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

Neuropsychiatr Dis Treat. 2025 Jan 29:21:141-155. doi: 10.2147/NDT.S500337. eCollection 2025.

Abstract

The incidence of mental health disorders is increasing worldwide. While there are multiple factors contributing to this problem, neuroinflammation underlies a significant subset of psychiatric conditions, particularly major depressive and anxiety disorders. Anti-inflammatory interventions have demonstrated benefit in these conditions. Psilocin, the active ingredient of mushrooms in the Psilocybe genus, is both a potent serotonin agonist and anti-inflammatory agent, increases neuroplasticity, and decreases overactivity in the default mode network. Studies using hallucinogenic doses of psilocin under the supervision of a therapist/guide have consistently demonstrated benefits to individuals with depression and end-of-life anxiety. Microdosing psilocybin in sub-hallucinogenic doses has also demonstrated benefit in mood disorders, and may offer a safe, less expensive, and more available alternative to full doses of psilocybin for mood disorders, as well as for other medical conditions in which inflammation is the principal pathophysiology.

Keywords: Psilocybin; anti-inflammatory; anxiety; depression; microdose; neuroinflammation; psilocin.

Publication types

  • Review