Cardiovascular and metabolic considerations in prolonged cannabinoid administration in man.

Safe therapeutic use of cannabinoids for prolonged periods of time requires an appreciation of pharmacologic actions with both acute and repetitive administration. Cardiovascular effects of acute delta 9-tetrahydrocannabinol (THC) administration included increased sympathetic and reduced parasympathetic tone, although sympathetic reflex responses were impaired. Thus, supine tachycardia and increased blood pressure with upright hypotension are observed. With repetitive dosing, there is a transition from increased to decreased sympathetic activity and from decreased to increased parasympathetic activity, and blood volume substantially increases. As a result, supine bradycardia and decreased blood pressure with tolerance to orthostatic hypotension are observed. Relevance of these observations to management of patients with THC, including considerations of potential drug interactions, is discussed. In other experiments, THC and cannabidiol were found to inhibit metabolism of other drugs (antipyrine and barbiturates) metabolized by liver mixed-function oxidase enzymes. Potential inhibition of drug metabolism must be considered in evaluating responses to chemotherapeutic agents in cancer patients receiving THC and responses to coadministered anticonvulsants in epileptic patients receiving cannabidiol.