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Drug addiction is a chronic disease that is characterized by loss of control, cravings, and compulsive use despite negative consequences. As a neuropsychiatric disease, addiction is conceptualized as a cycle of binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. The stages of the cycle are directed by activity and neuroadaptations that occur at different regions of the brain with repeated drug use. As reviewed in this chapter, key structures involved in each of these stages include the ventral tegmental area (VTA) in binge/intoxication, extended amygdala (including the bed of stria terminalis, nucleus accumbens, and amygdala) in withdrawal/negative affect and craving, and orbitofrontal cortex, basolateral amygdala, and hippocampus in preoccupation/anticipation.1

The transition to addiction involves changes in the mesolimbic dopamine system, hypothalamic pituitary axis (HPA), and other stress systems (corticotropin-releasing factor, norepinephrine, vasopressin, dynorphin), as well as dysregulation of anti-stress systems (neuropeptide Y, nociceptin), prefrontal cortex (PFC), and the extended amygdala. These changes contribute to an increase in reward threshold, heightened sensitivity to drug rewards versus nondrug rewards, decreased ability to feel pleasure in everyday activities, increased stress reactivity, and a decreased capacity for decision making and self-regulation associated with the compulsive nature of use in addiction.2

Treatment of drug addiction involves using evidence-based medications to help restore healthy brain function, while utilizing behavioral therapies to improve distress intolerance, coping skills, self-compassion, and enrichment of social relationships.


Genetic, social, and environmental factors contribute to an individual’s susceptibility to addiction. Family history, presence of comorbid mental illness, history of trauma, and early exposure to drug use are factors that increase the risk for development of substance use disorders (SUD). Individuals who have a mental illness, such as major depressive disorder, are more likely to have comorbid SUD, and vice versa. Studies have shown that the co-occurring SUD and psychiatric disorders can worsen the prognosis for each disorder.3

There are several resources that evaluate the impact of SUD on individuals and their communities. Nationally, the annual cost of substance use related to crime, lost work, and health care exceeds $740 billion.4 The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) is a cross-sectional study based on a nationally representative sample of the civilian noninstitutionalized population in the United States aged 18 and older sponsored by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). This study is meant to assess the prevalence of alcohol use disorder (AUD) and associated disease in the surveyed population. The results of 2016 showed a prevalence of 12 month and lifetime drug use disorders of 3.9% and 9.9%, respectively.5

Started in 1975, the Monitoring the Future (MTF) study is a survey study that explores attitudes (perceived risk, disapproval, and availability of drugs) and drug use among 8th, 10th, and 12th graders in over 380 public and private schools in the United States.6


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