Ethanol increases plasma delta-9-tetrahydrocannabinol (THC) levels and subjective effects after marihuana smoking in human volunteers Scott E. Lukas, and Sara Orozco1 McLean Hospital/Harvard Medical School, Behavioral Psychopharmacology Research Laboratory, East House III, 115 Mill Street, Belmont, MA 02478-9106. Drug and Alcohol Dependence 64(2): 143-149, 1 October 2001. Abstract Marihuana and alcohol are often used together, yet little is known about why they are combined. Male volunteers were assigned to one marihuana treatment group (placebo, low or moderate dose delta-9-tetrahydrocannabinol [THC]) and, on three separate study days, they also drank a different dose of ethanol (placebo, 0.35 or 0.7 g/kg). Plasma THC levels and changes in subjective mood states were recorded for 90 min after smoking. For many of the drug combinations, when subjects consumed ethanol they detected marihuana effects more quickly, reported more episodes of euphoria and had higher plasma THC levels than when they consumed placebo ethanol. These data suggest that ethanol may increase the absorption of THC resulting in an increase in the positive subjective mood effects of smoked marihuana and contributing to the popularity of this drug combination. [from the body of the article...] There are two possible explanations for this finding. The first is that ethanol-induced changes in vascular smooth muscle (Altura and Altura, 1982) may have increased the absorption of THC during each inhalation. Acute administration of ethanol lowers blood pressure and causes peripheral vasodilation ( Nakano; Altura and Friedman), and regardless of the route of administration, ethanol also dilates precapillary sphincters, arterioles and muscular venules in a dose-dependent manner (Altura; Altura and Altura). Further, norepinephrine-, epinephrine-, angiotensin-, serotonin-, vasopressin- and prostaglandin-induced vasoconstriction are blocked by ethanol (Nakano; Altura and Friedman). Although the precise mechanism of this effect is unknown, it is suspected to be due to ethanol-induced interference with the translocation of Ca2+ across vascular membranes (Altura and Altura, 1982). Thus, dilation of the pulmonary microcirculation would permit more THC to traverse the alveolar sac/capillary membrane with each inhalation. The second possible explanation for these findings is that alcohol may have altered marihuana smoking topography or the depth of inhalation during smoking. There is a report of such an effect on tobacco smoking topography (Griffiths et al., 1976), and so a standardized smoking procedure was used in the present study to minimize the variance. While there was some variance in the time it took to smoke the cigarette and the number of puffs each subject took, there were no systematic differences related to ethanol dose, yet the placebo marihuana cigarettes did burn faster than the two active doses. If ethanol had increased the depth of inhalation (which was not measured in this study), then the cigarettes would most likely have burned more quickly, and the subjects would have used fewer puffs to reach the 10 mm line. Nevertheless, a greater depth of inhalation per puff could result in higher plasma THC levels and increased subjective effects-- an effect that may very well occur in real world scenarios of polydrug use.
