To the Editor: While the correlations between schizophrenia and cannabis abuse are well corroborated, evidence for a causal correlation remains lacking. In their study, published in the April 2008 issue of the Journal, Monica Rais, M.D., et al. (1) found a more pronounced brain volume reduction over a 5-year follow-up period among cannabis using schizophrenia patients relative to schizophrenia patients without cannabis use. Dr. Rais et al. stated that their “study could not address the issue of direction of causality” (1, p. 494). Subsequently, they suggested “that some of the detrimental effects of cannabis on the course of illness may be explained by its effect on the progression of brain changes in schizophrenia” (1, p. 494).
If there was a specific effect of cannabis related to the outcome of schizophrenia, this should not be the case for other widely abused drugs, such as nicotine or alcohol. However, dose-dependent gray matter reductions have been described for individuals who smoke tobacco and abuse alcohol (e.g., 2). Although Dr. Rais et al. excluded patients who were addicted to alcohol at baseline, they did not exclude individuals who smoked tobacco, which admittedly would have been difficult to exclude because of the prevalence of smoking among schizophrenia patients. Neither alcohol nor tobacco consumption during follow-up was entered in the analyses. This may be particularly problematic concerning tobacco smoking because of its high prevalence among cannabis users (e.g., 3).
Since several addictive drugs seem to have similar effects on brain volume, the effect should not be considered specific. There is a possibility that there are discrete neurotoxic effects of different addictive drugs, and there is also a possibility that there are addiction-related factors common to each of the drugs that may contribute to volume loss. Consideration of these two possibilities might help to advance future studies in this area.
1.Rais M, Cahn W, Van Haren N, Schnack H, Caspers E, Hulshoff Pol H, Kahn R: Excessive brain volume loss over time in cannabis-using first-episode schizophrenia patients. Am J Psychiatry 2008; 165:490–4962.Gazdzinski S, Durazzo TC, Studholme C, Song E, Banys P, Meyerhoff DJ: Quantitative brain MRI in alcohol dependence: preliminary evidence for effects of concurrent chronic cigarette smoking on regional brain volumes. Alcohol Clin Exp Res 2005; 29:1484–14953.Degenhardt L, Hall W: The relationship between tobacco use, substance-use disorders and mental health: results from the National Survey of Mental Health and Well-Being. Nicotine Tob Res 2001; 3:225–234
Dr. Zullino receives or has received research support from the Swiss Federal Office of Public Health, the Swiss National Science Foundation, Eli Lilly, Organon, Wyeth, Sanofi-Synthelabo, Aventis, and Janssen-Cilag; he is/has been a member of advisory boards for Eli Lilly, Wyeth, and AstraZeneca; he has received speaker’s fees from AstraZeneca, Eli Lilly, Janssen-Cilag, GlaxoSmithKline, Novartis, Pfizer, Organon, and Wyeth; and he has received reimbursement for attending congresses for Eli Lilly, Wyeth, AstraZeneca, GlaxoSmithKline, Organon, and Janssen-Cilag. Dr. Khazaal receives or has received research support from the Swiss Federal Office of Public Health, the Swiss National Science Foundation, Eli Lilly, and AstraZeneca; he has received speaker’s fees from AstraZeneca, Eli Lilly, Bristol-Meyers Squibb, and Desitin; and he has received reimbursement for attending congresses for Eli Lilly, Wyeth, and AstraZeneca. Dr. Waber reports no competing interests.
This letter (doi: 10.1176/appi.ajp.2008.08040618) was accepted for publication in June 2008.