Abstract

Clinical findings suggested that there is an important variety of effects and in many cases, positive effects and benefits in their mental health. In part, these differences can be explained by the differences in dose and composition of the cannabis (balance THC /CBD), but part is related with individual vulnerability. To explore the possible molecular biological mechanism underline we used in-vitro human cultures of stem cells comparing groups of smokers and non-smokers of cannabis with and without a personal history of psychosis.

We investigated the expression levels and functionality of CB1R -5HT2AR heteromers in human olfactory neuroepithelial cells of cannabis users and control subjects and determined their molecular characteristics. We also assessed whether heteromer expression levels correlated with cannabis consumption, personal history of psychotic experiences and the cognitive performance.

Interestingly, CB1R -5HT2AR heteromer expression was significantly positively correlated with the amount of cannabis consumed, and negatively with age of onset of cannabis use. A negative correlation was found between heteromer expression levels and attention and working memory performance, and a positive correlation with the incidence of psychotic/paranoid. Our findings suggest that the formation of CB1R -5HT2AR heteromers may have a key role in the incidence of psychotic symptoms and negative cognitive processing. These heterodimers could be potential new targets to develop treatment alternatives for psychosis and cognitive impairments related with cannabis use.