Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin

Inflamm Res. 2003 Jun;52(6):238-45. doi: 10.1007/s00011-003-1162-z.


Objective and design: In the present study we examined the effects of the cannabinoid receptor agonist HU210 on histamine-evoked somatosensory and vascular responses in humans.

Subjects: Two sets of experiments were performed, in which twelve (Study 1, iontophoresis) and six participants (Study 2, microdialysis) were recruited.

Treatment: HU210 was administered peripherally by skin patch (50 mM) or dermal microdialysis (5 mM), whereas histamine was applied by iontophoresis (50 microAmps) or dermal microdialysis (5 microM).

Methods: Skin blood flow was monitored by laser Doppler, widespread flare reaction was evaluated planimetrically, extravasation of plasma proteins was measured in the dialysate and perceived itch was recorded using a visual analogue scale. Data were evaluated by analysis of variance.

Results: Experimentally induced itch was significantly reduced by peripheral administration of HU210 (p < 0.05). Additionally, skin blood flow and neurogenic mediated flare responses were attenuated (p < 0.003 and p < 0.03, respectively), whereas protein extravasation due to histamine was enhanced by co-administration of HU210, as investigated by dermal microdialysis.

Conclusions: In humans peripheral administration of a cannabinoid receptor agonist attenuates histamine-induced itch. The observation that protein extravasation was not decreased demonstrates that the alleviation of itch is not due to an anti-histaminergic property of HU210. The reduced neurogenic flare reaction indicates an attenuated antidromic nerve fibre activation and neuropeptide release.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Topical
  • Adult
  • Axons / pathology
  • Cannabinoid Receptor Agonists*
  • Capillary Permeability / drug effects
  • Dronabinol / administration & dosage
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology*
  • Ethanol / pharmacology
  • Female
  • Histamine / toxicity*
  • Histamine Antagonists*
  • Humans
  • Iontophoresis
  • Male
  • Microdialysis
  • Proteins / metabolism
  • Pruritus / chemically induced
  • Pruritus / drug therapy
  • Regional Blood Flow / drug effects
  • Skin / blood supply
  • Skin / drug effects*
  • Skin / metabolism
  • Vasodilation / drug effects


  • Cannabinoid Receptor Agonists
  • Histamine Antagonists
  • Proteins
  • Ethanol
  • Dronabinol
  • Histamine
  • HU 211