Opioid misuse and abuse is a major international public health issue. Opioid use disorder (OUD) is largely maintained by a desire to suppress aversive opioid withdrawal symptoms. Opioid withdrawal in patients seeking abstinence from illicit or prescribed opioids is often managed by provision of a m-opioid agonist/partial agonist in combination with concomitant medications. Concomitant medications are administered based on their ability to treat specific symptoms rather than a mechanistic understanding of the opioid withdrawal syndrome; however, their use has not been statistically associated with improved treatment outcomes. Understanding the central and/or peripheral mechanisms that underlie individual withdrawal symptom expression in humans will help promote medication development for opioid withdrawal management. To support focused examination of mechanistically supported concomitant medications, this review summarizes evidence from preclinical (N 5 68) and human (N 5 30) studies that administered drugs acting on the dopamine, serotonin, cannabinoid, orexin/hypocretin, and glutamate systems and reported outcomes related to opioid withdrawal. These studies provide evidence that each of these systems contribute to opioid withdrawal severity. The Food and Drug Administration has approved medications acting on these respective systems for other indications and research in this area could support the repurposing of these medications to enhance opioid withdrawal treatment. These data support a focused examination of mechanistically informed concomitant medications to help reduce opioid withdrawal severity and enhance the continuum of care available for persons with OUD.
|Number of pages||31|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 2019|
Bibliographical noteFunding Information:
Salary support for this review was provided by the National Institutes of Health National Institute on Drug Abuse [Grants R01DA042751, R01DA035246, R01DA040644, and R34DA042926 (to K.E.D.); UG3DA048734 (to A.S.H. and K.E.D.); and R21DA044479, R03DA045881, and R00DA036569 (to C.D.G.)], and the Arizona Alzheimer’s Consortium (to C.D.G.).
Copyright ª 2019 by The American Society for Pharmacology and Experimental Therapeutics
ASJC Scopus subject areas
- Molecular Medicine