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Joseph A. Hirsch
Steven Mandel
Kurt T. Hegmann
Alexandra G. Stratyner
Stuart Gitlow
James B. Talmage
, and
Christopher R. Brigham


There is an epidemic of drug overdose–related fatalities. Recent data indicate that the age-adjusted death rate from overdoses nearly quintupled over a 20-year period (2001-2021) to 32.4 per 100,000. More than 70% of these fatalities were caused by opioid overdose, especially the synthetic drug, fentanyl. Despite an increase in substance abuse and dependency treatment, mortality and morbidity associated with opioid, cocaine, psychostimulant, benzodiazepine, alcohol, and tobacco use disorders continue to rise. To better understand the factors contributing to this crisis, the multifaceted phenomenon of drug addiction is explored. The controversial chronic, relapsing “disease of the brain” model, which emphasizes the role of the neurotransmitter dopamine, the ventral tegmental area, and the nucleus accumbens, is critically considered. In addition, more expansive neurobiological models that include a host of other neurotransmitters, brain regions, and cognitive processes, as well as classical and operant conditioning and social learning theory to help better understand compulsive drug taking, tolerance, risk-taking, and relapse, were examined. For this, the roles of genetics and epigenetics vs individual agency in drug addiction were considered. The economic and occupational consequences borne both individually and societally are enormous. Ultimately, whether the presence of drug addiction satisfies the criteria for a disability remains a conundrum, especially from the perspectives of financial support (eg, Social Security, private insurance companies) vs regulation (eg, licensing agencies).

in AMA Guides® Newsletter