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  Disease summary:

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

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

    
    
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    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.

  
  
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  Differential diagnosis:

  
  
  
  
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    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.

    
    
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    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.

    
    
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    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.

    
    
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    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.

    
    
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    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.

  
  
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  Monogenic forms:

  
  
  
  
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    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.

  
  
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  Family history:

  
  
  
  
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    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.

  
  
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  Twin studies:

  
  
  
  
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    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.

  
  
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  Environmental factors:

  
  
  
  
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    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 associated with increased risk for a range of neuropsychiatric disorders as well as with, in most cases, a normal outcome.

  
  
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  Pharmacogenomics:

  
  
  
  
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    Despite the progress made in the prevention and treatment of drug addiction, available pharmacologic therapies are only effective in a fraction of addicted patients. The wide individual variation in therapeutic response has prompted a growing interest in the role that inherited factors play in the efficacy of various pharmacotherapies (Table 139-1).

  
  
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  Genome-wide associations:

  
  
  
  
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    Genes that affect addiction vulnerability have recently begun to emerge from large family and population studies (Table 139-2). However, all of the genes identified thus far only represent a small fraction of the overall genetic risk for addiction.

Diagnostic Criteria for Drug Addiction

According to DSM-IV criteria, drug dependence is diagnosed by three or more of the following, occurring at any time during the same 12-month period:

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   Tolerance—defined by either of the following

   
   
   
   
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      A need for markedly increased amounts of the substance to achieve intoxication or the desired effect or

      
      

      Markedly diminished effect with the continued use of the same amount of the substance

   
   

   Withdrawal—as manifested by either of the following

   
   
   
   
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      The characteristic withdrawal syndrome for the substance or

      
      

      The same (or closely related) substance is taken to relieve or avoid withdrawal symptoms

   
   

   The substance is often taken in larger amounts or over a longer period than intended.

   
   

   There is a persistent desire or unsuccessful efforts to cut down or control substance use.

   
   

   A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects.

   
   

   Important social, occupational, or recreational activities are given up or reduced because of substance use.

   
   

   Substance use is continued despite knowledge of having a persistent physical or psychological problem that is likely to have been caused or exacerbated by the substance.

Clinical Characteristics

Acute Intoxication

Addictive drugs affect multiple biologic systems, and their use can result in effects ranging from mild euphoria to psychotic episodes, respiratory or cardiovascular distress, accidental injury, or death. Signs and symptoms of drug use vary depending on the type and amount of drug used. Some examples are listed below:

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  Alcohol: Alcohol is a central nervous system (CNS) depressant. Its effects range from mildly impaired co-ordination and euphoria, marked ataxia, nausea or vomiting, and memory lapse, to severe respiratory failure, coma, and death.

  
  
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  Nicotine: Nicotine is a CNS stimulant characterized by euphoria, increased attention, and mild analgesia. Initial exposures can induce nausea, but this shows tolerance with repeated administration.

  
  
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  Marijuana: Marijuana generally causes mild euphoria, analgesia, and increased appetite. Other effects include impaired perception and motor skills, decreased short-term memory, anxiety, paranoia, and mild hallucinations.

  
  
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  Opiates: Opiates are commonly used clinically for their strong analgesic properties. Opiate overdose is characterized by respiratory depression, pinpoint pupils, decreased level of consciousness, or coma.

  
  
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  Stimulants: Stimulants such as cocaine, amphetamine, and methamphetamine cause hyperactivity and euphoria. They can also lead to fatal arrhythmias, seizures, or stroke and, after chronic administration, may induce paranoia.

  
  
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  Psychotomimetics: Phencyclidine (PCP) and related drugs (eg, ketamine) induce hallucinations and delusions as well as nausea or vomiting, seizures, coma, and death (often from accidental injury or suicide). Its sedative effects can interact with other CNS depressants, such as alcohol and benzodiazepines, leading to coma or accidental overdose.

Withdrawal