Psilocybin, a hallucinogen, produces dose-dependent increases in brain activity in awake rats, particularly in the somatosensory cortex, basal ganglia, and thalamus. Female rats showed greater activation than males at the 0.3 mg/kg dose in thalamic and basal ganglia regions. The drug also caused a global increase in functional connectivity, especially hyperconnectivity to the cerebellum. Higher doses activated circuits involved in sensory filtering and motor organization, such as the cortico-striato-thalamo-cortical circuit and claustrum. However, the direction of BOLD signal changes and neural network activity patterns differed from those reported in human studies.
Repetitive mild head injuries from sports, accidents, or military service cause lasting cognitive, motor, and behavioral problems and raise the risk of dementia, Parkinson's disease, and chronic traumatic encephalopathy, yet no approved treatment exists. Testing the psychedelic psilocybin in adult female rats with mild repetitive head injury, the authors report that psilocybin reduces vasogenic edema, restores normal vascular reactivity and functional connectivity, reduces buildup of phosphorylated tau, increases levels of brain-derived neurotrophic factor and its receptor TrkB, and modulates lipid signaling molecules. These findings suggest psilocybin may have healing effects on head injury-related brain damage.