| Summary: | Opioids are prescribed medically to reduce pain, but many nonmedical opioid users claim to use these drugs to alleviate stress and negative mood, and in animal models, opioids decrease indices of separation distress and behavioral responses to threatening stimuli. Perhaps unsurprisingly, given the effects of exogenous opioids, the endogenous opioid system plays an important role in emotion processing. However, beyond self-report, relatively few studies have examined the effects of opioid drugs on behavioral or physiological responses to affective stimuli in humans. The goal of this project is to examine how opioid drugs affect emotional responses in healthy human volunteers, through four separate studies, the results of which are presented here. Each was conducted in a controlled laboratory setting with healthy volunteers, using sensitive behavioral tasks and physiological measures, and double-blind drug administration. Study 1 reports that the mu-opioid partial agonist and kappa antagonist buprenorphine dampens responses to psychosocial stress. Study 2 investigates the behavioral mechanisms underlying these effects, reporting that buprenorphine reduces perception of simulated social rejection and attention to fearful facial expressions, while increasing ratings of positivity of images with social content. Study 3 assess the effects of the nonspecific opioid antagonist naltrexone on similar emotion processing tasks, finding that naltrexone increases visual attention to emotional faces, and reduces recognition of negative facial expressions. Finally, Study 4 assesses the effects of the pure mu agonist hydromorphone on responses to psychosocial stress, as compared to placebo and the non-opioid analgesic, acetaminophen, reporting that like buprenorphine, hydromorphone dampens cortisol responses to stress, but unlike buprenorphine, it does not reduce subjective threat appraisal ratings. Overall, our results suggest that the combination of actions of buprenorphine at the mu and kappa opioid receptors contributes its unique effects on emotion processing; dampening responses to negative social stimuli and enhancing responses to positive social stimuli. The questions addressed here lay the foundation for the development of novel, fast-acting, opioid-based treatments for mood disorders.
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