Intravenous delta9-Tetrahydrocannabinol: Effects of ventilatory control and cardiovascular dynamics.

Delta9-Tetrahydrocannabinol (THC), the active component of marijuana, was studies to determine whether it might be useful for preanesthetic medication. Ten healthy subjects received THC intravenously in logarithmically spaced incremental doses. Four subjects received a total cumulatine dose of 135 mug/kg and four others, 201 mug/kg, Two of the ten subjects discontinued the study because of anxiety reactions. Ventilatory minute volume at a controlled elevated CO2 tension, 48 plus or minus 2 (SD) torr, changed minimally with TCH, -0.49 1/min/50 per cent increase in dose. TCH shifted the ventilatory response to CO22.7 torr destrad at 20 1/min without a change in slope. Dose-related tachycardia was the most marked cardiovascular effect. Heart rates increased to more than 100/min in five of six subjects. Cardiac index increased from 4.04 plus or minus 0.62 1/min/m-2 before TCH to 6.92 plus or minus 2.34 1/min/m-2 after 134 mug/kg. Mean arterial pressure increased slightly, and total peripheral resistance fell. The cardiovascular changes suggest beta-adrenergic stimulation. Intense mental effects and anxiety prohibited higher THC doses.

Combination of delta9-tetrahydrocannabinol with oxymorphone or pentobarbital: Effects on ventilatory control and cardiovascular dynamics.

Marijuana is widely used, yet few data concerning its actions combined with other drugs exist. Psychologic, respiratory and cardiovascular effects of delta9-tetrahydrocannabinol (THC), the active component of marijuana, combined with oxymorphone (OXM) or with pentobarbital (PBL), were studies in 15 healthy volunteers. Oxymorphone, 1.0 mg/70 kg, iv, caused sedation and ventilatory depression (minute ventilation: 24.9 plus or minus 11.9 SD to 14.1 plus or minus 4.9 1/min with PETCO2 held at 50 torr) in eight volunteers. TCH (27, 40, 60, 90, and 134 mug/kg, iv) increased sedation and further decreased ventilation with each TCH dose to 6.6 plus or minus 3.7 1/min after 134 mug/kg. The combination of OXM and THC decreased the CO2-ventilation slope from 2.23 to 0.88 1/min/torr. When THC, 134 mug/kg, was added to OXM, which alone caused no significant cardiovascular change, cardiac index (4.1 plus or minus 1.3 to 5.0 plus or minus 2.2 1/min/m-2) and heart rate (66 plus or minus 12 to 107 plus or minus 31 beats/min) significantly increased and total peripheral resistance (1,030 plus or minus 260 to 660 plus or minus 200 dynes-sec/cm-5) decreased. Heart rates exceeded 150 beats/min in two subjects after 27 and 134 mug/kg THC. Pentobarbital alone, 100 mg/70 kg, iv, caused no significant ventilatory or cardiovascular change. THC, after PBL pretreatment, induced hallucinations and anxiety in five of seven volunteers; four failed to complete all five doses of THC becuase of the severe psychologic effects. The combination of PBL and 40 to 134 mug/kg THC did not affect ventilation significantly. After PBL pretreatment, THC significantly increased heart rate (76 plus or minus 17 to 130 plus or minus 32 beats/min). Cardiac index also increased (3.8 plus or minus 0.8 to 5.6 plus or minus 1.9 1/min/m-2) and total peripheral resistance decreased (1,070 plus or minus 240 to 720 plus or minus 300 dynes-sec/cm-5). Three subjects developed heart rates esceeding 150 beats/min after 27, 27, and 90 mug/kg THC; in all three, heart rates fell from maximal value with a further dose of THC.

Effects of acute and chronic ethanol administration on isoflurane requirement in mice.

Inspired isoflurane concentration for anesthetizing 50 percent of adult albino mice (ED50) was 1.33 percent (1.20 to 1.47, 95 percent confidence interval). Ethanol anesthetizing dose was 5.09 (4.74 to 5.47) gm./kg. intraperitoneally (I.P.). Twenty, 39, and 79 percent of this ethanol anesthetic dose reduced isoflurane ED50 by 0, 8, and 70 percent, respectively. Thus, acute combinations of ethanol and isoflurane are more effective than either alone but less than the expected sum. Mice receiving no other fluid than 10 percent alcohol developed cross-tolerance to isoflurane. After 10 days of continuous alcohol ingestion, isoflurane ED50 increased to 1.54 (1.36 to 1.75) and after 20 days to 1.69 (1.55 to 1.84) percent. Combined with 2 and 4 gm./kg. of alcohol I.P., isoflurane ED50 in these mice decreased to 1.34 (1.26 to 1.42) and 0.73 (0.62 to 0.85) percent. Cross-tolerance acquired by these alcohol-consuming mice persisted through 55 days after stopping alcohol (ED50 1.65 percent), but returned to control values after 80 days (1.32 percent).