We encourage you to read and follow maps.org/safety for detailed information regarding MAPS Code of Ethics for Psychedelic Psychotherapy and our practices to create a culture of safety in psychedelic therapy.
You may safely and confidentially direct misconduct reports related to MAPS-sponsored studies, MAPS staff, MAPS PBC staff, or collaborators to MAPS’ Compliance Team via email or by calling (844) 627-7722.
If you are a former participant in a MAPS-sponsored trial, we want to include your experience in the drug development program data. If you have not already, please contact your study coordinator to participate in the Long-Term Follow-Up study.
If you are a former participant in a MAPS-sponsored trial and are concerned that your experiences represented an ethical breach, we encourage you to report it to compliance@maps.org and the Institutional Review Board.
The post has been edited for clarity and to provide additional links for more information. We may continue to make additional edits for clarity and information. Any edits which change the meaning of the content will be clearly identified.
“Cover Story” is a podcast described as an investigative series which “uncovers the secrets and exposes the darkest corners of the psychedelic revolution.” The first five episodes, released in December 2021, related individual experiences of harm in underground psychedelic therapy and discussed some of the challenges associated with preventing abuses, establishing ethical frameworks, and holding abusers accountable. Fundamentally, the goals expressed by the hosts and guests have long been shared by MAPS, as described and cataloged at maps.org/safety.
The Multidisciplinary Association for Psychedelic Studies (MAPS), MAPS Public Benefit Corporation (MAPS PBC), and MAPS Europe are committed to cultivating safety in psychedelic therapy and to Open Science, Open Books. We firmly believe that our work is strengthened through balanced, well-informed public discussion of the potential risks of psychedelic therapy and past harms in therapy, underground psychedelic therapy, and clinical research. We are eager to engage in such discussions.
Ethical Violations by Phase 2 Trial Sub-Investigators
Episode 6 discusses ethical violations of sexual abuse committed by Richard Yensen and Donna Dryer, sub-investigators on a MAPS-sponsored Phase 2 trial. MAPS views these violations as a breach of trust between patient and clinician and a violation of the MAPS Code of Ethics. Yensen and Dreyer had previously been removed as investigators on MAPS-sponsored trials for not complying with MAPS PBC’s requirements for providing study records in a timely and organized fashion. The study was terminated in 2016 due to insufficient rate of accrual.
All data from all trials is required to be submitted to the FDA. MAPS will not use any of the data from that site to demonstrate the effectiveness or safety of MDMA-assisted therapy to the FDA. These ethical violations were reported to the FDA, Health Canada, and the Institutional Review Board when MAPS was informed that an ethical violation had been committed. You can read more about our direct response, including providing funding for additional therapy on a compassionate basis, here. Read more about our organization-wide work to prevent future ethical misconduct at maps.org/safety.
Participant Experiences During or Following Trials
If you are a former participant in a MAPS-sponsored trial, we are interested and obligated to include your experiences –positive and negative — in the drug development data. If you have not already, please contact your study coordinator to participate in the Long-Term Follow-Up study.
During follow-up interviews with reporters from Cover Story, MAPS and MAPS PBC staff were informed about several anecdotal reports of former participants having negative experiences during or after the trials, brief descriptions of which were included in Episode 6. We reiterate our request that these participants volunteer for the Long-Term Follow-Up trial. Those who are unwilling to participate in that study may contact the Institutional Review Board and submit a report to compliance@maps.org so our Compliance Team may initiate reviews of the circumstances.
Updated March 15, 2022: MAPS’ Comments Regarding Episode 7
MAPS cares profoundly about the well-being of all of the participants in our studies and we are grateful for their courage. Living with severe, chronic PTSD is in itself an emotionally challenging experience which is associated with serious physical and mental health conditions. We understand that undergoing MDMA-assisted therapy, and even going through the screening process, can exacerbate a person’s emotional response to the trauma. No treatment for PTSD, including MDMA-assisted therapy, works for everyone, so we train clinicians to discuss how important it is that participants accurately and honestly share their experiences.
All reported participant experiences — regardless of outcomes — have been an important contribution to the research, helping maximize the benefits and minimize the risks of the therapy. Clinical drug development and clinical trials have strict constraints, including specific treatment protocols that limit the number of MDMA-assisted therapy sessions that can be offered. We are only able to offer the therapy within those rigorous constraints unless and until the FDA approves MDMA-assisted therapy for the treatment of PTSD.
Unfortunately, many of the details included in episode 7 of the podcast regarding MAPS’ published trial results, practices, and policies were not accurate. These misrepresentations — and lack of familiarity with the subject matter — led to a substantially incomplete and inaccurate picture of the work of MAPS and MAPS PBC’s teams, collaborators, and volunteer participants. We are including the most important corrections in the FAQ below and will continue to update this FAQ as more information becomes available.
Our research teams and independent raters seek to fully understand all the risks and benefits of participation in MAPS-sponsored trials, using that information to guide improvements to the treatment protocol, training program, and our understanding of the myriad ways individuals respond to the therapy. We were first notified of some of these difficult experiences as we were being interviewed for, or listening to, the podcast. Nevertheless, we are committed to understanding those experiences and responding appropriately. We have requested the hosts’ participation in encouraging the participants to volunteer in the Long-Term Follow-Up Study and provide additional information to MAPS.
MAPS has sought to develop medical, legal, and cultural contexts for the careful uses of psychedelics for more than 35 years. Developing medical contexts for the use of psychedelics in therapy is a project imbued with the challenges of scientific rigor in drug development — and a profound responsibility to those who choose to participate in clinical trials. We encourage you to learn more about our efforts through our resource collections at Open Science, Open Books and at maps.org/safety.
The safety and efficacy of MDMA as an adjunct to therapy is currently under investigation. It has not yet been approved by any regulatory body, does not work for everyone, and carries risks even in therapeutic settings. These statements are no guarantee of future regulatory approval or availability of MDMA as an adjunct to therapy. These statements necessarily involve known and unknown risks and uncertainties, which may cause actual outcomes to differ materially from our projections.
FAQ
Update note: This FAQ is being updated regularly as our small Communications team is able to collect and verify answers to the questions raised in relationship to the podcast. We will not be including an update log, but will identify any updates that change the meaning of a previously published answer.
I was a trial participant. How do I make sure my experiences after the trial are included in the data?
Your experiences, whether positive or difficult, should be included in the information available to MAPS, the public, and the FDA. By volunteering to participate in the Long-Term Follow-Up study, you can help us understand the strengths and weaknesses of the treatment protocol. You can make sure your experiences are included in reports to the FDA and considered in trial design and the approval process. If you have not already, please contact your study coordinator to participate in the Long-Term Follow-Up study.
If you are not eligible for participation in the current Long-Term Follow-Up study, please check this page again soon for alternative reporting methods.
Most MAPS-sponsored clinical research is overseen by WCG Institutional Review Board. An IRB is a group of people who perform independent review of research studies. You may talk to them at 1-855-818-2289 or or Researchquestions@wcgirb.com if:
- You have questions, concerns, or complaints that are not being answered by the research team.
- You are not getting answers from the research team.
- You cannot reach the research team.
- You want to talk to someone else about the research.
- You have questions about your rights as a research subject.
MP16 and MP17 are overseen by IRBs affiliated with the institutions where the research was conducted. You can find that information on the study documents provided to you or by contacting the institution directly.
How does MAPS address suicidality among participants?
PTSD is considered a life-threatening illness because the condition, especially when severe or chronic, can lead to a very high risk of suicidal ideation or behaviors. If you or someone you know is struggling with suicidal thoughts, please reach out to the National Suicide Prevention Lifeline at 1-800-273-8255.
Of participants enrolled in the first MAPS-sponsored Phase 3 trial, 90% reported a history of suicidal ideation or behavior. Most studies of PTSD treatments exclude people with a history of suicidal behavior because it is perceived as “too difficult” to address suicidality within a clinical trial. Further, withdrawal from the most commonly-prescribed medications for PTSD or PTSD symptoms, such as SSRIs and benzodiazepines, is known to increase suicidal ideation or behavior in some people.
MAPS-sponsored studies do allow participants with such a history because we believe it is our obligation to ensure the treatment will be appropriate for those who have the greatest need — those for whom PTSD is acutely life-threatening.
So, we take particular care to attend to the risks and address them appropriately. Study protocols and information provided to participants specify gradually tapering off medications that might interact with the study drug. The Columbia Suicide Severity Rating Scale (C-SSRS), only FDA- accepted validated questionnaire that measures suicide risk in clinical trials, is administered more than 35 times during the 12-18 week treatment period being investigated in Phase 3.
Practitioners are trained to respond to any signals that a participant is experiencing suicidal thoughts or behaviors. Such instances are documented and reported to the FDA, on clinicaltrials.gov, and, as appropriate, in published trial results.
Thus far, safety signals in MAPS-sponsored clinical trials do not suggest that MDMA-assisted therapy for PTSD increases suicide risk. Learn more:
Does the treatment require participants to focus on one traumatic event?
The CAPS and PTSD Checklist (PCL) measurements of PTSD symptoms are the validated measures taken before and after treatment, as required by the FDA. The Independent Raters who conduct screening and other testing are required to ask participants to focus on one “index trauma.”
Focusing on a single traumatic event is not part of the method described in our Treatment Manual, taught in our therapist trainings, nor assessed in our adherence ratings. In fact, it is antithetical to the “inner directed” approach we take in the therapy.
In the therapy sessions the participants are specifically not asked to focus on one trauma, but are encouraged to not create an agenda about what comes up at any given time. This allows the individual’s experience to unfold in their own unique way. If nothing about their trauma comes up spontaneously (which is unusual), the therapists may ask about the index trauma, but even then participants are not asked to narrow their focus to only one trauma. We don’t have control over the limitations of the DSM and the CAPS and other measures, but we don’t carry those limitations into the therapy sessions.
Why does MAPS use the CAPS measurement for PTSD?
The Clinician-Administered PTSD Scale (CAPS) is a highly structured clinical assessment tool designed to diagnose PTSD and assess symptom severity. Endpoints of clinical trials are typically based on the average experience of a group. The CAPS assessment is the gold standard measure because for most people, decreases in PTSD symptoms also tend to relate to global life and well-being improvements.
However, CAPS isn’t designed to capture lived experiences; that is why we often use multiple assessment tools. This is why we also measured change in functional impairment as a key secondary endpoint in the Phase 3 trial, which was also positive in the published study. Individual-level effectiveness analyses can give us more informative ways of characterizing how many people experienced a certain type of outcome. Additional measurement tools allow us to understand more about participant experiences in the trials. You can see the measurement tools used for each study at maps.org/research/mdma.
Why do Phase 2 trials have different designs?
Differences in Phase 2 trial design such as dose, number of therapy sessions, timing of outcome assessment, and other factors are used to inform efficient exploratory design of Phase 3 trials. Exploratory design adequately tests safety and efficacy when traditional drug development budgets are not available — a priority when seeking to develop novel treatments for serious conditions. See the open access journal publication MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials for more information.
It is important to note that the Phase 2 trials used to inform the Phase 3 trial design had consistent participant inclusion criteria, and similar study design and treatment protocols, as reported in Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials: “The six studies were similar in study design and treatment protocol and were conducted between April 2004 and March 2017 at five study sites, including the USA (two sites; MP-1, MP-8, and MP-12), Canada (MP-4), Switzerland (MP-2), and Israel (MP-9). Eligibility criteria included 18 years of age or older, chronic PTSD (6 months or longer), a CAPS-IV score of ≥ 50 (all studies except MP-4) or ≥ 60 (MP-4), and inadequate response to previous psychotherapy and/or medication for PTSD.”
Where are study results reported?
Study results are reported in different ways for different audiences:
- All data from all studies is presented to FDA in the form of Clinical Study Reports and raw data files. The FDA reanalyzes the data during the New Drug Application review (when a drug is assessed for potential approval).
- Data on the effects on the main study questions and the adverse events is presented to the public on clinicaltrials.gov.
- Questions of academic interest are presented in peer-reviewed journal publications. Each has a different audience and purpose and presents the data differently. MAPS has always adopted an Open Science, Open Books principle and pays a fee for each publication to be available with “open access” so anyone can read the publications without requiring a subscription or additional fees.
For example: The Phase 3 journal publication focused on the adverse events after dosing sessions that were more common in the MDMA group than placebo group, while the ClinicalTrials.gov page includes all the adverse events from all subjects throughout the study.
Did the End of Phase 2 Meeting Briefing Packet contain unpublished information?
There seemed to be a great deal of confusion about the purpose of the End of Phase 2 meeting briefing packet. The purpose of that document is not to assert that the treatment is safe and effective. Rather, it was a tool to discuss whether the information presented, along with other information already provided to the FDA but not included in that page-limited document, makes the case that proceeding to Phase 3 clinical trials is warranted.
Certain information contained in that document may still be confidential to protect the integrity of the trials. Certain presentations of data were designed specifically for the purposes of that meeting and have not been published elsewhere in order to prevent confusion among lay readers. However, the vast majority of the data and information in the packet has been published in the following open-access, peer reviewed journal articles:
- Scaling Up: Multisite Open-Label Clinical Trials of MDMA-Assisted Therapy for Severe Posttraumatic Stress Disorder
- Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials
- Frontiers | Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline
- MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials
How is information about negative experiences reported in publications?
It is important to note that negative experiences during or following a clinical trial may not be considered an Adverse Event by the FDA. The Phase 3 clinical trial design was to look at the differential between MDMA and placebo, both of which were delivered with the same therapy protocol. Adverse events that were equally common in both treatment arms — and, notably, are commonly experienced by people with severe, chronic PTSD — are not typically highlighted in the publication of study results. They are described in our Investigator’s Brochure.
For example: The Phase 3 academic publication focused on the adverse events after dosing sessions that were more common in the MDMA group than placebo group, while the ClinicalTrials.gov page includes all the adverse events from all subjects throughout the study.
How is information about Adverse Events reported to regulators?
Adverse events that occur during a clinical trial (both primary trials and long term follow up trials) are collected by investigators and reported to MAPS (the sponsor). Adverse events are regularly reviewed by Medical Monitors and are reported to the FDA in keeping with FDA guidance on reporting.
All Adverse Events are reported in aggregate in the Investigator’s Brochure, which is updated and submitted annually to the FDA (in keeping with requirements) and publicly on our website (in keeping with our values). For information on reporting of individual events, please see page 2 of the guidance, which describes reports from sponsors for individual events of “Serious adverse experiences that were likely to have been manifestations of the underlying disease…and that commonly occurred in the study population independent of drug exposure” as “generally uninformative when reported as single events (i.e. without a comparison of the incidence of the event in the treated and untreated subjects).”
Do different therapy teams have significantly different outcomes?
As reported in the open access, peer reviewed results for the first Phase 3 trial, “Results were consistent across all 15 study sites with no effect by study site (P = 0.1003).”
Different outcomes in Phase 2 trials are likely attributable to the variations in the number of treatment sessions, length of time between end of study and follow up assessments, or other factors, all of which were intentional differences used to find the best treatment protocol for the largest percentage of participants.
Does MAPS say that 89% of participants in trials are cured of their PTSD?
Absolutely not. There is no known cure for PTSD and no reported clinical study has shown 89% of participants no longer having a PTSD diagnosis after MDMA-assisted therapy.
In MAPP1, 88% of participants had a “clinically significant reduction in symptom severity” as defined in our statistical analysis plan as a 10 point drop in CAPS, which was reported in publications and media. We also report that 67% of participants in the MDMA-assisted therapy group no longer qualified as having a PTSD diagnosis.
How many participants received MDMA in MAPS-sponsored trials?
As of the last reported data cut-off on October 1, 2021, 358 participants had received MDMA in a MAPS-sponsored clinical trial (See 2021 DSUR, Table 1). All MDMA exposures in MAPS-sponsored clinical trials are reported in the Development Safety Update Report (DSUR), which is updated and submitted annually to the FDA and other regulatory authorities (in keeping with requirements) and publicly on our website (in keeping with our company values).
Does MAPS do anything to support participants after the therapy in the trial ends?
Termination of trial activities and feeling dependent on the therapists are often challenges in many types of therapy. This can be especially challenging in clinical trials of therapy because of the relatively brief time period. Clinical trial data suggest that MDMA helps people do deep work in a relatively short time, and that may make this even more challenging. Therapists are trained to discuss this challenge, starting from early in each person’s screening and enrollment and having a solid after-care plan for each person.
The treatment manual addresses this extensively. Our trauma-focused therapy is designed to foster participants’ inner healing intelligence and help prevent such feelings of dependence, so it is embedded throughout, including, for example, the Elements of the Therapeutic Method:
6. A nondirective approach to therapy based on empathetic rapport and empathetic presence should be used to support the participant’s own unfolding experience and the body’s own healing process. A non-directive approach emphasizes invitation rather than direction.
7. It is essential to encourage the participant to trust their inner healing intelligence, which is a person’s innate capacity to heal the wounds of trauma. It is important to highlight the fact that the participant is the source of their own healing. The MDMA and the therapists are likely to facilitate access to a deep healing process, but they are not the source of this healing process.
Each clinical trial protocol includes a follow-up period and exit plan, i.e.:
8.4.1 Follow-up Period After the last Integrative Session 3.3, participants will enter follow-up for approximately 4 weeks (±2 weeks) with no protocol-required visits until the final CAPS-5 assessment followed by Study Termination Visit. Participants will have access to therapy teams for support if needed, and additional visits via phone, telemedicine, or in person can be scheduled if requested. Participants will continue to comply with protocol requirements for concomitant medications until after Study Termination.
8.4.2.2 Exit Plan At Study Termination, participants will be provided with an Exit Plan. This Exit Plan will summarize treatments completed, current medications, and contact information for more information about the study if needed. Participants may request a referral for further therapeutic or medical care if appropriate. Enrolled participants who terminate the study early will be provided an Exit Plan at their last contact. Screen Failures will be provided a referral if requested.
Are therapists allowed to treat participants after they complete the trial protocol?
Private therapeutic relationships following the conclusion of participation in a clinical trial are neither prescribed nor categorically restricted by MAPS.
Each clinical trial protocol includes a follow-up period and exit plan, i.e.:
8.4.1 Follow-up Period After the last Integrative Session 3.3, participants will enter follow-up for approximately 4 weeks (±2 weeks) with no protocol required visits until the final CAPS-5 assessment followed by Study Termination Visit. Participants will have access to therapy teams for support if needed, and additional visits via phone, telemedicine, or in person can be scheduled if requested. Participants will continue to comply with protocol requirements for concomitant medications until after Study Termination.
8.4.2.2 Exit Plan At Study Termination, participants will be provided with an Exit Plan. This Exit Plan will summarize treatments completed, current medications, and contact information for more information about the study if needed. Participants may request a referral for further therapeutic or medical care if appropriate. Enrolled participants who terminate the study early will be provided an Exit Plan at their last contact. Screen Failures will be provided a referral if requested.
Do practitioners have multiple calls a week with participants?
Each trial protocol (since our first) requires that telephone calls take place in the days after the MDMA-assisted therapy sessions. These phone calls are mandated to ensure that participants receive adequate support in the period immediately following the MDMA-assisted therapy session, as they may be experiencing difficulty processing information or emotions related to the trauma they are processing in the sessions. You can find the specific contact schedule in each trial protocol at maps.org/mdma/ptsd/.
These contact schedules can also be found in materials provided to participants. For example, the materials provided to participants in MAPP1 state:
”After you return home from the therapy session, the therapy team will talk to you by phone on Days 2, 4, 6, 7, 8, 10, 12, and 14 after each Experimental Session to ask how you are feeling and see whether you should see the therapy team before your next scheduled non-drug therapy session…The phone calls will take approximately 15 minutes, though they can be as long as you need them to be. The therapy team will ask you about thoughts about killing or harming yourself during the second and seventh day of phone contact. You can call the therapy team at any time; except for a few times when they may be unavailable. At those times the study doctor will be on call and can be called at the 24-hour number provided on this consent form.”
Do calls under 30 minutes have to be included in the study record?
Each protocol requires all participant contact to be documented in the participant’s file, referred to as the “source data.” All site staff working on a MAPS-sponsored trial are clearly and explicitly instructed to document those contacts in the source worksheets, which contain these instructions:
“Document any participant contact outside of study visits or not otherwise noted in source or printed emails here. Per contact (phone call/text) describe briefly any information collected and the purpose of the contact (e.g., “Participant called to notify us of a mild headache she has had for the past 24 hours. Information added to AE Log. Will follow until resolution.”) Print as many contact log pages as needed.”
Collecting and incorporating information about individual participant experiences is a critical component in refining the trial protocols. While we know that there is no one-size-fits-all protocol design for all people with PTSD, having an accurate and detailed understanding of the real-world experiences of participants allows MAPS to recommend trial protocols to the FDA which will be most likely to meet the needs of the largest number of participants.
What are the qualifications to enter MAPS Therapy Training Program?
The MDMA Therapy Training Program was expanded in 2016 to include 100 hours of both online and in-person courses and experiential learning, an increase from 50 hours of in-person training provided to therapists in the early Phase 2 studies from 2012-2015.
Applicants to the training program must be licensed mental health providers, enrolled in a post-graduate training or residency program in the field of mental health, or have over 1,000 hours of experience in providing behavioral health services, and are required to have prior experience providing therapy or counseling services to adults affected by trauma. Prior to delivering the treatment at a clinical site, trainees are paired in co-therapist dyads according to professional training and experience, so that every co-therapist dyad has at least one licensed practitioner with extensive clinical experience.
What does “creative latitude” mean in the treatment manual?
“Creative latitude,” a phrase mentioned once in MAPS’ MDMA-assisted Treatment Manual, refers to one element of what is known as an Integrative Therapy. This means we acknowledge that researchers are informed by their previous training, professional style, and clinical experience in addition to the instruction provided via the MAPS training, manual, and protocols.
The manual is very clear that using previous training and experience is only permissible as long as the framework and interventions offered fit within the inner-directed approach described in the manual and taught in the training program. Researchers should not attempt to introduce or practice another therapeutic approach or modality unless the trial protocol is specifically researching that approach, such as in MAPS-sponsored CBCT trials. There may be shared characteristics between the MAPS Treatment Manual and other modalities, however specific procedures — including touch — or scripts from other modalities should not be administered. This is described in significant detail in both the Treatment Manual and training program.
In the inner-directed approach, interventions are selected based on the participant’s process and direction, in addition to safety and adherence to the protocol. The approach includes:
- inquiry through open-ended questions,
- preparation with the participant prior to each experimental session,
- collaborating with the participant to identify language and resources they would like to use during the course of the study,
- creating a container for the participant to engage with their experience,
- invitation for the participant to express feelings and thoughts,
- tracking the participant’s emotional state and process,
- inviting discussion about the participant’s experience,
- managing one’s own (the researcher’s) internal state, and
- practicing therapeutic presence.
Was psychosynthesis developed by Salvador Roquet?
Psychosynthesis was developed by Roberto Assagioli, not Salvador Roquet. MAPS therapy trainers are not aware of any connection between Roquet and Assagioli. Assigioli’s 1973 book titled “Psychosynthesis” is cited on page 62 of the Treatment Manual.
A quick internet search shows that Rouquet referred to his treatment center as the Institute for Psychosynthesis, but describes it as “unrelated to the psychosynthesis of Roberto Assagioli.”
Why aren’t you naming the participant in this post?
While the participant has self-identified as the person subjected to ethical misconduct, and has previously given MAPS permission to identify her as a research participant, we are relying on a variety of best practices in disclosure and discussion of ethical matters to inform our decision not to name her. However, MAPS and MAPS PBC are in full support of the participant sharing her experiences, including electing to not require the participant to restrict future speech about her experiences. If any participant featured in the story tells us they prefer to be named in this post, we will edit according to their wishes.
Does the FDA require clinical trials with children and adolescents?
Under the provisions of the Pediatric Research Equity Act, the FDA has required MAPS to require pediatric studies of MDMA-assisted therapy for PTSD if the treatment is approved for adults. The study must test the safety and efficacy of the treatment in 80 children and adolescents with severe PTSD, first among 12-17 year olds and then 7-12 year olds.
For much more information about pediatric drug testing, please visit fda.gov.
