The potential of oxytocin to reduce opioid abuse liability and pain among older adults - ABSTRACT
Opioid use is a major source of morbidity and mortality in the U.S. and represents an urgent public health
crisis. In recent years, a surge of adults over the age of 50 have developed opioid use disorder (OUD), a
significant and alarming trend that is increasing. Increases in OUD in mid-life and older adults is partially
due to high rates of pain, surgery, and physical ailments in aging populations that necessitate opioid prescription
medications, including oxycodone. Oxycodone (in Percocet™ and Oxycontin™) is consistently among the
medications most widely prescribed for pain, but is also most widely abused and involved in overdose deaths.
Despite its potential for abuse, oxycodone can be highly effective for reducing acute pain. There is an urgent
need for interventions that preserve the analgesic properties of oxycodone while curtailing its abuse potential. A
promising adjunct treatment option for pain management, that could simultaneously reduce the abuse
potential of opioids, is intranasal administration of the neuropeptide oxytocin. Oxytocin has no
recognized addiction potential, and simultaneously has analgesic properties. Preclinical evidence
suggests that oxytocin co-administered with opioids may reduce opioid reinforcing effects. Oxytocin also
decreases experimental pain in human and animal models. Further, evidence in animals and humans support
the shared brain structure and function changes associated with both addiction and chronic pain, which may be
modulated by oxytocin administration. Doses of oxytocin are also well-tolerated by individuals receiving
medications for OUD (e.g., methadone). Based on this evidence, we propose that oxytocin will significantly
reduce abuse liability of opioids and reduce experimental pain. Thirty healthy 55-75 year old volunteers with
some opioid experience will self-administer 48 IUs of intranasal oxytocin (or placebo) shortly after oral oxycodone
(0, 2.5, 5.0 mg) in a double-blind, randomized, placebo-controlled, within-subjects laboratory study. Subject-
rated abuse liability and cardiovascular and respiratory responses will be assessed before and repeatedly for 5
hours following drug administration. Pain measures will also be collected, including a standardized experimental
pain battery (i.e., quantitative sensory testing with thermal and mechanical testing). This study has tremendous
potential for public health impact in examining intranasal oxytocin as a promising agent for reducing opioid
addictive potential and producing opioid-sparing effects, while effectively reducing pain, which could substantially
advance the field of pharmacotherapy and carve out a novel treatment option, specifically in mid-life and older
adults who may be at higher risk for pain. Results from this project will also advance scientific understanding of
behavioral mechanisms underlying the link between abuse potential and pain. Our multidisciplinary team is
well-suited to address the proposed aims with expertise in (i) intranasal oxytocin administration (ii) human
drug administration and abuse liability testing of drugs of abuse (iii) opioid administration and experimental pain
testing (iv) multi-modal pain assessments and (v) aging.
