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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol that is rapidly distributed in the body and brain. Ethanol alters many neurochemical systems 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 5th edition of the 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). In the DSM-5, all types of substance abuse and dependence have been combined into a single substance use disorder (SUD) on a continuum from mild to severe. A diagnosis of AUD requires that at least two of the 11 DSM-5 behaviors be present within a 12-month period (mild AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria). The four main behavioral effects of AUD are impaired control over drinking, negative social consequences, risky use, and altered physiological effects (tolerance, withdrawal). This chapter presents an overview of the prevalence and harmful consequences of AUD in the U.S., the systemic nature of the disease, neurocircuitry and stages of AUD, comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and pharmacotherapies for AUD.



ADH: alcohol dehydrogenase

ALDH: aldehyde dehydrogenase

AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

APA: American Psychiatric Association

ARBD: alcohol-related birth defect

ARDS: acute respiratory distress syndrome

ARND: alcohol-related neurodevelopmental disorder

AUD: alcohol use disorder

BEC: blood ethanol concentration

CDC: U.S. Centers for Disease Control and Prevention

CYP: cytochrome P450

DSM-5: Diagnostic and Statistical Manual of Mental Disorders (5th edition)

FAS: fetal alcohol syndrome

GABA: γ-aminobutyric acid

GHB: γ-hydroxybutyric acid

GI: gastrointestinal

5HT: 5-hydroxytryptamine, serotonin

LPS: lipopolysaccharide

NMDA: N-methyl-D-aspartate

PTSD: posttraumatic stress disorder

SSRI: selective serotonin reuptake inhibitor

SUD: substance use disorder


The use of alcoholic beverages is 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. The increase in ethanol consumption in the 1800s, along with industrialization and the need for a dependable workforce, contributed to 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, ...

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