title: Cannabidiol potentiates pharmacological effects of Delta(9)-tetrahydrocannabinol via CB(1) receptor-dependent mechanism.
abstract: Cannabidiol, a non-psychoactive component of cannabis, has been reported to have interactions with Delta(9)-tetrahydrocannabinol (Delta(9)-THC). However, such interactions have not sufficiently been clear and may have important implications for understanding the pharmacological effects of marijuana. In the present study, we investigated whether cannabidiol modulates the pharmacological effects of Delta(9)-THC on locomotor activity, catalepsy-like immobilisation, rectal temperature and spatial memory in the eight-arm radial maze task in mice. In addition, we measured expression level of cannabinoid CB(1) receptor at striatum, cortex, hippocampus and hypothalamus. Delta(9)-THC (1, 3, 6 and 10 mg/kg) induced hypoactivity, catalepsy-like immobilisation and hypothermia in a dose-dependent manner. In addition, Delta(9)-THC (1, 3 and 6 mg/kg) dose-dependently impaired spatial memory in eight-arm radial maze. On the other hand, cannabidiol (1, 3, 10, 25 and 50 mg/kg) did not affect locomotor activity, catalepsy-like immobilisation, rectal temperature and spatial memory on its own. However, higher dose of cannabidiol (10 or 50 mg/kg) exacerbated pharmacological effects of lower dose of Delta(9)-THC, such as hypoactivity, hypothermia and impairment of spatial memory. Moreover, cannabidiol (50 mg/kg) with Delta(9)-THC (1 mg/kg) enhanced the expression level of CB(1) receptor expression in hippocampus and hypothalamus. Cannabidiol potentiated pharmacological effects of Delta(9)-THC via CB(1) receptor-dependent mechanism. These findings may contribute in setting the basis for interaction of cannabinoids and to find a cannabinoid mechanism in central nervous system.
authors.affiliation: Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka City, Fukuoka, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Mai
authors.initials: M
authors.lastname: Hazekawa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sano
authors.forename: Keiichi
authors.initials: K
authors.lastname: Irie
authors.forename: Kensuke
authors.initials: K
authors.lastname: Orito
authors.forename: Takashi
authors.initials: T
authors.lastname: Egawa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Naoki
authors.initials: N
authors.lastname: Uchida
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nishimura
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002185:Cannabidiol / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004357:Drug Synergism; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000378:metabolism
chemical_list: D011619:Psychotropic Drugs; D043884:Receptor, Cannabinoid, CB1; D002185:Cannabidiol; D013759:Dronabinol