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Mushrooms, Microdosing, and Mental Illness: The Effect of Psilocybin on Neurotransmitters, Neuroinflammation, and Neuroplasticity

Summary

This review examines how psilocybin, the active compound in certain mushrooms, may help treat depression and anxiety by reducing brain inflammation and promoting healthy neurotransmitter function. Both full doses under medical supervision and smaller ‘microdoses’ show promise for mental health conditions. The research suggests psilocybin works by calming the immune system’s inflammatory response while simultaneously supporting the brain’s natural healing and adaptation processes, offering a potential alternative treatment when standard medications don’t work.

Background

Mental health disorders are increasing worldwide and are leading causes of disability. Neuroinflammation underlies a significant subset of psychiatric conditions, particularly major depressive and anxiety disorders. Psilocin, the active ingredient of Psilocybe mushrooms, is both a potent serotonin agonist and anti-inflammatory agent with potential therapeutic applications.

Objective

To review the pathophysiology of mental health conditions with emphasis on immune dysregulation and neuroinflammation associated with depression and anxiety disorders, and to analyze emerging research demonstrating the potential of psilocybin to address physiologic dysregulation associated with mental illness, including both macrodosing and microdosing approaches.

Results

Studies demonstrate that hallucinogenic doses of psilocybin under therapeutic supervision consistently show benefits for treatment-resistant depression, major depressive disorder, and anxiety disorders. Microdosing studies show mixed results, with prospective observational studies suggesting mood improvements but two double-blind placebo-controlled trials showing no significant differences from placebo. Psilocybin’s mechanisms include serotonin 5-HT2A receptor agonism, TNF-α and IL-1β blockade, NF-κB suppression, BDNF promotion, and default mode network downregulation.

Conclusion

Microdosed psilocybin represents a novel and inexpensive anti-inflammatory intervention targeting neuroinflammation without immune suppression. While the evidence for microdosing is less robust than for macrodosing, psilocybin’s multifaceted mechanisms addressing serotonergic, dopaminergic, glutaminergic, and inflammatory pathways suggest therapeutic potential for depression, anxiety, PTSD, and other inflammation-associated conditions. Further controlled research is needed to clarify optimal dosing strategies and long-term safety.
  • Published in:Neuropsychiatric Disease and Treatment,
  • Study Type:Literature Review,
  • Source: PMC11787777, PMID: 39897712, DOI: 10.2147/NDT.S500337
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