Alcohol (drug)

Alcohol, sometimes referred to by the chemical name ethanol, is a depressant drug[11] found in fermented beverages such as beer, wine, and distilled spirit[12] -- in particular, rectified spirit.[13] Ethanol is colloquially refereed to as "alcohol" because it is the most prevalent alcohol in alcoholic beverages, but technically all alcoholic beverages contain several types of psychoactive alcohols,that are categorized as primary, secondary, or tertiary; Primary alcohols are oxidized to aldehydes, secondary alcohols undergo oxidation to form ketones, while tertiary alcohols are generally resistant to oxidation;[14] Ethanol is a primary alcohol that has unpleasant actions in the body, many of which are mediated by its toxic metabolite acetaldehyde.[15] Less prevalent alcohols found in alcoholic beverages, are secondary, and tertiary alcohols. For example, the tertiary alcohol 2M2B which is up to 50 times more potent than ethanol and found in trace quantities in alcoholic beverages, has been synthesized and used as a designer drug. Alcoholic beverages are sometimes laced with toxic alcohols, such as methanol (the simplest alcohol) and isopropyl alcohol.[12] A mild, brief exposure to isopropyl alcohol (which is only moderately more toxic than ethanol) is unlikely to cause any serious harm, but many methanol poisoning incidents have occurred through history, since methanol is lethal even in small quantities, as little as 10–15 milliliters (2–3 teaspoons). Ethanol is used to treat methanol and ethylene glycol toxicity.

Ethanol
Skeletal formula of ethanol
Ball-and-stick model of ethanolSpace-filling model of ethanol
Clinical data
Pronunciation/ˈɛθənɒl/
Other namesAbsolute alcohol; Alcohol (USPTooltip United States Pharmacopeia); Cologne spirit; Drinking alcohol; Ethanol (JANTooltip Japanese Accepted Name); Ethylic alcohol; EtOH; Ethyl alcohol; Ethyl hydrate; Ethyl hydroxide; Ethylol; Grain alcohol; Hydroxyethane; Methylcarbinol
Pregnancy
category
  • X (Contraindicated in pregnancy)
Dependence
liability
Physical: Very HighPsychological: Moderate[1]
Addiction
liability
Moderate (10–15%)[2]
Routes of
administration
Common: Oral
Uncommon: suppository, inhalation, ocular, insufflation, injection[3]
Drug classAnalgesic; Anxiolytic; Depressant; Euphoriant; GABAA receptor positive modulators; Sedative
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability80%+[4][5]
Protein bindingWeakly or not at all[4][5]
MetabolismLiver (90%):[6][8]
Alcohol dehydrogenase
MEOS (CYP2E1)
MetabolitesAcetaldehyde; Acetic acid; Acetyl-CoA; Carbon dioxide; Ethyl glucuronide; Ethyl sulfate; Water
Onset of actionPeak concentrations:[6][4]
• Range: 30–90 minutes
• Mean: 45–60 minutes
Fasting: 30 minutes
Elimination half-lifeConstant-rate elimination at typical concentrations:[7][8][6]
• Range: 10–34 mg/dL/hour
• Mean (men): 15 mg/dL/hour
• Mean (women): 18 mg/dL/hr
At very high concentrations (t1/2): 4.0–4.5 hours[5][4]
Duration of action6–16 hours (amount of time that levels are detectable)[9]
Excretion• Major: metabolism (into carbon dioxide and water)[4]
• Minor: urine, breath, sweat (5–10%)[6][4]
Identifiers
  • ethanol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
Chemical and physical data
FormulaC2H6O
Molar mass46.069 g·mol−1
3D model (JSmol)
Density0.7893 g/cm3 (at 20 °C)[10]
Melting point−114.14 ± 0.03 °C (−173.45 ± 0.05 °F) [10]
Boiling point78.24 ± 0.09 °C (172.83 ± 0.16 °F) [10]
Solubility in waterMiscible mg/mL (20 °C)
  • InChI=1S/C2H6O/c1-2-3/h3H,2H2,1H3
  • Key:LFQSCWFLJHTTHZ-UHFFFAOYSA-N

Ethanol is classified as a Group 1 carcinogen,[16] hepatotoxin[17] neurotoxin,[18][19] and birth defect agent.[20][21] The World Health Organization published a statement in The Lancet Public Health in April 2023 that "there is no safe amount that does not affect health".[22] A DrugScience 2010 study rated alcohol the most harmful drug overall, and the only drug more harmful to others than to the users themselves.[23]

Alcohol serves various purposes, for example, it is one of the oldest and most commonly consumed recreational drugs, it is used for self-medication, and it is frequently involved in alcohol-related crimes such as drunk driving, public intoxication, and underage drinking. Some esoteric religions and schools incorporate the use of alcohol for spiritual purposes. However, alcohol has a variety of short-term and long-term adverse effects on health. Short-term effects from moderate consumption include happiness and euphoria, decreased anxiety, decreased social inhibition, sedation, impairment of cognitive, memory, motor, and sensory function, while binge drinking may result in generalized impairment of neurocognitive function, dizziness, analgesia, nausea, vomiting, hangover-like symptoms, blackout, and generalized depression of central nervous system (CNS) function. In high amounts, alcohol may cause alcohol intoxication characterized by loss of consciousness or, in severe cases, death; In 2016, 3.0 million deaths was responsible for excessive alcohol use worldwide.[24] Long-term effects are considered to be a major global public health issue[25] and includes alcoholism, abuse, withdrawal, fetal alcohol spectrum disorder (FASD), liver disease, hepatitis, cardiovascular disease such as cardiomyopathy, polyneuropathy, dementia, hallucinosis, brain damage, and cancers such as breast cancer. Most health risks from alcohol stem from excessive or frequent use, but some, like cancer risk, can occur even with light to moderate drinking.[26][27][28]

Alcohol works in the brain primarily by increasing the effects of γ-Aminobutyric acid (GABA),[29] the major inhibitory neurotransmitter in the brain; by facilitating GABA's actions, alcohol suppresses the activity of the CNS.[29] The substance also directly affects a number of other neurotransmitter systems including those of glutamate, glycine, acetylcholine, and serotonin.[30][31] The pleasurable effects of alcohol ingestion are the result of increased levels of dopamine and endogenous opioids in the reward pathways of the brain.[32][33]

Uses

Dutch courage

Dutch courage, also known as pot-valiance or liquid courage, refers to courage gained from intoxication with alcohol.

Alcohol use among college students is often used as "liquid courage" in the hookup culture, for them to make a sexual advance in the first place.[34]: 200 

Criminal

Albeit not a valid intoxication defense, weakening the inhibitions by drunkenness is occasionally used as a tool to commit planned offenses such as property crimes including theft and robbery, and violent crimes including assault, murder, or rape -- which sometimes but not always occurs in alcohol-facilitated sexual assaults where the victim is also drugged.

Consuming alcohol prior to visiting female sex workers is a common practice among some men.[35] Also, sex workers often resort to using drugs and alcohol to cope with stress. However, female sex workers in low- and middle-income countries have high rates of harmful alcohol use, which is associated with increased risk of risky sexual behavior.[36]

Warfare

A soldier reward himself with a pint of beer on returning from a long and arduous deployment to Afghanistan.

Alcohol has a long association of military use, and has been called "liquid courage" for its role in preparing troops for battle, anaesthetize injured soldiers, and celebrate military victories. It has also served as a coping mechanism for the intense stress of war and a means of decompression from combat to everyday life. However, this reliance on alcohol can have negative consequences for physical and mental health.[37] Military and veteran populations face significant challenges in addressing the co-occurrence of PTSD and alcohol use disorder.[38]

War has specific rules under international law, including the Geneva Conventions. These rules allow for the use of force against enemy combatants, but also prohibit targeting civilians or using unnecessary force. If a soldier kills an enemy combatant while intoxicated, it wouldn't necessarily be considered a crime under international law (though it might violate military regulations). However, intoxication leading to civilian casualties or unnecessary force constitutes a war crime.

Food energy

Drunkorexia is a major risk factor for alcoholic liver disease such as cirrhosis.

The use of alcohol as a staple food source is considered inconvenient due to the fact that it increases the blood alcohol content (BAC). However, alcohol is a significant source of food energy for individuals with alcoholism and those who engage in binge drinking; For example, individuals with drunkorexia, engage in the combination of self-imposed malnutrition and binge drinking to avoid weight gain from alcohol, to save money for purchasing alcohol,[39] and to facilitate alcohol intoxication.[40]

The USDA uses a figure of 6.93 kilocalories (29.0 kJ) per gram of alcohol (5.47 kcal or 22.9 kJ per ml) for calculating food energy.[41] For distilled spirits, a standard serving in the United States is 44 ml (1.5 US fl oz), which at 40% ethanol (80 proof), would be 14 grams and 98 calories.

Alcoholic drinks are considered empty calorie foods because other than food energy they contribute no essential nutrients. Alcohol increases insulin response to glucose promoting fat storage and hindering carb/fat burning oxidation.[42][43] This excess processing in the liver acetyl CoA can lead to fatty liver disease and eventually alcoholic liver disease.

Medical

When taken by mouth or injected into a vein ethanol is used to treat methanol or ethylene glycol toxicity[44] when fomepizole is not available.[45]

Ethanol, when used for toxicity, competes with other alcohols for the alcohol dehydrogenase enzyme, lessening metabolism into toxic aldehyde and carboxylic acid derivatives, and reducing more serious toxic effect of the glycols to crystallize in the kidneys.[46]

Recreational

The Merry Drinker (c. 1628–1630) by Frans Hals

Drinking culture is the set of traditions and social behaviors that surround the consumption of alcoholic beverages as a recreational drug and social lubricant. Although alcoholic beverages and social attitudes toward drinking vary around the world, nearly every civilization has independently discovered the processes of brewing beer, fermenting wine and distilling spirits.[47]

Common drinking styles include social drinking, binge drinking, drinking games, pub crawls, and sober curious.

Self-medication

A group of merry, dancing invalids discarding their medicines in favour of alcohol as a cure. Coloured aquatint by G. Hunt, 1827, after T. Lane.

The therapeutic index for ethanol is only 10%.[48]

Alcohol can have analgesic (pain-relieving) effects, which is why some people with chronic pain turn to alcohol to self-medicate and try to alleviate their physical discomfort.[49]

People with social anxiety disorder commonly self-medicate with alcohol to overcome their highly set inhibitions.[50] However, self-medicating excessively for prolonged periods of time with alcohol often makes the symptoms of anxiety or depression worse. This is believed to occur as a result of the changes in brain chemistry from long-term use.[51][52][53] A 2023 systematic review highlights the non-addictive use of alcohol for managing developmental issues, personality traits, and psychiatric symptoms, emphasizing the need for informed, harm-controlled approaches to alcohol consumption within a personalized health policy framework.[54]

Unscientific

The World Health Organization warns that drinking alcohol does not protect you against COVID-19 and can be dangerous.

In folk medicine, consuming a nightcap is for the purpose of inducing sleep. However, alcohol is not recommended by many doctors as a sleep aid because it interferes with sleep quality.[55]

"Hair of the dog", short for "hair of the dog that bit you", is a colloquial expression in the English language predominantly used to refer to alcohol that is consumed as a hangover remedy (with the aim of lessening the effects of a hangover). Many other languages have their own phrase to describe the same concept. The idea may have some basis in science in the difference between ethanol and methanol metabolism. Instead of alcohol, rehydration before going to bed or during hangover may relieve dehydration-associated symptoms such as thirst, dizziness, dry mouth, and headache.[56][57][58][59][60][61]

Drinking alcohol will not prevent or cure COVID-19,[62] contrary to some claims.[63] Instead, drinking alcohol may cause subclinical immunosuppression.[64]

Spiritual

Sake offered on a sanbo altar

Spiritual use of moderate alcohol consumption is found in some religions and schools with esoteric influences, including the Hindu tantra sect Aghori, in the Sufi Bektashi Order and Alevi Jem ceremonies,[65] in the Rarámuri religion, in the Japanese religion Shinto,[66] by the new religious movement Thelema, in Vajrayana Buddhism, and in Vodou faith of Haiti.

Contraindication

Baby with fetal alcohol syndrome, showing some of the characteristic facial features.

In the US, alcohol is subject to the FDA drug labeling Pregnancy Category X (Contraindicated in pregnancy).

Ethanol is classified as a teratogen[20][21][medical citation needed]—a substance known to cause birth defects; According to the U.S. Centers for Disease Control and Prevention (CDC), alcohol consumption by women who are not using birth control increases the risk of fetal alcohol syndrome. The CDC currently recommends complete abstinence from alcoholic beverages for women of child-bearing age who are pregnant, trying to become pregnant, or are sexually active and not using birth control.[67]

Minnesota, North Dakota, Oklahoma, South Dakota, and Wisconsin have laws that allow the state to involuntarily commit pregnant women to treatment if they abuse alcohol during pregnancy.[68]

Adverse effects

Deaths from alcohol and drug use disorders.

Alcohol has a variety of short-term and long-term adverse effects. Alcohol has both short-term, and long-term effects on the memory, and sleep. It also has reinforcement-related adverse effects, including addiction, dependence, and withdrawal. Alcohol use is directly related to considerable morbidity and mortality, for instance due to overdose and alcohol-related health problems.[69] The World Health Organization advises that there is no safe level of alcohol consumption.[70]

Drunkorexia is a colloquialism for anorexia or bulimia combined with an alcohol use disorder.[71]

Alcohol is a common cause of substance-induced psychosis or episodes, which may occur through acute intoxication, chronic alcoholism, withdrawal, exacerbation of existing disorders, or acute idiosyncratic reactions.[72] Research has shown that excessive alcohol use causes an 8-fold increased risk of psychotic disorders in men and a 3 fold increased risk of psychotic disorders in women.[73][74] While the vast majority of cases are acute and resolve fairly quickly upon treatment and/or abstinence, they can occasionally become chronic and persistent.[72] Alcoholic psychosis is sometimes misdiagnosed as another mental illness such as schizophrenia.[75]

An inability to process or exhibit emotions in a proper manner has been shown to exist in people who consume excessive amounts of alcohol and those who were exposed to alcohol while fetuses (FAexp).[76]

Short-term effects

Symptoms of varying BAC levels. Additional symptoms may occur.

The amount of ethanol in the body is typically quantified by blood alcohol content (BAC); weight of ethanol per unit volume of blood. Small doses of ethanol, in general, are stimulant-like[77] and produce euphoria and relaxation; people experiencing these symptoms tend to become talkative and less inhibited, and may exhibit poor judgement. At higher dosages (BAC > 1 gram/liter), ethanol acts as a central nervous system (CNS) depressant,[77] producing at progressively higher dosages, impaired sensory and motor function, slowed cognition, stupefaction, unconsciousness, and possible death. Ethanol is commonly consumed as a recreational substance, especially while socializing, due to its psychoactive effects.

Central nervous system impairment

A young man lying comatose after a binge drinking session

Alcohol causes generalized CNS depression, is a positive allosteric GABAA modulator and is associated and related with cognitive, memory, motor, and sensory impairment. It slows and impairs cognition and reaction time and the cognitive skills, impairs judgement, interferes with motor function resulting in motor incoordination, loss of balance, confusion, sedation, numbness and slurred speech, impairs memory formation, and causes sensory impairment. At high concentrations, it can induce amnesia, analgesia, spins, stupor, and unconsciousness as result of high levels of ethanol in blood.

At very high concentrations, alcohol can cause anterograde amnesia, markedly decreased heart rate, pulmonary aspiration, positional alcohol nystagmus, respiratory depression, shock, coma and death can result due to profound suppression of CNS function alcohol overdose and can finish in consequent dysautonomia.

Gastrointestinal effects

Woman vomits, after drinking too much alcohol.

Alcohol can cause nausea and vomiting in sufficiently high amounts (varying by person).

Alcohol stimulates gastric juice production, even when food is not present, and as a result, its consumption stimulates acidic secretions normally intended to digest protein molecules. Consequently, the excess acidity may harm the inner lining of the stomach. The stomach lining is normally protected by a mucosal layer that prevents the stomach from, essentially, digesting itself. However, in patients who have a peptic ulcer disease (PUD), this mucosal layer is broken down. PUD is commonly associated with the bacteria Helicobacter pylori, which secretes a toxin that weakens the mucosal wall, allowing acid and protein enzymes to penetrate the weakened barrier. Because alcohol stimulates the stomach to secrete acid, a person with PUD should avoid drinking alcohol on an empty stomach. Drinking alcohol causes more acid release, which further damages the already-weakened stomach wall.[78] Complications of this disease could include a burning pain in the abdomen, bloating and in severe cases, the presence of dark black stools indicate internal bleeding.[79] A person who drinks alcohol regularly is strongly advised to reduce their intake to prevent PUD aggravation.[79]

Ingestion of alcohol can initiate systemic pro-inflammatory changes through two intestinal routes: (1) altering intestinal microbiota composition (dysbiosis), which increases lipopolysaccharide (LPS) release, and (2) degrading intestinal mucosal barrier integrity – thus allowing LPS to enter the circulatory system. The major portion of the blood supply to the liver is provided by the portal vein. Therefore, while the liver is continuously fed nutrients from the intestine, it is also exposed to any bacteria and/or bacterial derivatives that breach the intestinal mucosal barrier. Consequently, LPS levels increase in the portal vein, liver and systemic circulation after alcohol intake. Immune cells in the liver respond to LPS with the production of reactive oxygen species, leukotrienes, chemokines and cytokines. These factors promote tissue inflammation and contribute to organ pathology.[80]

Holiday heart syndrome

Holiday heart syndrome, also known as alcohol-induced atrial arrhythmias, is a syndrome defined by an irregular heartbeat and palpitations[81] associated with high levels of ethanol consumption.[82][83] Holiday heart syndrome was discovered in 1978 when Philip Ettinger discovered the connection between arrhythmia and alcohol consumption.[84] It received its common name as it is associated with the binge drinking common during the holidays.[85] It is unclear how common this syndrome is. 5-10% of cases of atrial fibrillation may be related to this condition, but it could be as high 63%.[86]

Positional alcohol nystagmus

Positional alcohol nystagmus (PAN) is nystagmus (visible jerkiness in eye movement) produced when the head is placed in a sideways position. PAN occurs when the specific gravity of the membrane space of the semicircular canals in the ear differs from the specific gravity of the fluid in the canals because of the presence of alcohol.[87]

Specific population

Allergic-like reactions
Facial flushing. Before (left) and after (right) drinking alcohol. A 22-year-old East Asian man who is ALDH2 heterozygous showing the reaction.[88][89]

Ethanol-containing beverages can cause alcohol flush reactions, exacerbations of rhinitis and, more seriously and commonly, bronchoconstriction in patients with a history of asthma, and in some cases, urticarial skin eruptions, and systemic dermatitis. Such reactions can occur within 1–60 minutes of ethanol ingestion, and may be caused by:[90]

  • genetic abnormalities in the metabolism of ethanol, which can cause the ethanol metabolite, acetaldehyde, to accumulate in tissues and trigger the release of histamine, or
  • true allergy reactions to allergens occurring naturally in, or contaminating, alcoholic beverages (particularly wine and beer), and
  • other unknown causes.

Long-term effects

How alcohol affects your body

Due to the long term effects of alcohol abuse, binge drinking is considered to be a major public health issue.[25]

Prolonged heavy consumption of alcohol can cause significant permanent damage to the brain and other organs, resulting in dysfunction or death. The impact of alcohol on aging is multifaceted. The relationship between alcohol consumption and body weight is the subject of inconclusive studies. Alcoholic lung disease is disease of the lungs caused by excessive alcohol. However, the term 'alcoholic lung disease' is not a generally accepted medical diagnosis.

Alcoholism

Alcohol use disorders deaths per million persons in 2012
  0–0
  1–3
  4–6
  7–13
  14–20
  21–37
  38–52
  53–255

Alcoholism or its medical diagnosis alcohol use disorder refers to alcohol addiction, alcohol dependence, dipsomania, and/or alcohol abuse. It is a major problem and many health problems as well as death can result from excessive alcohol use.[91][69] Alcohol dependence is linked to a lifespan that is reduced by about 12 years relative to the average person.[91] In 2004, it was estimated that 4% of deaths worldwide were attributable to alcohol use.[69] Deaths from alcohol are split about evenly between acute causes (e.g., overdose, accidents) and chronic conditions.[69] The leading chronic alcohol-related condition associated with death is alcoholic liver disease.[69] Alcohol dependence is also associated with cognitive impairment and organic brain damage.[91] Some researchers have found that even one alcoholic drink a day increases an individual's risk of health problems by 0.4%.[92]

Two or more consecutive alcohol-free days a week have been recommended to improve health and break dependence.[93][94]

Dry drunk is an expression coined by the founder of Alcoholics Anonymous[95] that describes an alcoholic who no longer drinks but otherwise maintains the same behavior patterns of an alcoholic.[96]

A high-functioning alcoholic (HFA) is a person who maintains jobs and relationships while exhibiting alcoholism.[97][98][99]

Many Native Americans in the United States have been harmed by, or become addicted to, drinking alcohol.[100]

Alcohol withdrawal syndrome
Chlordiazepoxide (trade name Librium) is the most commonly used benzodiazepine for alcohol detoxification.[101]

Discontinuation of alcohol after extended heavy use and associated tolerance development (resulting in dependence) can result in withdrawal. Alcohol withdrawal can cause confusion, paranoia, anxiety, insomnia, agitation, tremors, fever, nausea, vomiting, autonomic dysfunction, seizures, and hallucinations. In severe cases, death can result.

Delirium tremens is a condition that requires people with a long history of heavy drinking to undertake an alcohol detoxification regimen.

Alcohol is one of the more dangerous drugs to withdraw from.[102] Drugs which help to re-stabilize the glutamate system such as N-acetylcysteine have been proposed for the treatment of addiction to cocaine, nicotine, and alcohol.[103]

Alcoholic ketoacidosis

Alcoholic ketoacidosis (AKA) is a specific group of symptoms and metabolic state related to alcohol use.[104] Symptoms often include abdominal pain, vomiting, agitation, a fast respiratory rate, and a specific "fruity" smell.[105] Consciousness is generally normal.[106] Complications may include sudden death.[106]

Alcoholic polyneuropathy

An illustration of a neuron's structure. In alcoholic polyneuropathy myelin loss and axonal degeneration occurs.

Alcoholic polyneuropathy is a neurological disorder in which peripheral nerves throughout the body malfunction simultaneously. It is defined by axonal degeneration in neurons of both the sensory and motor systems and initially occurs at the distal ends of the longest axons in the body. This nerve damage causes an individual to experience pain and motor weakness, first in the feet and hands and then progressing centrally. Alcoholic polyneuropathy is caused primarily by chronic alcoholism; however, vitamin deficiencies are also known to contribute to its development.

Alcohol-related dementia

Alcohol-related dementia (ARD) is a form of dementia caused by long-term, excessive consumption of alcohol, resulting in neurological damage and impaired cognitive function.[107]

Alcohol and cardiovascular disease

Alcoholic cardiomyopathy
Idiopathic cardiomyopathy.

Alcoholic cardiomyopathy (ACM) is a disease in which the long-term consumption of alcohol leads to heart failure.[108] ACM is a type of dilated cardiomyopathy. The heart is unable to pump blood efficiently, leading to heart failure. It can affect other parts of the body if the heart failure is severe. It is most common in males between the ages of 35 and 50.

Austrian syndrome

Austrian syndrome, also known as Osler's triad, is a medical condition that was named after Robert Austrian in 1957. The presentation of the condition consists of pneumonia, endocarditis, and meningitis, all caused by Streptococcus pneumoniae. It is associated with alcoholism due to hyposplenism (reduced splenic functioning) and can be seen in males between the ages of 40 and 60 years old.[109] Robert Austrian was not the first one to describe the condition, but Richard Heschl (around 1860s) or William Osler were not able to link the signs to the bacteria because microbiology was not yet developed.

The leading cause of Osler's triad (Austrian syndrome) is Streptococcus pneumoniae, which is usually associated with heavy alcohol use.

Brain damage

Alcohol can cause brain damage,[110] Wernicke's encephalopathy and Alcoholic Korsakoff syndrome which frequently occur simultaneously, known as Wernicke–Korsakoff syndrome.[111] Lesions, or brain abnormalities, are typically located in the diencephalon which result in anterograde and retrograde amnesia, or memory loss.[111]

Cancer

The International Agency for Research on Cancer lists ethanol in alcoholic beverages as a Group 1 carcinogen in humans and argues that "There is sufficient evidence and research showing the carcinogenicity of acetaldehyde (the major metabolite of ethanol) which is excreted by the liver enzyme when one drinks alcohol."[16]

A 2001 meta-analysis did not find a clear safe level of alcohol consumption where there is no increased risk of cancer.[26] In 2020, alcohol was estimated to cause 750,000 cases of cancer worldwide, particularly esophagus, liver, and breast cancer.[112]

Cortisol

Research has looked into the effects of alcohol on the amount of cortisol that is produced in the human body. Continuous consumption of alcohol over an extended period of time has been shown to raise cortisol levels in the body. Cortisol is released during periods of high stress, and can result in the temporary shut down of other physical processes, causing physical damage to the body.

Liver damage

Depiction of a liver failure patient

Consuming more than 30 grams of pure alcohol per day over an extended period can significantly increase the risk of developing alcoholic liver disease.[113] During the metabolism of alcohol via the respective dehydrogenases, nicotinamide adenine dinucleotide (NAD) is converted into reduced NAD. Normally, NAD is used to metabolize fats in the liver, and as such alcohol competes with these fats for the use of NAD. Prolonged exposure to alcohol means that fats accumulate in the liver, leading to the term 'fatty liver'. Continued consumption (such as in alcohol use disorder) then leads to cell death in the hepatocytes as the fat stores reduce the function of the cell to the point of death. These cells are then replaced with scar tissue, leading to the condition called cirrhosis.

Specific population

  • Pregnant women: Babies exposed to alcohol, benzodiazepines, barbiturates, and some antidepressants (SSRIs) during pregnancy may experience neonatal withdrawal.[114]

Other effects

Frequent drinking of alcoholic beverages is a major contributing factor in cases of elevated blood levels of triglycerides.[115]

Social issues

Table from the 2010 DrugScience study ranking various drugs (legal and illegal) based on statements by drug-harm experts. This study rated alcohol the most harmful drug overall, and the only drug more harmful to others than to the users themselves.[23]
Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational substances. Alcohol was ranked 2nd in social harm, 6th in dependence, and 11th in physical harm.[116]

Alcohol causes a plethora of detrimental effects in society.[91] Many emergency room visits involve alcohol use.[91] As many as 15% of employees show problematic alcohol-related behaviors in the workplace, such as drinking before going to work or even drinking on the job.[91]

Individuals who engage with or share alcohol-related content on social networking services tend to exhibit higher levels of alcohol use and related issues.[117] Alcohol availability and consumption rates and alcohol rates are positively associated with nuisance, loitering, panhandling, and disorderly conduct in public space.[118] Recent research indicates that the abundance of alcohol retailers and the availability of inexpensive alcoholic beverages are linked to heavy alcohol consumption among college students.[119] Also, joblessness can heighten the risk of alcohol consumption and smoking.[120]

Alcohol-related crimes

A drunk tank in Norway. It is easy to clean with minimal features.

Alcohol use is stereotypically associated with crime,[118] both violent and non-violent.[91] Some crimes are uniquely tied to alcohol, such as public intoxication or underage drinking, while others are simply more likely to occur together with alcohol consumption. Crime perpetrators are much more likely to be intoxicated than crime victims. Many alcohol laws have been passed to criminalize various alcohol-related activities.[118][121] Underage drinking and drunk driving are the most prevalent alcohol‐specific offenses in the United States[118] and a major problem in many countries worldwide.[122][123][124] About one-third of arrests in the United States involve alcohol misuse,[91] and arrests for alcohol-related crimes constitute a high proportion of all arrests made by police in the U.S. and elsewhere.[125] In general, programs aimed at reducing society's consumption of alcohol, including education in schools, are seen as an effective long-term solution. Strategies aiming to reduce alcohol consumption among adult offenders have various estimates of effectiveness.[126] Policing alcohol‐related street disorder and enforcing compliance checks of alcohol‐dispensing businesses has proven successful in reducing public perception of and fear of criminal activities.[118]

In the early 2000s, the monetary cost of alcohol-related crime in the United States alone has been estimated at over $205 billion, twice the economic cost of all other drug-related crimes.[127] In a similar period in the United Kingdom, the cost of crime and its antisocial effects was estimated at £7.3 billion.[126] Another estimate for the UK for yearly cost of alcohol-related crime suggested double that estimate, at between £8 and 13 billion.[128] Risky patterns of drinking are particularly problematic in and around Russia, Mexico and some parts of Africa.[129] Alcohol is more commonly associated with both violent and non-violent crime than are drugs like marijuana.[91]

Passive drinking, like passive smoking, refers to the damage done to others as a result of drinking alcoholic beverages. These include the unborn fetus and children of parents who drink excessively, drunk drivers, accidents, domestic violence and alcohol-related sexual assaults[130]

Automobile accidents

An Estonian billboard warning against drunk driving

A 2002 study found 41% of people fatally injured in traffic accidents were in alcohol-related crashes.[131] Misuse of alcohol is associated with more than 40% of deaths that occur in automobile accidents every year.[91] The risk of a fatal car accident increases exponentially with the level of alcohol in the driver's blood.[132]

Most countries have passed laws prohibiting driving a motor vehicle while impaired by alcohol. In the U.S., these crimes are generally referred to as driving under the influence (DUI), although there are many naming variations among jurisdictions, such as driving while intoxicated (DWI).[133] With alcohol consumption, a drunk driver's level of intoxication is typically determined by a measurement of blood alcohol content or BAC; but this can also be expressed as a breath test measurement, often referred to as a BrAC. A BAC or BrAC measurement in excess of the specific threshold level, such as 0.08% in the U.S.,[134] defines the criminal offense with no need to prove impairment.[135] In some jurisdictions, there is an aggravated category of the offense at a higher BAC level, such as 0.12%, 0.15% or 0.25%. In many jurisdictions, police officers can conduct field tests of suspects to look for signs of intoxication.

Methanol laced alcohol

Russian poster warning people about the dangers of drinking methanol.

Outbreaks of methanol poisoning have occurred when methanol is used to lace moonshine (bootleg liquor).[136] This is commonly done to bulk up the original product to gain profit. Because of its similarities in both appearance and odor to ethanol (the alcohol in beverages), it is difficult to differentiate between the two.

Methanol is a toxic alcohol. If as little as 10 mL of pure methanol is ingested, for example, it can break down into formic acid, which can cause permanent blindness by destruction of the optic nerve, and 30 mL is potentially fatal,[137] although the median lethal dose is typically 100 mL (3.4 fl oz) (i.e. 1–2 mL/kg body weight of pure methanol[138]). Reference dose for methanol is 2.0 mg/kg/day.[139] Toxic effects take hours to start, and effective antidotes can often prevent permanent damage.[137]

India has a thriving moonshine industry, and methanol-tainted batches have killed over 2,000 people in the last 3 decades.

Public drunkenness

Drunkard passed out on a bench

Public drunkenness or intoxication is a common problem in many jurisdictions. Public intoxication laws vary widely by jurisdiction, but include public nuisance laws, open-container laws, and prohibitions on drinking alcohol in public or certain areas. The offenders are often lower class individuals and this crime has a very high recidivism rate, with numerous instances of repeated instances of the arrest, jail, release without treatment cycle. The high number of arrests for public drunkenness often reflects rearrests of the same offenders.[125]

Rape

Rape is any sexual activity that occurs without the freely given consent of one of the parties involved. This includes alcohol-facilitated sexual assault which is considered rape in most if not all jurisdictions,[140] or non-consensual condom removal which is criminalized in some countries (see the map below).

Risky sexual behaviors like unprotected sex can lead to sexually transmitted infections and unintended pregnancy.

Non-consensual condom removal
left
  Court decision declaring stealthing as rape or sexual assault
  Law prohibiting stealthing

Non-consensual condom removal, or "stealthing",[141] is the practice of a person removing a condom during sexual intercourse without consent, when their sex partner has only consented to condom-protected sex.[142][143] Purposefully damaging a condom before or during intercourse may also be referred to as stealthing,[144] regardless of who damaged the condom.

Consuming alcohol can be risky in sexual situations. It can impair judgment and make it difficult for both people to give or receive informed sexual consent. However, a history of sexual aggression and alcohol intoxication are factors associated with an increased risk of men employing non-consensual condom removal and engaging in sexually aggressive behavior with female partners.[145][146]

Sexual assault
Most sexual assaults occur when the victim has consumed alcohol, rather than "spiked" drinks.[147]

One of the most common date rape drugs is alcohol,[148][149][150] administered either surreptitiously[151] or consumed voluntarily,[148] rendering the victim unable to make informed decisions or give consent. The perpetrator then facilitates sexual assault or rape, a crime known as drug-facilitated sexual assault (DFSA).[140][152] However, sex with an unconscious victim is considered rape in most if not all jurisdictions, and some assailants have committed "rapes of convenience" whereby they have assaulted a victim after he or she had become unconscious from drinking too much.[153] The risk of individuals either experiencing or perpetrating sexual violence and risky sexual behavior increases with alcohol abuse,[154] and by the consumption of caffeinated alcoholic drinks.[155][156]

Violent crime

In certain parts of Scotland, the caffeinated alcoholic drink Buckfast Tonic Wine (originally made by monks at Buckfast Abbey) is associated with drinkers who are prone to committing anti-social behaviour when drunk.[157]

The World Health Organization has noted that out of social problems created by the harmful use of alcohol, "crime and violence related to alcohol consumption" are likely the most significant issue.[129] In the United States, 15% of robberies, 63% of intimate partner violence incidents, 37% of sexual assaults, 45–46% of physical assaults and 40–45% of homicides (murders) involved use of alcohol.[158][127] A 1983 study for the United States found that 54% of violent crime perpetrators, arrested in that country, had been consuming alcohol before their offenses.[125] In 2002, it was estimated that 1 million violent crimes in the U.S. were related to alcohol use.[91] More than 43% of violent encounters with police involve alcohol.[91] Alcohol is implicated in more than two-thirds of cases of intimate partner violence.[91] Studies also suggest there may be links between alcohol abuse and child abuse.[118] In the United Kingdom, in 2015/2016, 39% of those involved in violent crimes were under alcohol influence.[159] International studies are similar, with an estimate that 63% of violent crimes worldwide involves the use of alcohol.[127]

The relation between alcohol and violence is not yet fully understood, as its impact on different individuals varies.[citation needed] Studies and theories of alcohol abuse suggest, among others, that use of alcohol likely reduces the offender's perception and awareness of consequences of their actions.[150][118][125][160] Heavy drinking is associated with vulnerability to injury, marital discord, and domestic violence.[91] Moderate drinkers are more frequently engaged in intimate violence than are light drinkers and abstainers, however generally it is heavy and/or binge drinkers who are involved in the most chronic and serious forms of aggression. Research found that factors that increase the likelihood of alcohol‐related violence include difficult temperament, hyperactivity, hostile beliefs, history of family violence, poor school performance, delinquent peers, criminogenic beliefs about alcohol's effects, impulsivity, and antisocial personality disorder. The odds, frequency, and severity of physical attacks are all positively correlated with alcohol use. In turn, violence decreases after behavioral marital alcoholism treatment.[118]

Binge drinking

Binge drinking can prompt police action for public intoxication and disturbing the peace.

Binge drinking is a style of drinking that is popular in several countries worldwide, and overlaps somewhat with social drinking since it is often done in groups. The degree of intoxication however, varies between and within various cultures that engage in this practice. A binge on alcohol can occur over hours, last up to several days, or in the event of extended abuse, even weeks. Due to the long term effects of alcohol abuse, binge drinking is considered to be a major public health issue.[25]

Binge drinking is more common in males, during adolescence and young adulthood. Heavy regular binge drinking is associated with adverse effects on neurologic, cardiac, gastrointestinal, hematologic, immune, and musculoskeletal organ systems as well as increasing the risk of alcohol induced psychiatric disorders.[161][162] A US-based review of the literature found that up to one-third of adolescents binge-drink, with 6% reaching the threshold of having an alcohol-related substance use disorder.[163] Approximately one in 25 women binge-drinks during pregnancy, which can lead to fetal alcohol syndrome and fetal alcohol spectrum disorders.[164] Binge drinking during adolescence is associated with traffic accidents and other types of accidents, violent behavior as well as suicide. The more often a child or adolescent binge drinks and the younger they are the more likely that they will develop an alcohol use disorder including alcoholism. A large number of adolescents who binge-drink also consume other psychotropic substances.[165]

Environment

Broken beer bottles.

Alcoholic beverage containers, particularly broken glass bottles, are a common source of litter that is difficult to clean up, which may puncture bicycle tires, hurt wild life animals, etc. Alcoholic bottles are often discarded improperly, not recycled, or left in public spaces, which have negative impacts on the environment. Alcohol may negatively impact decision making in taking environmental responsibility.

Hurtful communication

Alcohol may cause hurtful communication.

Drunk dialing

Drunk dialing refers to an intoxicated person making phone calls that they would not likely make if sober, often a lonely individual calling former or current love interests.

A 2021 study, that examined the relationship between drunk texting and emotional dysregulation, found a positive correlation. The findings suggest that interventions targeting emotional regulation skills may be beneficial.[166]

In vino veritas

In vino veritas is a Latin phrase that means 'in wine, there is truth', suggesting a person under the influence of alcohol is more likely to speak their hidden thoughts and desires.

Suicide

Most people are under the influence of sedative-hypnotic drugs (such as alcohol or benzodiazepines) when they die by suicide,[167] with alcoholism present in between 15% and 61% of cases.[168] Countries that have higher rates of alcohol use and a greater density of bars generally also have higher rates of suicide.[169] About 2.2–3.4% of those who have been treated for alcoholism at some point in their life die by suicide.[169] Alcoholics who attempt suicide are usually male, older, and have tried to take their own lives in the past.[168] In adolescents who misuse alcohol, neurological and psychological dysfunctions may contribute to the increased risk of suicide.[170]

Risky sexual behavior

Some studies have made a connection between hookup culture and substance use.[171] Most students said that their hookups occurred after drinking alcohol.[171][172][173] Frietas stated that in her study, the relationships between drinking and the party scene and between alcohol and hookup culture were "impossible to miss."[174]: 41 

Studies suggest that the degree of alcoholic intoxication directly correlates with the level of risky behavior.[175]

In 2018, the first study of its kind, found that alcohol and caffeinated energy drinks is linked with casual, risky sex among college-age adults.[176]

Sexually transmitted infections and unintended pregnancy

A poster that represents a warning against the risks posed by alcohol consumption, promiscuity, and venereal diseases.

Alcohol intoxication is associated with an increased risk that people will become involved in risky sexual behaviors, such as unprotected sex.[177] Both men,[178] and women,[179] reported higher intentions to avoid using a condom when they were intoxicated by alcohol.

Coitus interruptus, also known as withdrawal, pulling out or the pull-out method, is a method of birth control during penetrative sexual intercourse, whereby the penis is withdrawn from a vagina or anus prior to ejaculation so that the ejaculate (semen) may be directed away in an effort to avoid insemination.[180][181] Coitus interruptus carries a risk of STIs and unintended pregnancy. This risk is especially high during alcohol intoxication because lowered sexual inhibition can make it difficult to withdraw in time.

Women with unintended pregnancies are more likely to smoke tobacco,[182] drink alcohol during pregnancy,[183][184] and binge drink during pregnancy,[182] which results in poorer health outcomes.[183] (See also: fetal alcohol spectrum disorder)

Overdose

The Drunkenness of Noah by Michelangelo, 1509

Symptoms of ethanol overdose may include nausea, vomiting, CNS depression, coma, acute respiratory failure, or death. Levels of even less than 0.1% can cause intoxication, with unconsciousness often occurring at 0.3–0.4%.[185] Death from ethanol consumption is possible when blood alcohol levels reach 0.4%. A blood level of 0.5% or more is commonly fatal. The oral median lethal dose (LD50) of ethanol in rats is 5,628 mg/kg. Directly translated to human beings, this would mean that if a person who weighs 70 kg (150 lb) drank a 500 mL (17 US fl oz) glass of pure ethanol, they would theoretically have a 50% risk of dying. The highest blood alcohol level ever recorded, in which the subject survived, is 1.41%.[186]

Interactions

Disorders

Diabetes

See the insulin section.

Heptatitis

Alcohol consumption can be especially dangerous for those with pre-existing liver damage from hepatitis B or C. Even relatively low amounts of alcohol can be life-threatening in these cases,[24] so a strict adherence to abstinence is highly recommended.[187]

Hitamine intolerance

Alcohol may release histamine in individuals with histamine intolerance.[188]

Mental health disorder

Increased risk of developing alcohol dependency or abuse in individuals with a given mental health disorder relative to those without.

Mental health disorders can be a significant risk factor for alcohol abuse.

Dosage forms

Alcohol induced dose dumping (AIDD)

This dose dumping effect is an unintended rapid release of large amounts of a given drug, when administered through a modified-release dosage while co-ingesting ethanol.[189] This is considered a pharmaceutical disadvantage due to the high risk of causing drug-induced toxicity by increasing the absorption and serum concentration above the therapeutic window of the drug. The best way to prevent this interaction is by avoiding the co-ingestion of both substances or using specific controlled-release formulations that are resistant to AIDD.

Drugs

Alcohol can intensify the sedation caused by antipsychotics, and certain antidepressants.[185]

Alcohol combined with cannabis (not to be confused with tincture of cannabis which contains minute quantities of alcohol) — known as cross-fading and may easily cause spins in people who are drunk and smoke potent cannabis; Ethanol increases plasma tetrahydrocannabinol levels, which suggests that ethanol may increase the absorption of tetrahydrocannabinol.[190]

TOMSO is a lesser-known psychedelic drug and a substituted amphetamine. TOMSO is inactive on its own; it is activated with the consumption of alcohol.

Hypnotics/sedatives

Tranquillizers, sleeping pills, opiates and alcohol. Opioid-related deaths often involve alcohol.

Alcohol can intensify the sedation caused by hypnotics/sedatives such as barbiturates, benzodiazepines, sedative antihistamines, opioids, nonbenzodiazepines/Z-drugs (such as zolpidem and zopiclone).[185]

Disulfiram-like drugs

Disulfiram

Disulfiram inhibits the enzyme acetaldehyde dehydrogenase, which in turn results in buildup of acetaldehyde, a toxic metabolite of ethanol with unpleasant effects. The medication or drug is commonly used to treat alcohol use disorder, and results in immediate hangover-like symptoms upon consumption of alcohol, this effect is widely known as disulfiram effect.

Metronidazole

Metronidazole is an antibacterial agent that kills bacteria by damaging cellular DNA and hence cellular function.[191] Metronidazole is usually given to people who have diarrhea caused by Clostridium difficile bacteria. Patients who are taking metronidazole are sometimes advised to avoid alcohol, even after 1 hour following the last dose. Although older data suggested a possible disulfiram-like effect of metronidazole, newer data has challenged this and suggests it does not actually have this effect.

Insulin

Alcohol consumption can cause hypoglycemia in diabetics on certain medications, such as insulin or sulfonylurea, by blocking gluconeogenesis.[192]

NSAIDs

The concomitant use of NSAIDs with alcohol and/or tobacco products significantly increases the already elevated risk of peptic ulcers during NSAID therapy.[193][better source needed]

Stimulants

Coca wine

Ethanol interacts with cocaine in vivo to produce cocaethylene, another psychoactive substance which may be substantially more cardiotoxic than either cocaine or alcohol by themselves.[194][195]

Ethylphenidate formation appears to be more common when large quantities of methylphenidate and alcohol are consumed at the same time, such as in non-medical use or overdose scenarios.[196] However, only a small percent of the consumed methylphenidate is converted to ethylphenidate.[197]

A nicotini is any alcoholic drink which includes nicotine as an ingredient. Its name is modeled after the word "martini" in the fashion of such drinks as the appletini. Tobacco and nicotine increase alcohol craving.[198]

Methanol and ethylene glycol

The rate-limiting steps for the elimination of ethanol are in common with certain other substances. As a result, the blood alcohol concentration can be used to modify the rate of metabolism of toxic alcohols, such as methanol and ethylene glycol. Methanol itself is not highly toxic, but its metabolites formaldehyde and formic acid are; therefore, to reduce the rate of production and concentration of these harmful metabolites, ethanol can be ingested.[199] Ethylene glycol poisoning can be treated in the same way.

Warfarin

Excessive use of alcohol is also known to affect the metabolism of warfarin and can elevate the INR, and thus increase the risk of bleeding.[200] The U.S. Food and Drug Administration (FDA) product insert on warfarin states that alcohol should be avoided.[201] The Cleveland Clinic suggests that when taking warfarin one should not drink more than "one beer, 6 oz of wine, or one shot of alcohol per day".[202]

Special population

Isoniazid

Levels of liver enzymes in the bloodstream should be frequently checked in daily alcohol drinkers, pregnant women, IV drug users, people over 35, and those who have chronic liver disease, severe kidney dysfunction, peripheral neuropathy, or HIV infection since they are more likely to develop hepatitis from INH.[203][204]

Pharmacology

Pharmacodynamics

Stage Three of the Five stages of inebriation, c. 1863–1868, by Charles Percy Pickering

The principal mechanism of action for ethanol has proven elusive and remains not fully understood.[29][205] Identifying molecular targets for ethanol has proven unusually difficult, in large part due to its unique biochemical properties.[205] Specifically, ethanol is a very low molecular weight compound and is of exceptionally low potency in its actions, causing effects only at very high (millimolar mM) concentrations.[205][206] For these reasons, unlike with most drugs, it has not yet been possible to employ traditional biochemical techniques to directly assess the binding of ethanol to receptors or ion channels.[205][206] Instead, researchers have had to rely on functional studies to elucidate the actions of ethanol.[205] Moreover, although it has been established that ethanol modulates ion channels to mediate its effects,[31] ion channels are complex proteins, and their interactions and functions are complicated by diverse subunit compositions and regulation by conserved cellular signals (e.g. signaling lipids).[29][205]

Much progress has been made in understanding the pharmacodynamics of ethanol over the last few decades.[30][205] While no binding sites have been identified and established unambiguously for ethanol at present, it appears that it affects ion channels, in particular ligand-gated ion channels, to mediate its effects in the CNS.[29][30][31][205] Ethanol has specifically been found in functional assays to enhance or inhibit the activity of a variety of ion channels, including the GABAA receptor, the ionotropic glutamate AMPA, kainate, and NMDA receptors, the glycine receptor,[207] the nicotinic acetylcholine receptors,[208] the serotonin 5-HT3 receptor, voltage-gated calcium channels, and BK channels, among others.[29][30][31][209][210] However, many of these actions have been found to occur only at very high concentrations that may not be pharmacologically significant at recreational doses of ethanol, and it is unclear how or to what extent each of the individual actions is involved in the effects of ethanol.[205] In any case, ethanol has long shown a similarity in its effects to positive allosteric modulators of the GABAA receptor like benzodiazepines, barbiturates, and various general anesthetics.[29][205] Indeed, ethanol has been found to enhance GABAA receptor-mediated currents in functional assays.[29][205] In accordance, it is theorized and widely believed that the primary mechanism of action is as a GABAA receptor positive allosteric modulator.[29][205] However, the diverse actions of ethanol on other ion channels may be and indeed likely are involved in its effects as well.[30][205]

In 2007, it was discovered that ethanol potentiates extrasynaptic δ subunit-containing GABAA receptors at behaviorally relevant (as low as 3 mM) concentrations.[29][205][211] This is in contrast to previous functional assays of ethanol on γ subunit-containing GABAA receptors, which it enhances only at far higher concentrations (> 100 mM) that are in excess of recreational concentrations (up to 50 mM).[29][205][212] Ro15-4513, a close analogue of the benzodiazepine antagonist flumazenil (Ro15-1788), has been found to bind to the same site as ethanol and to competitively displace it in a saturable manner.[205][211] In addition, Ro15-4513 blocked the enhancement of δ subunit-containing GABAA receptor currents by ethanol in vitro.[205] Taken together, these findings suggest a binding site for ethanol on subpopulations of the GABAA receptor with specific subunit compositions via which it interacts with and potentiates the receptor.[29][205][211][213]

A 2019 study showed the accumulation of an unnatural lipid phosphatidylethanol (PEth) competes with PIP2 agonist sites on lipid-gated ion channels.[214] This presents a novel indirect mechanism and suggests that a metabolite, not the ethanol itself, can affect the primary targets of ethanol intoxication. Many of the primary targets of ethanol are known to bind PIP2 including GABAA receptors,[215] but the role of PEth will need to be investigated for each of the primary targets.

Rewarding and reinforcing actions

Chemical structures of selective dopamine receptor D1 receptor agonists[216][217]

The reinforcing effects of alcohol consumption are mediated by acetaldehyde generated by catalase and other oxidizing enzymes such as cytochrome P-4502E1 in the brain.[218] Although acetaldehyde has been associated with some of the adverse and toxic effects of ethanol, it appears to play a central role in the activation of the mesolimbic dopamine system.[219]

Ethanol's rewarding and reinforcing (i.e., addictive) properties are mediated through its effects on dopamine neurons in the mesolimbic reward pathway, which connects the ventral tegmental area to the nucleus accumbens (NAcc).[220][221] One of ethanol's primary effects is the allosteric inhibition of NMDA receptors and facilitation of GABAA receptors (e.g., enhanced GABAA receptor-mediated chloride flux through allosteric regulation of the receptor).[222] At high doses, ethanol inhibits most ligand-gated ion channels and voltage-gated ion channels in neurons as well.[222]

With acute alcohol consumption, dopamine is released in the synapses of the mesolimbic pathway, in turn heightening activation of postsynaptic D1 receptors.[220][221] The activation of these receptors triggers postsynaptic internal signaling events through protein kinase A, which ultimately phosphorylate cAMP response element binding protein (CREB), inducing CREB-mediated changes in gene expression.[220][221]

With chronic alcohol intake, consumption of ethanol similarly induces CREB phosphorylation through the D1 receptor pathway, but it also alters NMDA receptor function through phosphorylation mechanisms;[220][221] an adaptive downregulation of the D1 receptor pathway and CREB function occurs as well.[220][221] Chronic consumption is also associated with an effect on CREB phosphorylation and function via postsynaptic NMDA receptor signaling cascades through a MAPK/ERK pathway and CAMK-mediated pathway.[221] These modifications to CREB function in the mesolimbic pathway induce expression (i.e., increase gene expression) of ΔFosB in the NAcc,[221] where ΔFosB is the "master control protein" that, when overexpressed in the NAcc, is necessary and sufficient for the development and maintenance of an addictive state (i.e., its overexpression in the nucleus accumbens produces and then directly modulates compulsive alcohol consumption).[221][223][224][225]

Relationship between concentrations and effects

Blood alcohol levels and effects[226]
mg/dLmM% v/vEffects
50110.05%Euphoria, talkativeness, relaxation, happiness, gladness, pleasure, joyfulness.
100220.1%Central nervous system depression, anxiety suppression, stress suppression, sedation, nausea, possible vomiting. Impaired motor, memory, cognition and sensory function.
>14030>0.14%Decreased blood flow to brain, slurred speech, double or blurry vision.
300650.3%Stupefaction, confusion, numbness, dizziness, loss of consciousness.
400870.4%Ethylic intoxication, drunkenness, inebriation, alcohol poisoning or possible death.
500109>0.55%Unconsciousness, coma and death.

Recreational concentrations of ethanol are typically in the range of 1 to 50 mM.[212][29] Very low concentrations of 1 to 2 mM ethanol produce zero or undetectable effects except in alcohol-naive individuals.[212] Slightly higher levels of 5 to 10 mM, which are associated with light social drinking, produce measurable effects including changes in visual acuity, decreased anxiety, and modest behavioral disinhibition.[212] Further higher levels of 15 to 20 mM result in a degree of sedation and motor incoordination that is contraindicated with the operation of motor vehicles.[212] In jurisdictions in the U.S., maximum blood alcohol levels for legal driving are about 17 to 22 mM.[227][228] In the upper range of recreational ethanol concentrations of 20 to 50 mM, depression of the central nervous system is more marked, with effects including complete drunkenness, profound sedation, amnesia, emesis, hypnosis, and eventually unconsciousness.[212][227] Levels of ethanol above 50 mM are not typically experienced by normal individuals and hence are not usually physiologically relevant; however, such levels – ranging from 50 to 100 mM – may be experienced by alcoholics with high tolerance to ethanol.[212] Concentrations above this range, specifically in the range of 100 to 200 mM, would cause death in all people except alcoholics.[212]

List of known actions in the central nervous system

Ethanol has been reported to possess the following actions in functional assays at varying concentrations:[206]

Some of the actions of ethanol on ligand-gated ion channels, specifically the nicotinic acetylcholine receptors and the glycine receptor, are dose-dependent, with potentiation or inhibition occurring dependent on ethanol concentration.[206] This seems to be because the effects of ethanol on these channels are a summation of positive and negative allosteric modulatory actions.[206]

Pharmacokinetics

Absorption

Ethanol can be administered orally, by inhalation, rectally, or by injection (e.g., intravenous),[6][233] though it is typically ingested simply via oral administration.[4] The oral bioavailability of ethanol is around 80% or more.[4][5] In fasting volunteers, blood levels of ethanol increase proportionally with the dose of ethanol administered.[233] Blood alcohol concentrations may be estimated by dividing the amount of ethanol ingested by the body weight of the individual and correcting for water dilution.[6]

Onset
People drinking spritzers at a festival in Hungary. Carbonated alcoholic drinks seem to have a shorter onset.

Peak circulating levels of ethanol are usually reached within a range of 30 to 90 minutes of ingestion, with an average of 45 to 60 minutes.[6][4] People who have fasted overnight have been found to reach peak ethanol concentrations more rapidly, at within 30 minutes of ingestion.[6]

The onset varies depends on the type of alcoholic drink:[234]

  • Vodka tonic: 36 ± 10 minutes
  • Wine: 54 ± 14 minutes
  • Beer: 62 ± 23 minutes

Also, carbonated alcoholic drinks seem to have a shorter onset compare to flat drinks in the same volume. One theory is that carbon dioxide in the bubbles somehow speeds the flow of alcohol into the intestines.[235]

Food in the gastrointestinal system and hence gastric emptying is the most important factor that influences the absorption of orally ingested ethanol.[6][233] The absorption of ethanol is much more rapid on an empty stomach than with a full one.[6] The delay in ethanol absorption caused by food is similar regardless of whether food is consumed just before, at the same time, or just after ingestion of ethanol.[6] The type of food, whether fat, carbohydrates, or protein, also is of little importance.[233] Not only does food slow the absorption of ethanol, but it also reduces the bioavailability of ethanol, resulting in lower circulating concentrations.[6]

Distribution

Upon ingestion, ethanol is rapidly distributed throughout the body.[4] It is distributed most rapidly to tissues with the greatest blood supply.[6] As such, ethanol primarily affects the brain, liver, and kidneys.[4] Other tissues with lower circulation, such as bone, require more time for ethanol to distribute into.[6] Ethanol crosses biological membranes and the blood–brain barrier easily, through a simple process of passive diffusion.[4][233] The volume of distribution of ethanol is around .55 L/kg (0.53 US pt/lb).[4] It is only weakly or not at all plasma protein bound.[4][5]

Metabolism

Alcohol dehydrogenase

Approximately 90% of the metabolism of ethanol occurs in the liver.[6][8] This occurs predominantly via the enzyme alcohol dehydrogenase, which transforms ethanol into its metabolite acetaldehyde (ethanal).[6][8] Acetaldehyde is subsequently metabolized by the enzyme aldehyde dehydrogenase into acetate (ethanoate), which in turn is broken down into carbon dioxide and water.[6] Acetate also combines with coenzyme A to form acetyl-CoA, and hence may participate in metabolic pathways.[4] Alcohol dehydrogenase and aldehyde dehydrogenase are present at their highest concentrations in the liver, but are widely expressed throughout the body, and alcohol dehydrogenase may also be present in the stomach and small intestine.[4] Aside from alcohol dehydrogenase, the microsomal ethanol-oxidizing system (MEOS), specifically mediated by the cytochrome P450 enzyme CYP2E1, is the other major route of ethanol metabolism.[6][8] CYP2E1 is inducible by ethanol, so while alcohol dehydrogenase handles acute or low concentrations of ethanol, MEOS is predominant with higher concentrations or with repeated/chronic use.[6][8] A small amount of ethanol undergoes conjugation to form ethyl glucuronide and ethyl sulfate.[4] There may also be another metabolic pathway that metabolizes as much as 25 to 35% of ethanol at typical concentrations.[5]

At even low physiological concentrations, ethanol completely saturates alcohol dehydrogenase.[6] This is because ethanol has high affinity for the enzyme and very high concentrations of ethanol occur when it is used as a recreational substance.[6] For this reason, the metabolism of ethanol follows zero-order kinetics at typical physiological concentrations.[8] That is, ethanol does not have an elimination half-life (i.e., is not metabolized at an exponential rate), and instead, is eliminated from the circulation at a constant rate.[8][7] The mean elimination rates for ethanol are 15 mg/dL per hour for men and 18 mg/dL per hour for women, with a range of 10 to 34 mg/dL per hour.[8][6] At very high concentrations, such as in overdose, it has been found that the rate of elimination of ethanol is increased.[5] In addition, ethanol metabolism follows first-order kinetics at very high concentrations, with an elimination half-life of about 4 or 4.5 hours (which implies a clearance rate of approximately 6 L/hour/70 kg).[5][4] This seems to be because other processes, such as the MEOS/CYP2E1, also become involved in the metabolism of ethanol at higher concentrations.[4] However, the MEOS/CYP2E1 alone does not appear sufficient to fully explain the increase in ethanol metabolism rate.[5]

Some individuals have less effective forms of one or both of the metabolizing enzymes of ethanol, and can experience more marked symptoms from ethanol consumption than others.[236] However, those having acquired alcohol tolerance have a greater quantity of these enzymes, and metabolize ethanol more rapidly.[236]

Elimination

Ethanol is mainly eliminated from the body via metabolism into carbon dioxide and water.[6] Around 5 to 10% of ethanol that is ingested is eliminated unchanged in urine, breath, and sweat.[4] Transdermal alcohol that diffuses through the skin as insensible perspiration or is exuded as sweat (sensible perspiration) can be detected using wearable sensor technology[237] such as SCRAM ankle bracelet[238] or the more discreet ION Wearable.[239] Ethanol or its metabolites may be detectable in urine for up to 96 hours (3–5 days) after ingestion.[4]

Chemistry

Ethanol is also known chemically as alcohol, ethyl alcohol, or drinking alcohol. It is a simple alcohol with a molecular formula of C2H6O and a molecular weight of 46.0684 g/mol. The molecular formula of ethanol may also be written as CH3−CH2−OH or as C2H5−OH. The latter can also be thought of as an ethyl group linked to a hydroxyl (alcohol) group and can be abbreviated as EtOH. Ethanol is a volatile, flammable, colorless liquid with a slight characteristic odor. Aside from its use as a psychoactive and recreational substance, ethanol is also commonly used as an antiseptic and disinfectant, a chemical and medicinal solvent, and a fuel.

Production

Ethanol is produced naturally as a byproduct of the metabolic processes of yeast and hence is present in any yeast habitat, including even endogenously in humans, but it does not cause raised blood alcohol content as seen in the rare medical condition auto-brewery syndrome (ABS). It is manufactured through hydration of ethylene or by brewing via fermentation of sugars with yeast (most commonly Saccharomyces cerevisiae). The sugars are commonly obtained from sources like steeped cereal grains (e.g., barley), grape juice, and sugarcane products (e.g., molasses, sugarcane juice). Ethanol–water mixture which can be further purified via distillation.

Home-made alcoholic beverages

Homebrewing
A homebrewing kit consisting of hopped malt extract, yeast and instructions

Homebrewing is the brewing of beer or other alcoholic beverages on a small scale for personal, non-commercial purposes. Supplies, such as kits and fermentation tanks, can be purchased locally at specialty stores or online. Beer was brewed domestically for thousands of years before its commercial production, although its legality has varied according to local regulation. Homebrewing is closely related to the hobby of home distillation, the production of alcoholic spirits for personal consumption; however home distillation is generally more tightly regulated.

Moonshine

Although methanol is not produced in toxic amounts by fermentation of sugars from grain starches,[240] it is a major occurrence in fruit spirits.[241] However, in modern times, reducing methanol with the absorption of a molecular sieve is a practical method for production.[242]

Analogues

Lucas test: negative (left) with ethanol and positive with t-butanol.

Ethanol has a variety of analogues, many of which have similar actions and effects. Methanol (methyl alcohol) and isopropyl alcohol (also called rubbing alcohol) are toxic alcohols, and thus unsafe for human consumption.[12] Methanol is the most toxic alcohol; the toxicity of isopropyl alcohol lies between that of ethanol and methanol, and is about twice that of ethanol.[243] In general, higher alcohols are less toxic.[243] n-Butanol is reported to produce similar effects to those of ethanol and relatively low toxicity (one-sixth of that of ethanol in one rat study).[244][245] However, its vapors can produce eye irritation and inhalation can cause pulmonary edema.[243] Acetone (propanone) is a ketone rather than an alcohol, and is reported to produce similar toxic effects; it can be extremely damaging to the cornea.[243]

The tertiary alcohol tert-amyl alcohol (TAA), also known as 2-methylbutan-2-ol (2M2B), has a history of use as a hypnotic and anesthetic, as do other tertiary alcohols such as methylpentynol, ethchlorvynol, and chloralodol. Unlike primary alcohols like ethanol, these tertiary alcohols cannot be oxidized into aldehyde or carboxylic acid metabolites, which are often toxic, and for this reason, these compounds are safer in comparison.[246] Other relatives of ethanol with similar effects include chloral hydrate, paraldehyde, and many volatile and inhalational anesthetics (e.g., chloroform, diethyl ether, and isoflurane).

The Lucas test differentiates between primary, secondary, and tertiary alcohols.

Ethchlorvynol is not compatible with intravenous injection like ethanol—serious injury (including the loss of limbs due to vascular injury) or death can occur when it is used in this manner.[247]

Society and culture

Usage

Consumption recommendations

Share of over-fifteen-year-old population who haven't drunk alcohol in the past year (interactive version); in most countries, it exceeds a third.

The recommended maximum intake (or safe limits) of alcohol varies from no intake, to daily, weekly, or daily/weekly guidelines provided by health agencies of governments. The World Health Organization published a statement in The Lancet Public Health in April 2023 that "there is no safe amount that does not affect health".[22]

According to a 2024 systematic review and meta-analysis, even at 20 g/day (1 large beer), the risk of developing an alcohol use disorder (AUD) is nearly 3 times higher than non-drinkers, and the risk of dying from an AUD is about 2 times higher than non-drinkers.[248] According to the U.S. Department of Agriculture, based on NHANES 2013–2014 surveys, women in the US ages 20 and up consume on average 6.8 grams/day and men consume on average 15.5 grams/day.[249]

Drinking culture

Great British Beer Festival, London

Ethanol is typically consumed as a recreational substance by mouth in the form of alcoholic beverages such as beer, wine, and spirits. It is commonly used in social settings due to its capacity to enhance sociability.

Drinking alcohol is generally socially acceptable and is legal in most countries, unlike with many other recreational substances. Many students attending colleges, universities, and other higher education institutions consume alcoholic beverages. However, there are often restrictions on alcohol sale and use, for instance a minimum age for drinking and laws against public drinking and drinking and driving.[250] Alcohol has considerable societal and cultural significance and has important social roles in much of the world. Drinking establishments, such as bars and nightclubs, revolve primarily around the sale and consumption of alcoholic beverages, and parties, festivals, and social gatherings commonly involve alcohol consumption. Alcohol is related to various societal problems, including drunk driving, accidental injuries, sexual assaults, domestic abuse, and violent crime.[91] Alcohol remains illegal for sale and consumption in a number of countries, mainly in the Middle East.

Research on the societal benefits of alcohol is rare, but a 2017 study suggested there it was beneficial.[251] Alcohol is often used as a social lubricant; it increases occurrences of Duchenne smiling, talking, and social bonding, even when participants are unaware of their alcohol consumption or lack thereof.[252] In a study of the UK, regular drinking was correlated with happiness, feeling that life was worthwhile, and life satisfaction. According to a causal path analysis the cause was vice versa; alcohol consumption was not the cause, but rather that the life satisfaction resulted in greater happiness and an inclination to visit pubs and develop a regular drinking venue. City centre bars were distinguished by their focus on maximizing alcohol sales. Community pubs had less variation in visible group sizes and longer, more focused conversations than those in city centre bars. Drinking regularly at a community pub led to higher trust in others and better networking with the local community, compared to non-drinkers and city centre bar drinkers.[251]

Religion

A chaplain pouring sacramental wine from a cruet into a chalice

The relationship between alcohol and religion exhibits variations across cultures, geographical areas, and religious denominations. Some religions emphasize moderation and responsible use as a means of honoring the divine gift of life, while others impose outright bans on alcohol as a means of honoring the divine gift of life. Moreover, within the same religious tradition, there are many adherents that may interpret and practice their faith's teachings on alcohol in diverse ways. Hence, a wide range of factors, such as religious affiliation, levels of religiosity, cultural traditions, family influences, and peer networks, collectively influence the dynamics of this relationship.

The levels of alcohol use in spiritual context can be broken down into:

Christian views on alcohol are varied. For example, in the mid-19th century, some Protestant Christians moved from a position of allowing moderate use of alcohol (sometimes called moderationism) to either deciding that not imbibing was wisest in the present circumstances (abstentionism) or prohibiting all ordinary consumption of alcohol because it was believed to be a sin (prohibitionism).[254]
During the Jewish holiday of Purim, Jews are obligated to drink (especially Kosher wine) until their judgmental abilities become impaired according to the Book of Esther.[255][256][257] However, Purim has more of a national than a religious character.

Law

Legal status

Sobriety checkpoint in Stralsund, Germany

Alcohol consumption is fully legal and available in most countries of the world.[258] Home made alcoholic beverages with low alcohol content like wine, and beer is also legal in most countries, but distilling moonshine outside of a registered distillery remains illegal in most of them.

Some majority-Muslim countries, such as Saudi Arabia, Kuwait, Pakistan, Iran and Libya prohibit the production, sale, and consumption of alcoholic beverages because they are forbidden by Islam.[259][260][261] Laws banning alcohol consumption are found in some Indian states as well as some Native American reservations in the U.S.[258]

In addition, there are regulations on alcohol sales and use in many countries throughout the world.[258] For instance, the majority of countries have a minimum legal drinking age to purchase or consume alcoholic beverages, although there are often exceptions such as underage consumption of small amounts of alcohol with parental supervision. Also, some countries have bans on public intoxication.[258] Drinking while driving or intoxicated driving is frequently outlawed and it may be illegal to have an open container of alcohol or liquor bottle in an automobile, bus or aircraft.[258]

In Iran, consumption of alcohol (one glass) is punished by 80 lashes, but repeated offences may lead to death penalty, although rarely exercised. In 2012, two men were sentenced to death after a third offense in Khorasan.[262][263]

Alcohol packaging warning messages

Intervention alcohol warning labels (actual size 5.0 cm × 3.2 cm each). The label intervention included three rotating labels: (a) a cancer warning, (b) national drinking guidelines, and (c) standard drink information (four separate labels were developed for wine, spirits, coolers, and beer; wine example shown above)

Alcohol packaging warning messages (alcohol warning labels, AWLs[264]) are warning messages that appear on the packaging of alcoholic drinks concerning their health effects.

A World Health Organization report, published in 2017, stated:[265]

Alcohol product labelling could be considered as a component of a comprehensive public health strategy to reduce alcohol-related harm. Adding health labels to alcohol containers is an important first step in raising awareness and has a longer-term utility in helping to establish a social understanding of the harmful use of alcohol.

Criticism of the alcohol industry

An Absolut LGBT marketing flyer in Portland, Oregon. The LGBT+ community has historically suffered from higher levels of substance abuse than non-LGBT+ individuals.

A 2019 survey conducted by the American Institute for Cancer Research (AICR) showed that only 45% of Americans were aware of the associated risk of cancer due to alcohol consumption, up from 39% in 2017.[266] The AICR believes that alcohol-related advertisements about the healthy cardiovascular benefits of modest alcohol overshadow messages about the increased cancer risks.[266]

Drinking alcoholic beverages increase the risk for breast cancer. Several studies indicate that the use of marketing by the alcohol industry to associate their products with breast cancer awareness campaigns, known as pinkwashing, is misleading and potentially harmful.[267][268][269][270]

The alcohol industries have marketed products directly to the LGBT+ community. In 2010, of the sampled parades that listed sponsors, 61% of the prides were sponsored by the alcohol industry.[271]

Standard drink

A standard drink is a measure of alcohol consumption representing a fixed amount of pure ethanol, used in relation to recommendations about alcohol consumption and its relative risks to health. The size of a standard drink varies from 8g to 20g across countries, but 10g alcohol (12.7 millilitres) is used in the World Health Organization (WHO) Alcohol Use Disorders Identification Test (AUDIT)'s questionnaire form example,[272] and has been adopted by more countries than any other amount.[273]

Sober curious

Average per capita alcohol consumption measured in litres of pure alcohol per person per year.

Sober curious is a cultural movement and lifestyle of consuming no or limited alcohol that started in the late 2010s.[citation needed] It differs from traditional abstinence in that it is not founded on asceticism, religious condemnation of alcohol or previous alcohol abuse, but motivated by a curiosity of a sober lifestyle. Markets have reacted by offering a wider selection of non-alcoholic beverages.[274]

Sober curiosity is often defined as having the option to question or change one's drinking habits, for mental or physical health reasons.[275] It may be practised in many ways, ranging from complete abstinence to more thought about when and how much is consumed.[276]

Since the onset of the COVID-19 pandemic, more people in Europe have reduced their alcohol consumption.[277]

History

Ancient World

Since antiquity, prior to the development of modern agents, alcohol was used as a general anesthetic.[278]

Beer is one of the earliest known ingredients for wound healing. A medical prescription from Mesopotamia describes a method for healing wounds:[279][280]

Pound together fur-turpentine, pine-turpentine, tamarisk, daisy, flour of inninnu strain; mix in milk and beer in a small copper pan; spread on skin; bind on him, and he shall recover.

Late Middle Ages

Alcohol has been used as an antiseptic as early as 1363 with evidence to support its use becoming available in the late 1800s.[citation needed]

Early modern period

Gin Lane by William Hogarth, 1751

The popular story dates the etymology of the term Dutch courage to English soldiers fighting in the Anglo-Dutch Wars[281] (1652–1674) and perhaps as early as the Thirty Years' War (1618–1648). One version states that jenever (or Dutch gin) was used by English soldiers for its calming effects before battle, and for its purported warming properties on the body in cold weather. Another version has it that English soldiers noted the bravery-inducing effects of jenever on Dutch soldiers.[282][283]

The Gin Craze was a period in the first half of the 18th century when the consumption of gin increased rapidly in Great Britain, especially in London. By 1743, England was drinking 2.2 gallons (10 litres) of gin per person per year. The Sale of Spirits Act 1750 (commonly known as the Gin Act 1751) was an Act of the Parliament of Great Britain (24 Geo. 2. c. 40) which was enacted in order to reduce the consumption of gin and other distilled spirits, a popular pastime[284] that was regarded as one of the primary causes of crime in London.[285]

Modern period

"Andy and his prime minister": Lantern slide of U.S. president Andrew Johnson drinking with the devil, painted by abolitionist and folk artist Samuel J. Reader (Liljenquist Collection, LOC)

The Andrew Johnson alcoholism debate is the dispute, originally conducted amongst the general public, and now typically a question for historians, about whether or not Andrew Johnson, the 17th president of the United States (1865–1869), drank to excess.

The Bratt System was a system that was used in Sweden (1919–1955) and similarly in Finland (1944–1970) to control alcohol consumption, by rationing of liquor. Every citizen allowed to consume alcohol was given a booklet called a motbok (viinakortti in Finland), in which a stamp was added each time a purchase was made at Systembolaget (in Sweden) and Alko (in Finland).[286] A similar system also existed in Estonia between July 1, 1920 to December 31, 1925.[287] The stamps were based on the amount of alcohol bought. When a certain amount of alcohol had been bought, the owner of the booklet had to wait until next month to buy more.

The Medicinal Liquor Prescriptions Act of 1933 was a law passed by Congress in response to the abuse of medicinal liquor prescriptions during Prohibition.

The rum ration (also called the tot) was a daily amount of rum given to sailors on Royal Navy ships. It started 1866 and was abolished in 1970 after concerns that the intake of strong alcohol would lead to unsteady hands when working machinery.

Gilbert Paul Jordan (aka The Boozing Barber) was a Canadian serial killer who is believed to have committed the so-called "alcohol murders" between 1965-c. 2004 in Vancouver, British Columbia.

See also

References

Further reading

External links

Pathophysiology of ethanol
Pharmacology of ethanol