How Does Alcohol Affect the Body? From the First Sip to the Hangover

Alcohol needs no digestion. About a fifth is absorbed through the stomach wall and the rest through the small intestine, and it spreads through the body's water within twenty to sixty minutes; food in the stomach slows the absorption, which is why drinking on an empty stomach hits harder. Removing it is the liver's job, done by two enzymes in sequence: alcohol dehydrogenase turns ethanol into acetaldehyde, a toxic compound related to formaldehyde, and aldehyde dehydrogenase turns that into harmless acetate, which is burned for energy. The liver works at a fixed rate of roughly eight grams of alcohol an hour, one unit in British terms, regardless of how much has been drunk, so that a bottle of wine takes most of a night to clear and nothing, not coffee, cold water or exercise, hurries it. About a third of East Asians carry a variant of the second enzyme that works slowly, so acetaldehyde builds up and produces flushing, nausea and a racing heart after a single drink.

Alcohol does not act on one receptor but on several, and its net effect is to turn down the brain's activity. It enhances GABA, the main inhibitory transmitter, which is what benzodiazepines and anaesthetics do, and it blocks glutamate, the main excitatory one, and the combination slows everything. It also triggers a release of dopamine in the reward circuit, which is the pleasure of the first drink and the hook of the habit, and of endorphins, which is the warmth. The order in which brain regions are affected explains the familiar sequence:

• •Low doses: the frontal cortex, seat of judgement and inhibition, is damped first, so people become talkative, confident and less careful; this is the stimulant phase, which is disinhibition rather than stimulation
• •Moderate doses: the cerebellum, which coordinates movement, and the areas that manage speech and reaction time, giving slurred words, unsteady walking and slowed reflexes; driving ability falls measurably at levels well below the legal limit
• •High doses: the hippocampus stops forming memories, producing the blackout, in which a person acts and later recalls nothing
• •Very high doses: the brainstem, which runs breathing and the gag reflex, is suppressed, and alcohol poisoning kills by stopping breathing or by inhaled vomit

The molecule reaches every organ and touches most. It dilates blood vessels in the skin, giving the flush and the false feeling of warmth that has killed people in the cold. It suppresses the hormone that tells the kidneys to hold water, so the drinker urinates more than they drink and dehydrates, which is part of the next morning. It irritates the stomach lining, disrupts the second half of the night's sleep by suppressing REM and then rebounding, and lowers blood sugar. Over years the liver, which does all the processing, is the organ that suffers: fat accumulates, then inflammation, then the scarring of cirrhosis, and alcohol is also a cause of cancers of the mouth, throat, oesophagus, liver, bowel and breast, since acetaldehyde damages DNA. The idea that a moderate amount protects the heart, which rested on comparing drinkers with abstainers who were often ill, has largely collapsed under better studies, and the current view is that the safest amount is none and that the risk rises with every drink.

A hangover is what the body does in the hours after the alcohol has gone, and it is several things at once: dehydration, from the lost water; acetaldehyde, which lingers if the second enzyme is behind; the inflammatory response the immune system mounts to the toxin, which produces the same aching malaise as a mild flu; low blood sugar; poor sleep; and the rebound of a brain that had been sedated, overshooting into anxiety and sensitivity to light and sound. Congeners, the flavour compounds in dark spirits and red wine, make it worse, which is why vodka hangovers are milder than whisky ones. There is no cure. Water, food, sleep and time help; the hair of the dog postpones the reckoning by re-sedating the brain and adds to the bill.

The brain adapts to a drug that is always present. Faced with constant GABA enhancement and glutamate blockade, it makes fewer GABA receptors and more glutamate ones, so that the same dose does less, which is tolerance, and so that removing the alcohol leaves the brain overexcited, which is withdrawal: tremor, sweating, anxiety, and in heavy drinkers seizures and the hallucinations of delirium tremens, which can kill. Alcohol dependence is one of the few addictions in which stopping abruptly is medically dangerous, and it is treated with a tapering sedative. Around one drinker in ten develops dependence, more where the habit starts young and where genes make the drink more rewarding or the hangover less punishing, and the drug that a majority of adults use without harm is, for that minority, the most destructive one in common use.

Alcohol is absorbed without digestion, reaches the brain in minutes, and is cleared by the liver at a fixed rate of about one drink an hour through a toxic intermediate, acetaldehyde. It sedates the brain by boosting GABA and blocking glutamate, damping judgement first, coordination next, memory after that and breathing last, while dopamine supplies the pleasure; a hangover is dehydration, inflammation, poor sleep and rebound; and long use damages the liver, causes several cancers and rewires the brain into dependence.