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 μAmps) or dermal microdialysis (5 μM). 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.