Frontiers in Neuroscience
February 4, 2020
Claire J. Foldi, Paul Liknaitzky, M.l. Williams et al.
52 citations
Anorexia nervosa has the highest mortality rate of any psychiatric disease, and current medications are largely ineffective partly because the neurobiological drivers are poorly understood. Recent research into psychedelic medicine suggests psilocybin may alleviate symptoms related to serotonin signaling and cognitive inflexibility. Clinical trials for treatment-resistant depression show promise but have methodological biases. The first clinical trial using psilocybin for anorexia nervosa began in 2019, highlighting the need to understand the neurobiological mechanisms. Animal models, such as the activity-based anorexia rodent model, allow detailed study of brain function and behavior without the confounds of expectancy and bias, and are argued to be crucial for informing which patient subpopulations may benefit most from psychedelic medicine.
bioRxiv (Cold Spring Harbor Laboratory)
December 13, 2023
Kyna‐anne Conn, Lk Milton, Kaixin Huang et al.
6 citations
preprint
In a rat model of anorexia nervosa (activity-based anorexia), psilocybin improved body weight maintenance and facilitated cognitive flexibility, particularly by enhancing adaptation when reward contingencies were reversed. The cognitive benefits depended on signaling through the serotonin 5-HT1A receptor, as blocking that receptor negated the effects. Psilocybin also transiently altered cortical expression of serotonin receptor genes, increasing Htr2a and decreasing Htr1a transcripts, with a further reduction in Htr2a in anorexic-model rats. These findings suggest psilocybin could help break cognitive inflexibility in anorexia nervosa and indicate that therapeutic mechanisms may extend beyond 5-HT2A receptor binding.
Physiology & Behavior
May 20, 2025
Kaspar McCoy, Felicia Reed, Kyna‐anne Conn et al.
4 citations
Psilocybin, a serotonergic psychedelic, shows promise for treating anorexia nervosa by enhancing cognitive flexibility and modifying reward processing—two core processes disrupted in the disorder. Its effects are primarily mediated by the 5-HT2A receptor, but recent evidence indicates broader interactions with dopaminergic pathways in brain regions like the prefrontal cortex and nucleus accumbens. Rodent models demonstrate that psilocybin induces rapid and enduring neuroplastic changes, improving cognitive flexibility through complex neurochemical mechanisms. Advances in real-time neurochemical recording now allow simultaneous monitoring of serotonin and dopamine signaling, which will provide insights into their coordinated actions during cognitive performance. Further research into psilocybin's dual modulation of these systems is needed to optimize therapeutic applications for anorexia nervosa.
bioRxiv (Cold Spring Harbor Laboratory)
May 17, 2024
Elizabeth L. Fisher, Ryan Smith, Andrew W. Corcoran et al.
2 citations
preprint
Rats treated with psilocybin achieved more rewards in a decision-making task, driven by increased task engagement, altered forgetting rates, and reduced loss aversion. Computational modeling of the rats' behavior revealed that psilocybin may induce an optimism bias through changes in how beliefs are updated. This finding has potential relevance for clinical populations characterized by a lack of optimism, such as those with depression.
Psychedelics.
February 3, 2026
Sheida Shadani, Erika Greaves, Zane B. Andrews et al.
Psilocybin did not alter sociability in female mice under metabolic stressors—activity-based anorexia, food restriction, or running wheels—but increased preference for social familiarity (reduced novelty-seeking) in control mice. Both activity-based anorexia and running wheel groups showed elevated novelty-seeking behavior, though with distinct social patterns. Psilocybin raised levels of the proinflammatory cytokine interleukin-6 (IL-6) in running wheel mice, and that increase correlated with preference for novelty; no such relationship appeared in the other groups. These context-dependent effects on social behavior and inflammation highlight the need for further research on psilocybin's mechanisms across sexes and disease models.
bioRxiv (Cold Spring Harbor Laboratory)
December 22, 2025
Sheida Shadani, Kaspar McCoy, Lina Ong et al.
A single dose of psilocybin (1.5 mg/kg) alters social behaviors in C57BL/6J mice in sex-specific ways. In females, psilocybin acutely triggers huddling linked to body temperature changes, enhances preference for social novelty 4 hours after administration lasting about 24 hours, but reverses to a preference for familiar over novel conspecifics 7 days later, associated with prolonged nucleus accumbens dopamine signaling during familiar sniffing. In males, psilocybin reduces stress-related behaviors at 24 hours and increases preference for familiar conspecifics, with blunted novelty-evoked dopamine responses at both 24 hours and 7 days. Both 5-HT1A and 5-HT2A receptors modulate these behaviors in sex-specific ways. The prosocial effects of psychedelics are not universal, emphasizing the need for sex-informed approaches.
bioRxiv (Cold Spring Harbor Laboratory)
October 15, 2025
Sheida Shadani, Erika Greaves, Zane B. Andrews et al.
preprint
A single dose of psilocybin did not alter sociability in female mice exposed to activity-based anorexia, food restriction, or exercise, but increased preference for familiarity in control mice. Novelty-seeking behavior rose in both anorexia-model and exercise mice, with distinct social patterns. Psilocybin elevated the inflammatory marker interleukin-6 in exercised mice, which correlated with novelty preference; no such link appeared in other groups. These context-dependent effects on social behavior and inflammation underscore the need to study psilocybin's mechanisms across sexes and disease models.
The International Journal of Neuropsychopharmacology
August 1, 2025
Nicolo Fabila, Nimshitha Pavathuparambil Abdul Manaph, V Rudkowsky et al.
Psilocybin, at a dose of 2 mg/kg, did not reduce compulsive eating in a rat model of binge eating disorder. Female rats given intermittent access to a high-fat/high-sugar diet for 10 weeks showed no change in how quickly they started eating or how much they ate after psilocybin treatment, compared to saline. The compound may have affected freezing behavior, suggesting possible modulation of fear-related learning and memory circuits, though analysis is ongoing. Binge eating disorder is the most common eating disorder and current treatments are limited. Psilocybin is known to promote neuroplasticity, but at this dose it did not alter compulsive-like eating behavior in the conditioned suppression test.
March 31, 2025
Ryan J. Keenan, Rezaul Haque, Xianbo Jin et al.
A single dose of psilocybin exacerbated diet-induced weight loss over four weeks in diet-induced obese mice switched to low-fat chow, increasing susceptibility to more profound weight loss. Psilocybin modulated food intake without affecting energy expenditure. No changes in body weight or food intake occurred in mice maintained on a high-fat diet, indicating psilocybin does not directly promote weight loss or reduce food intake but may facilitate weight loss when combined with other interventions. The findings support further investigation of psychedelic compounds as an adjunct therapy for obesity.