The aim of the study was to assess the feasibility of naltrexone as a potential pharmacotherapy for amphetamine dependence. The study design was an open-label clinical trial with 20 amphetamine-dependent patients receiving 12 weeks of treatment comprised of naltrexone (50 mg) along with relapse prevention therapy. Patients were assessed weekly for adverse events and compliance to medication. Tolerability to naltrexone was measured by patient's self-report and observed adverse effects along with plasma markers of hepatotoxicity. Compliance to treatment was measured by number of treatment days attended and by the presence of naltrexone's metabolite, 6-beta-naltrexol in urine. Majority of the patients tolerated the medication well, also during relapse. Mild headache, nausea and abdominal pain were reported (n=3) but subsided within 2 weeks. Plasma levels of hepatic markers did not reveal any significant increase from baseline. Eleven out of 20 patients complied with the treatment and there was a significantly higher proportion of positive tests of 6-beta-naltrexol in urine among patients completing 12 weeks of treatment compared to those who did not (77% vs. 22%). The frequency and amount of amphetamine consumed was significantly lower during treatment compared with pre-treatment consumption (P<0.01). In conclusion, naltrexone was well tolerated with moderate rates of compliance, supporting the feasibility of investigating this compound in a larger placebo-controlled trial as a potential pharmacotherapy for amphetamine dependence.