Endocannabinoid System and Alcohol Abuse Disorders

Basavarajappa, Balapal S.

doi:10.1007/978-3-030-21737-2_6

Cited by 26 publications

(18 citation statements)

References 274 publications

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“…The role of the endocannabinoid (eCB) neurotransmitter system in the regulation of several alcohol-related behaviors is well documented and summarizable with cannabinoid CB 1 receptor antagonists/inverse agonists inhibiting and cannabinoid CB 1 receptor agonists stimulating alcohol drinking, operant alcohol selfadministration, and reinstatement of alcohol seeking in rats and mice. [1][2][3][4] The adverse neuropsychiatric ef-fects of the prototypic cannabinoid CB 1 receptor antagonist/inverse agonist, rimonabant, have regrettably prevented a proper translation to patients affected by alcohol use disorder (AUD) of the large number of remarkably consistent rodent studies reporting its ''antialcohol'' properties.…”

Section: Introductionmentioning

confidence: 99%

Reducing Effect of Cannabidiol on Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats

Maccioni

Bratzu

Carai

et al. 2022

Cannabis and Cannabinoid Research

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Introduction: Cannabidiol (CBD) is a major cannabinoid extracted from Cannabis sativa with no abuse potential. Data from recent rodent studies suggest that amelioration of alcohol-motivated behaviors may be one of the numerous pharmacological effects of CBD. This study was designed to contribute to this research, assessing the effect of CBD on operant oral alcohol self-administration in selectively bred Sardinian alcohol-preferring (sP) rats, a validated animal model of excessive alcohol consumption. In addition, this study investigated the effect of CBD on operant self-administration of a highly palatable chocolate solution in Wistar rats. Materials and Methods: Male sP rats were trained to lever respond for alcohol (15% v/v) under the fixed ratio 4 (FR4) schedule of reinforcement. Once lever responding had stabilized, rats were exposed to test sessions under the FR4 and progressive ratio (PR) schedules of reinforcement. Test sessions were preceded by acute treatment with CBD (0, 6.25, 12.5, and 25 mg/kg or 0, 25, 50, and 100 mg/kg, i.p.; each dose range was tested in an independent experiment). Male Wistar rats were trained to lever respond for a chocolate solution (5% w/v chocolate powder) under the FR10 schedule of reinforcement. Once lever responding had stabilized, rats were exposed to test sessions under the same schedule. Test sessions were preceded by acute treatment with CBD (0, 6.25, 12.5, and 25 mg/kg or 0, 25, 50, and 100 mg/kg, i.p., in two independent experiments). Results: Under the FR schedule, treatment with doses of CBD ‡ 12.5 mg/kg markedly reduced lever responding for alcohol and amount of self-administered alcohol. Under the PR schedule, treatment with CBD produced a slight tendency toward a decrease in lever responding and breakpoint for alcohol. Finally, no dose of CBD affected lever responding for the chocolate solution and amount of self-administered chocolate solution. Discussion: These results extend previous data on CBD ability to affect alcohol-motivated behaviors to an animal model of genetically-determined proclivity to high alcohol consumption. Because of the predictive validity of sP rats, these results may be of relevance in view of possible future studies testing CBD in patients affected by alcohol use disorder.

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Section: Introductionmentioning

confidence: 99%

Reducing Effect of Cannabidiol on Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats

Maccioni

Bratzu

Carai

et al. 2022

Cannabis and Cannabinoid Research

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“…In neurons, the CB1 receptor is expressed in the plasma membrane and mitochondria 17,18 . Dynamin-related protein 1 (Drp1) is a key protein that regulates mitochondrial fission after brain ischemia 19 .…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid CB1 receptor agonist ACEA alleviates brain ischemia/reperfusion injury via CB1–Drp1 pathway

Yang

Wang

et al. 2020

Cell Death Discov.

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Activation of the cannabinoid CB1 receptor induces neuroprotection against brain ischemia/reperfusion injury (IRI); however, the mechanism is still unknown. In this study, we used oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in neuronal cells and middle cerebral artery occlusion (MCAO)-induced brain IRI in rats to mimic ischemic brain injury, and hypothesized that the CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA) would protect ischemic neurons by inhibiting mitochondrial fission via dynamin-related protein 1 (Drp1). We found that OGD/R injury reduced cell viability and mitochondrial function, increased lactate dehydrogenase (LDH) release, and increased cell apoptosis, and mitochondrial fission. Notably, ACEA significantly abolished the OGD/R-induced neuronal injuries described above. Similarly, ACEA significantly reversed MCAO-induced increases in brain infarct volume, neuronal apoptosis and mitochondrial fission, leading to the recovery of neurological functions. The neuroprotective effects of ACEA were obviously blocked by coadministration of the CB1 receptor antagonist AM251 or by the upregulation of Drp1 expression, indicating that ACEA alleviates brain IRI via the CB1–Drp1 pathway. Our findings suggest that the CB1 receptor links aberrant mitochondrial fission to brain IRI, providing a new therapeutic target for brain IRI treatment.

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“…The discovery of the endocannabinoid system created considerable curiosity in the psychiatric research community due to its influence on neurobiological processes and neurotransmitter systems in the brain. Due to recruitment of the endocannabinoid system in reward, mood and related motivational processes (2)(3)(4)(5), its dysfunction plays an important role in the pathophysiology of mood disorders. This review suggests that the endocannabinoid system is a viable treatment target for depressive and suicidal behavior, and discusses directions for future research.…”

Section: Introductionmentioning

confidence: 99%

Exo- and Endo-cannabinoids in Depressive and Suicidal Behaviors

2021

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Cannabis (marijuana) has been known to humans for thousands of years but its neurophysiological effects were sparsely understood until recently. Preclinical and clinical studies in the past two decades have indisputably supported the clinical proposition that the endocannabinoid system plays an important role in the etiopathogeneses of many neuropsychiatric disorders, including mood and addictive disorders. In this review, we discuss the existing knowledge of exo- and endo-cannabinoids, and role of the endocannabinoid system in depressive and suicidal behavior. A dysfunction in this system, located in brain regions such as prefrontal cortex and limbic structures is implicated in mood regulation, impulsivity and decision-making, may increase the risk of negative mood and cognition as well as suicidality. The literature discussed here also suggests that the endocannabinoid system may be a viable target for treatments of these neuropsychiatric conditions.

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Endocannabinoid System and Alcohol Abuse Disorders

Cited by 26 publications

References 274 publications

Reducing Effect of Cannabidiol on Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats

Reducing Effect of Cannabidiol on Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats

Cannabinoid CB1 receptor agonist ACEA alleviates brain ischemia/reperfusion injury via CB1–Drp1 pathway

Exo- and Endo-cannabinoids in Depressive and Suicidal Behaviors

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