Attenuation of Allergic Contact Dermatitis Through the Endocannabinoid System

Meliha Karsak,^1* Evelyn Gaffal,^2* Rahul Date,¹ Lihua Wang-Eckhardt,³ Jennifer Rehnelt,¹ Stefania Petrosino,⁴ Katarzyna Starowicz,⁴ Regina Steuder,² Eberhard Schlicker,⁵ Benjamin Cravatt,⁶ Raphael Mechoulam,⁷ Reinhard Buettner,⁸ Sabine Werner,⁹ Vincenzo Di Marzo,⁴ Thomas Tüting,² Andreas Zimmer¹

Abstract: Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity, we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase–deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated allergic inflammation, whereas receptor agonists attenuated inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin and suggest a target for therapeutic intervention.

¹ Department of Molecular Psychiatry, University of Bonn, Germany.
² Laboratory of Experimental Dermatology, Department of Dermatology, University of Bonn, Germany.
³ Life & Brain GmbH, Bonn, Germany.
⁴ Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (Napoli), Italy.
⁵ Institute of Pharmacology and Toxicology, University of Bonn, Germany.
⁶ The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
⁷ Department of Medicinal Chemistry and Natural Products, The Hebrew University of Jerusalem, Israel.
⁸ Department of Pathology, University of Bonn, Germany.
⁹ Institute of Cell Biology, Eidgenössische Technische Hochschule, Zurich, Switzerland.

To whom correspondence should be addressed. E-mail: a.zimmer{at}uni-bonn.de (A.Z.); thomas.tueting{at}ukb.unibonn.de (T.T.)

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