Neuroprotective effects of psilocybin in a rat model of stroke.

Psilocybin, the psychedelic compound in magic mushrooms, reduced brain damage and improved movement in rats after a stroke. In lab dishes, it protected rat neurons from damage caused by glutamate, a chemical that can kill brain cells during stroke. This protection was blocked by a drug that inhibits BDNF, a protein that supports neuron health. In rats, giving psilocybin before or soon after a stroke reduced the size of brain infarction and improved locomotor behavior. It also increased markers of healthy neurons and decreased markers of inflammation in the brain. The findings suggest psilocybin's protective effects involve BDNF, supporting its potential as a novel stroke treatment.

Study at a glance

Abstract

Psilocybin is a psychedelic 5HT2A receptor agonist found in "magic mushrooms". Recent studies have indicated that 5HT2A agonists, such as dimethyltryptamine, given before middle cerebral artery occlusion (MCAo), improve staircase behavior, increased BDNF expression, and reduce brain infarction in stroke rats. The objective of this study is to determine the protective effect of psilocybin in cellular and animal models of stroke. Adult male and timed-pregnant Sprague-Dawley rats were used for this study. The neural protective effects of psilocybin were determined in primary rat cortical neurons and adult rats. Rats were subjected to a 60-min middle cerebral artery occlusion. Brain tissues were collected for histological and qRTPCR analysis. Psilocybin reduced glutamate-mediated neuronal loss in rat primary cortical neuronal cultures. Psilocybin-mediated protection in culture was antagonized by the BDNF inhibitor ANA12. Pretreatment with psilocybin reduced brain infarction and neurological deficits in stroke rats. Early post-treatment with psilocybin improved locomotor behavior, upregulated the expression of MAP2 and synaptophysin, and down-regulated the expression of IBA1 in the stroke brain. ANA12 significantly attenuated psilocybin-mediated reduction in brain infarction and improvements in locomotor behavior. Psilocybin reduced brain infarction and improved locomotor behavior in stroke rats; the protective mechanisms involve regulating BDNF expression. Our data support a novel therapeutic approach of psilocybin in stroke.