Artherosclerosis

Letters to Nature

Nature 434, 782-786 (7 April 2005) | doi:10.1038/nature03389; Received 26 October 2004; Accepted 21 January 2005

There is a Corrigendum (26 May 2005) associated with this document.

Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice

Sabine Steffens1, Niels R. Veillard1,5, Claire Arnaud1,5, Graziano Pelli1, Fabienne Burger1, Christian Staub3, Andreas Zimmer4, Jean-Louis Frossard2and François Mach1

  1.  Division of Cardiology, Department of Medicine, Foundation for Medical Research, University Hospital, Faculty of Medicine, 1211 Geneva, Switzerland
  2.  Division of Gastroenterology, University Hospital, Faculty of Medicine, 1211 Geneva, Switzerland
  3.  Institute of Legal Medicine, University Hospital, Faculty of Medicine, 1211 Geneva, Switzerland
  4.  Laboratory for Molecular Neurobiology, Department of Psychiatry, University of Bonn, 53105 Bonn, Germany
  5.  These authors contributed equally to this work

Correspondence to: François Mach1 Correspondence and requests for materials should be addressed to F.M. (Email: Francois.Mach@medecine.unige.ch).

Atherosclerosis is a chronic inflammatory disease, and is the primary cause of heart disease and stroke in Western countries1. Derivatives of cannabinoids such as delta-9-tetrahydrocannabinol (THC) modulate immune functions2 and therefore have potential for the treatment of inflammatory diseases. We investigated the effects of THC in a murine model of established atherosclerosis. Oral administration of THC (1 mg kg-1 per day) resulted in significant inhibition of disease progression. This effective dose is lower than the dose usually associated with psychotropic effects of THC. Furthermore, we detected the CB2 receptor (the main cannabinoid receptor expressed on immune cells2, 3) in both human and mouse atherosclerotic plaques. Lymphoid cells isolated from THC-treated mice showed diminished proliferation capacity and decreased interferon-pastedgraphic-2_textmedium secretion. Macrophage chemotaxis, which is a crucial step for the development of atherosclerosis1, was also inhibited in vitro by THC. All these effects were completely blocked by a specific CB2 receptor antagonist4. Our data demonstrate that oral treatment with a low dose of THC inhibits atherosclerosis progression in the apolipoprotein E knockout mouse model, through pleiotropic immunomodulatory effects on lymphoid and myeloid cells. Thus, THC or cannabinoids with activity at the CB2 receptor may be valuable targets for treating atherosclerosis.

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