What does this research mean for the field?

Psychedelic compounds, including psilocin, directly increase the excitability and firing of 5-HT2A receptor-expressing neurons in the medial prefrontal cortex via a mechanism dependent on 5-HT2A receptors and intracellular Gαq signaling. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To identify how psychedelic compounds alter the activity of 5-HT2A receptor-expressing neurons in the medial prefrontal cortex and determine the downstream intracellular signaling mechanisms involved.

October 6, 2025Translational PsychiatryOpen Access

Psychedelic compounds directly excite 5-HT2A layer V medial prefrontal cortex neurons through 5-HT2A Gq activation

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To identify how psychedelic compounds alter the activity of 5-HT2A receptor-expressing neurons in the medial prefrontal cortex and determine the downstream intracellular signaling mechanisms involved.
Measured changes in medial prefrontal cortex activity after psilocin exposure using functional magnetic resonance imaging.
Assessed neuronal excitability and firing across current injections in prelimbic and anterior cingulate 5-HT2AR neurons exposed to psilocin, 25-CN-NBOH, or a novel non-hallucinogenic psychedelic.
Psilocin significantly increased functional magnetic resonance imaging activity within the 5-HT2AR-enriched medial prefrontal cortex.
Psilocin and the selective agonist 25-CN-NBOH increased neuronal excitability and stimulated firing in prelimbic/anterior cingulate neurons through a mechanism dependent on both 5-HT2AR and Gαq.
A novel non-hallucinogenic psychedelic compound produced similar Gαq-dependent excitatory effects on medial prefrontal cortex neurons.

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Implication

Laboratory study reveals direct excitation of prefrontal cortex neurons by psychedelics via Gq signaling, highlighting a key molecular target for therapeutic neuroplasticity.

Cite This Study

Schmitz et al. (2025) studied this question.

synapsesocial.com/papers/6a1b41685853c704fce59d32 https://doi.org/10.1038/s41398-025-03611-0

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Implication

Laboratory study reveals direct excitation of prefrontal cortex neurons by psychedelics via Gq signaling, highlighting a key molecular target for therapeutic neuroplasticity.

Psychedelic compounds directly excite 5-HT2A layer V medial prefrontal cortex neurons through 5-HT2A Gq activation

Key Points

Discussion

Implication

Cite This Study

Psychedelic compounds directly excite 5-HT2A layer V medial prefrontal cortex neurons through 5-HT2A Gq activation

Key Points

Discussion

Implication

Cite This Study