The Dose Makes the Poison: Understanding Alcohol’s Effects

“The dose makes the poison.” —Paracelsus, 1538

There are only a few molecules that humans consume that are both a nutrient and a drug. Coffee and alcohol are two excellent examples. The antioxidants in coffee offer many health benefits, although the caffeine, in sufficiently high doses, can be lethal. Obviously, dose matters. The same is true for alcohol.

How Alcohol Affects the Body and Brain

Let’s look at what alcohol does in the brain—particularly, how it interacts with three different neurotransmitters.

First, at low doses, alcohol enhances the action of the neurotransmitter GABA. GABA is the brain’s primary inhibitory neurotransmitter, effectively turning off activity in the brain wherever it acts. When we start drinking, the initial effects—relief from anxiety and alterations in personality and judgment—occur because GABA is inhibiting activity in our cortex.

With higher doses, the parts of the brain that control movement and coordination are affected. Finally, at particularly high doses, the parts of our brain that control breathing and heart rate are inhibited, creating a risk of death.

Second, alcohol stimulates the release of dopamine, which may underlie feelings of pleasure.

Finally, at higher doses, alcohol inhibits the neurotransmitter glutamate, essential for producing memories. This explains why we might not remember events that occurred while intoxicated.

Alcohol’s Journey Through the Body

Alcohol travels to the stomach and liver, where an enzyme called alcohol dehydrogenase metabolizes it into an aldehyde—a type of organic compound—that is irritating to tissues. This aldehyde is then metabolized into acetate and finally into carbon dioxide and water. Some acetate is converted into fatty acids that deposit in the liver, fat pads, and other organs.

Is Drinking Alcohol Ever Quality for You?

Considering alcohol’s various effects, does it offer any benefits? The answer depends on dose, age, and the tissues involved.

According to the National Institute on Alcohol Abuse and Alcoholism, less than 7 drinks per week for women and less than 14 drinks per week for men is considered “low-risk drinking.” At these dosages, numerous epidemiological studies have reported some health benefits, including:

• Lowered risk of cardiovascular disease, possibly because alcohol raises levels of HDL cholesterol. This benefit was particularly seen in post-menopausal women.
• Improved insulin sensitivity, lowering the risk of type 2 diabetes.
• Reduced platelet stickiness and aggregation, temporarily thinning the blood and lowering clot risk.
• A 60 percent reduction in the incidence of colds. Red wine, due to its antioxidants, provides immune system benefits.
• A 23 percent reduction in the risk of Alzheimer’s disease, although this benefit is reduced for individuals with two copies of the APOE-ε4 gene.
• A 33 percent reduction in the risk of developing gallstones.
• Prevention of kidney stones by increasing urine volume, reducing the saturation of solids that form stones (provided sufficient fluids are consumed to avoid dehydration).

When Does Alcohol Consumption Develop into Harmful?

The harmful effects of alcohol are as well dose-, time-, and tissue-dependent. Like all drugs, alcohol consumption leads to tolerance, where the body adapts to consumption levels, requiring larger doses to achieve the same effect. The liver becomes more efficient at removing alcohol, while the brain demands greater amounts to experience the pleasurable effects on GABA and dopamine function.

Long-term, high-dose alcohol consumption leads to inflammation and fat deposition in the liver, eventually causing cirrhosis and functional failure. The effects of aldehydes on blood vessels are linked to a linear association between alcohol consumption and the risk of hypertension. Aldehydes can also alter estrogen levels, increasing the risk of breast cancer, and may damage DNA, affecting tissues directly exposed, leading to cancers of the colorectum, esophagus, and throat.

Finally, alcohol dose-dependently turns off neurons, leading to impaired judgment, slower reaction times, and an increased risk of accidents and death.

What We Still Don’t Know About Alcohol’s Effects

Many early alcohol studies had methodological flaws, failing to account for other healthy habits of moderate drinkers, such as good diet and regular exercise. It’s also difficult to determine an appropriate control group—very low alcohol consumers or abstainers. Some abstain due to existing health problems, and abstainers generally have higher rates of death and chronic disease than moderate consumers.

younger generations, particularly Gen Z, are drinking less alcohol and less frequently than previous generations, increasingly opting for marijuana. Whether this is a safer choice is still under debate, but the brain often induces consumption of substances the body dislikes.