Responses of the Neurobiological Craving Signature to smoking versus alternative social rewards predict craving and monthly smoking in adolescents

Background Smoking remains the leading cause of preventable mortality worldwide. Adolescents are particularly vulnerable to the development of tobacco addiction due to ongoing brain maturation and susceptibility to social influences, such as exposure to environmental tobacco smoke (ETS). Craving – the strong desire to use drugs – already emerges with non-daily tobacco smoking and predicts continued use and relapse. However, the roles of craving and ETS exposure during the early stages of tobacco use in adolescence remain poorly understood. Methods: In this pre-registered study, we harnessed a recently developed fMRI marker of craving – the Neurobiological Craving Signature (NCS) – to compare craving-related brain responses to social smoking versus neutral and romantic cues in adolescent Experimental Smokers (ExpSmo, N=100) and Non-smokers (NonSmo, N=48). We tested the associations of craving-related brain activity with individual differences in the amount of non-daily-smoking, ETS exposure, and self-reported craving. Results: Results showed that NCS responses to smoking cues compared to alternative social rewards were higher in ExpSmo compared to NonSmo and predicted individual differences in self-reported craving and monthly smoking. Both smoking behavior and NCS responses were correlated with the relative amount of ETS exposure from peers compared to exposure from family members. Conclusions: Together, these findings indicate a heightened sensitivity of craving-related brain circuits already during experimental smoking and suggest an important role of peer social norms on craving and smoking initiation in the critical period of adolescence.