Dr. Rais Replies

To the Editor: Drs. Zullino, Waber, and Khazaal state that evidence for a causal correlation between cannabis use and schizophrenia was lacking in our study. Indeed, we could not address the direction of causality. Nevertheless, in our opinion, finding a relationship between cannabis use and brain volume loss in patients with first-episode schizophrenia was a first step toward examining a possible causality. We agree with Dr. Zullino et al. that, theoretically, gray matter reduction might be a common effect of several addictive drugs, specifically alcohol and tobacco. However, as described in our article, alcohol use was not significantly different between the three study groups. Moreover, we examined the effect of tobacco smoking among noncannabis using patients by applying a general linear model univariate analysis of covariance, with percentage gray matter volume changes as a dependent variable; group (noncannabis using patients, smokers, and nonsmokers) as an independent variable; and age, gender, and intracranial volume as covariates. Smokers and nonsmokers in the noncannabis using schizophrenia group did not differ significantly in gray matter change over the follow-up interval (F=4.81, df=4, 27, p=0.49). Thus, it is unlikely that the effect reported in our study could be attributed to the concomitant smoking of cigarettes.