Given that most cannabis-dependent subjects smoked cigarettes and the documented differences between cigarette smokers and non-smokers in terms of Neuroticism [33], we evaluated whether nicotine use may be the factor driving behavioral specificity in cannabis-dependent subjects. In our sample, there were no differences as to temperamental traits, affect, reward learning, inhibitory control and SNPs between cannabis-dependent subjects who smoked cigarettes daily compared to those who did not. To further address this issue, we also examined PENK SNPs in another population (homogenous Caucasian Greek army conscripts; Table 4 ) in which personality traits had been obtained (N = 559, 247 smokers and 312 non-smokers; mean age = 23.4 years), as described previously [34]. Cigarette smoking without cannabis use was associated with Neuroticism (p = 0.02), but it was not significantly related to the PENK SNPs (rs2609997, rs2576573). Interestingly, although the cannabis-dependence diagnosis was not assessed in this population, an additive-interaction effect between Neuroticism and both PENK SNPs predicted the history of cannabis use (rs2609997, p = 0.01; rs2576573, p = 0.02).
