title: Impact of prospectively determined A118G polymorphism on treatment response to injectable naltrexone among methamphetamine-dependent patients: an open-label, pilot study.
abstract: OBJECTIVE
  Methamphetamine (MA) addiction has no known effective pharmacotherapy. Small trials showed beneficial effects for oral naltrexone in amphetamine users. Trials in alcohol-dependent subjects showed better response in persons with the A118G single nucleotide polymorphism of the μ-opioid receptor. We conducted a pharmacogenetic trial of sustained release intramuscular naltrexone to examine the role of the A118G single nucleotide polymorphism in MA dependence.
  
  
  METHODS
  All eligible A118G subjects screened were enrolled; an equal number of wild type (A118A) subjects were selected using modified urn randomization, balanced on sex and frequency of recent MA use. Enrolled subjects received a single 380 mg naltrexone injection and weekly psychotherapy for 4 weeks. Self-report of MA use and urine toxicology for MA was assessed twice weekly. Urine samples with less than 1000 ng/mL of MA were considered negative.
  
  
  RESULTS
  Eleven A118G and 11 A118A subjects were enrolled. There were no significant differences between the groups in days of abstinence from MA use (11.5 vs 14.8, respectively, P = 0.51), the number of MA-negative urine samples (1.7 vs 1.8, respectively, P = 0.97), consecutive MA-negative urine samples (1.0 vs 1.5, respectively, P = 0.91), or the number of MA-negative urine samples before first relapse (0.9 vs 1.5, respectively, P = 0.86).
  
  
  CONCLUSIONS
  Although A118G polymorphism has been shown to be associated with improved treatment response to naltrexone among alcoholics, whether this polymorphism impacts naltrexone treatment response among MA users is unclear at this time.
authors.affiliation: From the Addiction and Pharmacology Research Laboratory (RP, JEM, KG, GY, GPG), California Pacific Medical Center Research Institute, San Francisco, CA; School of Medicine (KF), University of California, San Francisco, CA; and Department of Statistics (JRC), University of California, Berkeley, CA.
authors.forename: Reshmi
authors.initials: R
authors.lastname: Pal
authors.forename: John E
authors.initials: JE
authors.lastname: Mendelson
authors.forename: Keith
authors.initials: K
authors.lastname: Flower
authors.forename: Kathleen
authors.initials: K
authors.lastname: Garrison
authors.forename: Garret
authors.initials: G
authors.lastname: Yount
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Coyle
authors.forename: Gantt P
authors.initials: GP
authors.lastname: Galloway
mesh_terms: D000293:Adolescent; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000235:genetics / Q000652:urine; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects* / Q000652:urine; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics*; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D008694:Methamphetamine; D009271:Naltrexone