Psilocybin Shows Early Promise for Anorexia Nervosa

Megan Brooks

July 25, 2023

The psychedelic psilocybin may have a role in the treatment of anorexia nervosa (AN), an eating disorder that is notoriously difficult and costly to treat.

In a very small phase 1 trial of 10 women with AN, a single 25-mg dose of psilocybin coupled with psychological support, was safe and well-tolerated and decreased eating-disorder behaviors in some of the participants.

Stephanie Knatz Peck, PhD, and colleagues with the Eating Disorders Treatment & Research Center, University of California San Diego, write that the "robust response" in a subset of women after a single dose of psilocybin is "notable," given that currently available treatments for adult anorexia result in only modest improvements in symptoms and often focus on weight and nutritional rehabilitation without adequately addressing underlying psychopathology.

However, given this was a small, phase 1, open-label feasibility study, these effects are "preliminary and inconclusive," they caution.

The study was published online July 24 in Nature Medicine.

Meaningful Experience

The 10 women in the study met DSM-5 criteria for AN or partial remission of AN. They were between age 18 and 40 years with a mean BMI of 19.7 kg/m2.

Following the single 25-mg dose of psilocybin, no clinically significant changes were observed in ECG, vital signs, laboratory values, or suicidality. 

All adverse events were mild and mirrored typical psilocybin-associated symptoms such as transient headache, nausea, and fatigue.

Psilocybin was associated with reduced levels of anxiety and preoccupations surrounding food, eating, and body shape at the 1-month follow-up.

Weight concerns decreased significantly at the 1-month (P = .036, Cohen's d = .78) and 3-month (P = .04, d = .78) follow-up, with a medium to large effect.

Shape concerns significantly decreased at 1-month follow-up (P = .036, d = .78) but were no longer significant at 3-month follow-up (P = .081, d = .62).

Four of the 10 women (40%) had clinically significant reductions in eating disorder scores at 3 months, which qualified for remission from eating-disorder psychopathology. 

However, the researchers caution, that the effects on eating disorder psychopathology were "highly variable."

On average, changes in BMI were not significant during the 3 months following psilocybin treatment. However, five women had an increase in BMI at 3 months, ranging from 0.4 to 1.2 kg/m2.

Overall, the psilocybin experience was regarded as meaningful by participants; 80% endorsed the experience as one of the top five most meaningful of life; 90% endorsed feeling more positive about life endeavors; and 70% reported experiencing a shift in personal identity and overall quality of life.

The vast majority of women (90%) felt that one dosing session was not enough.

The fact that the treatment was regarded as beneficial by most women and that there were no dropouts are "promising signs of engagement," given that dropout rates for currently available AN treatments tend to be high, the researchers note.

They urge caution in interpreting the results considering they were based on a small sample size and did not include a placebo group. They note that larger, adequately powered, randomized controlled trials are needed to draw any conclusions about the role of psilocybin for anorexia nervosa.

Encouraging Data

The co-authors of a Nature Medicine News & Views commentary say this "encouraging" phase 1 trial "underscores the necessity for more research into classic psychedelics to address the urgent need for effective treatments" for AN.

Outside experts also weighed in on the study in a statement from the UK-based nonprofit Science Media Centre.

Alexandra Pike, DPhil, MSc, with University of York, UK, noted that this study is "a first step in showing that psilocybin may be a safe treatment for those with anorexia nervosa, but we cannot conclude from this work that it will be effective in this chronic, complex illness."

Also weighing in, Trevor Steward, MD, with University of Melbourne, Australia, noted that psilocybin therapy has provided "glimmers of hope in other mental health disorders, notably by providing evidence that it can improve anxiety, cognitive flexibility, and self-acceptance for some people. These are all features of anorexia nervosa and the rationale for exploring psilocybin therapy as an option in the case of anorexia is strong."

Steward also noted that the field is only beginning to "scratch the surface in terms of understanding how psilocybin impacts the brain. Dedicated funding to exploring how it specifically acts to target anorexia nervosa symptoms is crucial to advancing this important avenue of research.

"As there are no approved medications available specifically for anorexia nervosa treatment, psilocybin therapy may prove to be a promising option, though additional research is needed to test this," Steward said.

The study used an investigational synthetic formulation of psilocybin (COMP360 psilocybin) developed by COMPASS Pathways, which funded the study. T wo authors have financial and scientific relationships with COMPASS Pathways. The News & Views authors and Steward report no relevant financial relationships. Disclosures for Pike were unavailable at press time.

Nature Med. Published online July 24, 2023. Full text, Editorial

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