Tobacco, alcohol, stimulants, opiates, and marijuana are all capable of leading to addiction. Some of these drugs are more addictive than others. Some people are more prone to becoming addicted than others. Authors of a recent review article in the New England Journal of Medicine define addiction as “the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug.”

This paper was written by three experts in the field, Nora Volkow, George Koob, and Thomas McLellan. Notably, Volkow directs the National Institute of Drug Abuse and Koob directs the National Institute of Alcohol Abuse and Alcoholism. In the article, they describe three stages that a person goes through on the road to addiction: 1) binge and intoxication, 2) withdrawal and negative affect, and 3) preoccupation and anticipation (or craving). These three stages occur with each of the drugs mentioned above, and each stage is associated with neurobiological changes in specific brain systems. Once addiction develops, reversing the accompanying brain changes is difficult and can take many years depending on the individual and the specific drug involved.

Drugs that cause addiction elicit pleasurable and enjoyable feelings by activating the brain’s reward and motivational systems through the release of dopamine in specific brain regions. The pleasurable feelings may lead a person to use the drug more frequently. Eventually, the ability of a given dose of the drug to release dopamine decreases as a result of changes in the brain, and a person must then use more drug to get the same degree of pleasure. The more exposure to the drug, the more changes occur in the brain. This is referred to as the binge and intoxication stage.

As an individual continues to push the pleasure system with increasing exposure to a drug, the drug begins to influence how various nerve cells in the limbic system communicate with each other. The brain regions in the limbic system are known to be involved in emotional regulation. With continued frequent exposure to the drug, the limbic system adapts to a state where the presence of the drug is the new “normal.” In fact, when the drug is absent, the limbic system sends out “anti-reward” signals, and the person can feel anxious, down, and restless. This is the second phase of drug addiction, the withdrawal and negative affect stage. Instead of the drug causing pleasure, its presence is needed to avoid feeling bad. 

Repeated exposure to addictive drugs also leads to rewiring of higher brain regions that regulate motivation, and this system becomes preoccupied with a strong desire to get more drug. A person’s ability to resist strong urges is compromised, leading to compulsive behaviors that can be so powerful as to cause an individual to obtain more drug by whatever means necessary, including stealing. These changes in higher brain function can also interfere with the person’s ability to follow through with decisions to discontinue drug use. This is the preoccupation and anticipation (craving) stage. This stage also involves changes in neurocircuitry underlying how we think, learn, plan, and make decisions. These latter changes can result in persistent cognitive dysfunction and can significantly impair an individual’s ability to function at work or in a social network.

As we’ve discussed, addictive drugs interfere with brain systems that are important for everyday behavior. The reward system, when working correctly, helps reinforce productive behaviors, for example, feeling good about doing a good job at work or helping a neighbor. The emotional regulatory system involving the limbic system helps keep our emotions in balance. The motivational system drives us toward actions that are usually beneficial. Cognitive systems allow us to keep some level of control over emotions, motivation, and decision making. The sinister power of addictive drugs is that they have the ability to literally hijack the brain systems that are central to our behaviors.

It is also important to realize that not everyone who is exposed to drugs becomes addicted. One factor that increases susceptibility is early exposure, particularly during adolescence while the brain is still maturing. Public policy and other efforts aimed at preventing the use of addictive drugs, including alcohol and nicotine, by teenagers could have a major impact on preventing addiction.

Once addictive drugs lead to physical and functional changes in the connections between various brain regions, it is extremely difficult to undo the changes and recovery can take a long time. Group and individual therapies, such as Alcoholics Anonymous (AA), are often helpful, but a person who is in recovery knows that relapse could occur quickly. The desire to use the drug often still remains.

There is reason for cautious optimism, however. The research elucidating the specific brain pathways involved in addiction is also providing targets for intervention. There is increasing knowledge about rewiring brain systems. It is conceivable that such research will be translated into clinically important therapies over the next decade.

This column was authored by Eugene Rubin MD, PhD and Charles Zorumski MD

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