A single dose of psilocybin—the psychoactive compound in magic mushrooms—altered the electrical properties of brain cells in rats for months, even after the physical changes to neurons had disappeared. Published in Molecular Psychiatry, the research offers a mechanistic clue to how psychedelics produce long-lasting antidepressant effects from a single administration.

Here's what makes this interesting: the distinction between structural and electrical changes in neurons.

Previous research has shown that psilocybin promotes neuroplasticity—growing new dendritic spines (the tiny protrusions where neurons connect). This structural remodeling peaks within days and gradually returns to baseline over weeks. It's been the leading explanation for psilocybin's therapeutic effects.

But this study found something different. Months after the dendritic spines returned to normal, the neurons' electrical properties remained altered. Specifically, cells showed increased excitability and different firing patterns compared to controls.

Think of it this way: the hardware returned to its original configuration, but the firmware stayed updated.

The researchers used patch-clamp electrophysiology—a technique that measures ion channel activity in individual neurons—to detect these changes in the prefrontal cortex, a brain region critical for mood regulation and heavily implicated in depression.

Now, the important caveats. This was conducted in rats, not humans. The relevance to human depression remains inferential. The study doesn't prove these electrical changes cause the antidepressant effects—only that they correlate temporally with the sustained behavioral changes observed.

But it does suggest a hypothesis: psilocybin's therapeutic window may extend far beyond the acute psychedelic experience and even beyond visible structural changes. The brain may be functionally different in ways we couldn't previously measure.

This has implications for dosing strategies and understanding relapse. If therapeutic effects depend on sustained electrical changes rather than just transient structural plasticity, treatment protocols might need to account for the gradual return to baseline excitability.

It also raises questions about mechanism. What maintains these electrical changes after the dendritic spines have retracted? Are specific ion channels being remodeled? Is gene expression durably altered?

The research is part of a broader scientific effort to understand psychedelics through rigorous mechanistic study rather than vague appeals to "consciousness expansion." We're finally moving beyond phenomenology to cellular physiology.

One more thing: the rats received a single dose. That's the striking part. Most antidepressants require daily administration and weeks to take effect. Psilocybin appears to induce a state change that persists.

Whether that translates to human clinical outcomes is the billion-dollar question. But the neuroscience is getting clearer.