title: Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis.
abstract: OBJECTIVE
  It has been proposed that medicinal strains of cannabis and therapeutic preparations would be safer with a more balanced concentration ratio of Δ(9) -tetrahydrocannabinol (THC) to cannabidiol (CBD), as CBD reduces the adverse psychotropic effects of THC. However, our understanding of CBD and THC interactions is limited and the brain circuitry mediating interactions between CBD and THC are unknown. The aim of this study was to investigate whether CBD modulated the functional effects and c-Fos expression induced by THC, using a 1:1 dose ratio that approximates therapeutic strains of cannabis and nabiximols.
  
  
  METHODS
  Male C57BL/6 mice were treated with vehicle, CBD, THC or a combination of CBD and THC (10 mg·kg(-1) i.p. for both cannabinoids) to examine effects on locomotor activity, anxiety-related behaviour, body temperature and brain c-Fos expression (a marker of neuronal activation).
  
  
  RESULTS
  CBD potentiated THC-induced locomotor suppression but reduced the hypothermic and anxiogenic effects of THC. CBD alone had no effect on these measures. THC increased brain activation as measured by c-Fos expression in 11 of the 35 brain regions studied. CBD co-administration suppressed THC-induced c-Fos expression in six of these brain regions. This effect was most pronounced in the medial preoptic nucleus and lateral periaqueductal gray. Treatment with CBD alone diminished c-Fos expression only in the central nucleus of the amygdala compared with vehicle.
  
  
  CONCLUSIONS
  These data confirm that CBD modulated the pharmacological actions of THC and provide new information regarding brain regions involved in the interaction between CBD and THC.
authors.affiliation: Brain and Mind Centre, University of Sydney, Sydney, Australia.|Discipline of Pharmacology, School of Medical Science, University of Sydney, Sydney, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Todd
authors.affiliation: Brain and Mind Centre, University of Sydney, Sydney, Australia.|Discipline of Pharmacology, School of Medical Science, University of Sydney, Sydney, Australia.
authors.forename: J C
authors.initials: JC
authors.lastname: Arnold
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002185:Cannabidiol / Q000494:pharmacology*; D013759:Dronabinol / Q000494:pharmacology*; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D064086:Medical Marijuana; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*
chemical_list: D064086:Medical Marijuana; D002185:Cannabidiol; D013759:Dronabinol