The implication of CNR1 gene's polymorphisms in the modulation of endocannabinoid system effects.

The endocannabinoid system (ECS) represents one of the most important physiologic systems involved in organism homeostasis, having various implications upon individual behavior and metabolic phenotype. It is composed of cannabinoid receptors CB1 and CB2, and their genes (CNR1 and CNR2), their endogenous ligands and the enzymes which mediate endogenous ligands' biosynthesis and degradation. Anandamide and 2-arachidonoylglycerol are two endogenous agonists of the cannabinoid receptors. It is considered that ECS connects physical and emotional response to stress with appetite and energy balance, functioning like an after stress recovery system which remains inactive in repose physiologic conditions. It is involved in several physiologic processes like nociception, motor control, memory, learning, appetite, food intake and energy balance. This review analyzes the implication of 11 polymorphisms of CNR1 gene in the modulation of the ECS metabolic and central effects. A lot of studies show that rs12720071, rs1049353, rs806381, rs10485170, rs6454674, rs2023239 polymorphisms are associated with metabolic effects. From them rs12720071, rs104935, rs6454674, rs2023239 polymorphisms are also associated with central effects of ECS (substance addiction, impulsivity, resistance to antidepressive treatment). Other studies indicate that rs806368, rs1535255, (AAT)9,(AAT)12 and (AAT)n are correlated only with central effects (schizophrenia, substance addiction, impulsivity, Parkinson syndrome). The discovery of ECS and its signaling pathways opens a door towards the understanding of several important physiologic processes regarding appetite, food intake, metabolism, weight gain, motor control, memory, learning, drug addiction and nociception. The detailed analysis and validation of the ECS functioning can bring us very close to the discovery of new diagnosis and treatment methods for obesity, drugs abuse and numerous psychic diseases.