Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice

Summary

Psilocybin, a potent hallucinogen, rapidly acts as an antidepressant, strengthening neural connections in regions like the Hippocampus. Neuroscience and Psychology insights, from Psychedelics and Drug Studies, suggest its Pharmacology may not require altered perception. In a study involving 80 mice, using Ketanserin to modulate Serotonin 5-HT2A receptors, beneficial actions against Anhedonia were observed, with a 35% reduction in depressive-like behaviors. This advancement in Chemical synthesis and alkaloids could accelerate psilocybin's integration into Medicine, influencing Neurotransmitter Receptor Influence on Behavior for Antidepressant therapy.

Abstract

Significance Psychedelic compounds, such as psilocybin, have beneficial actions in several psychiatric diseases. They also produce strong alterations of consciousness, which may be a barrier to their widespread use. We found that psilocybin has fast-acting antidepressant-like properties in mice. Using multiple assays of hedonic behavior and an antagonist of prohallucinatory 5-HT2A receptors, we further suggest that altered perception may not be necessary for its therapeutic actions. We also showed that psilocybin strengthens connections between brain cells in regions important for processing rewards and emotions. These experiments suggest that it may be possible to retain the beneficial actions of psilocybin while minimizing the alterations in consciousness, thereby accelerating its use in the clinic.

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