Pharmacological characterization of cannabidiol as a negative allosteric modulator of the 5-HT2A receptor.
Cellular signalling March 1, 2025 Etienne Billard, Alexandre Torbey, Antonio Inserra et al. 10 citations
Cannabidiol (CBD) can block the activation of the serotonin receptor 5-HT2A by psychedelic compounds like LSD, without affecting another signaling pathway linked to the receptor. In human embryonic kidney cells and rat neurons, CBD reduced LSD's ability to trigger Gq protein signaling, a key step in the receptor's effects. Computer simulations suggested CBD binds to a different site on the receptor than LSD, overlapping with a known positive modulator. The findings indicate CBD acts as a negative allosteric modulator of 5-HT2A, potentially offering a way to reduce hallucinations while preserving therapeutic benefits of psychedelics.