Figure 1.

Conceptual model of how cortisol is implicated for substance use progressions.

A generalized progression from behavioral risk to initiation, through increasing use to problematic use, and after quit attempts, withdrawal and relapse is depicted in order to illustrate where key theories and mechanisms are hypothesized to explain cortisol-substance use associations. Solid arrows depict predicted associations whereby cortisol would predict substance use phenotypes. Hashed arrows depict predicted associations whereby substance use would predict cortisol levels or changes. Specific theories or mechanisms are named within each box in bold text. Italiziced text within boxes describe predictions or findings of cortisol unless explicitly about cortisol. Changes in gene expression are depicted in a hashed box, as they are expected to impact the predicted associations depicted as passing through the hashed box. MAPK = mitogen-activated protein kinase pathway; GPCR = G-protein-coupled receptor pathways; DA = dopamine; PFC = prefrontal cortex; SU = substance use.