Adolescent cannabis use increases risk for cocaine-induced paranoia

Kalayasiri, Rasmon; Gelernter, Joel; Farrer, Lindsay; Weiss, Roger; Brady, Kathleen; Gueorguieva, Ralitza; Kranzler, Henry R.; Malison, Robert T.

doi:10.1016/j.drugalcdep.2009.10.006

« Previous Next »Drug and Alcohol Dependence
Volume 107, Issue 2 , Pages 196-201, 1 March 2010

Adolescent cannabis use increases risk for cocaine-induced paranoia

Rasmon Kalayasiri
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Joel Gelernter
- Department of Psychiatry, Yale School of Medicine, New Haven, CT 06520, USA
Lindsay Farrer
- Departments of Medicine (Genetics Program) and Neurology and Genetics, Boston University School of Medicine, and Departments of Biostatistics and Epidemiology, Boston University School of Public Health, Boston, MA 02218, USA
Roger Weiss
- Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA
- Division of Alcohol and Drug Abuse, McLean Hospital, Belmont, MA 02478, USA
Kathleen Brady
- Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425, USA
Ralitza Gueorguieva
- School of Public Health, Yale School of Medicine, New Haven, CT 06520, USA
Henry R. Kranzler
- Departments of Psychiatry and Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington, CT 06030, USA
Robert T. Malison
- Department of Psychiatry, Yale School of Medicine, New Haven, CT 06520, USA
- Corresponding author at: Clinical Neuroscience Research Unit, Yale University School of Medicine, 34 Park Street, New Haven, CT 06519, USA. Tel.: +1 203 974 7557; fax: +1 203 974 7662.

Received 3 June 2009; received in revised form 13 October 2009; accepted 21 October 2009.

Abstract

Cannabis can produce and/or exacerbate psychotic symptoms in vulnerable individuals. Early exposure to cannabis, particularly in combination with genetic factors, increases the risk of a subsequent, primary, psychotic disorder. Because paranoia is a common feature of stimulant abuse and cocaine-dependent individuals frequently endorse a history of cannabis abuse, we examined whether early cannabis exposure, in conjunction with polymorphic variation in the catechol-O-methyl transferase gene (COMT Val158Met), influences the risk for cocaine-induced paranoia (CIP).

Methods

Cannabis-use history was obtained in 1140 cocaine-dependent individuals from a family-based (affected sibling pair) study using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). Logistic regression and generalized estimating equations’ analyses were used to examine the role of adolescent-onset cannabis use (≤15 years of age) on CIP risk, both controlling for previously implicated CIP risk factors and familial relationships, and considering potential interactions with COMT Val158Met genotype.

Results

Cocaine-dependent individuals who endorsed CIP had significantly higher rates of adolescent-onset cannabis use than those without CIP (62.2% vs. 50.2%; χ²=15.2, df=1, p<0.0001), a finding that remained after controlling for sibling correlations and other risk factors. There were no effects of COMT genotype or genotype by early cannabis onset interactions. A modest (OR=1.4) and nearly significant (p=0.053) effect of CIP status in probands on CIP status in siblings was also noted.

Conclusions

Adolescent-onset cannabis use increases the risk of CIP in cocaine-dependent individuals. COMT genotype and its interaction with early cannabis exposure did not emerge as significant predictors of CIP. In addition, trait vulnerability to CIP may also be familial in nature.

Keywords: Cocaine, Paranoia, Cannabis, Adolescent