Neurobiology of Addiction

Excerpt

Over the past 2 decades, addiction has been at the forefront of American society, media, and politics through coverage of the opioid epidemic. The most recent data from the Centers for Disease Control and Prevention (CDC) reports that 645,000 Americans died from opioid overdose between 1999-2021. Historically, the stigma of addiction being driven by character flaws and ethical shortcomings has been a significant barrier to addiction treatment. Advancements in scientific research have proven this historical perspective to be categorically false and potentially harmful by fostering negative attitudes toward those seeking help for addictive disorders.

Contemporary models of addiction utilize a neurobiological framework for the onset, development, and maintenance of an addiction. This approach defines addiction as a chronic and relapsing disorder marked by specific neuroadaptations predisposing an individual to pursue substances irrespective of potential consequences. Furthermore, these neuroadaptations occur in the 3 distinct neurobiological stages of intoxication/binge, withdrawal/negative affect, and preoccupation/anticipation. The focal regions of the brain involved with these stages in respective order are the basal ganglia, the extended amygdala, and the prefrontal cortex.

During the binge/intoxication stage, dopaminergic firing in the basal ganglia increases for substance-associated cues while diminishing for the substance, also known as incentive salience. In the withdrawal/negative affect stage, the extended amygdala activates stress systems in the brain, leading to withdrawal symptoms and a diminished baseline level of pleasure. During the preoccupation/anticipation stage, executive control systems in the prefrontal cortex are hijacked, presenting as diminished impulse control, executive planning, and emotional regulation. Cravings are a part of the third stage of this model and predispose the individual to repeat the cycle. Notably, specific elements of nature (genetic) and nurture (epigenetic) predispose an individual to the addiction cycle.

Translating this 3-stage neurobiological framework into medical practice is a goal of clinicians. One tool that aids this translation at the bedside is the Addictions Neuroclinical Assessment (ANA). This clinical instrument developed by the National Institute of Alcohol Abuse and Alcoholism (NIAAA) translates the 3 neurobiological stages of addiction into 3 neurofunctional domains: incentive salience, negative emotionality, and executive dysfunction. Utilizing the ANA allows clinicians to employ targeted treatments for specific clinical presentations and ideally lessen the frequently negative attitudes of healthcare providers treating patients with addictive disorders.