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This review describes what is known about effects of marijuana and cannabinoids in relation to human physiological and disease outcomes. The acute physiological effects of marijuana include a substantial dose-dependent increase in heart rate, generally associated with a mild increase in blood pressure. Orthostatic hypotension may occur acutely as a result of decreased vascular resistance. Smoking marijuana decreases exercise test duration in maximal exercise tests, increases the heart rate at submaximal levels of exercise. Tolerance develops to the acute effects of marijuana smoking and Δ9-tetrahydrocannibol (THC) over several days to a few weeks. The cardiovascular responses that occur in response to THC are mediated by the autonomic nervous system, with recent findings also demonstrating that the human cannabinoid receptor system plays a role in regulating the cardiovascular response. Although several mechanisms exist by which marijuana use might contribute to the development of chronic cardiovascular conditions or acutely trigger cardiovascular events, there are few data regarding marijuana/THC use and cardiovascular disease outcomes. A large cohort study showed no association of marijuana use with cardiovascular disease hospitalization or mortality. However, acute effects of marijuana use include a decrease of the time until the onset of chest pain in patients with angina pectoris; one study has shown that marijuana may trigger the onset of myocardial infarction. Patients who have coronary heart disease or are at high risk for the development of CHD should be cautioned about the potential hazards of marijuana use as a precipitant for clinical events. Research directions might include more studies of cardiovascular disease outcomes and relationships of marijuana with cardiovascular risk factors, studies of metabolic and physiologic effects of chronic marijuana use that may affect cardiovascular disease risk, increased understanding of the role of the cannabinoid receptor system in cardiovascular regulation, and studies to determine if there is a therapeutic role for cannabinoids in blood pressure control or for neuroprotection after stroke.