title: Association between a cannabinoid receptor gene (CNR1) polymorphism and cannabinoid-induced alterations of the auditory event-related P300 potential.
abstract: Numerous studies demonstrated a close relationship between cannabis abuse and schizophrenia with similar impairments in cognitive processing, particularly in P300 generation. Recently, an (AAT)n triplet repeat polymorphism within the cannabinoid receptor gene CNR1 has been found to be associated with both schizophrenia and substance dependence, and to modulate the P300 potential. As previously reported, both acute oral Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the main psychoactive constituent of cannabis, and standardized cannabis extract containing Δ(9)-THC and cannabidiol (CBD) revealed a significant reduction of P300 amplitudes in healthy subjects but did not show any differences among each other. The aim of this study was to investigate whether the (AAT)n polymorphism differentially modulates the effects of Δ(9)-THC and cannabis extract on P300 generation in 20 healthy volunteers during an auditory choice reaction task. For the >10/>10 genotype, there was a significant decrease of P300 amplitude as well as a significant prolongation of P300 latency under pure Δ(9)-THC but not under cannabis extract. Moreover, we found a significant correlation between the number of AAT repeats and P300 variables for the Δ(9)-THC condition. Our data thus indicate that the CNR1 gene seems to be involved in the regulation of the P300 wave as a marker of selective attention and working memory. Moreover, it appears that variations within CNR1 may differentially alter the sensitivity to the acute effects of cannabinoids on P300 generation in healthy subjects.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité University Hospital Berlin, Berlin, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Stadelmann
authors.forename: Georg
authors.initials: G
authors.lastname: Juckel
authors.forename: Larissa
authors.initials: L
authors.lastname: Arning
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Epplen
authors.forename: Patrik
authors.initials: P
authors.lastname: Roser
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000328:Adult; D013759:Dronabinol / Q000494:pharmacology*; D004569:Electroencephalography; D018913:Event-Related Potentials, P300 / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol