“Preaddiction” construct and reward deficiency syndrome: genetic link via dopaminergic dysregulation

Abstract

From 1999-2020, over 932,000 Americans died from a drug overdose, and over 564,000 of those deaths involved opioids (1,2). Since 1999, practically every year, excluding 2018, has seen a record-setting number of deaths and overdoses (1-13). According to preliminary data from the Centers for Disease Control and Prevention's (CDC) National Center for Health Statistics (NCHS), there were approximately 100,306 drug overdose deaths in the United States (US) during a 12-month period that ended in April 2021, which is a 28.5% increase when compared to the 78,056 deaths that occurred during the same period the year before (3). This trend is particularly disturbing given the new drug czar's projection of the annual number of overdose deaths to reach 165,000 by 2025.Approximately 9.5 million Americans, aged 12 or older, misused opioids in 2020 (13). In addition, in 2020, approximately 2.5 million Americans, aged 12 or older, suffered from opioid use disorder (OUD), but only about 11% (278,000 individuals) received medication-assisted treatment (13). Untreated individuals are more likely to experience increased criminal activity, HIV infection, and mortality ( 14). Additionally, it is estimated that these individuals will cost society more than $500 billion annually (15). Hence, there is a need to revisit our pathophysiological conceptualizations and ensuing therapeutic approaches (16).