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Endocannabinoid System and Alcohol Abuse Disorders

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Recent Advances in Cannabinoid Physiology and Pathology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1162))

Abstract

Δ9-tetrahydrocannabinol (Δ9-THC), the primary active component in Cannabis sativa preparations such as hashish and marijuana, signals by binding to cell surface receptors. Two types of receptors have been cloned and characterized as cannabinoid (CB) receptors. CB1 receptors (CB1R) are ubiquitously present in the central nervous system (CNS) and are present in both inhibitory interneurons and excitatory neurons at the presynaptic terminal. CB2 receptors (CB2R) are demonstrated in microglial cells, astrocytes, and several neuron subpopulations and are present in both pre- and postsynaptic terminals. The majority of studies on these receptors have been conducted in the past two and half decades after the identification of the molecular constituents of the endocannabinoid (eCB) system that started with the characterization of CB1R. Subsequently, the seminal discovery was made, which suggested that alcohol (ethanol) alters the eCB system, thus establishing the contribution of the eCB system in the motivation to consume ethanol. Several preclinical studies have provided evidence that CB1R significantly contributes to the motivational and reinforcing properties of ethanol and that the chronic consumption of ethanol alters eCB transmitters and CB1R expression in the brain nuclei associated with addiction pathways. Additionally, recent seminal studies have further established the role of the eCB system in the development of ethanol-induced developmental disorders, such as fetal alcohol spectrum disorders (FASD). These results are augmented by in vitro and ex vivo studies, showing that acute and chronic treatment with ethanol produces physiologically relevant alterations in the function of the eCB system during development and in the adult stage. This chapter provides a current and comprehensive review of the literature concerning the role of the eCB system in alcohol abuse disorders (AUD).

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Abbreviations

Δ9-THC:

Δ9-tetrahydrocannabinol

2-AG:

2-arachidonylglycerol

5HT3 :

serotonin type 3

AA:

arachidonic acid

ABHD4:

abhydrolase domain 4

AC:

adenylate cyclase

AEA:

arachidonoyl ethanolamine, or anandamide

AMPAR:

amino-3-hydroxy-5-methyl--4-isoxazolepropionic acid receptor

Arc:

activity-regulated cytoskeleton-associated protein

AUD:

alcohol use disorders

BLA:

basolateral amygdala

CaMKIV:

calcium/calmodulin-dependent protein kinase IV

CB:

cannabinoid

CB1R:

CB1 receptors

CB2R:

CB2 receptors

CBD:

cannabidiol (CBD)

CDK5:

a cyclin dependent kinase 5

CeA:

central nucleus

CHO:

chinese hamster ovary

c-JNK:

c-Jun N-terminal kinase

CREB:

cAMP-response-element binding protein

DAGL:

Diacylglycerol lipases

eCB:

endocannabinoid

EPSP:

excitatory postsynaptic potential

ERK1/2:

extracellular signal-regulated kinase 1/2

ERP:

evoked related potentials

FAAH:

fatty acid amidohydrolase

FAK:

focal adhesion kinase

FASD:

fetal alcohol spectrum disorders

GABA:

γ-aminobutyric acid

GDE1:

glycerophosphodiesterase

GPCR:

G-protein coupled receptor

IP3:

inositol 1,4,5-triphosphate

IPSC:

inhibitory postsynaptic currents

KO:

knock-out

LTP:

long-term potentiation

MAGL:

monoacylglycerol lipase

MAPK:

mitogen-activated protein kinase

MeCP2:

methyl-CpG-binding protein 2

MetAEA:

R(+)-methanandamide

MLC:

mantle cell lymphoma

msP:

marchigian sardinian alcohol-preferring

NAc:

nucleus accumbens

NAPE-PLD:

N-acylphosphatidylethanolamine-specific phospholipase D

NMDA:

N-methyl-D-aspartate

PFC:

prefrontal cortex

PKA:

protein kinase A

PLC:

phospholipase C

PPARs:

peroxisome proliferator-activated receptors

PTPN22:

phosphatase

Rac1:

Ras-related C3 botulinum toxin substrate 1

SNP:

single nucleotide polymorphism

TRPV1:

transient receptor potential vanilloid 1

VTA:

ventral tegmental area

WT:

wild type

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Acknowledgments

National Institute of Alcohol and Alcoholism grant (R01 AA019443) to BSB.

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Authors and Affiliations

  1. Division of Analytical Psychopharmacology, New York State Psychiatric Institute, New York, NY, USA

    Balapal S. Basavarajappa

  2. Department of Psychiatry, College of Physicians & Surgeons, Columbia University, New York, NY, USA

    Balapal S. Basavarajappa

  3. Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA

    Balapal S. Basavarajappa

  4. Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA

    Balapal S. Basavarajappa

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Correspondence to Balapal S. Basavarajappa .

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  1. Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA

    Anna N. Bukiya

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Basavarajappa, B.S. (2019). Endocannabinoid System and Alcohol Abuse Disorders. In: Bukiya, A. (eds) Recent Advances in Cannabinoid Physiology and Pathology. Advances in Experimental Medicine and Biology, vol 1162. Springer, Cham. https://doi.org/10.1007/978-3-030-21737-2_6

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