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The synthetic cannabinoid JWH-018 modulates Saccharomyces cerevisiae energetic metabolism

Lookup NU author(s): Professor Tiago OuteiroORCiD

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Abstract

© 2019 FEMS 2019. Synthetic cannabinoids are a group of novel psychoactive substances with similar properties to Δ9-THC. Among the vast number of synthetic cannabinoids, designed to be tested in clinical trials, JWH-018 was the first novel psychoactive substance found in the recreational drug marketplace. The consumption of JWH-018 shows typical effects of CB1 agonists including sedation, cognitive dysfunction, tachycardia, postural hypotension, dry mouth, ataxia and psychotropic effects, but appeared to be more potent than Δ9-THC. However, studies on human cells have shown that JWH-018 toxicity depends on the cellular line used. Despite these studies, the underlying molecular mechanisms to JWH-018 action has not been clarified yet. To understand the impact of JWH-018 at molecular and cellular level, we used Saccharomyces cerevisiae as a model. The results showed an increase in yeast growth rate in the presence of this synthetic cannabinoid due to an enhancement in the glycolytic flux at expense of a decrease in pentose phosphate pathway, judging by 2D-Gel proteomic analysis, qRT-PCR experiments and ATP measurements. Overall, our results provide insights into molecular mechanisms of JWH-018 action, also indicating that Saccharomyces cerevisiae is a good model to study synthetic cannabinoids.

Publication metadata

Author(s): Ferreira C, Couceiro J, Familia C, Jardim C, Antas P, Santos CN, Outeiro TF, Tenreiro S, Quintas A

Publication type: Article

Publication status: Published

Journal: FEMS Yeast Research

Year: 2019

Volume: 19

Issue: 5

Print publication date: 01/08/2019

Online publication date: 20/06/2019

Acceptance date: 18/06/2019

ISSN (print): 1567-1356

ISSN (electronic): 1567-1364

Publisher: Oxford University Press

URL: https://doi.org/10.1093/femsyr/foz042

DOI: 10.1093/femsyr/foz042

PubMed id: 31329229

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