Phytomedicine 14 (2007) 333–337 Anticoagulant effects of a Cannabis extract in an obese rat model C. Coetzee, R.-A. Levendal, M. van de Venter, C.L. Frost à Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031, South Africa Abstract Blood coagulation studies were conducted to determine the possible anti-/prothrombotic effect of an organic cannabis extract and the three major cannabinoids, THC, CBD and CBN. The in vitro effect of the cannabis extract on thrombin activity produced an IC 50 value of 9.89 mg/ml, compared to THC at 1.79 mg/ml. It was also found that the extract, THC and CBN showed considerable inhibition of thrombin-induced clot formation in vitro with IC 50 values of 600, 87 and 83 mg/ml for the extract, THC and CBN respectively. In an in vivo model used to determine clotting times of lean and obese rats treated with a cannabis extract, 50% clotting times were found to be 1.5 and 2 fold greater than their respective control groups, supporting the results obtained in the in vitro model. The study thus shows that Cannabis sativa and the cannabinoids, THC and CBN, display anticoagulant activity and may be useful in the treatment of diseases such as type 2 diabetes in which a hypercoagulable state exists. r 2006 Elsevier GmbH. All rights reserved. Keywords: Cannabis; Blood coagulation; Obesity; Anticoagulant; Cannabinoids Introduction The cannabinoids are the major active constituents of Cannabis sativa. Cannabinoids are oxygen-containing aromatic hydrocarbon compounds (Pertwee, 1999). There are about 70 known naturally occurring canna- binoids (Williamson and Evans, 2000). The three major cannabinoids are Cannabidiol (CBD), Cannabinol (CBN) and Tetrahydrocannabinol (THC) (Ashton, 2001). THC and its homologues have been found to be the main psychoactive constituents of Cannabis (Katzung, 1989). Cannabis has been used as a therapeutic agent against numerous diseases for many years (Berry and Mechou- lam, 2002). In South African indigenous medicine it is used to treat a wide range of conditions such as bronchitis, pain and diabetes (van Wyk and Gericke, 2000). The entire coagulation cascade is dysfunctional in diabetes. Both thrombosis and defective clot dissolution are favoured in diabetics (Vinik et al., 2001). Insulin resistance (IR), which occurs in type 2 diabetes, appears to be a common precursor of both diabetes and macrovascular disease. Metabolic distur- bances that commonly occur in patients with IR are atherogenic dyslipidemia, hypertension, glucose intoler- ance and a prothrombotic state. The prothrombotic state is characterized by increased fibrinogen levels, increased plasminogen activator inhibitor (PAI)-1 and different abnormalities in platelet function. Thrombosis is thus promoted and thrombolysis is retarded (Vinik et al., 2001). Insulin resistance affects the procoagulant state by co- segregating with abnormalities involved in coagulation, including platelet aggregability, platelet adhesion and ARTICLE IN PRESS www.elsevier.de/phymed 0944-7113/$ - see front matter r 2006 Elsevier GmbH. All rights reserved. doi:10.1016/j.phymed.2006.02.004 à Corresponding author. Tel.: +27 41 504 4123; fax: +27 41 504 2814. E-mail address: carminita.frost@nmmu.ac.za (C.L. Frost).