In female mice modeling schizophrenia, a single dose of psilocybin restored sensory filtering for days
People with schizophrenia are usually excluded from psychedelic trials. A new mouse study suggests the picture is complicated: psilocybin amplified immediate reactions in a schizophrenia model but lastingly improved sensory filtering in females.
A single dose of psilocybin, the active ingredient in magic mushrooms, temporarily alters perception and mood in mice bred to exhibit signs of schizophrenia, according to new research published in the journal Neuropsychopharmacology. However, the study also found that the compound produces a lasting improvement in sensory filtering among female mice, suggesting that its immediate psychedelic-like effects and longer-term influence on brain function may operate through separate biological pathways that differ between sexes.
Psilocybin is converted into psilocin, which activates serotonin 2A receptors on brain cells, leading to changes in perception, mood, and thought. While psilocybin is being investigated in clinical trials for depression and anxiety, its effects on schizophrenia are still poorly understood. Schizophrenia is characterized by hallucinations, delusions, social withdrawal, and trouble filtering sensory information.
The study focused on a different member of the same receptor family as serotonin 2A receptors, metabotropic glutamate receptor 5, which is involved in learning, emotional control, and the strength of connections between neurons. Mice genetically engineered to lack this specific glutamate receptor exhibit traits similar to human schizophrenia, such as hyperactivity and impaired sensory filtering. These mice treated with psilocybin showed eased symptoms of sensory filtering.
The research involved male and female mice that were genetically modified to lack the metabotropic glutamate receptor 5 and a comparison group of genetically typical mice. Both groups were subjected to a series of behavioral tests before and after receiving an injection of either psilocybin or an inactive saline solution. The behavioral tests measured the mice's movement and head-twitch responses, which indicate hallucinogen-driven activation of serotonin 2A receptors.
Two weeks after the initial injection, a subset of mice received a second injection to test whether repeated exposure altered their immediate reactions. The study found that psilocybin's effects on brain function relevant to schizophrenia are distinct in males and females, with female mice showing more persistent improvements in sensory filtering compared to males.
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