Effects and Interactions of Natural Cannabinoids on the Isolated Heart

Abstract A Langendorff perfused rat heart preparation was designed to process dose-response effects of cardioactive drugs on rate, coronary flow, and supraaortic differential pressure (ΔP; an index of cardiac performance). In this preparation, Δ9--tetrahydrocannabinol (THC) 2 × 10-6 M to 10-5 M induces in the isolated perfused rat heart a biphasic increase in rate (maximal at 8 × 10-6 M). Tachycardia is associated with decreases in (ΔP) and no change or decreased coronary flow. Cardiac toxicity is observed with 3 × 10-5 M. Cannabidiol (CBD) at concentrations of 9 × 10-6 M to 10-4 M has limited effect on rate while increasing ΔP and coronary flow. Cannabinol (CBN) 8 × 10-6 M to 3 × 10-4 M depresses rate and ΔP while coronary flow remains constant. Simultaneous equimolar administration of THC with CBD antagonizes or mitigates the cardiac effects of THC on rate, ΔP, and coronary flow.