Opioids and non-opioid analgesics affect different types of stress

Mu-opioids and non-opioid analgesics appear to differentially affect the psychological and physiological components of psychosocial stress, according to a recent study funded by NIDA, NIGMS, and NIMH.

In a between-subject design, healthy young adults (18-40 y) were randomly assigned to receive either 2 or 4 mg of hydromorphone (mu-opioid analgesic), 1000 mg of acetaminophen (non-opioid analgesic), or placebo and were tested in the Trier Social Stress Test (TSST) and a non-stressful control task (NSCT). Physiological responses to stress included heart rate, blood pressure, salivary cortisol and pupillometry, and psychological measures included subjective reports of mood and stress.

TSST successfully increased all measures of physiological stress and increased anxiety and negative mood compared to the control task. Hydromorphone (4 mg) dose dependently decreased cortisol stress response, but acetaminophen did not. Both hydromorphone and acetaminophen reduced ratings of how challenging participants found the task. This suggests acetaminophen, the non-opioid analgesic, affects psychological responses to stress, not physiological, whereas hydromorphone affects both. Only the mu-opioid system was involved with physiological stress responses in humans, which builds upon similar results in preclinical studies. The results here contribute a greater understanding of the role of opioid and non-opioid systems in the complex physiological and psychological responses to social stress.