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Psychedelics and the Serotonin Hypothesis of Eating Disorders

Summary

This review explores how psychedelic drugs like psilocybin (found in certain mushrooms) might help treat eating disorders by promoting flexible thinking and breaking rigid eating patterns. The authors summarize evidence from animal studies and early clinical trials showing that psychedelics work differently than traditional antidepressants by triggering brain changes that help people adopt new, healthier behaviors. While results are promising, more research is needed to determine the best doses, patient populations, and long-term safety.

Background

Eating disorders (AN, BN, BED) are increasingly prevalent psychiatric conditions characterized by cognitive and behavioral rigidity. Recent psychedelic research has demonstrated potential therapeutic effects through serotonergic modulation, particularly via 5-HT2A receptor agonism. The serotonin hypothesis suggests that dysregulation of serotonergic signaling underlies the cognitive inflexibility central to eating disorder pathophysiology.

Objective

This review examines the rationale for using serotonergic psychedelics—particularly psilocybin—to treat eating disorders by targeting cognitive and behavioral rigidity. The paper synthesizes evidence from animal models, neuroimaging studies, and emerging clinical trials to evaluate psychedelics’ mechanistic potential and early efficacy in treating AN, BN, and BED.

Results

Preclinical studies demonstrate that psilocybin and other 5-HT2A agonists enhance cognitive flexibility and promote neuroplasticity in rodent models of behavioral inflexibility. Early-stage human trials show feasibility and preliminary efficacy with improvements in ED symptoms and quality of life, though most studies remain unpublished or in early phases. Adverse events were generally mild and transient in reported cases.

Conclusion

While early evidence suggests psychedelics may offer a novel mechanistically distinct approach to treating entrenched eating disorder psychopathology, significant methodological limitations and regulatory barriers currently constrain research. Well-powered, controlled trials are needed to clarify efficacy, optimal dosing, patient selection criteria, and long-term safety before psychedelics can be considered standard treatment.
  • Published in:Brain Sciences,
  • Study Type:Review,
  • Source: PMID: 40867224
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