What is Alcohol Use Disorder?
Before diving into the skills of diagnosing substance use disorders, it’s fair to take a step back and ask what a substance use disorder actually is. Is it a brain disease? Is it self-medication? Is it a life choice? The answer can be any of the above, or a combination, depending on the person and the substance. For the opioid addict with overwhelming cravings who is stealing money from her friends to buy her next fix, it is primarily a brain disease involving opiate receptors.
For the college student taking Adderall a couple of times a week—borrowed from friends—to study for exams and write papers, it may be a lifestyle choice (though it can devolve into neurochemical dependency if the habit becomes a daily one). For the man with social anxiety disorder who downs a few shots of vodka before going to a social event, it may be a form of self-medication. Like most disorders in medicine and psychiatry, substance use is multifactorial, and for this same reason, it can be treated in different ways.
Neurobiology of Addiction
While our knowledge of the neurobiology of addiction is limited, researchers are beginning to work out some of the mechanisms. One particular neurotransmitter, dopamine (DA), seems to play a central role for most addictions. Most psychiatrists are familiar with DA in the setting of psychosis. All antipsychotics block DA receptors, which implies that excessive DA can be a bad thing, as it may be one of the chemicals that can cause psychosis. However, there is another side of DA—it’s the primary neurotransmitter for the brain’s reward system.
Our brain releases high levels of DA during joyful events, like graduating from high school, winning a race, or enjoying a Thanksgiving dinner. Another experience that can cause a kind of “joy” is abusing drugs. Cocaine and methamphetamine cause the most DA release, leading the user to feel intensely exhilarated and powerful.
While a large release of DA can indeed produce positive emotions, the brain quickly institutes measures to maintain a stable internal environment, or homeostasis. One measure is to quickly clear the DA away, which the brain does by breaking the DA down with enzymes or recycling it. But when someone is consistently using drugs, there’s too much DA for this process to work.
Therefore, the brain alters itself to make the neurons a little less receptive to DA. This process is called “desensitization,” and it occurs in various ways biochemically, such as decreasing the number of DA receptors or slowing down receptor activation. As the brain desensitizes to DA, the drug user experiences this as tolerance, meaning the person does not experience the same high from a given dose.
If the dose is increased to compensate, the user will get high, but the brain will go through its homeostasis process again, forming tolerance to the higher dose. This is a simplistic neurobiological explanation of tolerance.
What about withdrawal—why does that happen? When there’s no external stimulation causing the brain to release DA, the user must depend on the old-fashioned process of the brain releasing DA as it normally would: that is, in response to the prosaic pleasurable events of life, like having a snack or watching a ball game.
But a brain that has gotten used to relying on high levels of DA has fewer DA receptors, and those receptors are less sensitive. Therefore, the normal amount of DA doesn’t produce much, if any, pleasure compared to what the addict experiences when getting a “fix.” When an addict’s drug of choice is taken away, a DA deficiency results. This is one reason withdrawal is so unpleasant, and why stimulant withdrawal causes depression. With a damaged reward circuit, it becomes very hard for a user to experience normal healthy behaviors as motivating. The temptation to use drugs is extreme, because the user now feels the drugs are needed simply to feel normal.
Genetics of addiction
Drug addiction often runs in families, though the strength of the development of addiction varies between substances. Familial transmission of substance abuse does not necessarily imply genetic involvement; however, there is in fact a large amount of evidence that genes play a role. One piece of evidence comes from studies of identical and fraternal twins.
The most interesting of these studies compares these two types of twins when they have been separated at birth and put up for adoption. If addiction had nothing to do with genes, but everything to do with upbringing, one might expect that the diagnostic concordance rate of identical and fraternal twins would be the same—but in fact the identical twin concordance rate is higher.
Using this kind of data, studies have estimated that the heritability of addiction to alcohol and drugs in general is 60%. This does not mean that a patient has a 60% chance of developing an addiction if one of the patient’s parents had an addiction, although this is a common misunderstanding. Instead, if a person becomes addicted, about 60% of the reason for that addiction will be genetic, while about 40% of it will be non-genetic—such as the effects of upbringing.
If genetics has so much to do with addiction, what are some of the possible genes that play a part, and how might they work? A number of genetic variants have been identified that might contribute to increasing a person’s vulnerability to addiction. For example, genes for certain subtypes of GABA-A receptors have an association with alcohol use disorder, and a different cluster of genes is associated with a higher risk for nicotine use disorder.
Other gene variants can protect against addiction. In several Asian populations, gene variants for alcohol dehydrogenase cause disulfiram-like reactions, making drinking very unpleasant. Overall, however, we’re still quite far from truly understanding the genetics of addiction, and there is no clinically useful genetic test for helping us predict who is likely to become addicted.