Tobacco smoking and obesity are worldwide important health problems with a growing impact in adolescent and young adults. One of the consequences of nicotine withdrawal is an increase in body weight that can act as a risk factor to relapse. Experimental therapies with a cannabinoid receptor antagonist have been recently proposed for both cigarette smoking and complicated overweight. In the present study, we aimed to investigate metabolic and hormonal effects of chronic nicotine treatment (during treatment and in abstinence) in an animal model of adolescence as well as to address the pharmacological effects of the novel selective CB1 cannabinoid receptor antagonist, SR 147778 (Surinabant). Adolescence (postnatal days 37-44) and/or post-adolescence (postnatal days 45-59) administration of Surinabant reduced body weight gain, as well as plasma glucose levels and triglycerides. The drug also reduced insulin and leptin secretion, and increased adiponectin and corticosterone levels. The effects showed sexual dimorphisms and, in general, were more pronounced in females. Chronic exposure to nicotine (0.8 mg/kg), from postnatal days 30-44 did not result in overt effects on food intake or body weight gain. However, it altered certain responses to the administration of Surinabant, both when the two drugs were given simultaneously and when Surinabant was administered during the post-adolescence period, along nicotine withdrawal. The present results indicate that the endogenous cannabinoid system is active as a metabolic modulator during adolescence and that nicotine exposure can induce long-lasting effects on metabolic regulation, altering cannabinoid modulation of energy expenditure and metabolism.