Effects of opioid- and non-opioid analgesics on responses to psychosocial stress in humans

Abstract

Both preclinical and clinical evidence suggests that the endogenous opioid system is involved in responses to stress. For example, in animal models opioid agonists reduce isolation distress whereas opioid antagonists increase isolation distress. We recently reported that the mixed mu agonist and kappa antagonist buprenorphine dampened responses to acute psychosocial stress in humans. Now we extend this to study the effects of a pure mu-opioid agonist, hydromorphone, and a non-opioid analgesic, acetaminophen, on response to social stress. We compared the effect of hydromorphone (2 and 4 mg), acetaminophen (1000 mg) to a placebo using a between subject design. Healthy adult volunteers were randomly assigned to receive placebo (N = 13), 2 mg hydromorphone (N = 12), 4 mg hydromorphone (N = 12), or 1000 mg acetaminophen (paracetamol; N = 13) under double-blind conditions before undergoing a stress task or a control task on two separate sessions. The stress task, consisting of a standardized speaking task and the non-stressful control task were presented in counterbalanced order. Dependent measures included mood ratings, subjective appraisal of the stress (or no-stress) task, salivary cortisol, pupil diameter, heart rate, and blood pressure. The stress task produced its expected increase in heart rate, blood pressure, salivary cortisol, pupil diameter, and subjective ratings of anxiety and negative mood. Hydromorphone dose-dependently dampened cortisol responses to stress, and decreased ratings of how "challenging" participants found the task. Acetaminophen did not affect physiological responses, but, like hydromorphone, decreased ratings of how "challenging" the task was. The hydromorphone results support the idea that the mu-opioid system is involved in physiological responses to acute stress in humans, in line with results from preclinical studies. The non-opioid analgesic acetaminophen did not dampen physiological responses, but did reduce some components of psychological stress. It remains to be determined how both opioid and non-opioid systems mediate the complex physiological and psychological responses to social stress.

Keywords: Acetaminophen; Hydromorphone; Opioids; Stress; Trier Social Stress Test.

Conflict of interest statement

Disclosure

The authors report no conflicts of interest.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Figure 1. Time-course of subjective drug effects

Ratings of “feel drug” throughout the non -stressful control session. Shaded area indicates the time during which the task took place. Bars depict mean ± SEM.

Figure 2. Drug effects on ratings of anxiety as measured by the POMS during a) the non-stressful control session and b) the TSST session

Shaded area indicates the time during which the TSST took place. Bars depict mean ± SEM.

Figure 3. Drug effects on heart rate responses during a) the non-stressful control session and b) the TSST session

Shaded area indicates the time during which the TSST took place. Bars depict mean ± SEM.

Figure 4. Drug effects on cortisol during a) the non-stressful control session and b) the TSST session

Shaded area indicates the time during which the TSST took place. Bars depict mean ± SEM.