Distinct functions of endogenous cannabinoid system in alcohol abuse disorders

Abstract

Δ9‐tetrahydrocannabinol, the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signalling by binding to cannabinoid CB1 and CB2 receptors on the cell surface. The CB1 receptors are present in both inhibitory and excitatory presynaptic terminals and the CB2 receptors are found in neuronal subpopulations in addition to microglial cells and astrocytes and are present in both presynaptic and postsynaptic terminals. Subsequent to the discovery of the endocannabinoid (eCB) system, studies have suggested that alcohol alters the eCB system and that this system plays a major role in the motivation to abuse alcohol. Preclinical studies have provided evidence that chronic alcohol consumption modulates eCBs and expression of CB1 receptors in brain addiction circuits. In addition, studies have further established the distinct function of the eCB system in the development of fetal alcohol spectrum disorders. This review provides a recent and comprehensive assessment of the literature related to the function of the eCB system in alcohol abuse disorders.

Association of the Fatty Acid Amide Hydrolase C385A Polymorphism With Alcohol Use Severity and Coping Motives in Heavy‐Drinking Youth

“…Increased alcohol preference and reduced sensitivity to the effects of alcohol are believed to be mediated, at least in part, through the cannabinoid 1 (CB1) receptor, with the majority of preclinical studies, suggesting that CB1 stimulation increases alcohol consumption, while CB1 receptor antagonism/inverse agonism decreases alcohol intake (Cippitelli et al, 2005; Colombo et al, 2002; Hansson et al, 2007; Linsenbardt and Boehm, 2009; Malinen and Hyytiä, 2008). It has therefore been proposed that reduced FAAH activity, resulting in increased anandamide, may influence alcohol intake via a CB1 receptor‐mediated mechanism (Basavarajappa et al, 2019).…”

GPCR and Alcohol-Related Behaviors in Genetically Modified Mice

“…In the present review, we will give updated progress that has been made in studying the role of GPCRs in alcohol actions using transgenic mouse models and in particular knockout animals. We decided to discuss below only 1) GPCRs that have recognized a role in drug use disorders and that represent key neurotransmitter systems (DA, serotonin, glutamate, and γ-aminobutyric acid (GABA) receptors) and 2), based on our current knowledge, GPCRs that constitute current therapeutic or emerging targets for the treatment of AUD (opioid [36], endocannabinoid [37], ghrelin receptor [215], corticotropin-releasing factor (CRF) [38], melanocortin receptors [39], and orphan GPCRs). However, we have also broadly catalogued reports that addressed GPCR function in alcohol drinking using knockout mice (see Table 1) which will enhance the system-wide view of GPCR genes role in alcohol actions.…”

“…Owing to its key role in neurotransmission, synaptic plasticity, and addiction-related behaviors, the endocannabinoid system has emerged as a reasonable target for the treatment of alcohol abuse [169,171,175]. This possibility has been further strengthened by human studies indicating that genetic polymorphisms including SNPs (e.g., rs1049353 and rs2023239) within the CNR1 gene encoding CB1R were associated with several features of AUD [37,176,177]. Thus, the development of endocannabinoid-based compounds and the generation of CB1R and CB2R mutant mice have understandably spurred scientists to preclinical and clinical initiatives [37,175,[178][179][180][181].…”

“…Most importantly, this compound was withdrawn from the market in 2008 due to serious psychiatric side effects. Consequently, more attention was naturally devoted to CB2R [37,109].…”

A Systematic Review of the Effects of Perinatal Alcohol Exposure and Perinatal Marijuana Exposure on Adult Neurogenesis in the Dentate Gyrus

“…CB 2 receptors are expressed sparsely in microglia, macrophages, and some neurons in the central nervous system, but are more ubiquitous in the peripheral nervous system (Roche and Finn, 2010). There is evidence that alcohol acts to reduce endogenous cannabinoid levels through a CB 2 receptor–mediated pathway and that this mechanism is important in alcohol use disorders (Basavarajappa et al, 2019; Martín‐Sánchez et al, 2019). CB 1 receptors are expressed in both inhibitory and excitatory neurons, at perinatal timepoints in the rodent cortex, basal forebrain, and telencephalon (Scheyer et al, 2019).…”