Ethanol: this molecule, made of little
more than a few carbon atoms, is responsible for drunkenness. Often simply referred to as alcohol, ethanol is the active ingredient
in alcoholic beverages. Its simplicity helps it
sneak across membranes and nestle into a many different nooks, producing a wide range of effects
compared to other, clunkier molecules. So how exactly does it cause drunkenness, and why does it have dramatically
different effects on different people? To answer these questions, we’ll need to follow alcohol
on its journey through the body. Alcohol lands in the stomach
and is absorbed into the blood through the digestive tract,
especially the small intestine. The contents of the stomach
impact alcohol’s ability to get into the blood because
after eating, the pyloric sphincter, which separates the stomach
from the small intestine, closes. So the level of alcohol that reaches
the blood after a big meal might only be a quarter that
from the same drink on an empty stomach. From the blood,
alcohol goes to the organs, especially those that get
the most blood flow: the liver and the brain. It hits the liver first,
and enzymes in the liver break down the alcohol molecule
in two steps. First, an enzyme called ADH turns alcohol
into acetaldehyde, which is toxic. Then, an enzyme called ALDH converts the
toxic acetaldehyde to non-toxic acetate. As the blood circulates, the liver
eliminates alcohol continuously— but this first pass of elimination
determines how much alcohol reaches the brain and other organs. Brain sensitivity is responsible
for the emotional, cognitive, and behavioral effects of alcohol—
otherwise known as drunkenness. Alcohol turns up the brain’s
primary brake, the neurotransmitter GABA, and turns down its primary gas,
the neurotransmitter glutamate. This makes neurons
much less communicative, and users feel relaxed at moderate doses,
fall asleep at higher doses, and can impede the brain activity
necessary for survival at toxic doses. Alcohol also stimulates
a small group of neurons that extends from the midbrain
to the nucleus accumbens, a region important for motivation. Like all addictive drugs, it prompts a squirt of dopamine
in the nucleus accumbens which gives users a surge of pleasure. Alcohol also causes some neurons
to synthesize and release endorphins. Endorphins help us to calm down
in response to stress or danger. Elevated levels of endorphins
contribute to the euphoria and relaxation associated
with alcohol consumption. Finally, as the liver’s breakdown of alcohol
outpaces the brain’s absorption, drunkenness fades away. Individual differences
at any point in this journey can cause people
to act more or less drunk. For example, a man and a woman who weigh
the same and drink the same amount during an identical meal will still have
different blood alcohol concentrations, or BACs. This is because women
tend to have less blood— women generally have
a higher percentage of fat, which requires less blood than muscle. A smaller blood volume,
carrying the same amount of alcohol, means the concentration
will be higher for women. Genetic differences in the liver’s alcohol
processing enzymes also influence BAC. And regular drinking can
increase production of these enzymes, contributing to tolerance. On the other hand, those who drink
excessively for a long time may develop liver damage,
which has the opposite effect. Meanwhile, genetic differences
in dopamine, GABA, and endorphin transmission
may contribute to risk for developing an alcohol use disorder. Those with naturally low endorphin
or dopamine levels may self-medicate through drinking. Some people have a higher risk
for excessive drinking due to a sensitive endorphin response
that increases the pleasurable effects of alcohol. Others have a variation
in GABA transmission that makes them especially sensitive
to the sedative effects of alcohol, which decreases their risk of developing
disordered drinking. Meanwhile, the brain adapts to chronic
alcohol consumption by reducing GABA, dopamine, and endorphin transmission,
and enhancing glutamate activity. This means regular drinkers tend
to be anxious, have trouble sleeping, and experience less pleasure. These structural and functional changes
can lead to disordered use when drinking feels normal,
but not drinking is uncomfortable, establishing a vicious cycle. So both genetics and previous experience
impact how a person experiences alcohol— which means that some people
are more prone to certain patterns
of drinking than others, and a history of consumption leads
to neural and behavioral changes.
