Both, cannabinoid compounds and nicotine affect appetite and metabolism as well as emotional responses. In view of the high incidence of drug abuse, emotional disturbances and weight concerns among adolescents, analysis of cannabinoids-nicotine functional interactions in this period is of special relevance. We have demonstrated that nicotine administration in adolescent rats alters their acute emotional responses to a cannabinoid agonist and induces long-term effects on brain CB1 cannabinoid receptors. We have also analysed possible functional interactions between the CB1 receptor antagonist Surinabant (SR) and nicotine, as regards energy balance and metabolism. The effects induced by SR indicated that the endogenous cannabinoid system plays an active functional role as metabolic modulator during adolescence. Moreover, nicotine-SR interactions suggested that moderate tobacco smoking during the periadolescent period may exert long-term effects on the metabolic regulation exerted by the endogenous cannabinoid system. Besides, our data showed intriguing sexual dimorphisms. Analysis of possible behavioural side effects of SR did not reveal anxiogenic-like responses in the elevated plus maze, though it induced increased immobility times in the Porsolt test, which is classically considered as a depressive-like response, with this effect being more marked in males than in females. Moreover, SR reversed some of the depressive-like responses induced by nicotine in females. We provide the first evidences for robust sex-dependent metabolic and endocrine effects of Surinabant in adolescent rats and extend our previous studies regarding nicotine-cannabinoids functional interactions. Acknowledgements: Ministerio de Sanidad y Consumo (PND) 3SI/05/08; Red de Trastornos Adictivos (RD06/001); Sanofi-Aventis for Surinabant.