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Kirsten C Morley,1 Paul S Haber,1,2 Madeleine L Morgan,3 Fares Samara3,41Discipline of Addiction Medicine, Sydney Medical School, University of Sydney, NSW, Australia; 2Drug Health Services, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; 3Drug and Alcohol Services, North Coast Area Health Service, Kempsey and Port Macquarie, NSW, Australia; 4Durri Aboriginal Medical Service, Kempsey, NSW, AustraliaAbstract: Cannabis is one of the most widely used illicit drugs worldwide. However, while the rates of cannabis dependence and treatment increase, there remains no medications approved for this use. Due to its sedative effects and low abuse liability, the typical antipsychotic pericyazine has been utilized in some parts of Australia for the treatment of cannabis dependence. We aimed to provide documentation of preliminary outcomes and acceptability of pericyazine treatment in a small sample. A naturalistic case series study was conducted in which 21 patients were enrolled for a 4-week course of pericyazine (up to 8 × 2.5 mg tablets daily) and weekly medical review. Levels of cannabis use were reported and side effects with electrocardiography and blood tests were monitored. Measures of dependence severity, depression, anxiety, and insomnia were taken at baseline and follow-up utilizing validated psychometric tools. Significant reductions in cannabis use, depression, anxiety, and insomnia severity occurred across time. Pericyazine appeared to be well tolerated and easily administered in the community clinics. The results provide some preliminary evidence that low-dose short-term pericyazine may be an acceptable mode of treatment in this population. Given the open-label nature of the design, we cannot conclude that pharmacotherapy was uniquely responsible for the treatment effect. Nonetheless, low-dose pericyazine may be a potentially effective approach to the treatment of cannabis dependence, and further evaluation via a randomized placebo-controlled trial is warranted.Keywords: cannabis, antipsychotic, pharmacotherapy, addiction, pericyazine