A single psilocybin dose relieved chronic pain and depression-like behaviors in mice by calming hyperactive brain cells

A study in mice found that one systemic dose of psilocybin rapidly reversed chronic pain sensitivity and anxiety- and depression-like behaviors for at least twelve days. The effect appeared to depend on activity in the anterior cingulate cortex, a brain region involved in pain unpleasantness and emotion: direct psilocin administration there reproduced the benefits, while spinal administration did not. Two-photon imaging showed that psilocin suppressed abnormal hyperactivity in this region. Blocking either the 5-HT2A or 5-HT1A serotonin receptor prevented the response, whereas full activation of both receptors did not reproduce it, suggesting that psilocin's partial, balanced receptor activity may be important. The findings are limited to mouse models, and the effective dose, durability beyond twelve days, and safety for humans remain unknown.