Psilocybin and its active metabolite psilocin show different cytotoxic and immunomodulatory effects on mouse macrophages. Psilocybin is nearly twice as cytotoxic as psilocin, with LC50 values of 12 ng/ml and 28 ng/ml, respectively. In resting macrophages, both compounds triggered significant release of the pro-inflammatory cytokine TNF-α after 4 hours, with lower doses inducing higher levels than higher doses. Only the highest dose of psilocin increased the anti-inflammatory cytokine IL-10 in resting cells. In LPS-activated macrophages, psilocin reduced TNF-α more than psilocybin in both pre-treatment and post-treatment. Psilocin, but not psilocybin, significantly increased IL-10 in post-treatment, indicating that psilocin exerts anti-inflammatory effects on classically activated macrophages.
Harmine, a compound found in certain medicinal plants, reduces anxiety-like behaviors in mice by calming brain inflammation and restoring normal nerve cell activity. In a mouse model where anxiety was triggered by a bacterial immune challenge, harmine lowered levels of inflammatory proteins IL-1β and TNF-α in the brain. It also corrected an overactive connection between the medial prefrontal cortex and the basolateral amygdala, rebalancing excitatory and inhibitory signals. Additionally, harmine reduced the heightened excitability of amygdala neurons. These results suggest harmine may work as an anxiety treatment by both reducing neuroinflammation and reversing stress-related changes in brain cell communication.