Tuesday, August 29, 2017

Ecstasy for PTSD: Some Background

You may have heard that the Food and Drug Administration has given the drug ecstasy (MDMA) its "breakthrough designation" for the treatment of PTSD. See this very thoughtful article in the Washington Post for details. 

I came out of blog-slumber to post about this because we're in the midst of planning an upcoming issue of TCPR (The Carlat Psychiatry Report) on PTSD, and because we've recently published a fair amount of material about MDMA. 

First, here's why we need better PTSD treatments. Only two drugs are FDA approved for PTSD: Paxil and Zoloft. Neither are very effective. In the original FDA trials, the drugs beat placebo but not by much; in fact, about 80% of the drug's efficacy is likely due to placebo factors. (See an older issue of TCPR for more on these trials). Various other drugs are used off label, such as Prazosin which helps with insomnia and nightmares, atypical antipsychotics, and alpha agonists such as clonidine and guanfacine. 

Psychotherapy is more effective than drugs, though the treatments most validated are imperfect and are variations of exposure therapy. Patients are asked to recount the trauma over and over again until they are desensitized to the anxiety elicited by the memory. The problem is that this process is emotionally painful and many patients just can't bear the idea of having to recall their trauma (such as a rape, a military attack, or a natural catastrophe) repetitively. 

Enter MDMA. Last March we published an issue of CATR (The Carlat Addiction Treatment Report) on psychiatric uses of street drugs. Psychiatrist Philip Wolfson wrote an overview of the many therapeutic uses of hallucinogens and other substances (full article here), and we interviewed the training project manager of the MDMA/PTSD research program, Shannon Clare Petitt (full interview here). I've reproduced a portion of Petitt's interview at the end of my post below. These are clearly boom times for those seeking creative ways to repurpose "recreational" drugs for healing purposes. In my opinion, that's a good thing for psychiatry, as we have been in something of a pharmacological rut for many years now. 

Excerpt from "MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder", an interview with Shannon Clare Petitt, MA, first published in The Carlat Addiction Treatment Report, Vol 5, No. 2, March/April 2017. Ms. Petitt is the MDMA therapy training program manager at MAPS Public Benefit Corporation (MPBC), Santa Cruz, CA.
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?
S. 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?
S. 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?
S. Petitt: It’s relational. Working with trauma is about establishing trust and safety, and MDMA facilitates that.
CATR: In what way?
S. 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.