The therapeutic potential of
cannabinoids has been studied and investigated through centuries, although many interesting discoveries have emerged from this field in the past decades. Indeed, peripheral
analgesic effects of
cannabinoids are a new avenue of treatment since they are avoiding the deleterious central side effects of systemic administration. Recently, it has been demonstrated that
cannabinoid receptors (more specifically CB(1) and CB(2) receptors) and their endogenous
ligands are present at the peripheral level, especially in different layers of skin, and mostly, in the epidermis and dermis. Those findings are reinforcing and confirming the efficacy of peripheral administration of
cannabinoids used to alleviate
pain in many different animal models. However, many studies have shown that the
endocannabinoid system interacts with other receptors and pathways to modulate
pain at the peripheral level. Thereof, the main goal of this review is to explain, in a better way, the different interactions regarding the
cannabinoid system with other cellular components of its environment, its involvement in the modulation of
pain at the peripheral level and, more precisely, in different layers of the skin.