BRONCHIAL EFFECTS OF AEROSOLIZED DELTA-9-TETRAHYDROCANNABINOL IN HEALTHY AND ASTHMATIC SUBJECTS

Abstract

Effects on airway dynamics, heart rate and the CNS of various doses of .DELTA.9-tetrahydrocannabinol administered in a random, double blind fashion using a Freon-propelled, metered-dose nebulizer were evaluated in 11 healthy men and 5 asthmatic subjects. Effects of aerosolized .DELTA.9-tetrahydrocannabinol were compared with aerosolized placebo and isoproterenol and with 20 mg of oral and smoked .DELTA.9-tetrahydrocannabinol. In the normal subjects, after 5 to 20 mg of aerosolized .DELTA.9-tetrahydrocannabinol, specific airway conductance increased immediately, reached a maximum (33-41% increase) after 1-2 h, and remained significantly greater than placebo values for 2-3 hr. The bronchodilator effect of aerosolized .DELTA.9-tetrahydrocannabinol was less than that of isoproterenol after 5 min, but significantly greater than that of isoproterenol after 1-3 hr. The magnitude of bronchodilatation after all doses of aerosolized .DELTA.9-tetrahydrocannabinol was comparable, but 5 mg of .DELTA.9-tetrahydrocannabinol caused a significantly smaller increase in heart rate and level of intoxication than the 20-mg dose. Smoked .DELTA.9-tetrahydrocannabinol produced greater cardiac and intoxicating effects than either aerosolized or oral .DELTA.9-tetrahydrocannabinol. Side effects of aerosolized .DELTA.9-tetrahydrocannabinol included slight cough and/or chest discomfort in 3 of the 11 normal subjects. Aerosolized .DELTA.9-tetrahydrocannabinol caused significant bronchodilatation in 3 of 5 asthmatic subjects, but caused moderate to severe bronchoconstriction associated with cough and chest discomfort in the other 2. Aerosolized .DELTA.9-tetrahydrocannabinol, although capable of causing significant bronchodilatation with minimal systemic side effects, has a local irritating effect on the airways, which may make it unsuitable for therapeutic use.