QUESTIONS AND ANSWERS: Psilocybin for AN?

Q. A patient recently mentioned hearing that a psychedelic drug was being tested for anorexia nervosa. Is this true? (GH, Austin, TX)

A. Yes, your patient was correct. The drug she mentioned was probably psilocybin, a naturally occurring psychedelic pro-drug compound produced by more than 200 species of fungi. It has been known for its mind-altering effects.

In their Phase 1 open-label study, Dr. Stephanie Knatz Peck and colleagues at the University of California, San Diego, tested a single 25-mg dose of synthetic psilocybin among women who with a mean body mass index of 19.7 kg/m2 (Nature Medicine. 2023. 29:1947). Their preliminary study showed good results when 10 adult women (mean age: 28 years) with DSM5 diagnoses of anorexia nervosa (AN) or partial remission AN received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support.

The authors’ goal was to assess safety, tolerability, and feasibility of synthetic psilocybin post-treatment by noting any incidences and occurrences of adverse events (AEs) and clinically significant changes in ECGs, laboratory tests, vital signs, and suicidality. Among their group, no clinically significant changes were observed in these tests. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 hr. (The authors hypothesized that this was related to a prolonged period of fasting on the dosing day, a common effect of psilocybin, rather than due to any direct relationship to the drug.) No other clinically significant changes were observed in laboratory values. All adverse effects were mild and transient.

Overall, the psilocybin experience was regarded as meaningful by participants. Ninety percent endorsed feeling more positive about life challenges.

Why test psilocybin? The authors noted that despite the seriousness of AN, there are no proven treatments for adult AN that can reverse core symptoms and no approved pharmacological interventions currently available. Findings suggest that psilocybin may increase emotional and brain network plasticity, which may be responsible for sustained improvements in mental health status. Psilocybin therapy typically involves the administration of psilocybin in conjunction with psychological support delivered by one or two trained therapists. When administered in a safe and therapeutic setting in conjunction with psychological support, participants report transformative experiences characterized by profound changes in values, beliefs, and perspectives, which can lead to positive changes in subjective well-being, increased openness, and greater cognitive flexibility.

Results from this open-label, single-arm study suggest that psilocybin therapy is safe and tolerable in patients with AN; however, the study sample was small, and the authors note that adequately powered, randomized controlled trials are needed before any conclusions can be drawn.

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