139: Genetics of Drug Addiction

Key Points

• Disease summary:

  • Drug addiction (termed as substance dependence or drug dependence by DSM-IV) is a complex neurobiologic disease characterized by genetic, psychosocial, and environmental factors.

  • Drug addiction is considered to be a maladaptive pattern of drug use that leads to clinically significant impairment or distress.

  • Addictive drugs are characterized by their ability to produce, after acute exposure, euphoria, a positive emotional state that motivates users to take the drug repeatedly. Addictive drugs include alcohol, nicotine, marijuana, opiates (eg, heroin, OxyContin), stimulants (cocaine, amphetamine, methamphetamine), psychotomimetics (eg, phencyclidine [PCP]), 3,4-methylenedioxymethamphetamine [MDMA or “ecstasy”]), etc.

• Differential diagnosis:

  • Drug abuse: In comparison with drug addiction, this is a milder disorder, in which the individual chooses to use a drug in spite of illegal, unsafe consequences, or inappropriateness of the drugging experience. This differs from drug addiction, which is characterized by impaired control over drug use.

  • Physical or physiologic dependence: This is an adaptive physiologic state that occurs with regular or prolonged drug use, and results in a characteristic withdrawal syndrome (characterized by a range of physical or psychological symptoms) when drug intake is terminated. Physical or physiologic dependence can exist in the absence of drug addiction.

  • Tolerance: This describes the diminished response that occurs with repeated drug use, such that larger doses of the drug are required to achieve the same effect. Tolerance can exist in the absence of drug addiction.

  • Sensitization: This is the opposite of tolerance, where repeated exposure to a constant dose of a drug elicits greater responses. Repeated exposure to a given drug can simultaneously produce tolerance and sensitization to its varying effects.

  • Pseudoaddiction: This represents patient behaviors that may occur when pain is not being adequately treated. Such patients may exhibit “drug seeking” behaviors or resort to taking illegal drugs. In contrast to true addiction, pseudoaddiction stops once the patient’s pain is effectively controlled.

• Monogenic forms:

  • Genetic studies have failed to support single-gene models for the inheritance of addiction vulnerability. Addiction is a complex disorder that receives contributions from allelic variations in multiple genes.

• Family history:

  • Drug addiction vulnerability is familial. Indeed, genetic factors contribute to 40% to 60% of the overall vulnerability to drug addiction, while environmental factors provide the remainder.

• Twin studies:

  • Twin studies have shown a higher concordance rate for monozygotic twins in tobacco, alcohol, and other drug addictions. Twin data support the idea that much of the genetic vulnerability to the abuse of different addictive substances is shared. Although some elements of addiction vulnerability may be specific to particular substances, most genetic influences are common to different addictive substances.

• Environmental factors:

  • Environmental factors that contribute to addiction vulnerability have been identified in a number of epidemiologic studies. Shared and unique environmental factors contribute significantly to the risk for lifetime drug addiction, accounting for 28% to 38% of the phenotypic variance. Nonetheless, some individuals avoid addiction even in environments rich in addictive drugs. Moreover, none of these environmental influences is specific, as each is ...