Stress Allostasis in Substance Use Disorders: Promise, Progress, and Emerging Priorities in Clinical Research

By: Gaylen E. Fronk, Sarah J. Sant’Ana, Jesse T. Kaye, John J. Curtin
Published in Annual Review of Clinical Psychology, 2020, 16:1. (Review in Advance, first posted online on February 10, 2020: Changes may still occur before final publication.)

The goal of our review paper was to distill lessons from basic stress biology research and use them as a lens through which to evaluate our progress studying the relationship between stress and substance use disorders (SUDs) in humans. Specifically, we critically evaluated two theses that are central to SUD etiology: Stressors cause drug use, and chronic drug use alters stress responding. We also considered our success to date translating research in this area into stress-focused treatment for SUDs.

Figure by Peter Shireman

We limited our review to studies that manipulated or measured explicit stressors, used well-established measures of stress responding, and had sufficient statistical power to produce credible findings.

In general, the qualify and rigor of existing clinical research in this area warrant much humbler, more cautious conclusions than previous reviews regarding what we know and do not yet know about the roles of stressors and stress responding in SUDs. Here’s what we DO know:

  • Basic stress research has clearly established that stressor characteristics and context matter, but these factors are largely neglected in clinical SUD research
  • Feedback among biological stress systems dictates we avoid collapsing into a single stress reactivity construct
  • Stressors cause craving in the laboratory, but at this point there is insufficient evidence of stressor-induced use in humans
  • In situ research has only just begun to measure stressful events explicitly, but this methodology holds high promise for these questions
  • Individuals with SUD display decreased peripheral stress responding, increased central stress responding (possibly selective to unpredictable stressors), and unchanged subjective distress compared to healthy controls
  • Acute drug deprivation does not affect stress responding
  • Medications that target biological stress systems (e.g., CRH, NE medications) do not offer clinical benefit for individuals with SUDs.
  • Psychosocial interventions that appear to target stress mechanisms improve SUD clinical outcomes, but mechanisms have yet to be confirmed

Future research should employ rigorous and transparent methodology to refine in situ work, examine stressor characteristics and context, explore individual differences systematically, and advance stress-relevant treatment. We’re excited for these next steps!