Impact of Prospectively Determined A118G Polymorphism on Treatment Response to Injectable Naltrexone Among Methamphetamine-Dependent Patients: An Open-Label, Pilot Study

Objectives: 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 mu-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. Method: 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.