experienced a research-related injury, please contact 
the study doctor:  
 
Principal Investigator Name: 
  
 
Daytime telephone number(s): 
 
 
24-hour contact number(s): 
 
 
Cellular number:  
 
 
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If you have any questions or concerns about your rights as a research subject or want to discuss a 
problem, get information or offer input, you may contact Copernicus Group Independent Review 
Board (IRB) at 1-888-303-2224 (toll free).  An IRB is a group of scientific and non-scientific 
individuals who perform the initial and ongoing ethical review of the research study with the 
study subject’s rights and welfare in mind.  Copernicus Group IRB has reviewed and approved 
the research study described in this Subject Information and Consent Form.  If you have study-
related comments, complaints or concerns, you should first contact the study investigator.  Please 
call the IRB if you want to talk to someone other than the study investigator or have difficulty 
reaching the study investigator.  For further information regarding the clinical trials process and 
your role as a research subject, you may visit the Copernicus Group IRB website at 
www.cgirb.com. 
 
Do not sign this consent form unless you have had a chance to ask questions and have received 
satisfactory answers to all of your questions.  


Approved 06/20/2011 
SUBJECT’S STATEMENT OF CONSENT 
 
“An Open-Label Proof-of-Principle Study Testing the Use of an Additional MDMA-Assisted 
Psychotherapy Session in People who Relapsed after Participating in a Phase 2 Clinical Trial of 
MDMA-Assisted Psychotherapy to Treat Chronic, Treatment-Resistant Posttraumatic Stress 
Disorder (PTSD)” 
 
My participation in this study is voluntary.  I may refuse to take part in or I may stop taking part 
in this study at any time.  I will contact the study doctor if I decide to do this.  My decision will 
not affect my current or future regular medical care or any benefits to which I am entitled at this 
site.  The study doctor and/or the Sponsor may stop my participation in this study at any time 
without my consent if he decides it is in my best interest or if I do not follow the study doctor’s 
instructions.   
 
I agree to have my sessions audio- and videotaped during this study. 
 
I have read the information in this consent form and it has been discussed with me.  I have been 
given sufficient opportunity to consider whether to participate in this study.  All of my questions 
so far about the study and my participation in it have been answered.  I freely consent to 
participate in this research study.   
 
By signing this consent form, I have not waived any of the legal rights which I otherwise would 
have as a subject in a research study.  I have been told that I will be given a copy of this consent 
form signed by me and the investigator. 
 
 
SUBJECT 
 
INVESTIGATOR: I certify that 
the information provided was 
given in a language that was 
understandable to the subject. 
 
Printed Name 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
Date 
 
 
 
 
 
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If you withdraw from the study and withdraw your Authorization, no new information will be 
collected for the study purposes unless the information concerns an adverse event (a bad effect) 
related to the study.  If an adverse event occurs, your entire medical record may be reviewed.  
All information that has already been collected for the study purposes, and any new information 
about the adverse event related to the study, will be sent to the study Sponsor. 
 
If you withdraw from the study but do not withdraw your Authorization, new personal health 
information may be collected until this study ends. 
 
This Authorization does not have an expiration date.  If you do not withdraw this Authorization 
in writing, it will remain in effect indefinitely.  Your study doctor will keep this Authorization 
for at least 6 years. 
 
If you do not sign this Authorization, you cannot participate in this research study or receive the 
study drug.  If you withdraw this Authorization in the future, you will no longer be able to 
participate in this study.  Your decision to withdraw your Authorization or not to participate will 
not involve any penalty or loss of access to treatment or other benefits to which you are entitled. 
 


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AUTHORIZATION 
I authorize the release of my medical records and personal health information related to this 
study to the Sponsor and its representatives, the Copernicus Group Independent Review Board, 
the FDA, and other regulatory agencies as described above.  I have been told that I will receive a 
signed and dated copy of this Authorization for my records. 
 
 
SUBJECT 
 
INVESTIGATOR 
 
Printed Name 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
Date 
 
 
 
 
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