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Table of Contents > Genomics > Genes linked to drug addiction Print

Genes linked to drug addiction

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Related terms
Background
Methods
Research
Implications
Limitations
Safety
Future research
Author information
Bibliography

Related Terms
  • Abuse, abusers, addiction, alcohol, alcohol dehydrogenase (ADH), alcohol use, behavior, catechol-O-methyltransferase (COMT), chromosomes, cocaine, dependence, desensitization, disorder, dopamine, drug use, expression, factors, genes, genetics, genetics counseling, glutamate, heroin, inheritance, marijuana, microarray, mood, mu-opioid (?-opioid) receptor (MOR), nicotine, opiates, opioid, pharmacogenetics, prescription drugs, prodynorphin (PDYN), protein, proteomics, recreational drugs, stimulants, substance abuse, tolerance.

Background
  • Drug addiction, also known as substance abuse, occurs when individuals use drugs for recreational purposes. Abused drugs may be legal or illegal. Drugs available by prescription or over the counter (available without a prescription) are considered legal, but it is illegal to abuse these drugs.
  • Commonly abused drugs include alcohol, central nervous system (CNS) stimulants (such as nicotine, caffeine, and methamphetamine), cocaine, opiates (such as morphine and heroin), benzodiazepines, and marijuana. Drugs can be taken by mouth, injected into a vein, snorted through the nose, applied to the skin, dropped in the eye, inhaled, or smoked.
  • When individuals abuse drugs, they are at risk of becoming physically (chemically) dependent. People who have difficulty dealing with emotional issues may abuse drugs as a way to resolve their problems and thereby become emotionally dependent. Over time, individuals begin to develop a tolerance for the drugs. As a result, they may start to use the drug more frequently and/or in larger amounts.
  • When an addictive substance is discontinued or taken away, withdrawal can occur. Because the body is not receiving the drugs or alcohol it has become used to getting, individuals may experience uncomfortable physical or mental changes including nausea, sweating, shakiness, and anxiety.
  • Drug addiction can cause compulsive drug cravings. Severe addictions may cause individuals to seek drugs, even at the expense of jobs, families, and other important parts of their lives.
  • Drug addiction involves positive and/or negative effects on mood and behavior. People may feel euphoria (or a high) or negative effects such as paranoia and anxiety after short-term use of drugs. Long-term use of drugs may lead to changes in mental health such as depression, aggression, and hallucinations.
  • Drug addiction has been linked to many factors, including the environment, genetics, and personality traits. These factors may determine why some people start using drugs and how easily they may become addicted. These factors may also determine how effective treatment is and the potential for relapse or recurrence of drug use.
  • While it is known that genetics play a role in substance abuse, research is still limited. Identifying genes that are linked to addiction can be very challenging due to the genetic diversity within and among different populations.

Methods
  • To identify the genes and chromosome regions involved in addiction, various technologies and methods have been used.
  • Hypothesis testing of single genes is a statistical procedure used to determine if genes are expressed differently. Expression is when the inheritable part of a gene, such as the DNA sequence, is made into a functional gene product, such as protein or RNA.
  • Genomic and proteomic technologies, such as microarray analysis, may be used to identify candidate genes and protein expression level changes during different stages of addiction.
  • In microarray analysis, probes that represent various genes are placed on a glass or plastic slide (also called a gene chip). The genes or proteins that are expressed by cells in various biological stages are then identified by the chip in a pattern to be used in biochemical or genetic analysis.
  • Proteomics is a branch of biotechnology that involves the genetic analysis of the proteins produced by genes during different biological stages or responses. Proteomics may be used to identify protein expression level changes during different stages of addiction.
  • Association studies may be used to compare genetic markers, or pieces of DNA that differ among individuals, in those who have the disease (drug addiction) and in those who do not have the disease.
  • Linkage studies are used to examine the inheritance of genetic markers in families. These studies may be used to link inherited genes with different traits, such as addiction. Linkage studies may also help determine the risks of inheriting a genetic marker for addiction.

Research
  • General: There are as many as 1,500 human genes that may be linked to addiction, but not all of these genes have supportive or strong evidence of their association. Only about 400 genes linked to addiction are backed by strong scientific evidence.
  • These genes may be categorized by the drug or substance to which they are linked, including genes related to alcohol addiction, cocaine addiction, opioid addiction, and nicotine addiction.
  • Genes linked to alcohol addiction: Evidence from studies have identified a link between a marker found on chromosome 11 and alcohol abuse. There may also be a region on chromosomes 1, 4, and 7 that links to this particular addiction. Alcohol dehydrogenase (ADH) is the enzyme involved in the breakdown of alcohol, and the ADH gene (particularly the ADH2 and ADH3 variants) may be involved in alcohol dependence. The genes in the dopamine, GABA, opiate, and serotonin systems may also be involved in alcohol addiction.
  • Genes linked to drug addiction: Dopamine, which is responsible for transferring nerve impulses, is perhaps the most well studied subject in addiction research. The motivation to seek reward is linked to dopamine, and some abused substances have been shown to increase dopamine levels. The dopamine receptors D2, D3, and D4 are most strongly linked with reward. Research suggests that lower levels of D2 receptors may increase the potential for drug abuse. It is not known if the D3 receptor is involved in drug addiction, but this receptor has been studied in individuals addicted to cocaine. The D4 receptor is most likely involved in the novelty-seeking aspect of drug use. Novelty seeking individuals are those who are impulsive and eager to take on new interests but may quickly become bored. However, environmental factors and gender differences (men are more likely to be impulsive than women) also need to be taken into account. Studies have shown that the D4 receptor may also be involved in heroin dependence.
  • The mu-opioid (?-opioid) receptor, also known as MOR, is also involved in reward-seeking behavior. In studies, animals without the MOR gene show less interest for opiate and stimulants and do not self-administer heroin or cocaine if they are provided. Thus, the MOR gene may determine the motivation to use drugs.
  • On the other hand, the prodynorphin (PDYN) opioid system, particularly the PDYN gene, may be involved with the negative effects of drug use such as paranoia and anxiety. Studies suggest that abnormal prodynorphin systems may increase the potential for drug addiction. However, since the mechanism of this system in drug addiction is not well understood, further research is necessary to determine a clearer association.
  • Besides reward and novelty-seeking behavior, drug use is also associated with inhibition control (or self-control). Genes involved with inhibition may explain the inability of drug abusers to stop their destructive behavior. Catechol-O-methyltransferase (COMT), which is involved in the breakdown of dopamine, has been associated with cognitive control in addiction. Some studies have shown that heroin addicts and multiple-substance abusers have lower dopamine levels and lower cognitive control. However, the mechanism of COMT in drug addiction is not well understood.
  • The glutamate (excitatory neurotransmitter that transfers nerve impulses) system may also play a role in inhibitory control and reinforcement. Abnormalities in this system may result in repeated drug-seeking behavior and relapse or recurrence of the disease. The three genes involved in this system are HOMER1, HOMER2, and HOMER3. The HOMER1 gene has been linked to cocaine addiction, but has not been well-studied in opioid abuse.

Implications
  • By identifying the genes associated with addiction, researchers may better understand the biological pathways involved in substance abuse. Understanding the biology behind addiction may lead to new strategies in the treatment or prevention of drug abuse.
  • Linking genes to drug addiction may also provide ways to optimize treatment plans for patients. Type, dose, and duration of treatment may be adjusted to suit individual patients and their genotypes, possibly leading to better outcomes.

Limitations
  • There are as many as 1,500 human genes that may be linked to addiction, but not all of these genes have supportive or strong evidence of their association. Only about 400 genes linked to addiction are backed by strong scientific evidence.
  • It is still difficult to distinguish the specific genes that are associated with addiction and abuse. Therefore, further research is needed, especially studies that involve different populations. Tools and technologies are continually made and modified to identify genes and their association to addiction.

Safety




Future research
  • Studies on genes and drug addiction are limited. It is still difficult to distinguish the specific genes that are associated with addiction and abuse. Therefore, further research is needed, especially studies that involve different populations. Tools and technologies are continually made and modified to identify genes and their association to addiction.
  • Physicians may need further training in clinical genetics and genetic counseling to better educate their patients and also to enforce new treatment strategies that best suit each individual.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Ball D. Addiction science and its genetics. Addiction. 2008 Mar;103(3):360-7.
  2. Hurd YL. Perspectives on current directions in the neurobiology of addiction disorders relevant to genetic risk factors. CNS Spectr. 2006 Nov;11(11):855-62.
  3. Li CY, Mao X, Wei L. Genes and (common) pathways underlying drug addiction. PLoS Comput Biol. 2008 Jan; 4(1): 28-34.
  4. Mayer P, Hollt V. Genetic disposition to addictive disorders - current knowledge and future perspectives. Current Opinion in Pharmacology. 2005 Feb; 5(1): 4-8.
  5. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2008. Accessed March 12, 2008.
  6. Rhodes JS, Crabbe JC. Gene expression induced by drugs of abuse. Curr Opin Pharmacol. 2005 Feb;5(1):26-33.
  7. Rosenthal RN, Levounis P. "Polysubstance Use." In: Clinical Textbook of Addictive Disorders. 3rd ed. Edited by Richard J. Frances and Sheldon I. Miller. New York, New York: Guilford Press, 2005: 245-270.
  8. Shields AE, Lerman C. Anticipating Clinical Integration of Pharmacogenetic Treatment Strategies for Addiction: Are Primary Care Physicians Ready? Clin Pharmacol Ther. 2008 Mar 5; 83(4): 1-5.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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