Repeated low doses of psilocybin, similar to human microdosing, were tested in rats. The regimen was well tolerated, causing no signs of anhedonia, anxiety, or altered movement, and did not downregulate or desensitize 5-HT2A receptors. The treatment increased resilience to injection stress, reduced self-grooming (a proxy for compulsive actions), and raised 5-HT7 receptor expression and synaptic density in the paraventricular nucleus of the thalamus. These findings support anecdotal reports of benefits from psilocybin microdosing and suggest a possible physiological mechanism.
Psilocybin shows pronounced antidepressant and pro-social effects in both Wistar-Kyoto rats, which model treatment-resistant depression, and normal Wistar rats, but with distinct time courses. The study found behavioral differences between the strains, including passive behavior and social withdrawal in Wistar-Kyoto rats. Psilocybin modulated brain-derived neurotrophic factor signaling differently in each strain and altered activity-regulated cytoskeleton-associated protein expression specifically in Wistar-Kyoto rats. These strain-specific neuroplasticity changes offer insights into the mechanisms behind psilocybin's efficacy in treatment-resistant depression.
Repeated low doses of psilocybin, a serotonergic psychedelic drug, were given to rats in a regimen that mimics human microdosing. The rats tolerated the doses well, showing no signs of anhedonia, anxiety, or altered movement. The treatment did not downregulate or desensitize the 5-HT2A receptor. It did impart resilience against stress from repeated injections and reduced self-grooming frequency, a proxy for compulsive actions. Additionally, it increased 5-HT7 receptor expression and synaptic density in the paraventricular nucleus of the thalamus. These findings support anecdotal reports of benefits from psilocybin microdosing and suggest a possible physiological mechanism.