A new study examined the effects of psilocybin in an animal model for treating anorexia nervosa, showing that the compound improves body weight maintenance in female rats, facilitating what they call cognitive flexibility.

Anorexia nervosa (AN) is deadly—having one of the highest mortality rates of any known psychiatric disease. It killed people such as Karen Carpenter of The Carpenters, or list of famous models who dealt with unrealistic body goals. It affects women more often but also 10-15% of people with AN are male.

The study, called “Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms,”  was led by Dr. Claire Foldi of the Monash University Biomedicine Discovery Institute and published recently in the journal Molecular Psychiatry.

People with eating disorders often suffer from symptoms like body dysmorphia and a poor self-image. These rigid thought patterns are difficult to overcome, and conventional medicine may not make much of a difference. Researchers observed a specific mechanism within the brain, allowing psilocybin to make “anorexic thinking” more pliable.

Meanwhile, serotonin reuptake inhibitors, aka antidepressants, are the leading treatment, however they are used off-label and don’t appear to improve clinical symptoms in underweight people with anorexia, Foldi said. “Cognitive inflexibility is a hallmark of the condition often arising before symptoms of anorexia nervosa are obvious, and persisting after weight recovery—making this symptom a primary target for therapeutic intervention,” Foldi told MSN News.

Researchers used young female rats in the study because they are particularly vulnerable to developing a particular ABA phenotype—a feature that is not fully understood but has been connected to the increased prevalence of AN in young women. 

To test the effects of psilocybin on cognitive flexibility, saline or 5-HTR antagonists were administered 30 minutes prior to either saline or psilocybin treatment, at the completion of a training session. The following day the reward contingencies of the nose-poke ports were reversed, and rats underwent more testing.

“Clinical trials evaluating the safety and efficacy of psilocybin in people with AN have been ongoing since 2019, with the first pilot study recently reporting that it improves eating disorder symptoms in some individuals, but not others. Psilocybin may have transdiagnostic efficacy through several mechanisms relevant to the pathology of AN, including actions on the serotonergic system and cognitive flexibility. However, the details of how such mechanisms are altered by psilocybin in the context of AN remains unknown. 

The ABA paradigm, as they call it, involves unlimited access to a running wheel and time-restricted food access. At seven weeks of age, rats were individually housed in transparent living chambers with a removable food basket and a running wheel. They were given access to the wheel for seven days to determine baseline running wheel activity (RWA). The following day, psilocybin or saline was administered, wheels were locked for five hours and then it was reopened. Running activity was recorded electronically.

“Here, we show that psilocybin improves body weight maintenance in the ABA rat model and enhances cognitive flexibility in a reversal learning task by both reducing perseverative responding and promoting task engagement when reward contingencies are initially reversed. That psilocybin did not elicit changes in motivated responding (PR) or response suppression (extinction) following the same training and drug administration protocol suggests a selective improvement in adaptive cognition in the face of changing rules.”

Other Studies Show Psilocybin May Be Effective for Eating Disorders

Other studies linked psilocybin with eating disorders (EDs) like anorexia. Recently researchers Elena Koning and Elisa Brietzke explored the ways psilocybin can treat ED by its therapeutic benefits—also in combating rigid thought patterns. Koning, who is doctoral student, recently wrote about her discoveries for PsyPost, explaining the reasoning behind her research.

Koning mentioned that in the age of social media, EDs are becoming increasingly troublesome, and that new approaches to those types of disorders are needed.

An earlier study, “Psilocybin-Assisted Psychotherapy as a Potential Treatment for Eating Disorders: a Narrative Review of Preliminary Evidence,” was published online ahead of print for Trends Psychiatry.

“Eating disorders (ED) are a group of potentially severe mental disorders characterized by abnormal energy balance, cognitive dysfunction and emotional distress,” researchers wrote. “Cognitive inflexibility is a major challenge to successful ED treatment and dysregulated serotonergic function has been implicated in this symptomatic dimension. Moreover, there are few effective treatment options and long-term remission of ED symptoms is difficult to achieve. There is emerging evidence for the use of psychedelic-assisted psychotherapy for a range of mental disorders. Psilocybin is a serotonergic psychedelic which has demonstrated therapeutic benefit to a variety of psychiatric illnesses characterized by rigid thought patterns and treatment resistance.”

The new study show’s psilocybin’s potential in the treatment of anorexia and other EDs.

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