TY - JOUR
T1 - Non-opioid neurotransmitter systems that contribute to the opioid withdrawal syndrome
T2 - A review of preclinical and human evidence
AU - Dunn, Kelly E.
AU - Huhn, Andrew S.
AU - Bergeria, Cecilia L.
AU - Gipson, Cassandra D.
AU - Weerts, Elise M.
N1 - Publisher Copyright:
Copyright ª 2019 by The American Society for Pharmacology and Experimental Therapeutics
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1124/jpet.119.258004
DO - 10.1124/jpet.119.258004
M3 - Review article
C2 - 31391211
AN - SCOPUS:85073584306
SN - 0022-3565
VL - 371
SP - 422
EP - 452
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 2
ER -