The current results are consistent with the animal

The current results are consistent with the animal models of cannabinoid exposure during adolescence (Rubino et al., 2008; Schramm-Sapyta et al., 2007) and suggest that more human research is needed on the long-term effects of cannabis use in adolescence. In consideration of the animal studies and the link between early cannabis use and mood disorders later in life, acute THC consumption effects in the adolescent ceramidase may be different or, indeed, the long-lasting effects of repeated exposure may be different beyond the acute intoxication phase. As adolescents tend to be more reactive to emotional stimuli, especially face processing in the amygdala, the observed differences in adolescent cannabis-users may suggest evidence of maladaptive cognitive and affective systems related to psychosocial development. An alternative explanation regarding the observed differences in affective face processing may be attributed to unmeasured preexisting differences in emotional functioning, which might have contributed to the adolescents’ experimentation with cannabis. Indeed, we have previously shown that activation in response to these angry faces in the left PFC predicted binge drinking two years later, which would suggest altered emotional reactivity may precede use (Whelan et al., 2014). However, in the present analyses the measured psychiatric symptomology results failed to show elevated levels of any of the affective disorders, therefore, it is unclear which preexisting differences, if any, might have been present in the cannabis-experimenting group.
Acknowledgements This work received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the FP7 projects IMAGEMEND (602450; IMAging GEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EU-AIMS (115300-2), a Medical Research Council Programme Grant “Developmental pathways into adolescent substance abuse” (93558), the Swedish funding agency FORMAS, the Medical Research Council and the Wellcome Trust (Behavioural and Clinical Neuroscience Institute, University of Cambridge), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King\'s College London, the Bundesministerium für Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc 01ZX1311A; Forschungsnetz AERIAL), the Deutsche Forschungsgemeinschaft (DFG): Reinhart-Koselleck Award SP 383/5-1 and grants SM 80/7-1, SFB 940/1, FOR 1617), the French MILDT (Mission Interministé rielle de Lutte contre la Drogue et la Toxicomanie), the CENIR (Centre de NeuroImagerie de Recherche, Pr. S. Lehéricy) within the ICM institute, the National Institute of Mental Health (MH082116), and a National Institutes of Health Center of Biomedical Research Excellence award P20GM103644 from the National Institute of General Medical Sciences. HG was supported, in part, by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centers of Excellence. We thank Jackson Mathews for his assistance on figures and references.
Introduction Marijuana is the most commonly used illicit drug in the United States, with 36.4% of high school seniors reporting past-year use (Miech et al., 2015). Recent trends show an increase in marijuana use coupled with a substantial decrease in perceptions of harm (Johnston et al., 2014). This is concerning given the adverse outcomes associated with marijuana use, including cognitive impairment, lower lifetime achievement, and increased risk for addiction (Hall, 2014; Volkow et al., 2014). Adolescent marijuana users may be at particular risk for adverse outcomes. Compared to adult-onset users, adolescent-onset marijuana users are more likely to experience symptoms of dependence within two years of use onset (Chen et al., 2009), are at increased risk of developing other drug dependence (Lynskey et al., 2003), and show increased deficits in executive functioning (Fontes et al., 2011). Furthermore, studies of brain functioning during cognitive tasks have demonstrated differences in brain activation and connectivity in marijuana users compared with controls (Abdullaev et al., 2010; Harding et al., 2012; Padula et al., 2007; Schweinsburg et al., 2008; Smith et al., 2010; Tapert et al., 2007), some of which are more apparent in those with adolescent-onset use (Becker et al., 2010; Gruber et al., 2012; Jager et al., 2010; Lopez-Larson et al., 2015).