Cannabidiol is a negative allosteric modulator of the cannabinoid CB 1 receptor

BACKGROUND AND PURPOSE: Cannabidiol has been reported to act as an antagonist at cannabinoid CB1 receptors. We hypothesized that cannabidiol would inhibit cannabinoid agonist activity through negative allosteric modulation of CB1 receptors. EXPERIMENTAL APPROACH: Internalization of CB1 receptors, arrestin2 recruitment, and PLCβ3 and ERK1/2 phosphorylation, were quantified in HEK 293A cells heterologously expressing CB1 receptors and in the STHdh(Q7/Q7) cell model of striatal neurons endogenously expressing CB1 receptors. Cells were treated with 2-arachidonylglycerol or Δ(9)-tetrahydrocannabinol alone and in combination with different concentrations of cannabidiol. KEY RESULTS: Cannabidiol reduced the efficacy…

• HS
  Huntington Society of Canada
• NS
  Nova Scotia Health Research Foundation
• KA
  King Abdulaziz University
• KT
  Killam Trusts
• CI
  Canadian Institutes of Health Research

  Awards: ROP-97185, MOP-97768