The reasons why individuals use this combination are not entirely clear, however, it has been speculated that marihuana may potentiate cocaine's subjective effects. Five male recreational drug users provided informed consent and volunteered to participate in this study. Each subject participated on 3 different days, separated by at least 1 week. Subjects sat in an isolated chamber and were prepared with electrocardiographic (ECG) electrodes for heart rate monitoring and an IV catheter for blood withdrawal. After adapting to the experimental chamber, they smoked a marihuana cigarette containing either 0.004% (placebo), 1.24%, or 2.64% delta 9-tetrahydrocannabinol (THC). Thirty minutes later they received an intranasal dose of 0.9 mg/kg cocaine. On subsequent visits, the marihuana dose was varied on a random basis. Subjects continuously reported changes in their mood state via an instrumental joystick device and filled out visual analog scales. Marihuana-induced tachycardia was increased even more after cocaine. The duration of all marihuana- and cocaine-related positive subjective effects was unchanged when both drugs were given, but marihuana pretreatment significantly reduced the latency to cocaine effects, from 1.87 to 0.53 min, and decreased the duration of dysphoric or bad effects, from 2.1 to 0.5 min. Peak plasma cocaine levels were 122.8 +/- 26.6 ng/ml after placebo marihuana, but pretreatment with the high-dose marihuana resulted in a significant increase in peak cocaine levels (233.8 +/- 19.2 ng/ml) and the apparent bioavailability as determined by area under the curve (AUC) analysis. We conclude that marihuana-induced vasodilation of the nasal mucosa attenuates the vasoconstrictive effects of cocaine and thus increases its absorption.