The goal of the proposed study is to evaluate the efficacy and safety of N-Acetyl Cysteine (NAC) in combination with naltrexone in methamphetamine dependence.

Forty subjects with DSM-IV methamphetamine dependence will receive 8 weeks of double-blind combination medication (NAC plus naltrexone) or placebo. The hypothesis to be tested is that NAC plus naltrexone will be effective and well tolerated in patients with methamphetamine dependence compared to placebo. The proposed study will provide needed data on the treatment of a public health crisis that currently lacks a clearly effective treatment.

Inclusion Criteria:

1. men and women age 18-65
2. current DSM-IV methamphetamine dependence.

Exclusion Criteria:

1. unstable medical illness
2. history of seizures
3. myocardial infarction within 6 months
4. current pregnancy or lactation, or inadequate contraception in women of childbearing potential
5. any thoughts of suicide
6. lifetime history of DSM-IV bipolar disorder type I, dementia, or schizophrenia or any other DSM-IV psychotic disorder
7. previous treatment with N-Acetyl Cysteine or naltrexone
8. treatment with investigational medication or depot neuroleptics within 3 months, with fluoxetine within 6 weeks, or with other psychotropics within 2 weeks prior to study baseline
9. abnormal liver function tests at screening
10. diagnosis of asthma
11. current use of opiates.