CANNABINOID RECEPTOR GENE (CNR1) - ASSOCIATION WITH IV DRUG-USE

The receptors for tetrahydrocannabinol, the active ingredient of marij uana, have been identified, A microsatellite polymorphism (AAT)(n) at the cannabinoid CB1 (brain) receptor gene (CNR1) consists of 9 alleles , Since the cannabinoid system is part of the reward pathway we examin ed the hypothesis that genetic variants of the CNR1 gene might be asso ciated with susceptibility to alcohol or drug dependence, The study co nsisted of 92 subjects on an Addiction Treatment Unit (ATU) and 114 co ntrols, All were non-Hispanic Caucasians. The ATU subjects were screen ed for all types of substance dependence using the Diagnostic Intervie w Schedule (DIS), and for a variety of substance abuse symptoms using the Addiction Severity Index (ASI), Since inspection of the distributi on of alleles in controls vs IV drug use showed a decrease in the freq uency of the 4 allele, and the <4 alleles were rare, the alleles were divided into two groups, <5 and greater than or equal to 5, and three genotypes <5/<5, heterozygotes, and greater than or equal to 5/greater than or equal to 5. When all variables were subjected to factor analy sis, factor 1 showed a clustering of drug dependence variables and fac tor 2 of alcohol dependence variables, By ANOVA only factor 1 showed s ignificant differences by genotype consistent with a model where homoz ygosity for the greater than or equal to 5 repeat alleles showed the g reatest effect. The number of IV drugs used was significantly greater for those carrying the greater than or equal to 5/greater than or equa l to 5 genotype than for other genotypes (P = 0.005), The association with specific types of drug dependence was greatest for cocaine, amphe tamine, and cannabis dependence, The results are consistent with a rol e of cannabinoid receptors in the modulation of dopamine and cannabino id reward pathways, Independent studies should be designed to further confirm the hypothesis that cannabinoid receptors may contribute to th e susceptibility to drug abuse.