Saccharomyces cerevisiae as a model to study synthetic cannabinoids: the impact of using different carbon sources

Abstract

Synthetic cannabinoids (SC) are potent agonists of cannabinoid receptors, that mime the psychoactive effect of Δ9-tetrahydrocannabinol (Δ9-THC), the principal psychoactive component of cannabis [1]. JWH-018 was the first novel psychoactive SC found in the recreational drug marketplace in 2008. A few years later, JWH-018 started to be controlled by authorities, so alternative molecules started to emerge. THJ-018 was designed to replace JWH-018, having a similar structural skeleton and also a naphthalene and pentyl chain connected via a middle core substructure. Eventually, THJ-018 was scheduled and alternatives emerged, such as EG-018 [2]. This practice makes almost impossible to characterise SC toxicological profiles on an acceptable time scale, mostly due to the time-consuming experiments that must be held in animal models or human cells by standard methods. The yeast Saccharomyces cerevisiae shares highly conserved molecular and cellular mechanisms with human cells and has been used before for synthetic cathinones [3]. The present work has studied the best carbon source (glucose or galactose) to measure the impact of synthetic cannabinoids on S. cerevisiae growth, aiming to develop a method able to profile synthetic cannabinoids toxicity in a short time scale. The difference between carbon sources is that in Crabtree-positive yeast strains, glucose induce a strong inhibition of mitochondrial oxidative phosphorylation [4].