better monitored. The fact that our sample was drawn from a population without significant psychiatric comorbidity also opens up the question as to whether these results may be generalizable to other comorbid subgroups. Replication of our results in a larger cohort will also be important to address potential stratification effects. Although not specific to cannabis dependence, results from the Greek Caucasian population suggest that the association between the PENK SNPs and Neuroticism could be replicated and generalized to other populations. An additional issue to address in interpreting the data is that a large percentage of the cannabis group also smoked cigarettes; thus, nicotine withdrawal could be a potential confound to the Neuroticism trait ascribed to cannabis-dependent subjects. However, study participants did not abstain from nicotine on the day of testing and behavioral traits were determined within an hour of the subject’s arrival to reduce potential withdrawal complications. Moreover, cigarette smoking was not associated with PENK SNPs in the large Caucasian population; cigarette smoking is thus unlikely to explain the genetic findings in our subgroup of cannabis-dependent subjects who also smoked cigarettes.
