If you were around in the 1980s, you remember Nancy Regan telling us to “just say no” to drugs. That campaign focused specifically on the effect crack had on the community.  In the 1990s and 2000s, we saw and increase in reports of methamphetamine and heroin overdoses. Though they are perfectly legal, nicotine and even more so, alcohol can be just as damaging on one’s life when used in excess. The War on Drugs launched in the 1970s along with the Just Say No campaign brought tougher sentences related to drug possession, however, this has done little to deter individuals from using drugs. If you have ever had a loved one (friend, family member, or significant other) addicted to drugs or alcohol, you know how devastating it can be to watch their lives spiral out of control. Though society shuns addicts for making such decrepit choices, you wonder, “how could a person possibly choose to live like this?”
Note: For the purposes of this blog, we consider alcoholism a form of drug addiction.

For decades, the scientific community has raised the question of whether drug addiction is a disease just like diabetes or heart disease or a moral issue and one must wrestle with the conscience to get clean. Those who argue against the disease model point at the fact that with diabetes and cancer, there are specific tests that can be done to diagnose the condition. However, when considering diseases associated with the brain, such as Parkinson’s, specific tests are not available since we simply do not know enough about brain function to design such a test.  Few would argue that Parkinson’s is anything other than a disease. Acute and chronic drug use can have dramatic effects on brain biochemistry and morphology.

In 2004, a powerful review article  was written in Nature Reviews Neuroscience by the directors of the National Institute of Drug Abuse and the National Institute of Alcohol Abuse. (If you can’t access that article or for a less technical summary check this out.)  Medical technology has improved by leaps and bounds over the last decade allowing us to gain more and more knowledge on the structure of the brain and related genetics.  The details described below are summarized from these articles.

” This new knowledge is helping us to understand why drug addicts relapse even in the face of threats such as divorce, loss of child custody and incarceration, even when, in some cases, the drug is no longer perceived as pleasurable, and is changing how we should approach prevention and treatment of addiction.”
-Volkow and Li, Nature Reviews/Neuroscience, 2004

It is true that for a person to become addicted in the first place, one must make the choice to use drugs or alcohol. The reasons for this choice are many, e.g. peer pressure, desire to escape stress or cope with mental illness. Most people reading this article will understand why one may continue to use a drug more than once. Just like eating great tasting food or having sex, using drugs causes an increase in the neurotransmitter, dopamine, which is a response to a pleasurable activity.  So why, if dopamine is a normal, physiological response, is drug addiction more common than food or sex addiction? It turns out that dopamine increases following drug use can be two to ten times the norm. Cocaine, amphetamines, methamphetamines and ecstasy appear to work by inhibiting dopamine reuptake and promoting dopamine release through transporters, while alcohol, opiates, nicotine, and marijuana stimulate cells that release dopamine.  This means that the pleasure response lasts longer following drug use than other activities such as eating or sex.  Because our brains are so good at learning and adapting, (remember Pavlov’s Dog?)  desire to use a drug becomes anticipation of a release of dopamine instead of the release itself. People become conditioned to seek out a drug even though using the drug may not even bring them the same pleasure or stress release as it did when they began using. The brain of a chronic drug user becomes used to the drug providing increase in dopamine, and will decrease its own production of dopamine. This means a chronic drug user will require the drug of choice to create a chemical balance in their brain.

Brain regions such as the orbitofrontal cortex, cingulate gyrus and mesocortical circuit are associated with behavioral control show morphological changes following chronic drug use.  Comparisons between brain images of healthy and drug addicted patients show reduced activity in these regions, which have been associated with compulsive behavior and poor impulse control.

Studies on rats showed that cocaine and methamphetamine use changed regulation of FosB and CREB genes, which may cause structural changes in neurons associated with brain circuitry regulated by dopamine. These changes could make the difference between a person who associates a drug with a pleasant feeling and a person who actively desires a drug.

An estimated 40-60% of what makes one individual more vulnerable to drug addiction could be related to genetics. For example, why are some people able to control the amount of alcohol they drink while others cannot? Genes involved in the metabolism of alcohol (ADH1B and ALDH2), nicotine (P-450 2A6), and codeine (P-450 2D6) appear to be protective against addiction.  GABA receptors are components of brain cells that are associated with inhibition. When GABA receptors are active, your brain is likely telling you not to do something. A decrease in expression of particular type of GABA receptor known as D2 has been associated with higher vulnerability to addiction.

Environmental and social factors undoubtedly play a huge role in vulnerability to addiction and to address them properly would require a separate blog post. However, studies in non-human primates have shown that stressors related to social status have been associated with GABA D2 receptors. Individuals with higher expression levels of GABA D2 are less likely to self-administer cocaine or alcohol.

Clearly, drug addiction is correlated with distinct changes to the brain on all levels from genetic to cellular to structural. Recognizing drug addiction as a chronic brain disease may have a huge impact in how it is viewed, handled, treated and studied. Some drug addicted individuals find it helpful to understand that they are suffering from an illness and are not just morally-decrepit or weak-willed. Some argue that the “addiction as a disease” model will only give addicts an excuse to remain addicted. A closer look at treatment strategies may give some insight here, but must be reserved for a future blog post. Those of us struggling with addiction, either as addicts or loved ones of addicts, can find hope in the knowledge that improvements in technology help us  learn more about the science of addiction every day.  This will undoubtedly lead to development of effective treatments.

Resources

1. Valkow, N.D. and Li T-K. Drug Addiction: The Neurobiology of Behaviour Gone Awry. Nature Reviews/Neuroscience. December 2004
2. Slomski, A. (Fall 2006) The Addicted Brain. Proto. Accessed May 31, 2012 from http://protomag.com/assets/the-addicted-brain
3. Commentary from Kevin T. McCauley, M.D. Accessed on May 31, 2012 from the Institute for Addiction Study from http://www.instituteforaddictionstudy.com/PDF/Disease%20Argument.pdf
4. National Institute on Drug Abuse. Drugs, Brains, and Behavior. Accessed on May 31, 2012 from http://www.drugabuse.gov/publications/science-addiction

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Karen Reece

Karen served as a Senior Research Scientist in Nucleic Acid Technologies at Promega before switching careers. She has a BS in Biochemistry and MS and PhD in Physiology, all from University of Wisconsin-Madison. Karen was born and raised in Madison, WI.

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