Abstract Beyond being one the most widely used psychoactive drugs in the world, cannabis has been identified as an environmental risk factor for psychosis. Though the relationship between cannabis use and psychiatric disorders remains controversial, consistent association between early adolescent cannabis use and the subsequent risk of psychosis suggested adolescence may be a particularly vulnerable period. Previous findings on gene by environment interactions indicated that cannabis use may only increase the risk for psychosis in the subjects who have a specific genetic vulnerability. The type 1 cannabinoid receptor (CB1), encoded by the CNR1 gene, is a key component of the endocannabinoid system. As the primary endocannabinoid...

Abstract Endocannabinoid signaling depends upon the CB1 and CB2 cannabinoid receptors, their endogenous ligands anandamide and 2-arachidonoylglycerol, and intracellular proteins that mediate responses via the C-terminal and other intracellular receptor domains. The CB1 receptor regulates and is regulated by associated G proteins predominantly of the Gi/o subtypes, β-arrestins 1 and 2, and the cannabinoid receptor-interacting protein 1a (CRIP1a). Evidence for a physiological role for CRIP1a is emerging as data regarding the cellular localization and function of CRIP1a are generated. Here we summarize the neuronal distribution and role of CRIP1a in endocannabinoid signaling, as well as discuss investigations linking CRIP1a to development, vision and hearing sensory systems, hippocampus...

Please use this link to access this publication. Abstract The endocannabinoid (EC) system has been implicated in the pathogenesis of several metabolic diseases, including nonalcoholic fatty liver disease (NAFLD). With the current study we aimed to verify the modulatory effect of endocannabinoid receptor 1 (CB1)-signaling on perilipin 2 (PLIN2)-mediated lipophagy. Here, we demonstrate that a global knockout of the cannabinoid receptor 1 gene (CB1−/−) reduced the expression of the lipid droplet binding protein PLIN2 in the livers of CB1−/− and hepatitis B surface protein (HBs)-transgenic mice, which spontaneously develop hepatic steatosis. In addition, the pharmacologic activation and antagonization of CB1 in cell culture also caused an induction or reduction of PLIN2, respectively. The decreased PLIN2 expression was associated with suppressed lipogenesis and triglyceride (TG) synthesis and enhanced...

Please use this link to access this publication. Abstract The cannabinoid 1 receptor (CB1R) is the most abundant G protein-coupled receptor in the brain and plays crucial roles in emotion and behavior by modulating or mediating synaptic transmission and plasticity. Differences in CB1R density between male and female rodents may be associated with distinct behavioral phenotypes. In the rat brain, CB1R expression is significantly lower in the prefrontal cortex and amygdala of estrus females than in males. However, differences in CB1R distribution due to sex over the whole mouse brain are still largely unknown. Here, we systemically investigated the expression of CB1R mRNA in...

Please use this link to access this publication. Abstract Parkinson's disease (PD) is a neurodegenerative disease and its characteristic is the progressive degeneration of dopaminergic neurons within the substantia nigra (SN) of the midbrain. There is hardly any clinically proven efficient therapeutics for its cure in several recent preclinical advances proposed to treat PD. Recent studies have found that the endocannabinoid signaling system in particular the comprised two receptors, CB1 and CB2 receptors, has a significant regulatory function in basal ganglia and is involved in the pathogenesis of PD. Therefore, adding new insights into the biochemical interactions between cannabinoids and other signaling pathways may help develop new pharmacological strategies. Factors of the endocannabinoid system (ECS) are abundantly expressed...

Please use this link to access this publication. Abstract Background Recent approved medicines whose active principles are Δ9Tetrahidrocannabinol (Δ9-THC) and/or cannabidiol (CBD) open novel perspectives for other phytocannabinoids also present in Cannabis sativa L. varieties. Furthermore, solid data on the potential benefits of acidic and varinic phytocannabinoids in a variety of diseases are already available. Mode of action of cannabigerol (CBG), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabidivarin (CBDV) and cannabigerivarin (CBGV) is, to the very least, partial. Hypothesis/Purpose Cannabinoid CB1 or CB2 receptors, which belong to the G-protein-coupled receptor (GPCR) family, are important mediators of the action of those cannabinoids. Pure CBG, CBDA, CBGA, CBDV and CBGV from Cannabis sativa L. are differentially acting on CB1 or CB2 cannabinoid...

Please use this link to access this publication. Abstract According to the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), there were 179 different synthetic cannabinoids reported as of 2017. In the USA, 5F-MDMB-PINACA, or 5F-ADB, accounted for 28% of cannabinoid seizures 2016–2018. The synthetic cannabinoid, 5F-MDMB-PICA, is structurally similar to 5F-MDMB-PINACA with an indole group replacing the indazole. Limited data exist from in vivo or in vitro metabolic studies of these synthetic cannabinoids, so potential metabolites to identify use may be missed. The goals of this study were to (a) investigate 5F-MDMB-PICA and 5F-MDMB-PINACA in vitro metabolism utilizing human hepatocytes; (b) to...

Abstract The endocannabinoid system (ECS) acts as a negative feedback mechanism to suppress synaptic transmission and plays a major role in a diverse range of brain functions including, for example, the regulation of mood, energy balance, and learning and memory. The function and dysfunction of the ECS are strongly implicated in multiple psychiatric, neurological, and neurodegenerative diseases. Cannabinoid type 1 receptor (CB1R) is the most abundant G protein-coupled receptor (GPCR) expressed in the brain and, as for any synaptic receptor, CB1R needs to be in the right place at the right time to respond appropriately to changing synaptic circumstances. While CB1R is found intracellularly...

Abstract Background: Synthetic cannabinoid receptor agonists (SCRAs) have become the largest group of new psychoactive substances monitored by the European Union Early Warning System. Despite the wide diffusion on the market, data regarding effects, toxicities, and mechanisms as well as toxic/lethal doses are still scarce. Methods: A comprehensive literature search for articles published up to January 2019 was performed in multiple electronic databases. Only cases of death in which toxicological analyses revealed the presence of SCRAs in blood or urine and at least an external examination was performed, including those occurred in emergency departments, were included. Results: Of 380 studies identified, 354 were excluded, while 8 additional...