First, there is the drug, which might or might not be addicting (hence the + or –), but for our discussion it is an addicting substance. Then there is the person who has a genetic basis that might or might not (hence the + and –) support drug taking. Lastly, there is the complexity of the environment, in which there might be drugs and various factors that might or might not support drug taking. Thus, the overall vulnerability can be high or low depending on each factor and how they add up or interact. On the right, the range of possible outcomes are listed. Treatment should address all of the factors.
Our Genes and Proteins After a person’s first exposure to a drug, his or her biological makeup plays a major role in determining whether he or she will become a drug abuser. Because a person’s biological makeup is determined by genes, there has been a focus of research on genes that are involved in drug abuse. Studies of genes have developed exponentially over the last couple of decades. Many of these studies rely on mutations that we carry and they can be identified by amazing, high-throughput technologies.
Tracking Genes Understanding genes, their mutations, and how they are used gives us an appreciation of how genetic studies are carried out in addiction and even in other diseases. Imagine your ancestors, many, many generations ago. You have many men and women in your ancestral tree and the further you go back in time, the more there are. Over time, mutations occur in various genes, and if they are not fatal, then they are passed on from generation to generation.
The genetic markers that are used in studies of heritability are often single nucleotide polymorphisms (SNPs). Genes consist of strings of molecular units called nucleotides. Nucleotides come in four varieties, which differ from each other only in the subunits known as bases. Each nucleotide is named after its base: adenine (A), thymine (T), cytosine (C), or guanine (G). At many locations in the human genome, the nucleotide string that makes up a particular gene is identical in everyone. That is , if you start at one end of the gene and count off the nucleotides in order along one of the two DNA strands, the result is the same— for example, AAGGGATCCAC.
At certain places along the string, however , some people have one nucleotide and others have a different one—for example, AAGGAATCCAC, instead of the more common sequence . Such a variation is a SNP ( (Adapted from http:// en.wikipedia.org/ wiki/ File:Dna-SNP.svg , accessed on November 23, 2010.)
A powerful study was carried out by Dr. George Uhl and his colleagues at the National Institute on Drug Abuse. They used an approach called genome-wide association studies ( see the next sidebar “ Genome-Wide Association Studies [GWAS] ), where the genes in drug users are compared to those in non-drug users or in low level users
After examining the genes in these populations, they found that 89 genes were associated with drug use. Uhl explained further that “unlike cystic fibrosis which is caused by a single (defective) gene, in addiction and a number of complex disorders, many different genes must act together with environmental factors to create the illness.
No single gene is likely to have a large effect by itself; it’s the combination of effects that produce... the problem.” 1 Many of these 89 genes were known to be associated with memory formation, receptors, and adherence of neurons to each other. It makes sense that those kinds of genes would be involved in drug dependence, which produces biochemical and functional changes in the brain.
Genome-Wide Association Studies (GWAS) GWAS is a powerful way to identify genes that are associated with traits or diseases . It depends on having a test population that has the trait of interest (such as drug taking) and a control population that does not have the trait. Then, all the genes in all of the subjects are characterized and the occurrence of genetic markers in the populations are compared. The genetic markers that are used are SNPs (see previous sidebar, “Tracking Genes”). Studies can look at hundreds of thousands of SNPs that occur among our approximately 30,000 genes by relatively rapid, computerized teckniques
The variations (SNPs) might or might not make a difference in the way a gene functions. (For example, two similar model cars but with different color are like SNPs where there is no difference in function. But the same model cars with very different sized engines might function differently.) So, SNPs don’t have to be functionally powerful; but they are good markers for studying the heritability of specific genes.
Scientists can take advantage of the SNP variations to discover associations between genes and critical traits, such as vulnerability to drug addiction . For example, if a certain SNP occurs more often in drug abusers than in non-drug abusers, then the gene that contains the SNP is said to be associated with, and possibly partly causing, drug addiction. (Adapted from “New Techniques Link 89 genes to Drug Dependence,” NIDA Notes, Vol. 22, September 2008.) There have been interesting new discoveries about the genes related to smoking and the vulnerability for nicotine addiction. As noted, nicotine works in the brain by stimulating receptors for acetylcholine, which are referred to as nicotinic cholinergic receptors. Nicotinic receptors are made up of five separate proteins that bundle together to form a functioning receptor. These proteins, or subunits, have been identified and studied
This information tells us that the influence of our genes on drug taking varies from person to person, and that each person has a different level of biological vulnerability. Most people exposed to addicting drugs do not become addicts. Data shows that the likelihood of addiction is partly due to hereditary factors— our genes. But environmental factors (for example, the availability of drugs, high stress, emotional problems , and peer pressure to use drugs) are essential. Although genetics might account for as much as 20– 40 percent of our vulnerability
It isn’t correct to blame just our genetics for our level of drug use. Psychological Problems Drug use in individuals is often associated with a variety of emotional problems such as depression, anxiety, schizophrenia, post-traumatic stress disorder (PTSD), and other complicated problems referred to as antisocial personality disorders and conduct disorders. In one study, between 21 and 32 percent of nicotine-dependent subjects had an additional mental health diagnosis.
An individual may suffer from both drug use and a mental health disorder. Sometimes, withdrawal or cessation of drug use can precipitate problems such as anxiety; in this instance, treating the mental problem can make drug addiction treatment more successful. Related to this, it has been suggested that at least some drug addicts begin using drugs to self-medicate and treat problems such as anxiety. This means that if you use addicting drugs, you might have a mental health problem in addition to the use of drugs. If you do, then dealing with that will reduce your vulnerability to drug taking.
Mental problems can weaken our resolve to deal with other issues (such as drug use) in our lives . They can distract and exhaust us, and possibly lead to self-medicating, which might be problematic. Although treating our ills is, of course, important, a doctor’s involvement is often needed, particularly when abusable drugs are involved. Temperament and Personality Traits Many studies show a correlation between personal temperament and drug use. For example, impulsivity, physical activity level, having difficulty sitting still, and the tendency to become emotionally upset have been correlated with higher drug use. On the other hand, having a more positive mood and a desire to be around people have been negatively correlated with drug use. Often, personality traits in adolescence correlate with higher drug use as adults. This is clearly an important topic and an active area of research.
. Because abused drugs in the brain are chemical signals, they are similar to neurotransmitters. But they are different from neurotransmitters in important ways. Neurotransmitters and the brain have co -evolved over eons of time, and they coexist quite peacefully. Neurotransmitters are beautifully regulated by the brain. When their levels are low, they are synthesized. When made, they are safely stored in vesicles. When needed, they are released from specific neurons. After they are released and stimulate receptors, their action is terminated by breakdown, diffusion, or reuptake.
Morphine,for example, disrupts normal neurotransmission is morphine, which is an opioid or opiate drug. Morphine stimulates receptors in the brain for the neurotransmitters enkephalins and endorphins. Morphine does not do anything to the uptake , diffusion, or metabolism of a neurotransmitter . Rather, it stimulates receptors . Actually, most drugs work by doing something to receptors, either stimulating them or inhibiting them. When the drug user injects or takes morphine orally, it goes from the blood to the brain where it stimulates the receptors that are there for endorphins and enkephalin. However, the brain does not have a way to remove or stop the action of morphine like it does for enkephalin and endorphin (which is by diffusion and breakdown by peptidases). Morphine is metabolized in the body, but the process is slow compared to the time for a natural neurotransmission event, so the time course of neurotransmission is greatly distorted by the the use of the drug.
Kuhar, Michael (2011-10-31). The Addicted Brain: Why We Abuse Drugs, Alcohol, and Nicotine (FT Press Science) (Kindle Locations 804-810). Pearson Education. Kindle Edition. K
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