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

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.

Figure 1

The physiologic mechanisms of psilocybin as a serotonin agonist with an affinity for the 5-HT_2A and other 5-HT receptors, whereby psilocybin exerts psychedelic and antidepressant activity.

Figure 2

The central role of inflammation in the genesis of mental illness, autoimmunity, and chronic disease. Kinderlehrer DA. Inflammation as the Common Pathophysiology Linking Stress, Mental Illness, Autoimmunity, and Chronic Disease: Implications for Public Health Policy. J Biomed Res Environ Sci. 2024;5(3):242–255. Creative Commons.