Evaluation of Sex-Based Differences in Response to the Prototypical Opioid Hydromorphone: A Human Laboratory Study Evaluation

Abstract ID 96533 Poster Board 504 Introduction: Opioid receptor binding, coupling, and density vary as a function of androgen hormones, and men and women report different environmental influences with regard to opioid use. Question: These analyses examine whether men and women experience different responses to opioids (prior to development of opioid use disorder). Methods: Healthy men and women with little or no history of opioid exposure participated in one of three double-blind, randomized, placebo-controlled, within-subject comparisons of the prototypical opioid hydromorphone (4mg, oral) vs placebo. Data were harmonized together for these analyses. Participants received a double-blinded dose of hydromorphone or placebo in 2 sessions and completed a variety of self-report, observed, and physiological ratings at 30-minute intervals for >2 hrs. Outcomes were analyzed as a function peak or nadir response, reflecting the strongest experience per session day and results were compared statistically between groups as a function of sex assigned at birth. Results: Participants (N = 160) were 33.1 years old (±9.6), 51% women, 49% men, 44% white, 41% African American, 10% Asian, and 5% other race, 7% Hispanic ethnicity. Multivariate analyses revealed hydromorphone increased self-report ratings (0-100) of Drug Effects, Good Effects, Bad Effects, High, Like How I Feel, Nausea, and Talkative (p's Conclusions: Data suggested the opioid dose tested produced a mild agonist effect that was experienced more strongly in women than men, evidenced by higher ratings (and trends) on self-report ratings, more pronounced drug ratings from blinded observers, and stronger physiological responses. Women also assigned higher monetary value to the drug and were less interested in consuming it again. Overall, these data reveal that men and women may experience opioid medications differently and provide direction for future studies to examine differences using a prospectively designed approach. Funding: R01DA035246, R01DA040644, R01DA042751, R01DA056045, R01DA052937.