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.