title: Opioid use affects antioxidant activity and purine metabolism: preliminary results.
abstract: OBJECTIVE
  More must be learned about metabolic and biochemical alterations that contribute to the development and expression of drug dependence. Experimental opioid administration influences mechanisms and indices of oxidative stress, such as antioxidant compounds and purine metabolism. We examined perturbations of neurotransmitter-related pathways in opioid dependence (OD).
  
  
  METHODS
  In this preliminary study, we used a targeted metabolomics platform to explore whether biochemical changes were associated with OD by comparing OD individuals (n = 14) and non-drug users (n = 10).
  
  
  RESULTS
  OD patients undergoing short-term methadone detoxification showed altered oxidation-reduction activity, as confirmed by higher plasma levels of alpha- and gamma-tocopherol and increased GSH/GSSG ratio. OD individuals had also altered purine metabolism, showing increased concentration of guanine and xanthosine, with decreased guanosine, hypoxanthine and hypoxanthine/xanthine and xanthine/xanthosine ratios. Other drug use in addition to opioids was associated with partly different biochemical changes.
  
  
  CONCLUSIONS
  This is a preliminary investigation using metabolomics and showing multiple peripheral alterations of metabolic pathways in OD. Further studies should explore the metabolic profile of conditions of opioid abuse, withdrawal and long-term abstinence in relation to agonist and antagonist treatment and investigate biochemical signatures of opioid substances and medications.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 2218 Elder Street, Durham, NC 27705, USA. paolo.mannelli@duke.edu
authors.forename: Paolo
authors.initials: P
authors.lastname: Mannelli
authors.forename: Ashwin
authors.initials: A
authors.lastname: Patkar
authors.forename: Steve
authors.initials: S
authors.lastname: Rozen
authors.forename: Wayne
authors.initials: W
authors.lastname: Matson
authors.forename: Ranga
authors.initials: R
authors.lastname: Krishnan
authors.forename: Rima
authors.initials: R
authors.lastname: Kaddurah-Daouk
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods; D008691:Methadone / Q000627:therapeutic use; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000503:physiopathology* / Q000534:rehabilitation; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011687:Purines / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D000975:Antioxidants; D011687:Purines; D008691:Methadone