across patients with versus patients without marijuana abuse/dependence. In each follow-up ANCOVA, the dependent variable was frontal, temporal or parietal lobar brain volume. Genotype, marijuana misuse (presence versus absence of lifetime marijuana abuse or dependence) and genotype-by-marijuana misuse interaction terms were the independent measures (p≤.05). Covariates in the total cerebral and follow-up lobar brain volume analyses were intracranial volume, age, gender, imaging protocol, antipsychotic treatment (lifetime antipsychotic exposure) and alcohol/non-cannabis illicit substance abuse/dependence. Intracranial volume adjusted for individual differences in overall cranial size. Gender, age and antipsychotic treatment are known to influence brain volumes. To further ensure that scan sequence variation was not producing erroneous results, we included imaging protocol (i.e. ‘MR5’ versus ‘MR6’ scanning protocol) as a covariate in the analyses. Alcohol/other illicit substance use (presence versus absence of lifetime alcohol abuse/dependence or non-marijuana illicit substance abuse/dependence) may affect brain volumes and potentially confound brain volume-CNR1 relationships.
