Acute and subacute bronchial effects of oral cannabinoids.

The bronchodilating activity of oral cannabinoids was evaluated in three double-blind experiments that involved the study of dose-response and interactive relationships and the potential development of tolerance. Data indicated that delta 8-tetrahydrocannabinol (delta 8-THC), cannabinol (CBN), and cannabidiol (CBD) in maximal doses of 75 mg, 1200 mg, and 1200 mg, respectively, did not induce significant dose-related physiologic effects in experienced marijuana smokers. delta 8-THC (75 mg) was, however, associated with bronchodilation, tachycardia, and peak highs less than that after delta 9-tetrahydrocannabinol (delta 9-THC). The combinations of CBN and CBD with low-dose delta 9-THC (5 mg) did not induce significant bronchodilation but did exert interactive effects on heart rate and "high." A 20-day study of daily delta 9-THC (20 mg), CBN (600 mg), and CBD (1200 mg) did not indicate tolerance or reverse tolerance to any drug. We conclude that delta 9-THC and, to a lesser extent, delta 8-THC, have acute bronchodilator activity but that CBN, CBD, and their combinations do not provide effective bronchodilation. The daily use of delta 9-THC was not associated with clinical tolerance.