Non-Opioid Neurotransmitter Systems that Contribute to the Opioid Withdrawal Syndrome: A Review of Preclinical and Human Evidence

The Journal of Pharmacology and Experimental Therapeutics
Kelly E DunnElise M Weerts

Abstract

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 μ-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 = 68) and human (N = 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 withd...Continue Reading

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Citations

Aug 11, 2020·Drugs·Reda M Chalhoub, Peter W Kalivas
Nov 1, 2020·Current Psychiatry Reports·Andrew S Huhn, Kelly E Dunn
Apr 22, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Kelly E DunnClaudia M Campbell

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