AIM: Drug addiction is a chronic brain disease with constant relapse requiring long-term treatment. New pharmacological strategies focus on the development of an effective antirelapse drug. This study examines the effects of levotetrahydropalmatine (l-THP) on reducing heroin craving and increasing the abstinence rate among heroin-dependent patients. METHODS: In total, 120 heroin-dependent patients participated in the randomized, double-blinded, and placebocontrolled study using l-THP treatment. The participants remained in a ward during a 4-week period of l-THP treatment, followed by 4 weeks of observation after treatment. The patients were followed for 3 months after discharge. Outcome measures are the measured severity of the protracted abstinence withdrawal syndrome (PAWS) and the abstinence rate. RESULTS: Four weeks of l-THP treatment significantly ameliorated the severity of PAWS, specifically, somatic syndrome, mood states, insomnia, and drug craving, in comparison to the placebo group. Based on the 3 month follow-up observation, participants who survived the initial 2 weeks of l-THP medication and remained in the trial program had a significantly higher abstinence rate of 47.8% (95% confidence interval [CI]: 33%- 67%) than the 15.2% in the placebo group (95% CI: 7%-25%), according to a log- rank test (P<0.0005). CONCLUSION: l-THP significantly ameliorated PAWS, especially reducing drug craving. Furthermore, it increased the abstinence rate among heroin users. These results support the potential use of l-THP for the treatment of heroin addiction.