Delta(9)-tetrahydrocannabinol and cannabinol activate capsaicin-sensitive sensory nerves via a CB1 and CB2 cannabinoid receptor-independent mechanism

Research output: Contribution to journalArticle


Although Delta(9)-tetrahydrocannabinol (THC) produces analgesia, its effects on nociceptive primary afferents are unknown. These neurons participate not only in pain signaling but also in the local response to tissue injury. Here, we show that THC and cannabinol induce a CB1/CB2 cannabinoid receptor-independent release of calcitonin gene-related peptide from capsaicin-sensitive perivascular sensory nerves. Other psychotropic cannabinoids cannot mimic this action. The vanilloid receptor antagonist ruthenium red abolishes the responses to THC and cannabinol. However, the effect of THC on sensory nerves is intact in vanilloid receptor subtype 1 gene knock-out mice. The THC response depends on extracellular calcium but does not involve known voltage-operated calcium channels, glutamate receptors, or protein kinases A and C. These results may indicate the presence of a novel cannabinoid receptor/ion channel in the pain pathway.


Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences


  • receptors, pain, nociceptors, capsaicin, cannabis, cannabinol, calcitonin gene-related peptide, cannabinoids, sensory, tetrahydrocannabinol
Original languageEnglish
Pages (from-to)4720-4727
JournalJournal of Neuroscience
Issue number11
Publication statusPublished - 2002
Publication categoryResearch