Psilocybin for anorexia: 5 Questions for researcher Marissa Raymond-Flesch
Raymond-Flesch discusses a new study using psilocybin-assisted therapy to treat people with anorexia, and why psychedelics could potentially help patients with eating disorders.
As a 5th grader, Marissa Raymond-Flesch was named her school’s D.A.R.E. student of the year. She was a studious and active participant in the classes led by a police officer about rejecting alcohol, marijuana, and other drugs, including psychedelics. While growing up in Albuquerque, New Mexico, teen pregnancy and gun violence were part of daily life; it wasn’t until Raymond-Flesch left town for college at MIT that she realized it was unusual to have a daycare center on a high school campus for teenage parents, or to have a moment of silence for murdered classmates.
Despite the culture shock arriving in Cambridge, Raymond-Flesch excelled in her studies, graduating with a degree in brain and cognitive science. In between MIT and medical school at Cornell, she took a year off to earn a master’s degree in public health. After medical school, she completed residency in internal medicine and pediatrics at Mount Sinai in New York City, then landed at University of California at San Francisco for a fellowship in adolescent and young adult health. She is now an associate professor of pediatrics and health policy.
As part of her clinical practice, Raymond-Flesch works with young people who have become medically unstable due to severe malnutrition associated with eating disorders. After COVID hit, she and her colleagues noticed a dramatic spike in the number of patients with eating disorders in the hospital at UCSF. Before the pandemic, it might be typical to see three to four patients hospitalized at a time, but by the peak of the pandemic in 2020, the clinic had maxed out its capacity, caring for up to 14 patients at a time. But the treatment options for severe anorexia are limited and Raymond-Flesch was determined to find new options. She remembered she’d heard about studies at UCSF using psychedelics to treat mental health issues and she reached out to fellow UCSF professor and psychedelic researcher Josh Woolley to begin a collaboration.
The former D.A.R.E. student of the year never would have predicted she’d someday try to treat her patients with the very same drugs she’d been taught to avoid, but Raymond-Flesch is now leading a study using psilocybin to treat anorexia in young adults. The Microdose spoke with her about the study’s design and why psychedelics could potentially help patients with eating disorders.
Your clinical trial treats patients with anorexia. How common is anorexia, and what are the existing standard treatments?
I think many people are familiar with anorexia, but one thing they don’t realize is how deadly it is. It has the same fatality rates as the most common form of childhood cancer, leukemia. I bring this up not only because it’s a really powerful statistic, but also because I really admire the oncology field for the way it so painstakingly iterates upon its own research to improve quality of life for their patients. We haven’t yet had that approach in eating disorder care, but we’ve been making some big strides here at UCSF.
One approach we’re trying is called family-based treatment, where parents enroll with their child. Each week they try to feed their child; they go to the therapist together, and the kid gets weighed. They can assess things together: Did the weight go up or down? What worked? What was hard? They try to problem-solve together. The next phase of that is to help the young person be responsible for their own eating again, in an age-appropriate way, and the last stage is to think about what other supports the person needs moving forward. It’s an evidence-based, rigorous, highly manualized therapy — and unfortunately it only puts less than half of people into long-term remission. It’s a really, really powerful tool, but it’s also not enough. And up to this point, we also haven’t found any medications that shift the underlying disease progression.
When you are malnourished, as many people with anorexia are, it impacts the body and brain in so many ways. We see a depletion of brain matter in MRIs in malnourished patients, and often they develop depression. Sometimes clinicians prescribe antidepressants, but the problem is that people with anorexia are depressed for different reasons than other patients: they don't have any of the nutrition that they need to make serotonin. If you give them an SSRI like Prozac, what those drugs do is they keep the serotonin in the synapse that exists. But if you're not starting with any serotonin, it doesn’t help.
Why might psilocybin-assisted therapy help?
Psilocybin is a classical psychedelic that binds directly to the serotonin receptor; functionally, it mimics serotonin in the brain. You could, in theory, be very malnourished and not make any of your own serotonin, but still benefit from a psychedelic.
It’s also known that with anorexia, as with many severe enduring mental health issues, people get stuck in cognitive ruts. They get stuck in thoughts like, “I’m fat, I’m ugly, and it will never get better” — painful loops. And one leading theory about how psychedelics work is that it disrupts the default mode network, the loop in the brain that is responsible for self-referential thought. It’s how we think about ourselves, and where our brain rests when we don’t give it a task. In other clinical trials of people with depression, psilocybin opens up that default mode network, decreases the tightness of those loops and allows interconnectivity across the neocortex. It could decrease cognitive rigidity, which is a key challenge for people with anorexia.
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How are you all planning to study psilocybin in young people with anorexia?
Our project is called SPANYA, which stands for Study of Psilocybin for Anorexia in Young Adults. We’re working with people who are between 18 to 25, and it’s the first psychedelic trial to specifically focus on the developing brain. We really want to know what additional precautions we should be aware of as we work in this younger age range.
We’ve been really careful in developing this study, and specifically, in taking precautions to protect the health of our participants, who often are quite medically fragile. Our study is enrolling patients down to a body mass index of 12, so they may be very, very malnourished. (Reporter’s note: BMI is a measure based on a person’s height and weight, and is often the medical standard despite criticism from clinicians. A “normal” BMI falls between 18 and 25.)
As a result, this trial has a lot of medical guardrails, with extensive medical and psychological screenings before and during dosing sessions. There are three preparation sessions, then the first dose, which is 20mg of psilocybin, followed by two integration sessions; then they receive a second dose of 30mg of psilocybin, followed by four integration sessions. During the dosing session, we’ll be tracking participants’ vital signs, and we ask them to take in food before, since they are already prone to low blood sugar. We’ll also do blood work and track their electrolyte levels.
We’re also asking a family member to enroll, who will not be dosed but will attend a subset of the psychotherapy sessions. Many of these families had previously been through those family-based treatments, and a lot of our data suggests that even into adulthood, family support for recovery from anorexia is critical. We also did it for some other pragmatic reasons; if I had an 18-year-old enrolling in this trial, I would want to know what the heck they were doing! That anxiety is going to be in the ether and we can either bring it into the therapy sessions and make sure that everybody has all the information that they need, or we can leave it out of the room and have it influence the outcomes anyway.
We’re using a two facilitator model: one therapist with expertise in treating eating disorders, and one therapist with experience in psychedelic integration. We’re targeting a total of 40 participants, which we think will take around three years to complete. A lot of my work prior to this was in health equity, including access to clinical trials, so it was really important to our team to try to recruit a diverse population for this study. At UCSF, 45% of the patients in our eating disorder program do not identify as white. We have therapists with Spanish capabilities, and we are trying to do outreach to communities who may have been disproportionately targeted during the war on drugs. We’re also trying to enroll the sickest patients we can keep safe medically, and people of all genders.
What does success look like for anorexia recovery?
The standard measure, though imperfect, is something called the Eating Disorder Examination, which is a big review of a bunch of different symptoms related to the eating disorder, so that’s our primary outcome. We’ll be measuring that 28 days after participants’ second dose, and we’ll be following them for a year. We’re also following a lot of common comorbidities for anorexia, like depression, anxiety, PTSD, and obsessive-compulsive disorder. We’re also doing qualitative exit interviews with participants and their families to understand their perspective. We’ll ask things like, What does recovery mean to you? What has changed in your life?
Even before we started the study, we assembled two advisory boards to ask qualitative questions to help us design the study. One was a board of young adults who have lived experience with anorexia; the other were parents whose children have received treatment for anorexia. They really helped us think through messaging for the trial, and to give us feedback on some of the logistics.
Are there any insights from the board that have stuck with you?
The first time I floated our study design with the young adult advisory board, I told them that we really wanted to avoid seeing participants’ blood sugar drop during the study, and I asked them how best to talk to our participants about that. And it seems really obvious to me in retrospect, but one of the board members said, “At the peak of my illness, my assumption would have been that you were going to enroll me, get me in an altered state and force me to eat.” That was heartbreaking to hear, but it makes so much sense — thank goodness for the amazing advisors to see what was clearly a blind spot for me.
We’ve tried to put a lot of thought into this trial, and so much of it has come from collective wisdom; I’m sure we’re going to get some things wrong, but that’s why we’re doing exit interviews. There’s the Maya Angelou quote: “Do the best you can until you know better. Then when you know better, do better.” And that’s what we’ll be doing.
This interview has been edited and condensed for clarity and length.
