Cannabis is the most widely used illicit substance in the world. Estimates suggest that approximately 10-20% of cannabis users meet criteria for cannabis dependence and a significant proportion experience withdrawal discomfort on cessation of use. To date, there has been an absence of any clinically validated treatments to manage withdrawal. The current study is an open-label trial exploring the utility of lithium carbonate for the management of cannabis withdrawal symptoms in treatment seeking adult humans. In total, 20 participants were recruited to the study (19 men). All met DSM-IV cannabis-dependence criteria and had been smoking cannabis daily or almost daily for a mean 9 years. Participants were admitted to an inpatient detoxification facility and prescribed lithium 500 mg b.d. for 7 days. Cannabis withdrawal was assessed daily with the Marijuana Withdrawal Checklist (MWC). Two participants were withdrawn from the trial because of possible adverse effects. Sixty percent of participants completed the 7-day treatment program. Follow-up was conducted at a mean of 107 days following treatment. The mean percentage of days abstinent in the period between treatment cessation and follow-up was 87.57%. Twenty-nine percent of participants (n=5) reported continuous abstinence that was biochemically verified at follow-up. Agreement between self-reported cannabis use and urinalysis at follow-up was moderate (kappa=0.47). Significant reductions in symptoms of depression and anxiety and cannabis-related problems were also reported. This study provides evidence for the potential clinical utility and safety of lithium in the management of cannabis withdrawal. A randomised, placebo-controlled trial is recommended.