Impaired Reward System in Childhood Linked With Young Adult Opioid Use

adolescent taking pill, prescription, medication, opioid
A prospective longitudinal cohort study examined the prevalence of nonheroin opioid use and childhood risk factors associated with later opioid use.

Tobacco use and depression in childhood are key risk factors associated with young adult opioid use, according to research published in JAMA Pediatrics. Impaired reward system functioning may increase young adults’ vulnerability to opioid-associated euphoria.

Using data from the Great Smoky Mountains Study, a longitudinal representative cohort of children in 11 rural North Carolina counties, researchers conducted a prospective 23 longitudinal cohort study examining both the prevalence of nonheroin opioid use and which childhood risk factors may be associated with later opioid use.

A total of 1252 non-Hispanic white and American Indian participants were included (27% American Indian; 50% male). Participants between the ages 9 and 16 and their parents were interviewed up to 7 times via the Child and Adolescent Psychiatric Assessment; risk factors were reported across 6 domains. Assessments for nonheroin opioid use (any and weekly) and heroin use were also conducted at ages 19, 21, 25, and 30 using the Young Adult Psychiatric Assessment.

Cumulative lifetime estimates indicated that by age 30, 322 participants had used a nonheroin opioid (24.2%; 95% CI, 21.8-26.5); 155 used weekly (8.8%; 95% CI, 7.2-10.3), and 95 had used heroin (6.6%; 95% CI, 5.2-7.9).

Childhood risk factors were aggregated and divided into groups by no opioid use, any nonheroin opioid use, weekly nonheroin opioid use, and heroin use. Risk factors associated with at least 2 of 3 opioid-based outcomes included tobacco use, depressive or conduct disorders, peers exhibiting social deviance, parents with legal involvement, and elevated systemic inflammation. Childhood tobacco use, depressive disorders, and conduct disorders were associated with both nonheroin opioid and heroin use. Associations did not meaningfully vary by sex or race/ethnicity.

Final analytic models found that for any nonheroin opioid use, risk factors included tobacco use, cannabis use, depression, and male sex (odds ratios [ORs], 3.96, 3.28, 1.82, and 1.52, respectively). Risk factors for weekly nonheroin opioid use included tobacco use, depression, high C-reactive protein levels, and peers exhibiting social deviance (ORs, 5.89, 2.59, 2.25, and 2.17, respectively), while heroin use risk factors included depression, tobacco use, cannabis use, and male sex (ORs, 5.54, 3.64, 2.82, and 2.53, respectively).

Study limitations include not being able to distinguish between medical and nonmedical opioid use, the exclusion of black individuals due to a low sample size, and a nonexhaustive list of opioids included in the assessments to reflect those available on the market.

“Opioid-related premature mortality of young adults has skyrocketed. Although prescription practices have changed, no effective solution for the current epidemic or promising preventive measures against future opioid crises are in sight,” the researchers stated. “Our findings suggest strong opportunities for early prevention and intervention, including in primary care settings.”

“Known evidence-based prevention strategies could save lives, especially because mental health and substance use disorders are associated with opioid overdoses among the young,” the researchers concluded.


Shanahan L, Hill SN, Bechtiger L, et al. Prevalence and childhood precursors of opioid use in the early decades of life. Published online December 28, 2020. JAMA Pediatr. doi:10.1001/jamapediatrics.2020.5205