Understanding the pharmacodynamics of cannabinoids is an essential subject due to the recent increasing global acceptance of cannabis and its derivation for recreational and therapeutic purposes. Elucidating the interaction between cannabinoids and the vascular system is critical to exploring cannabinoids as a prospective therapeutic agent for treating vascular-associated clinical conditions. This review aims to examine the effect of cannabinoids on the vascular system and further discuss the fundamental pharmacological properties and mechanisms of action of cannabinoids in the vascular system. Data from literature revealed a substantial interaction between endocannabinoids, phytocannabinoids, and synthetic cannabinoids within the vasculature of both humans and animal models. However, the mechanisms and the ensuing functional response is blood vessels and species-dependent. The current understanding of classical cannabinoid receptor subtypes and the recently discovered atypical cannabinoid receptors and the development of new synthetic analogs have further enhanced the pharmacological characterization of the vascular cannabinoid receptors. Compelling evidence also suggest that cannabinoids represent a formidable therapeutic candidate for vascular-associated conditions. Nonetheless, explanations of the mechanisms underlining these processes are complex and paradoxical based on the heterogeneity of receptors and signaling pathways. Further insight from studies that uncover the mechanisms underlining the therapeutic effect of cannabinoids in the treatment of vascular-associated conditions is required to determine whether the known benefits of cannabinoids thus currently outweigh the known/unknown risks.
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