title: Zinc involvement in opioid addiction and analgesia--should zinc supplementation be recommended for opioid-treated persons?
abstract: BACKGROUND
  Zinc chelators were shown to facilitate some opioid-withdrawal signs in animals. Zinc deficiency, which affects more than 15% the world's population, is also common among opioid consumers and opioid-treated animals exhibit misbalances of zinc distribution.
  
  
  OBJECTIVE
  The present study focuses on how zinc ions interfere with opioid dependence/addiction and analgesia, trying to preliminary discuss if zinc supplementation in opioid-users should be recommended in order to reduce the risk of addiction.
  
  
  METHODS
  All relevant literature was searched up to April 2015. The search was performed using the term "zinc" plus combinations of following terms: "opioid receptors", "opioid" or representatives of this class, "addiction", "dependence", "analgesia", and "pain". Human, animal, in vitro studies and reviews were including.
  
  
  RESULTS
  Both human and animal studies revealed decreased serum zinc under opioid-administration conditions, attributed mainly to increased urinary elimination (humans) or redistribution (animals). Moreover, animal studies revealed decreased brain zinc levels in morphine-treated animals, with increased zinc hepatic levels, but also an enhancement of endogenous opioid system activity and a possible reduction of morphine withdrawal by zinc. In vitro studies revealed reduction of opioid ligands binding to receptors by zinc. However, the very few in vivo animal studies on opioid analgesia revealed controversial results, as zinc demonstrated clear analgesic effect, but zinc associated to opioids doesn't result in a potentiation of the analgesic effect.
  
  
  CONCLUSIONS
  Zinc dietary supplementation in patients treated with opioids for cancer-related chronic pain should be considered, due to the high incidence of zinc deficiency, also well-documented in opioid consumers. The low toxicity of orally-administered zinc also pleads for this idea. The main contra-argument to zinc administration in opioid-treated persons is related to the way zinc influences opioid-induced analgesia.
authors.affiliation: Pharmacology Department, University of Medicine and Pharmacy "Gr. T. Popa" Iași, Iași, Romania. diana.ciubotariu@umfiasi.ro.
authors.forename: Diana
authors.initials: D
authors.lastname: Ciubotariu
authors.affiliation: Pharmacology Department, University of Medicine and Pharmacy "Gr. T. Popa" Iași, Iași, Romania. cristina.ghiciuc@umfiasi.ro.
authors.forename: Cristina Mihaela
authors.initials: CM
authors.lastname: Ghiciuc
authors.affiliation: Pharmacology Department, University of Medicine and Pharmacy "Gr. T. Popa" Iași, Iași, Romania. celupusoru@yahoo.com.
authors.forename: Cătălina Elena
authors.initials: CE
authors.lastname: Lupușoru
mesh_terms: D000698:Analgesia; D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D018847:Opioid Peptides / Q000187:drug effects / Q000378:metabolism; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D015032:Zinc / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D018847:Opioid Peptides; D011957:Receptors, Opioid; D015032:Zinc