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 a 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 a 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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Much like the United States, Europe is currently figuring out how to incorporate psychedelic therapy into its healthcare landscape most effectively. A lobby group representing developers and professionals within the industry advocates for including seasoned practitioners as integral members of a “multidisciplinary advisory body.” They would serve as a guiding authority, offering essential insights to regulators and healthcare practitioners regarding optimal practices as the field expands and changes. This effort comes from the European Psychedelic Access Research and European Alliance (PAREA), as reported by Politico, as per a briefing document slated for submission to the European Medicines Agency (EMA).

It basically says that those with actual experience with psychedelics should have influence. In both legal cannabis and psychedelics space, there is often a feeling that those with an actual relationship with the substance, rather than simply a desire to profit from it, makes for better business. 

Europe still needs to legalize any psychedelic treatments. However, as Australia and parts of the United States are already offering psychedelic therapy, many lawmakers in Europe want to be prepared to hit the ground running. Having such an advisory board (with people who have experience with these substances) will make psychedelic treatment easier to implement. 

In July, Australia became the first country in the world to authorize psilocybin and MDMA use through a doctor’s prescription to treat mental health conditions like post-traumatic stress disorder (PTSD) and depression. Both were legalized for therapeutic use. 

In 2019, Denver, Colorado, became the first U.S. city to decriminalize psilocybin. Cities such as Oakland, Santa Cruz, and Washington D.C. have followed suit. In 2020, Oregon both decriminalized it and legalized supervised therapeutic use, with Colorado passing a similar law in 2022. 

Psilocybin remains illegal under federal law.

Ketamine, which is technically a (legal) dissociative anesthetic with hallucinogenic properties, is FDA-approved for treatment-resistant depression in the U.S. under as “esketamine,” the S enantiomer of ketamine, as that’s how Johnson & Johnson could patent and sell it under the brand name Spravato. Often, doctors prescribe an off-label actual ketamine nasal spray that one can have made in a compound pharmacy. 

A study by the American Medical Association, published late last month, found growing evidence that psilocybin, the mind-altering ingredient in magic mushrooms, is a potentially effective treatment for those suffering from depression. Psilocybin is also being tested to treat people with anorexia. 

MDMA is currently being studied with successful results for its capacity to treat PTSD, among other mental health conditions.

Such substances would be under review of the proposed multidisciplinary advisory body. Before an upcoming EMA workshop on psychedelic treatments, PAREA urged the regulator to provide centralized leadership for the practical and clinical aspects of these therapies, including their delivery methods.

Unlike conventional pills, such as SSRI antidepressants, psychedelics require a comprehensive regimen of pre- and post-care, as well as support during the experience itself. PAREA wants to ensure that this care is uniformly standardized, drawing upon consensus from a diverse group of stakeholders. 

In psychedelic spaces, this pre- and post-care is known as integration, or the belief that one needs more than the drug itself. Integration typically involves therapy before the trip and afterwards, helping one take what they learned and “integrate” it into everyday life. One may also need more than one session or return for boosters, as with ketamine IV therapy and other psychedelic therapies. Even within recreational psychedelic spaces, many people use a “trip sitter,” or at least one trusted person to abstain and look after them. 

An EU advisory body “would benefit from the collective knowledge of various stakeholders, including the EMA, [the European Monitoring Centre for Drugs and Drug Addiction], national competent authorities, professional organizations, health care professionals and managers, psychedelic organizations, patients’ organizations, drug developers, and the wider community,” the briefing states.

PAREA told POLITICO these professional organizations could include the Open Foundation and the Beckley Academy in the Netherlands and the Mind Foundation in Germany. These groups train therapists in psychedelics using the latest research from institutions like Imperial College London and Johns Hopkins University. Some programs include experiential learning (getting high) on substances like psilocybin or ketamine. The Beckley group teaches people to “navigate non-ordinary states to better serve your clients,” and also runs psilocybin retreats. 

“The importance of ensuring that the therapeutic model adopted is evidence-based and in the best interest of the patients cannot be overstated,” the lobby group’s briefing states.

PAREA also advocates for the EMA to ensure consistent delivery strategies throughout Europe. “Centralized coordination would offer an efficient mechanism to propel the field forward, rather than individual EU countries initiating their own work groups,” it states.

Meanwhile, setting the stage for future generations, psychedelic knowledge and industry are now being taken seriously in academia. Last month, the University of California, Berkeley’s Center for the Science of Psychedelics launched a free online course titled “Psychedelics and the Mind.” The new class is another expansion (and win) for the Center, launched three years ago. The course will be available for free. 

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