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. Author manuscript; available in PMC: 2019 May 13.
Published in final edited form as: Trends Mol Med. 2018 Jan 25;24(2):173–186. doi: 10.1016/j.molmed.2017.12.010

Table 2. Stress Response Disruptions Implicated in SUD Risk and in High Relapse Risk and Treatment Failure:

These measures may serve as potential biomarkers in acute, binge, and chronic/relapse use phases of SUDs and potential neurobiological targets for treatment development.

Acute Binge Chronic/Relapse Treatment Targets

Increase in Cortisol Response


Increase in ACTH Response
Decreases in Cortisol


Decreases in ACTH		 High Basal Cortisol
Blunted Phasic Cortisol

High Basal ACTH

Blunted Phasic ACTH
High Cortisol/ACTH Ratio as Relapse Predictor		 Pexacerfont
Mifepristone
Naltrexone
Neuroactive Steroids
Progesterone
Increase in HR Response Blunted Phasic HR High Basal HR
Blunted Phasic HR
Blunted HR Variability		 Doxazosin
Prazosin
vmPFC Activation VmPFC Hypoactivity in Stress and Cue States VmPFC Hyperactivity in Neutral States Guanfacine
Progesterone
graphic file with name nihms-1027249-t0002.jpg

ACTH: adrenocorticotropic hormone; CRF: corticotropin-releasing factor; HR: heart rate; vmPFC: ventromedial prefrontal cortex. Treatment Targets: Pexacerfont- CRF1 receptor antagonist [84]; Mifepristone- glucocorticoid receptor antagonist [86]; Naltrexone-opioid receptor antagonist [83]; Neuroactive Steroids- GABAA receptor agonists [91]; Progesterone [90]; Doxazosin- alpha-1 adrenergic antagonist [88]; Prazosin- alpha-1 adrenergic antagonist [87]; Guanfacine- alpha-2 receptor antagonist [89].