We have developed the Computational Analysis of Novel Drug Opportunities (CANDO) platform that constructs and analyzes the structural compound-proteome interaction signatures of 3,733 compounds with 48,278 proteins to infer homology of drug behavior at the proteomic level in a shotgun manner. We applied the CANDO platform to predict putative therapeutic properties of 428 psychoactive compounds belonging to the phenylethylamine, tryptamine, and cannabinoid chemical classes for the treatment of mental health indications. Our findings indicate that these 428 psychoactives are among the top-ranked predictions for a significant fraction of mental health indications, demonstrating a significant preference for treating such indications over non-mental health indications, relative to randomized controls. Additionally, we examined the inverse question to determine that mental health indications are the top-ranked indications for psychoactive compounds. To verify these results with known literature, we analyzed the use of specific tryptamines for the treatment of sleeping disorders, bupropion for substance abuse disorders, and cannabinoids for epilepsy. Finally, we have developed a new methodology to determine the relationship between different indications at both the proteomic and therapeutic levels and evaluated these relationships using these psychoactive compounds for the selected mental health indications. Not only do our findings reveal already known relationships between mental health indications, but they also suggest new ones that can be investigated in future works. Our innovative use of the CANDO platform may guide the identification and development of novel therapies for mental health indications and provide an understanding of their causal basis on a detailed mechanistic level. Given the recent change in perception of psychoactive compounds as treatments for a myriad of psychological disorders, we hope that these predictions can be used to provide new avenues for preclinical drug development for mental health and other neurological disorders.

Computational chemoproteomics to understand the role of psychoactives in treating mental health indications

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.