In an open-label trial, 12 patients with moderate-to-severe treatment-resistant depression received two doses of psilocybin (10 mg and 25 mg, one week apart) in a supportive setting. The psychedelic effects peaked 2-3 hours after dosing and subsided within 6 hours. No serious adverse events occurred; transient anxiety, confusion, nausea, and headache were noted. Depressive symptoms, measured with the Quick Inventory of Depressive Symptoms, were markedly reduced one week after the high dose (mean reduction of 11.8 points) and remained lower at three months (mean reduction of 9.2 points). Improvements in anxiety and anhedonia were also observed. The results provide preliminary support for psilocybin's safety and efficacy in treatment-resistant depression, warranting further controlled trials.
Major depression increases the risk of later dementia, and late-life depression may be an early sign of dementia. Adult hippocampal neurogenesis (AHN), the lifelong birth of new neurons in the dentate gyrus, supports learning, memory, and mood. Microglia, the brain's immune cells, regulate AHN, and disruptions in AHN and microgliosis are linked to both depression and neurodegenerative diseases. Psychedelics like psilocybin, a serotonergic agonist with rapid antidepressant effects, may promote neuroplasticity and modulate microglial function. This narrative review examines evidence that psilocybin could affect AHN and microglia, potentially altering the progression from major depression to dementia in at-risk individuals.