Alcohol's Effects in the Brain

Do You Know That Alcohol can make you laugh or it can make you cry, it can make you lively or make you sleepy, it can boost your confidence or make you act the fool. How can alcohol have all these different effects on people? If we want to know how alcohol affects our moods and behaviors we must first understand a bit about how the brain works.

The human brain is made up of about 100 billion nerve cells (also known as neurons). Everything that we think, feel or do is the result of electrical signals passing back and forth between neurons. These electrical signals require the help of chemicals called neurotransmitters in order to pass from neuron to neuron. Scientists have identified around 60 different neurotransmitters so far and tell us that there are probably many more yet to be identified.

Different neurotransmitters have different effects in the brain. For example, serotonin is connected with mood. People suffering from clinical depression tend to have a shortage of serotonin in their brains, and medications like Prozac can help to alleviate depression by increasing the availability of serotonin in the brain. Endorphins are a class of neurotransmitters which act as the brain's natural painkillers.

Electrical signals in the brain are transmitted in the following manner: The neuron which is sending the electrical signal releases a neurotransmitter, and the neuron which is receiving the electrical signal accepts the neurotransmitter at a site which is called a receptor. When the neurotransmitter from the first neuron chemically binds to the receptor of the second neuron the electrical signal is transmitted. Neurotransmitters and receptors work like locks and keys: there is at least one different receptor for each different neurotransmitter. For example, an endorphin receptor can only be triggered by and endorphin, a serotonin receptor can only be triggered by serotonin, and so on. Different neurons have different receptors. Some neurons will only be triggered by serotonin, some only by an endorphin, and so on for all the different neurotransmitters.

Okay--now what does all of this have to do with alcohol?

Every mood altering substance from heroin to coffee has an effect on the neurotransmitter system of the brain. Some psychoactive drugs affect only one specific neurotransmitter system, whereas others affect many. Morphine, for example, mimics the neurotransmitter beta-endorphin--a natural painkiller found in the brain. Morphine is shaped like beta-endorphin and binds to the beta-endorphin receptors thus acting as a painkiller and also giving rise to feelings of pleasure. Caffeine is shaped like Adenosine and acts on the adenosine receptors. Alcohol on the other hand affects many different neurotransmitters, not just one, Why is this?

Morphine and caffeine are both large molecules. Neurotransmitters are also large molecules. Morphine and caffeine have the effects which they do because of their similarity in shape to neurotransmitters which occur naturally in the brain. Alcohol on the other hand is a quite small molecule. Alcohol does not mimic a neurotransmitter. So then how does alcohol affect neurotransmitters?

Alcohol is a fat soluble molecule. Fats (called lipids) are a major component of all cell membranes, including the cell membranes of neurons. Alcohol enters the cell membranes of neurons and changes their properties. Receptors are located on cell membranes and this means that receptor properties are altered by the presence of alcohol. Cell membranes also control the release of neurotransmitters and this means that the release of neurotransmitters is also affected by the presence of alcohol.

The effects of alcohol on receptors and neurotransmitters have been well documented for several neurotransmitters and their corresponding receptors. These effects are summarized in Table 1.

Table 1: Alcohol's Effect on Neurotransmitters and Receptors


Glutamate
Alcohol inhibits glutamate receptor function
This causes muscular relaxation, discoordination, slurred speech, staggering, memory disruption, and blackouts
Ether and chloroform have similar effects on the glutamate system


GABA (gamma-aminobutyric acid)

Alcohol enhances GABA receptor function
This causes feelings of calm, anxiety-reduction and sleep
Valium has a similar effect on the GABA system


Dopamine

Alcohol raises dopamine levels
This leads to excitement and stimulation
Cocaine and amphetamine have similar effects on the dopamine system


Endorphins

Alcohol raises endorphin levels
This kills pain and leads to an endorphin "high"
Morphine and heroin have similar effects on the endorphin system

Drugs like morphine or cocaine have been referred to as "chemical scalpels" because of their very precise effects on just one neurotransmitter system. Alcohol on the other hand is much more like a chemical hand grenade in that it affects just about all parts of the brain and all neurotransmitter systems. Alcohol affects all these systems at the same time. When people drink alcohol they become lively and excited because alcohol raises dopamine levels just as cocaine does, although alcohol does not raise dopamine levels anywhere near as much as cocaine does. When people drink alcohol they feel calm and lose their anxieties because alcohol makes the GABA receptors function more efficiently just like valium does. The reason that people tend to fall asleep after drinking alcohol or taking valium is also due to this effect on the GABA receptor. And alcohol has a painkilling effect like morphine and produces a high similar to morphine because it causes a release of endorphins into the brain thus raising the endorphin levels. (Note that the effect of morphine is different from alcohol in its mechanism--morphine imitates endorphins and binds to endorphin receptors whereas alcohol increases the amounts of the endorphins in the brain.) Finally we come to glutamate. Alcohol greatly inhibits the functioning of the glutamate receptor. Glutamate is responsible for the formation of new memories as well as for muscular coordination. It is alcohol's effect on the glutamate receptor which leads to slurred speech, and staggering in people who have consumed alcohol, as well as the inability to remember what one did that night when the morning after comes. Perhaps the only positive effect of this effect on the glutamate receptor is a feeling of muscular relaxation. Many negative effects of alcohol such as automobile fatalities due to drunk driving are the result of the loss of coordination caused by alcohol's effect on the glutamate receptor. Even small amounts of alcohol have a major impact on coordination--so never, never drink and drive.

You have probably observed that alcohol seems to have different effects on different people. Some people quickly become sleepy after drinking just a little alcohol whereas others become animated and want to just go, go, go. Research on mice suggests that this difference is genetic. Scientists have been able to breed strains of mice which quickly go to sleep after ingesting alcohol. They have also been able to breed strains of mice which become very active after ingesting alcohol. This strongly suggests that genetics determines which neurotransmitter system is most strongly affected by alcohol in which individual. Individuals who become sleepy soon after drinking probably have their GABA system more strongly affected by alcohol. And individuals who become lively and excited after drink probably have their dopamine system most strongly affected.

The effects of alcohol on the brain do not end when alcohol is completely metabolized and out of the system--what happens next is something called neurotransmitter rebound. This rebound effect is most easily illustrated if we look at what happens to many people when they use a drink or two as a sleep aid. These people often tend to wake up in the middle of the night and find themselves unable to fall back asleep. What is happening is this--alcohol has enhanced the functioning of the GABA system and has made these people feel relaxed and sleepy. The entire time that alcohol is present the GABA system is struggling to overcome the effects of alcohol and return to normal functioning. When all the alcohol is finally out of the body, the GABA system overshoots the mark and leaves people feeling restless and wide awake. This is why alcohol is not a good sleep aid. Large quantities of alcohol can keep a person asleep longer, but drinking large quantities of alcohol has its own negative effects. Neurotransmitter rebound seems also to be implicated in symptoms of hangovers such as hyper-sensitivity to light and in alcohol withdrawal syndrome giving rise to feelings of anxiety and panic and other symptoms as well.

Some medications used to treat alcohol abuse such as campral and naltrexone work by affecting the neurotransmitter systems. Naltrexone (also called revia) is an opioid receptor antagonist. Naltrexone works by binding to the endorphin receptors (which are sometimes also called opioid receptors) and blocking them off so that opiates cannot bind to these receptors. Unlike opiates or endorphins naltrexone has no painkilling effects and no pleasurable effects. Naltrexone simply blocks off the endorphin receptors so that neither opiates nor endorphins can have their painkilling or pleasurable effects. Naltrexone is highly effective with people who use opiates such as morphine or heroin since these drugs have no effect at all when the receptors are blocked by naltrexone. Naltrexone has some effect in helping people to abstain from alcohol or to moderate their use, however it is not as effective with alcohol as with opiates because alcohol affects many different neurotransmitters. The downside of naltrexone is that the body's natural painkillers, the endorphins, are unable to do their job when it is present. People taking naltrexone are advised to wear medic-alert bracelets so that doctors will know that painkillers are ineffective on these people.

Campral (also known as acamprosate) is a glutamate receptor modulator. Campral helps eliminate cravings for alcohol in long term heavy drinkers. It is hypothesized that long term heavy drinking upsets the glutamate neurotransmitter system and that campral helps to restore this to normal.

No discussion of alcohol and the brain would be complete without a mention of possible brain damage caused by alcohol abuse. It is likely that we have all heard that drinking kills brain cells. However, does scientific evidence bear out this common folk saying? A 1993 study by Jensen and Pakkenberg published in Lancet titled "Do alcoholics drink their neurons away?" compared the brains of alcoholics to the brains of non-alcoholics. This study found that the white matter of the brains of alcoholics was significantly depleted. The gray matter, however, was the same in both alcoholics and non-alcoholics. This is interesting since it is the gray matter that does the thinking. The gray matter has been compared to a network of computers, and the white matter to the cables linking them together. The brain does not produce new gray matter to replace that which is lost. The brain can, however, produce new white matter to replace white matter which has been lost. The researchers concluded that loss of white matter do to heavy drinking may possibly not constitute irreparable damage.

There is, however, a form of irreparable brain damage which can be caused by long term heavy drinking. This is Wernicke-Korsakoff Syndrome, also known as "wet brain". Wernicke-Korsakoff Syndromeis not caused by a loss of brain cells--it is caused by a deficiency of vitamin B1 (also known as thiamine). Wernicke-Korsakoff Syndrome can have several causes including extreme malnutrition, prolonged periods of vomiting due to morning sickness or an eating disorder, kidney dialysis, stomach stapling, or alcohol abuse. The vast majority of cases of Wernicke-Korsakoff Syndrome which occur in the United States are caused by severe, long-term, heavy drinking. Alcohol can lead to Wernicke-Korsakoff Syndrome because it blocks the absorption of thiamine. Symptoms of Wernicke-Korsakoff Syndrome include amnesia, inability to form new memories, confusion, hallucinations, and confabulation. Some of the more severe symptoms of Wernicke-Korsakoff Syndrome can be treated with thiamine, however in most cases many of the symptoms persist for a lifetime.

Have scientists discovered everything that there is to know about alcohol's effects on the brain? It seems that this is clearly not the case. Scientists believe that alcohol likely affects many more neurotransmitters than the four discussed in this article. There is constant and ongoing research to discover how alcohol might affect other neurotransmitters. The future is likely to bring us much new knowledge about alcohol and the brain.