Psychedelics such as LSD are not only known for their recreational use; they’re also being actively investigated as potential treatments for neuropsychiatric conditions that are increasingly prevalent in developed countries, including addiction and depression. However, despite significant progress, we still lack a clear understanding of how these compounds influence neuronal and glial circuits at the intracellular, molecular level.
In this exciting collaboration with Juan F Lopez Gimenez and Javier González Maeso groups (and with Sandra M. Martin, Ph.D in my group), we mapped the signalling pathways modulated by four different hallucinogenic psychedelic drugs and compared them with those triggered by non-hallucinogenic analogues. Remarkably, we identified a distinct phospho-signature that reliably separates hallucinogenic from non-hallucinogenic compounds. This proteomic fingerprint could help accelerate the screening of next-generation therapeutics with tailored pharmacological profiles.
Biologically, our findings point to the regulation of carbohydrate metabolism as a key differentiator between the two classes of compounds. Results from follow-up experiments are consistent with this hypothesis and open new avenues for understanding how psychedelics alter perception and cognition, ultimately leading to therapeutic benefit.