BACKGROUND: Cannabinoid type-1 (CB1) receptor inverse agonists improve type 2 diabetes and dyslipidaemia but were discontinued due to adverse psychiatric effects. D9 -Tetrahydrocannabivarin (THCV) is a neutral CB1 antagonist producing hypophagia and body weight reduction in lean mice. We investigated its effects in dietary-induced (DIO) and genetically (ob/ob) obese mice. METHODS: We performed two dose-ranging studies in DIO mice; study 1: 0.3, 1, 2.5, 5 and 12.5 mg kg 1 , oral twice daily for 30 days and study 2: 0.1, 0.5, 2.5 and 12.5 mg kg 1 , oral, once daily for 45 days. One pilot (study 3: 0.3 and 3 mg kg...