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Psilocybin is a bioactive psychedelic compound present in certain varieties of mushrooms, commonly referred to as “magic” mushrooms. With clinical trials finding psilocybin treatment to be effective at reducing symptoms of treatment-resistant depression and obsessive compulsive disorder, increasingly more attention is being drawn to the potential mental health benefits of the compound. Findings from a recent study indicate that a single dose of psilocybin triggers a tangible and lasting proliferation of new neuronal connections in the mouse brain, improving brain plasticity.

In the first phase of their study, the researchers set out to identify a dose of psilocybin that was sufficient to trigger behavioral indicators of mice having a psychedelic-like experience. This involved injecting 82 mice with five doses of psilocybin or a saline solution (of 0, 0.25, 0.5, 1, and 2 milligrams per kilogram of bodyweight) and pinpointing the minimal dose of the drug that reliably caused the animals to twitch their heads. Then, after providing the animals a “psychedelic” dose of one milligram per kilogram of bodyweight, the researchers examined whether psilocybin had an influence on the neurons of the rodents’ frontal cortex – an area of the mammalian brain heavily involved in higher-level cognition, imagination, and decision-making. Their focus fell primarily on the neurons’ dendritic spines: tiny mushroom-like protrusions of membrane that act as neuronal connections by receiving signals and passing them on as electrical impulses.

To track these miniscule anatomical structures using a microscope, the researchers used genetically modified mice whose frontal cortex neurons (spines included) produced a glowing green fluorescent protein known as GFP. All mice began with receiving two microscopy sessions during which the researchers quantified baseline densities of dendritic spines in a tiny section of their frontal cortex. The animals were then randomly allocated to receive either a single dose of psilocybin or a control saline injection, after which the researchers quantified their spine densities on five more occasions (days 1, 3, 5, 7, and 34), blinded to whether the mice had received the active compound or saline.

Tracking spine densities this way revealed that a single dose of psilocybin reliably induced a significant increase in the formation of new spines, which peaked at a 12 percent increase one week after exposure. A proportion of these new connections persisted 34 days after drug exposure. Interestingly, the effect was more pronounced in female animals, although whether this has any therapeutic implications remains to be seen.

This study provides anatomical evidence that psilocybin is capable of stimulating new and lasting connections in the brain – an occurrence that may contribute to the drug’s ability to change mental state both in the short and longer terms. As recent studies report that psychedelic compounds promote mTOR signaling and protein synthesis to stimulate and support the production of new cellular machinery (e.g., dendritic spines), scientists are on the cusp of understanding the biological mechanisms and therapeutic potential of these compounds.

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