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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol that directly affects many different types of neurochemical systems and signaling cascades and has rewarding and addictive properties. It is the oldest recreational drug and likely contributes to more morbidity, mortality, and public health costs than all illicit drugs combined. The current Diagnostic and Statistical Manual of Mental Disorders (DSM-5) integrates alcohol abuse and alcohol dependence into a single disorder called alcohol use disorder (AUD), with mild, moderate, and severe subclassifications (American Psychiatric Association, 2013). This chapter presents an overview of the effects of ethanol on various physiological systems, then focuses on the mechanisms of ethanol’s effects in the CNS as the basis for understanding the rewards, disease processes, and treatments for ethanol-related conditions.



ACh: acetylcholine

ADH: alcohol dehydrogenase

ALDH: aldehyde dehydrogenase

ARBD: alcohol-related birth defect

ARND: alcohol-related neurodevelopmental disorder

AUD: alcohol use disorder

BEC: blood ethanol concentration

CHD: coronary heart disease

CYP: cytochrome P450

FAS: fetal alcohol syndrome

FASD: fetal alcohol spectrum disorder

GABA: γ-aminobutyric acid

HDL: high-density lipoprotein

5HT: serotonin

IHD: ischemic heart disease

LDL: low-density lipoprotein

LPS: lipopolysaccharide

nAChR: nicotinic acetylcholine receptor

NF-κB: nuclear factor kappa B

NMDA: N-methyl-D-aspartate

PTSD: post-traumatic stress disorder

SNP: single nucleotide polymorphism

SSRI: selective serotonin reuptake inhibitor

TLR: toll-like receptor


The use of alcoholic beverages has been documented as far back as 10,000 BC. By about 3000 bc, the Greeks, Romans, and inhabitants of Babylon were incorporating ethanol into religious festivals, while also using it for pleasure and in medicinal practice. Over the last 2000 years, alcoholic beverages have been identified in most cultures, including pre-Columbian America about AD 200 and the Islamic world in the 8th century.

The dangers of heavy consumption of alcohol have long been recognized by almost all cultures, with most stressing the importance of moderation; yet, problems with ethanol are as ancient as the use of this beverage itself. The increase in ethanol consumption in the 1800s, along with industrialization and the need for a more dependable work force, contributed to the development of more widespread organized efforts to discourage drunkenness, including a constitutional ban on the sale of alcoholic beverages in the U.S. from 1920 to 1933.

Today, AUD is one of the most prevalent psychiatric disorders worldwide. In the U.S. among adults 18 years and older, AUD is associated with other substance use and psychiatric disorders; despite its prevalence and comorbidity, AUD often goes untreated (Grant et al., 2015). The highest quantities of ethanol intake per occasion are usually observed in the late teens to early 20s (CDC, 2012). Older adults drink more often but consume fewer total drinks each month (White et al., 2015). In ...

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