Ms. Petitt’s manages the program that selects and trains researchers for the MDMA-assisted psychotherapy protocols MAPS Public Benefit Corporation is conducting. The program has reviewed 300 applicants, and is in the midst of training 80 people who will work on therapy teams for Phase 3 trials. In addition to the training program, Ms. Petitt has also served as co-therapist on the MAPS-sponsored Phase 2 trial of MDMA-assisted psychotherapy for anxiety associated with life-threatening illness.

CATR: You work for MPBC, MAPS Public Benefit Corporation, a subsidiary of the Multidisciplinary Association for Psychedelic Studies, as MDMA therapy training program manager. What does your work involve?

Petitt: My work is focused on managing the program that selects and trains researchers for the MDMA-assisted psychotherapy protocols MPBC is conducting. As you might imagine, it’s important to select applicants who have experience working with trauma and are truly well suited for MDMA-assisted psychotherapy. Over the past year, we have reviewed 300 applicants, and right now we are in the midst of training 80 people who will work on therapy teams for Phase 3 trials. In addition to the training program, I also served as co-therapist on the MAPS-sponsored Phase 2 trial of MDMA-assisted psychotherapy for anxiety associated with life-threatening illness.

CATR: Most people know MDMA as “ecstasy,” a drug of abuse. How does it assist in psychotherapy?

Petitt: We have two main hypotheses that drive our research. The first is that MDMA reduces activity in the amygdala, which is the fear center of the brain. This is supported by animal research showing MDMA facilitates fear extinction learning. This is important because the hallmark of PTSD is reexperiencing—feeling as though the traumatic experience that happened in the past is actually happening in the present moment. MDMA allows people to recall traumatic memories without the same fear response, and of course this makes it much easier to process and recontextualize those memories.

CATR: It sounds like MDMA helps make recalling traumatic memories less aversive. What’s the second hypothesis?

Petitt: It’s relational. Working with trauma is about establishing trust and safety, and MDMA facilitates that.

CATR: In what way?

Petitt: MDMA is not a classic psychedelic that induces hallucinations or distortions. It’s better described as an empathogen, or some people call it an entactogen, because it produces feelings of compassion for oneself and others and helps establish trust. It’s so effective in this area that it was actually used in couples therapy before it became illegal in the U.S.

CATR: I see. What does the therapist training involve?

Petitt: It’s a lengthy process totaling about 150 hours. We start with an online course that reviews the chemistry of MDMA and our hypotheses about its mechanism of action. Then trainees view video recordings of actual MDMA-assisted psychotherapy sessions, and discuss these with the facilitators of those sessions. During the next part, trainees identify a treatment modality they’re unfamiliar with that relates to trauma or non-ordinary states and complete a workshop or report in that area. This is to broaden trainees’ knowledge bases—we want our therapy teams to have many tools, to be fluid, and not to be overly attached to any one technique. The next part is experiential and involves learning key techniques like holotropic breathwork, which is using the breath to invoke a non-ordinary state of consciousness. During the final stage, a trainee works with an actual study subject who takes MDMA in an open-label trial under the close supervision of an experienced MDMA researcher.

CATR: What are the legal issues you need to navigate in order to do this kind of research?

Petitt: Well, first of all, MDMA is a Schedule I drug, so the only legal option to administer it is through FDA- and DEA-approved clinical trials like the ones we’re doing at MPBC. We hope that the data from upcoming Phase 3 trials will support making MDMA-assisted psychotherapy into a legal prescription medicine. It’s important for therapists who are just learning about MDMA to know there are big differences between doing clinical research, having the drug be legal, having FDA approval, and using MDMA recreationally.

CATR: What is the status of PTSD research using MDMA? 

Petitt: At MPBC, we are about to enter Phase 3 trials, and those will take 3 to 4 years to complete. If they show the treatment is safe and effective and the FDA agrees MDMA should be made legally available, then the DEA will need to reschedule the drug as Schedule II or Schedule III. At that point, clinicians will be able to prescribe it to patients who meet criteria. This probably won’t happen until around 2021 at the earliest.

CATR: Interesting. What does the MDMA-assisted psychotherapy protocol look like?

Petitt: We start by screening study subjects to make sure they meet eligibility requirements and don’t have medical conditions that could be exacerbated by MDMA. For example, MDMA increases heart rate and blood pressure, so people who have hypertension or a heart condition may not be eligible. Borderline personality disorder, dissociative identity disorder, or any kind of psychotic disorder are also contraindications—not because we believe MDMA couldn’t help with those conditions, but because they would require a different research protocol.

CATR: Is MDMA-assisted psychotherapy safe for people who have comorbid substance use disorders?

Petitt: Human and animal studies suggest MDMA has more abuse potential than “classic hallucinogens” like psilocybin, but less than psychostimulants like cocaine or methamphetamine. Readers who want to know more can look at our investigator’s brochure, which discusses risk mitigation in great detail (https://s3-us-west-1.amazonaws.com/mapscontent/research-archive/mdma/MDMA_IB_FINAL_30Mar2016_Linked.pdf).

CATR: Can you tell me about the psychotherapy model that is used?

Petitt: It’s an eclectic model that we developed specifically for our research protocol. One difference between our model and the way psychotherapy is usually practiced is that instead of one therapist per subject, we use two. We call this a co-therapy model, which means there is a male and female therapist for each subject. The reason is that people relate to different genders differently. For example, a female processing sexual trauma might project her trauma narrative on the male therapist, or she might simply feel safer speaking to another female. There are many different ways gender dynamics can play out, so we’ve found it’s best to have two therapists of different genders.

CATR: That makes sense. Once a study subject is accepted to the protocol, what’s the next step? 

Petitt: People can feel emotionally sensitive while under the influence of MDMA, so it’s important for study subjects to learn that “difficult” is not the same as “bad” before they confront traumatic memories during a psychedelic experience. We start with three 90-minute preparatory sessions. These involve orienting the subject to the study, describing what it’s like to take MDMA, explaining what happens during MDMA psychotherapy sessions, and helping subjects prepare. Part of this involves learning breathing techniques and other methods to manage anxiety they might experience during MDMA sessions. The other big part is trust: We spend lots of time getting to know our subjects and working to develop mutual trust before they take MDMA.

CATR: So there’s a lot of preparatory work that happens before subjects ever take MDMA. What happens next?

Petitt: After the preparatory sessions, subjects have their first experimental session where they get MDMA or placebo. We adhere to a specific treatment manual, which you can find on our website (http://www.maps.org/research/mdma/mdma-research-timeline/4887-a-manual-for-mdma-assisted-psychotherapy-in-the-treatment-of-ptsd). The therapy team doesn’t have an agenda or a list of interventions or questions that they have to ask during the session. In fact, a lot of our training involves “untraining” all the techniques and interventions therapists usually do with clients. Our treatment manual outlines a non-directive approach that is client-centered and works with the concept of an inner healing intelligence.

CATR: How long is a typical session and how long does treatment last?

Petitt: Experimental sessions with either MDMA or placebo are around 8 hours each. The effects of MDMA last approximately 4–6 hours. The session is filled with periods of rich processing and other times of being present and introspective. The subject is positioned on a comfortable couch with blankets and pillows around them—it’s kind of like a nest. After each session, the patient stays the night, does an integration session with their co-therapists in the morning, and then returns for two more integration sessions over the next few weeks. The whole process from screening until the end of treatment takes about four months.

CATR: It sounds like you work hard to help subjects feel safe. How do you address the trauma?

Petitt: We’ve found that when subjects have a safe, comfortable environment and are able to trust their co-therapists, most of them will begin talking about traumatic experiences on their own. We focus on the subject being present, feeling whatever is coming up instead of avoiding or rushing. With that said, if they don’t bring up the trauma at all, then we will raise the issue—subjects agree to that during the consent process.

CATR: Wow. Do the therapists have experience with taking MDMA?

Petitt: Yes. There is an FDA-approved protocol called MT-1 that allows us to offer MDMA-assisted psychotherapy to our researchers. This is important, because in therapy it’s common for clients to wonder if their therapists can relate to them. For example, they might ask, “Do you know what I’m talking about?” It would be really difficult to facilitate a MDMA session without having any firsthand experience of what it’s like.

CATR: What kind of study results are you seeing?

Petitt: They’re very promising. First of all, our subjects have severe, treatment-resistant PTSD. For example, in an open-label trial, subjects had PTSD for an average of 19 years before they got to us. In Phase 1, 10 of 12 subjects who received MDMA had such a big drop in their Clinician Administered PTSD Scale (CAPS) scores that they no longer met criteria for PTSD, compared with 2 of 8 in the placebo group (Mithoefer MC et al, J Psychopharmacol 2011;25(4):439–452). In Phase 2, the clinical response rate was 100% in the 7 subjects, 6 of whom had failed to respond to placebo and one of whom had relapsed after an initial placebo response (Mithoefer MC et al, J Psychopharmacol 2013:27(1):28–39).

CATR: That’s impressive. Has MDMA shown promise for treating other disorders?

Petitt: Yes, there are two ongoing Phase 2 trials using MDMA-assisted psychotherapy for anxiety disorders. One involves treating social anxiety in adults with autism. The other involves treating anxiety associated with life-threatening illness. Most subjects are cancer patients who are in remission, but are suffering anxiety about the cancer reoccurring. We don’t have final data for either study yet, but clinically MDMA is showing good results.

CATR: You mentioned people are very sensitive when they are under the influence of MDMA. What about adverse reactions—the proverbial “bad trip?”

Petitt: We do see people having anxiety and other uncomfortable feelings. To some extent, this is expected. The psychedelic experience involves an element of relinquishing control, and that can be daunting, especially for PTSD patients who have learned to counteract their symptoms by increasing their sense of control. Even so, we haven’t had a problem with “bad trips.” Part of this is because MDMA is an empathogen, not a hallucinogen, so it tends to be a milder experience than other psychedelics. Another reason is that resistance to the psychedelic experience is a major contributor to what people describe as a “bad trip.” We spend a lot of time establishing safety and trust, and preparing subjects to relinquish control as the substance takes effect and the experience kicks in. We also teach stress management techniques like diaphragmatic breathing that can help during the session. Often, the anxiety felt during the session has roots in the subject’s traumatic experience, and this can be a doorway to processing it.

CATR: It sounds like MDMA could turn out to be less dangerous than some other street drugs, at least for therapy. What are the downsides?

Petitt: MDMA is a stimulant, so we caution people that they may experience mild depressive symptoms a few days after taking it—we call this the “Monday blues.” These symptoms are transient, and not everyone experiences them. A big downside is cost. In our studies, each subject receives about 65 hours of therapy, and each therapist needs about 150 hours of training. On the other hand, we are talking about people that are used to taking daily medications and going to therapy every week. After completing our protocol, some of them don’t need those treatments anymore. For example, in a follow-up to the Mithoefer study I mentioned, subjects had no statistically significant change in CAPS score 16–74 months after the end of the original study (Mithoefer MC et al, J Psychopharmacol 2013). When you compare 65 hours of MDMA-assisted psychotherapy to years of “treatment as usual,” there is some real potential for cost savings.

CATR: If MDMA does become FDA-approved, it doesn’t sound like psychiatrists will be able to send patients home with a prescription and expect they will get better with MDMA alone.

Petitt: No. If there is approval, it will be for MDMA-assisted psychotherapy, not for the drug alone. It will be a package deal.

CATR: Thank you for your time, Ms. Petitt.