SPEAKERS

Introduction: The use of psychedelics has been proposed for treatment-resistant depression and other mental disorders. Still, therapeutic potential of psychedelics just started to be unravelled. 5-MeO-DMT is a natural psychedelic agonist of serotonin receptors, which has been shown to decrease depression and anxiety symptoms in naturalistic settings. Given the wide spectrum of biological processes regulated by serotonin signalling, serotonin agonists could be expected to have further therapeutic applications beyond those already observed. Here, we took a computational science approach by using proteomic dataset from human brain organoids exposed to 5-MeO-DMT in order to search for prospective, unaddressed effects of this compound.

Methods: The dataset of 5-MeO-DMT proteomics was re-analysed and searched in the Enrichr tool for bioinformatics against a databank of drug affected genes. Functional analysis was addressed using Ingenuity Pathway Analysis software and STRING databases for protein interactions. Results 5-MeO-DMT consistently regulated 158 proteins. Search in the databank of drug regulated genes matched hits regulated by Peroxisome Proliferator-activated Receptor Gamma (PPARγ) agonists. Those are insulin sensitizer drugs, which use has been proposed as therapy for cognitive decline and Alzheimer’s disease (AD). Regulated proteins participate in axon guidance, immune system pathways, synaptic recycling and glucose homeostasis.

Conclusion: Datamining approach suggests that 5-MeO-DMT has a role in brain insulin signalling, which should be further explored. Funding: CNPq, CAPES, FAPERJ, FINEP, BNDES and FAPESP.