Foregrounding the increasing global crisis of opioids as the “leading cause of deaths in fatal overdoses,” the World Drug Report 2023, published by the United Nations Office on Drugs and Crime (UNODC), mentioned that in 2021 more than 80,000 people died due to opioid overdose in the United States of America. The Centers for Disease Control and Prevention (CDC), the national public health protection agency in the United States, has reported that “the predicted number of drug overdose deaths showed an increase of 0.5% from the 12 months ending in December 2021 to the 12 months ending in December 2022, from 109,179 to 179,680” (“Provisional Data”). Although the trajectory of opioid use disorders (OUDs) has affected different sociodemographic groups in the country since its first wave in the 1990s, teenagers in poverty-stricken rural areas are more vulnerable to such addiction (Keyes et al.). Poor parental guidance, impoverishment, troubled childhoods, detrimental familial structure, scarce opportunities, and accessibility to opioids are often considered to be the primary risk factors for unprivileged teenagers to develop a psychic reliance on opioids for engendering a perpetual sense of contentment. According to the incentive sensitization theory, the persistent desire to transcend physical and psychical limitations for a sense of relief, triggered by chronic drug misuse, often evokes a sense of “wanting” or incentive salience, a compulsive inclination towards drug-associated stimuli (Berridge and Robinson, “Drug Addiction” 22). This intense desire of “wanting” often generates a perpetual sensitization of the mesolimbic systems in the brain which is also activated by mental representations of drug-associated cues (Robinson and Berridge 3139). Focusing on drug-induced changes in the brain such as hypersensitization and neuroadaptation, this study analyzes Barbara Kingsolver’s Demon Copperhead, a modern reimagining of David Copperfield by Charles Dickens. The selected text addresses primarily some pertinent socio-political crises, such as the poor foster care system, poverty, and the engrossing opioid endemic in Southern Appalachia. However, this study attempts to analyze the precarious state of some characters, who become addicted to opioids seeking recognition from peer groups and perpetual psychic stability, in the selected text from a neuropsychological perspective.