Psilocybin (Psilocybe spp.) given once at 0.3, 2, or 10 mg/kg failed to reduce inflammatory, neuropathic, or muscle pain in mice across mechanical, heat, cold, and functional pain tests. Apparent cold “relief” was traced to drug-induced hypothermia, not true analgesia, with core body temperature dropping sharply for ~30–60 minutes. The data show psilocybin does not act like a painkiller at the nerve or tissue level, supporting that its clinical benefits are psychological and perceptual rather than direct pain-blocking.