Mouse study splits psilocybin's nerve-growth effect from its trip-like effect

UC Santa Cruz researchers used receptor engineering in mice to pull apart psilocybin's brain-rewiring pathway from its hallucination pathway.

A team at the University of California, Santa Cruz, reports in Nature Neuroscience that psilocybin's effect on brain connectivity can be separated from its hallucination-like effects in mice. The work is early and animal-only.

The researchers gave psilocybin to groups of mice and tracked dendritic spines, the connection points nerve cells use to communicate. Within 24 hours, spine volume rose and spine development sped up. In mice stressed to mimic depression, spine formation increased more and the loss of existing connections was stopped. In healthy mice, psilocybin sped up both the growth of new spines and the clearing of old ones. By genetically altering the receptors psilocybin acts on, the team separated a plasticity pathway from a hallucination pathway. Head twitches served as the stand-in measure of trip-like responses.

This matters for mental health care because earlier work showed psilocybin boosts neuroplasticity, but it was unclear whether that benefit depended on the psychedelic experience. Molecular biologist Yi Zuo says therapeutics could keep fast, lasting antidepressant effects while removing the hallucinogenic side effects, which would make treatment more scalable. If that holds, a drug without a trip could in principle be easier to deliver widely. This is our reading, not a result of the study, and the research makes no claim about cost.

Caveats are large. The experiments were in mice, not people. Head twitches are only a proxy for hallucination-like experience, and stressed mice only roughly approximate human depression. Next steps include identifying the specific brain cells behind the hallucination response and comparing spine production with mood changes in the animals. Treatments remain at an early development stage.

Source: ScienceAlert