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.