Cardiovascular effects of delta-9-tetrahydrocannabinol in man

The effects o f a pharmacologic dose o f delta-9-tetrahydrocannabinol (Δ-9-THC) on the human circulatory system were investigated. Their relation to plasma drug levels, urinary catecholamine excretion, and psychic effects was observed. A-9-THC (0.3 mg. per kilogram) was administered orally to 8 male volunteers. Four subjects also received tracer amounts of C¹⁴-Δ-9-THC. Recumbent and upright heart rate, recumbent mean arterial blood pressure, forearm blood flow, and calculated forearm conductance all increased significantly following drug administration. Significant shortening of ventricular pre-ejection period and attenuation or abolition of reflex venoconstriction in response to a deep breath were also seen. Mean arterial pressure decreased transiently with head-up tilt and was associated with presyncope in 7 subjects, although cardioacceleratory response and forearm arteriolar constriction remained intact. Plasma levels of C¹⁴-Δ-9-THC and its metabolites were maximal at 3 hours. Gastrointestinal absorption was 95 per cent complete. Urinary excretion of free epinephrine was significantly higher during the 6 hour period following Δ-9-THC administration than during a similar control period. Free norepinephrine excretion was unchanged. Several of the cardiovascular effects seen appear to be consistent with increased sympathoadrenal activity. This suggests the possibility that augmented epinephrine secretion is in part responsible for these circulatory changes.