Peripheral, but not central effects of cannabidiol derivatives: Mediation by CB1 and unidentified receptors

Ester Fride*, Datta Ponde, Aviva Breuer, Lumir Hanuš

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Delta-9 tetrahydrocannabinol (Δ9-THC) and (-)-cannabidiol ((-)-CBD) are major constituents of the Cannabis sativa plant with different pharmacological profiles: (Δ9-THC activates cannabinoid CB 1 and CB2 receptors and induces psychoactive and peripheral effects. (-)-CBD possesses no, or very weak affinity for these receptors. We tested a series of (+)- and (-)-CBD derivatives for central and peripheral effects in mice. None of the (-)-CBD derivatives were centrally active, yet most inhibited intestinal motility. Of the five (+)-CBD derivatives, all with CB1 receptor affinity, only (+)-7-OH-CBD-DMH (DMH=1,1-dimethylheptyl), acted centrally, while all five arrested defecation. The effects of (+)-CBD-DMH and (+)-7-OH-CBD-DMH were inhibited by the CB 1 receptor antagonist SR141716. The CB2 receptor antagonist SR144528, and the vanilloid TRPV1 receptor antagonist capsazepine, had no influence. Further, the (-)-CBD derivatives (-)-7-COOH-CBD and (-)-7-COOH-CBD-DMH, displayed antiinflammatory activity. We suggest that (+)-CBD analogues have mixed agonist/antagonist activity in the brain. Second, (-)-CBD analogues which are devoid of cannabinoid receptor affinity but which inhibit intestinal motility, suggest the existence of a non-CB1, non-CB 2 receptor. Therefore, such analogues should be further developed as antidiarrheal and/or antiinflammatory drugs. We propose to study the therapeutic potential of (-)- and (+)-CBD derivatives for complex conditions such as inflammatory bowel disease and cystic fibrosis.

Original languageEnglish
Pages (from-to)1117-1129
Number of pages13
JournalNeuropharmacology
Volume48
Issue number8 SPEC. ISS.
DOIs
StatePublished - Jun 2005

Keywords

  • Cannabidiol
  • CB receptors
  • CB receptors
  • Inflammation
  • Intestinal motility
  • Vanilloid TRPV1 receptors

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