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Rabies Virus Helps Map Psilocybin’s Brain Altering Effects

The deadly pathogen is adept at jumping between neurons, making it an ideal tracer to reveal how connections change after a dose of psilocybin in mice

Colorful mushrooms glow under vibrant red and blue lighting in a dark, forest-like scene. Credit: Saska RF / Shutterstock.

Psychedelic mushrooms have attracted quite a bit of interest from researchers lately. Recent research has hinted both at the effectiveness of psilocybin, the psychoactive compound in psychedelic mushrooms, in treating clinical depression and at the ways that the hallucinogenic compound works to temporarily remodel the human brain.

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But exactly how psilocybin wields its mind-altering magic on a neural level remains mysterious. Now, researchers have co-opted defanged rabies viruses to help map the changes that the psychedelic molecule makes in mouse brains.

They suggest that psilocybin works by weakening feedback loops that typically fuel negative thinking in a brain’s outer layer and by increasing the connectivity of brain circuits that translate sensory perception into action. The international team of scientists from China, Hong Kong, and the United States recently published their findings in Cell.

Read more: “What Is Your Brain Doing on Psychedelics?

Psilocybin administered to mice seemed to affect much of the rodents’ brains. “This is really looking at brain-wide changes,” said Cornell University biomedical engineer and co-author Alex Kwan, in a statement. “That’s a scale that we have not worked at before. A lot of times, we’re focusing on a small part of the neural circuit.”

Kwan and his colleagues constructed that brain wide map by hooking psilocybin to two viruses, one of which was a rabies virus that had been genetically engineered to only infect and spread to designated neurons in the mouses’ brains. Capitalizing on the rabies virus’s ability to jump across neuronal synapses—part of why the pathogen is so deadly in nature—the team could trace the march of psilocybin across the brain as it led to neuronal changes that introduced more synapses into the organ.

The authors admit that such rabies tracing does have limitations. The virus could spread to neighboring neurons using a non-synaptic route, they wrote, and of course a mouse brain is very different from that of a human.

But the findings do offer tantalizing clues, and potentially useful therapeutic insights, into how psilocybin changes brains.

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Lead image: Saska RF / Shutterstock

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