Fifty-five clinical trials were conducted to determine the cardiovascular combined effects of stressful oral surgery and systemic cannabinols. In a first study, delta9-tetrahydrocannabinol (THC) was given IV as a premedicant and compared with diazepam and with a placebo. A classic dose-related tachycardia followed THC injection. The peak heart rate response of patients premedicated with 0.044 mg/kg THC was 24.1% higher (p less than 0.05) than the peak effect for a nonsurgerized control group, suggesting a synergistic effect between THC and surgical stress. A predisposition to syncopal hypotension followed THC premedication, and antiarrhythmic effects were observed after large doses. The injection of local anesthetic preparations containing epinephrine did not alter THC cardiovascular response. An apparent drug interaction was observed, however, in a second study, in patients given general anesthesia within 72 hours after smoking marijuana. These patients demonstrated sustained abnormal postoperative tachycardia when compared with control nonsmokers, an effect which may have resulted from an interaction between stored cannabinol metabolites and atropine administered as part of the anesthetic technic. It was concluded that THC had no particular advantage over diazepam or placebo as a premedicant. Further, THC altered the patients' adaptivity to stress and interacted undesirably with other anesthetic medications.