Psilocybin, a psychedelic substance approaching clinical use, enhances structural plasticity in the brain. In cultured mouse hippocampal neurons, robust effects on pre- and postsynaptic protein expression (Piccolo and Homer1) appeared 1–3 hours after treatment, while presynaptic Synapsin-1 peaked at 72 hours, suggesting a rapidly normalizing window of plasticity. In an immortalized microglia cell line, psilocybin demonstrated anti-inflammatory effects against a lipopolysaccharide challenge by reducing tumor necrosis factor-alpha secretion. These discrete, acute cell-type-specific effects provide insight into psilocybin's mechanisms of action and potential therapeutic value for conditions like depression and cluster headache.
Cluster headache (CH) is a debilitating condition with limited effective treatments. A survey of 314 Swedish CH patients found that less than half (46%) were satisfied with their abortive treatments, and 19% stopped functioning abortive treatments due to side effects. Among chronic CH patients, 17% had never tried the first-line preventive drug verapamil. A small subset (0–8%) had used illicit substances; psilocybin was reported effective as an abortive treatment by 100% (n = 8) and as a preventive treatment by 92% (n = 12). Verapamil showed some preventive effect for 68% (n = 85). Many patients are undertreated and experience side effects, indicating a need for new strategies and revised guidelines.