The biology of drug addiction

Abstract

Drug addiction is a devastating disease that affects millions of people worldwide. Often, addiction to illicit drugs accompanies other types of mental illness such as depression, bipolar disorder, or schizophrenia, and the use of drugs can severely worsen these conditions. Drug use becomes classified as addiction when there is a loss of control of drug intake, resultingin negative consequences. These consequences can be health related but also include the loss of employment, family, and friends. In addition, individuals can become addicted to other activities such as gambling, shopping, or sexual activity, which can also lead to devastating consequences. Drug dependence is defined by the development of tolerance to the drug, as well as the presentation of physical withdrawal symptoms when drug use ceases. Addiction and dependence often go hand in hand, but an individual may be dependent on a drug (such as caffeine) and not necessarily show signs of addiction. In turn, drugs and other activities can be addictive without producing a physical dependence. The risk of addiction is greater if drug use begins at an early age, if the individual is living in a stressful environment, or if there is a family history of addiction. Addiction is highly heritable, and studies in twins find amuch higher concordance among identical twins than among fraternal twins in the abuse of illicit drugs. From these studies, it is estimated that 60% to 80%of the differences in addiction rates between identical versus fraternal twins is due to genetic factors. This genetic influence is higher inmales than in females and differs somewhat between specific types of drugs. The genes that lead to the vulnerability for addiction in humans are currently unknown, and the genetics is likely to be complex, perhaps involvingmany different genes. The most well documented gene mutations that influence addiction vulnerability are the variants of the aldehyde (ALDH) and alcohol (ADH) dehydrogenase loci found primarily in Asian populations. These variants lead to the "flushing syndrome" in which the individual's skin becomes flush and they experience other unpleasant side effects after consuming alcohol. Because of these effects, these variants significantly reduce the risk for alcohol dependence and addiction. Whole genome association studies are currently being undertaken in various human populations to identify other genes that may be responsible for an increased or decreased vulnerability for addiction. One recent study conducted by Uhl and colleagues (2006) examined 639,401 single nucleotide polymorphisms (SNPs) in individuals that displayed heavy lifetime use of illegal substances versus control individuals who had no history of drug abuse. They identified SNPs in roughly 50 genes that were significantly associated with drug addiction in both European-American and African-American populations. These genes fall into many different functional categories, though many are associated with cell adhesion and communication. Similar whole genome scans are being conducted in mouse models of addiction to determine if there are overlaps between human studies and animal studies, which might help pinpoint the important genes in the addictive process.