Melanoma causes the greatest number of skin cancer-related deaths worldwide. Despite intensive research, prevention and early detection are the only effective measures against melanoma, so new therapeutic strategies are necessary for the management of this devastating disease. Here, we evaluated the efficacy of cannabinoid receptor agonists, a new family of potential antitumoral compounds, at skin melanoma. Human melanomas and melanoma cell lines express CB1 and CB2 cannabinoid receptors. Activation of these receptors decreased growth, proliferation, angiogenesis and metastasis, and increased apoptosis, of melanomas in mice. Cannabinoid antimelanoma activity was independent of the immune status of the animal, could be achieved without overt psychoactive effects...