The synthetic cannabinoid JWH-018 modulates Saccharomyces cerevisiae energetic metabolism

Carla Ferreira, Joana Couceiro, Carlos Família, Carolina Jardim, Pedro Antas, Cláudia N. Santos, Tiago F. Outeiro, Sandra Tenreiro, Alexandre Quintas

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article numberfoz042
JournalFems Yeast Research
Volume19
Issue number5
DOIs
Publication statusPublished - 8 Aug 2019

Keywords

  • JWH-018
  • proteomics
  • Saccharomyces cerevisiae
  • Synthetic cannabinoids
  • toxicity assays

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