Korean researchers uncover how 'magic mushroom' compound releases brain's neural brake

Korean researchers have become the first in the world to identify a new mechanism by which psilocybin, the hallucinogenic compound found in "magic mushrooms," releases the brain's neural inhibitory brake by regulating astrocytes — the star-shaped cells that surround neurons.

The findings are expected to lay the groundwork for developing new treatment strategies that preserve psilocybin's therapeutic benefits while reducing its hallucinogenic side effects.

The Korea Brain Research Institute (KBRI) announced Tuesday that a research team led by Dr. Koo Ja-wook of its Brain Disease Research Division had jointly identified the new brain mechanism with a team led by Professor Jang Su-chan of Daegu Haany University.

Psilocybin is a naturally occurring hallucinogen that acts on serotonin 2A receptors. While it has drawn growing attention for its potential in treating depression and restoring neuroplasticity, most previous research had focused on the cerebral cortex and neurons.

The research team turned its attention to psilocin, the active metabolite of psilocybin in the body. The team found that when psilocin binds to serotonin receptors on astrocytes, it activates calcium signaling within the cells and increases the expression of ALDH5A1, a GABA-metabolizing enzyme, through the transcription factor NFATc4.

GABA acts as a kind of brake that prevents neurons from becoming overly excited. As psilocin accelerated GABA breakdown, GABA concentrations inside astrocytes fell and the "tonic inhibition" that had been continuously suppressing neurons was lifted. As a result, activity in the nucleus accumbens — the brain region involved in motivation, reward and addictive behavior — increased significantly.

Notably, the study also found that hallucinogenic responses and drug-recognition behavior may be regulated through distinct pathways.

When the research team artificially strengthened GABA signaling in the nucleus accumbens, "drug discrimination behavior" — the ability to detect and distinguish the drug — decreased. The "head-twitch response," a standard animal behavioral indicator used to assess hallucinogenic reactions, showed no change.

This suggests that GABA signaling in the nucleus accumbens influences drug-recognition behavior but does not act in the same way on hallucination-related responses.

"This research is significant in that it expands our understanding of how hallucinogens act on the brain — shifting the focus from neurons alone to the interaction between neurons and astrocytes," Koo said. "We expect it to provide a new scientific foundation for separately understanding hallucination-related responses and therapeutically useful effects, and for developing treatment strategies with reduced hallucinogenic side effects."

The findings are set to be published in the international journal Experimental & Molecular Medicine.