Summary: A new study highlights the potential of psilocybin, found in magic mushrooms, as a treatment for anorexia nervosa (AN), a psychiatric disorder with one of the highest mortality rates. The research demonstrated that psilocybin enhances cognitive flexibility and body weight maintenance in an animal model of AN.
The study uncovered a specific brain mechanism by which psilocybin could alleviate rigid thought patterns associated with AN, suggesting a new direction for therapeutic strategies beyond traditional antidepressants, which are often ineffective in underweight AN patients. This breakthrough could lead to more effective, targeted treatments for the cognitive symptoms of anorexia.
Key Facts:
Source: Monash University
Characterised by pathological weight loss driven by restrictive feeding and excessive exercise behaviours, anorexia nervosa (AN) has one of the highest mortality rates of any psychiatric disease.
Some small clinical trials have shown that psilocybin, the active ingredient in magic mushrooms, may be a potential treatment for anorexia nervosa.
The condition is characterised by cognitive inflexibility, or rigid thinking and there is evidence that psilocybin acts to increase this flexibility.
However – crucial to the use of the drug as a recognised treatment for anorexia – is the need to understand how psilocybin actually works in the brain. Now, a study led by Dr Claire Foldi from the Monash University Biomedicine Discovery Institute and published in the journal Molecular Psychiatry, has studied psilocybin in an animal model of anorexia nervosa – revealing that it
improves body weight maintenance in female rats and facilitates cognitive flexibility.
Importantly, the Monash researchers found a specific mechanism within the brain by which psilocybin works to make “anorexic thinking” more pliable, opening the way for targeted therapies.
According to Dr Foldi, while selective serotonin reuptake inhibitors (antidepressants) are the leading pharmacological treatment, they are used off-label and “they do not improve clinical symptoms in underweight individuals with anorexia,” she 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.”
Author: Claire Foldi
Source: Monash University
Contact: Claire Foldi – Monash University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms” by Claire Foldi et al. Molecular Psychiatry
Abstract
Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms
Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility.
Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plausible that psilocybin could improve symptoms of AN by breaking down cognitive inflexibility.
A mechanistic understanding of the actions of psilocybin is required to tailor the clinical application of psilocybin to individuals most likely to respond with positive outcomes. This can only be achieved using incisive neurobiological approaches in animal models.
Here, we use the activity-based anorexia (ABA) rat model and comprehensively assess aspects of reinforcement learning to show that psilocybin (post-acutely) improves body weight maintenance in female rats and facilitates cognitive flexibility, specifically via improved adaptation to the initial reversal of reward contingencies.
Further, we reveal the involvement of signalling through the serotonin (5-HT) 1 A and 5-HT2A receptor subtypes in specific aspects of learning, demonstrating that 5-HT1A antagonism negates the cognitive enhancing effects of psilocybin.
Moreover, we show that psilocybin elicits a transient increase and decrease in cortical transcription of these receptors (Htr2a and Htr1a, respectively), and a further reduction in the abundance of Htr2a transcripts in rats exposed to the ABA model.
Together, these findings support the hypothesis that psilocybin could ameliorate cognitive inflexibility in the context of AN and highlight a need to better understand the therapeutic mechanisms independent of 5-HT2A receptor binding.
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Psilocybin Shows Promise in Anorexia Treatment – Neuroscience News
