How Science Explains Drunkenness and Hangovers

Since the dawn of the first civilizations, humanity has consumed alcohol in the form of different drinks, whether in celebrations or religious ceremonies or in moments of leisure and relaxation.

This is explained, in part, by the effects that its ingestion provokes, such as reduced anxiety, relaxation, increased self-esteem and sociability.

But heavy consumption reveals the other side of ethanol, as it causes drowsiness, sedation, memory failure, slow speech and movement, and, in extreme cases, coma and even death — not to mention a hangover the next day.

But why this happen?

In the book “The History and Chemistry of Cachaça” (ed. Athena, 2021), who recently published, researcher Leinig Antonio Perazolli, from the Chemistry Institute of the Araraquara campus of the São Paulo State University (Unesp), explains that, as well as several other antianxiety drugs and medications, the main action of the ethyl alcohol or ethanol is the inhibition of the central nervous system.

According to him, after being consumed, it is metabolized through the action of two enzymes, alcohol dehydrogenase and aldehyde dehydrogenase. The first, he explains in the book, converts ethanol into acetaldehyde, which is also a toxic substance for the body. Therefore, the second enzyme takes action, converting this compound into acetic acid.

Chemist Carlos Alberto da Silva Riehl, coordinator of the Forensic Chemistry Laboratory at the Chemistry Institute of the Federal University of Rio de Janeiro (UFRJ), explains why drunkenness occurs.

According to him, when consumed, alcohol enters the bloodstream, spreading throughout the body, reaching the brain.

“As it is a less polar molecule than water, but very soluble in this medium, upon reaching the synaptic clefts [local onde um neurônio troca informações químicas com outro], it makes it difficult for neurotransmitters to move between them, causing a certain slowness in our actions, which generates what we call drunkenness,” he says.

Riehl also explains why, at first, people are uninhibited and have a sense of general well-being. After being absorbed from the stomach, ethanol enters the bloodstream, quickly going to the liver, where it is metabolized.

“Initially, this organ transforms it into acetic acid, which is used to generate energy in the cells, which initially gives us a feeling of well-being”, he says. “Gradually, it reaches neurons and subtly inhibits the exchange of some neurotransmitters, which generates disinhibition, euphoria and, consequently, greater sociability (the person is usually very talkative).”

Diego Defferrari, also a chemist and doctoral candidate in Pharmaceutical Sciences, from the Federal University of Rio Grande do Sul (UFRGS), adds that alcohol is a sedative and a mild anesthetic.

“When ingested, it releases neurotransmitters in the brain such as dopamine and serotonin, which are related to the activation of the pleasure and reward centers”, he says. “Due to this exacerbated release, physiological changes occur in the body, such as a feeling of well-being, relaxation, disinhibition and euphoria.”

‘Inhibit inhibition’

According to the biochemical pharmacist and PhD in Toxicology, Maurício Yonamine, from the Department of Clinical and Toxicological Analysis of the Faculty of Pharmaceutical Sciences at the University of São Paulo (USP), the action of ethanol in the brain is complex.

“In small concentrations (for example, at the beginning of alcohol consumption), alcohol inhibits regions of the brain that naturally inhibit feelings of euphoria”, he explains. “It’s what we call ‘inhibiting inhibition’, that is, it causes euphoria.”

But not everything is joy and happiness. Doctor in biochemistry Guilherme Andrade Marson, from the Institute of Chemistry at USP, warns that, in this phase of euphoria and disinhibition, violent behavior, imprudence and difficulty in assessing risks can also occur.

“Furthermore, in some individuals, it can trigger anxiety attacks, persecutory delusions, depression or epileptic seizures, among other problems”, he says.

In his book, Perazolli uses more technical language to explain this process, which has to do with neurotransmitters, which are relatively simple molecules such as serotonin, dopamine, glutamate and gamma-aminobutyric acid (GABA). “These transmitters interact with the receptors and stimulate or inhibit body functions and sensations”, he explains in the work.

Also according to him, different types of receptors can interact with a transmitter to generate specific sensations, since each area of ​​the central nervous system regulates different functions and perceptions.

“When in contact with receivers, these transmitters will exert an excitatory or inhibitory effect, according to the charge of the transmitter sent”, he writes. Both are determined by the type of ionic interaction that takes place in the receptors, which can interact with sodium (Na+) or chloride (Cl-) ions.

The excitatory effect, explains Perazolli in the book, is caused by neurotransmitters such as acetylcholine, glutamate, serotonin and adrenaline, which open the selective sodium channels and enter the membrane, which in turn causes the receptor site to remain with a positive charge towards the outside. “Thus, the neuron is more likely to generate an action potential due to the increase in neurotransmission”, he says. It’s the euphoric phase.

On the other hand, “the inhibitory effects caused by the opening of GABA receptors are related to that of the selective ion channels of the Cl- ions”.

In this case, the chloride is more concentrated outside the neuron, “until the opening of the receptor sites, the ions enter and make the interior more negative in relation to the exterior, reducing neurotransmission and the action potential in that region”. It is time for drowsiness and sluggishness.

According to Dr André Brooking Negrão, from the Study Program on Alcohol and Drugs (GREA) at the Institute of Psychiatry at the Hospital das Clínicas of the Faculty of Medicine at USP, this occurs as the concentration of ethanol in the blood increases. “Initially, low doses disinhibit behavior, tension and anxiety,” he explains.

“As we drink more, the effects that we call alcohol depressants add up. Depressant in the sense of canceling out the activity of neurons. Then, we will have initial signs of drowsiness (tendency to sleep), sedation (removal of excitement), slow thinking and cognitive activities of attention and memory.”

If ingestion continues, a “neural blackout” may occur, that is, the dose will be so high that it will reach a large portion of the neurons. “The final result is intense sedation or pre-coma, which supersedes the initial effects of disinhibition or euphoria”, says Negrão. “To a more extreme degree, alcohol reduces the activity of neurons that control breathing and the person can have a respiratory arrest, which can be fatal.”

If the person who abused the drink overcomes all these effects and makes it to the next day alive, he could still find himself dealing with another disastrous consequence of ethanol — one that could make some swear never to drink again: a hangover.

Perazolli explains in his book, in scientific terms, that it occurs mainly due to the accumulation of acetaldehyde not converted into acetic acid. Individuals who have some deficiency in the activity of the enzyme aldehyde dehydrogenase “are more susceptible to these effects and usually exhibit some characteristic symptoms, such as redness in the face, headache, nausea and tachycardia”.

According to Yonamine, in addition to the accumulation of acetaldehyde, a hangover can have several other causes. “The physical mechanisms by which it occurs are not fully understood scientifically”, he says.

“Multiple factors must be involved, such as the direct action of ethanol in urine production itself (increasing diuresis and causing dehydration); as an irritant of the gastric mucosa (increasing the secretion of gastric juice and intestinal secretions, causing a burning sensation, nausea and diarrhea) and its effect of lowering blood glucose concentration (which may lead to hypoglycemia).”

What is known for certain is that the effects and consequences of drinking alcohol vary from person to person. “First of all, it is important to emphasize that the chemistry of ethanol in the body is complex and involves two areas of science: biochemistry and enzymology”, says Defferrari.

“Also remembering that we are dealing with the human organism, which is extremely complex, generating different responses in each person. Characteristics such as body mass, biological sex and age are also factors that must be taken into account.”

In the case of a hangover, for example, there is another peculiarity. “Although the potential explanations are numerous, genetic differences may explain a large part of the variation in hangovers between individuals”, says researcher Jemmyson Romário de Jesus, from the Federal University of Viçosa (UFV).

“For example, many people of Chinese, Japanese and Korean ancestry have a mutation that prevents their bodies from effectively metabolizing ethanol, leading to acetaldehyde buildup, and consequently worse hangovers.”

But, according to Jesus, there is a reward for this population: they have a lower chance of alcohol use disorder (alcoholism), due to the aversion they can create towards drinking. Regardless of ethnicity, there are also other factors that can enhance hangovers or not, such as diet, age, body mass, alcohol tolerance and level of consumption, for example,” he adds.

The effects and consequences of alcohol abuse do not just affect those who drink, however. The problem is collective. According to the Pan American Health Organization (PAHO), the arm of the World Health Organization (WHO) for the Americas, its abusive use can also result in harm to other people, such as family members, friends, co-workers or strangers. Furthermore, it results in a significant social, economic and health burden for the entire society.

Also according to PAHO, alcohol abuse is responsible for 3 million deaths per year worldwide, which represents 5.3% of all deaths. Furthermore, it is the cause of around 200 illnesses and injuries. Overall, 5.1% of the total are attributable to drinking, as calculated in terms of Disability Adjusted Life Years (DALY).

Ethanol consumption also causes death and disability relatively early in life, according to PAHO/WHO. In the age group from 20 to 39 years, approximately 13.5% of all deaths are attributable to drinking. Furthermore, there is a causal relationship between alcohol abuse and a series of mental and behavioral disorders, as well as non-communicable diseases and injuries.