Background. The biological processes linking chronic cannabis use and environmental tobacco smoke (ETS) exposure with poor health outcomes are not well understood. Study 1 examines the effect of cannabis use on hypothalamic-pituitary-adrenal (HPA)-axis activity, sympathetic nervous system (SNS) activity, and HPA-ANS coordination across a social evaluative stress task. Study 2 expands these findings by assessing HPA and ANS reactivity as moderators influencing the association between cannabis use and symptoms of depression and anxiety. Finally, Study 3 investigates inflammation as a mediator explaining the association between early childhood ETS exposure and adolescent behavior problems. Method. In Study 1 and 2, chronic cannabis users and non-users (N=75) underwent a standardized social evaluative stress task and provided saliva samples before, and 5, 20, and 40 minutes after the task. Samples were assayed for salivary cortisol and alpha amylase as indices of HPA and SNS activity, respectively. Symptoms of depression and anxiety were measured using self-report. Study 3 used data collected from a longitudinal birth cohort study of 1,292 children from low-income rural communities. Early childhood ETS exposure was measured using cotinine concentrations assayed from saliva samples collected at 6, 15, 24, 48, and 90 months of age. Inflammation was measured using salivary C-reactive protein, interleuikin-6, interleukin-1, and tumor necrosis factor-alpha assayed from samples collected at 90 months. Adolescent behavior problems were measured using primary caregiver-reported hyperactivity/impulsivity, conduct problems, emotional symptoms, peer problems, and prosocial relationship problems at 154 months.
Results. Findings showed that: (1) chronic cannabis users exhibited attenuated HPA-axis activity across a psychosocial stress task and quicker SNS recovery, relative to non-users; (2) among cannabis users, but not non-users, there was an association between HPA-axis activity and symptoms of depression and anxiety; and (3) higher levels of early childhood ETS exposure predicted higher levels of systemic and oral inflammation at 90 months as well as externalizing behavior problems in early adolescence.
Conclusion. Taken together, these studies provide a better understanding of neuroendocrine and immune processes affected by cannabis use and ETS exposure as well as multisystem processes that may also underlie health outcomes related to cannabis use and ETS exposure.