Ethanol increases plasma Δ9-tetrahydrocannabinol (THC) levels and subjective effects after marihuana smoking in human volunteers
Introduction
Polydrug use has increased over the last two decades with marihuana and alcohol being a popular combination (Grupp, 1972, Stein et al., 1983, Norton and Colliver, 1987). The use of marihuana by young adults is still high as 11.4, 21.8 and 11.5% of 12–17, 18–25 and 26–34 year olds, respectively reported using marihuana in the last year (Substance Abuse and Mental Health Services Administration, 1996). With the recent change in some state laws in the US allowing the use of oral Δ9-tetrahydrocannabinol (THC) for medical reasons, and the widespread use of alcoholic beverages, the incidence of using these two together may actually increase. Over the past 11 years, we have been tracking the reasons for using various drugs given by our subjects who participate in drug challenge studies by having them fill out a polydrug use questionnaire. About 70% of the 97 subjects queried reported that ‘to get a better high’ was the most important reason for combining alcohol and marihuana and 23–25% reported that they used the second drug to enhance the effects of the first drug (S. Lukas, pers. commun.).
Alcohol and marihuana combinations impair performance on various tasks more than those of either drug separately, but it is unclear why alcohol/marihuana combinations are so popular. Potentiation of intoxicating effects have been reported with smoked marihuana (Chait and Perry, 1994), and cognitive, perceptual and motor function tests are impaired more when ethanol is combined with oral THC (Chesher et al., 1976, Chesher et al., 1977, Bird et al., 1979, Belgrave et al., 1979a). One explanation may be that alcohol potentiates marihuana's effects on mood, producing a greater ‘high’ (Manno et al., 1971, Hollister, 1976). Even though pharmacodynamic interactions between marihuana and alcohol have been well documented (Benowitz and Jones, 1977, Consroe et al., 1979, Belgrave et al., 1979b, Perez-Reyes et al., 1988b, Lukas et al., 1992), the mechanism by which alcohol potentiates the behavioral effects of marihuana is unknown. The principal psychoactive component of marihuana, THC, has a high lipid-solubility and is rapidly transported from the bloodstream to the central nervous system. Thus, estimates of such interactions using plasma THC levels alone may be difficult because tissue or organ levels may still be substantial even as blood levels approach zero (Hunt and Jones, 1980).
One possible mechanism of this alcohol/marihuana interaction is that these drugs may alter the pharmacokinetic profile of each other. Several studies have focused on the effects of marihuana smoking on ethanol kinetics, and the majority of laboratories have found that blood ethanol levels are reduced after marihuana smoking (Benowitz and Jones, 1977, Consroe et al., 1979, Lukas et al., 1992), although one study found that the levels did not change (Belgrave et al., 1979a).
Fewer studies have been directed at exploring the reverse order of drug administration — the effects of ethanol on plasma THC levels. Although Perez-Reyes et al. (1988b) reported that plasma THC levels were increased (but not significantly) by ethanol, we decided to re-analyze the data from our earlier ethanol/marihuana study in which we reported only on the effects of marihuana smoking on plasma ethanol levels (Lukas et al., 1992). The aim of the present study was to analyze the plasma THC level data as a function of ethanol dose. Since ethanol causes peripheral vasodilation (Altura and Altura, 1982), we hypothesized that it would increase the absorption of THC in subjects who smoked marihuana with a concomitant increase in positive or good subjective mood effects.
Section snippets
Subjects
All procedures and consents were approved by the McLean Hospital Institutional Review Board. Informed consent was obtained from 22 healthy male Caucasian volunteers; the demographic profile of the subjects is depicted in Table 1. Subjects reported using marihuana (1.5–2 joints per week) and alcohol (4–8 beers per week) on an occasional basis. None of the variables, including drug use history and current use patterns of licit and illicit drugs, differed significantly among the three treatment
THC levels
THC levels were not detected in the plasma of any of the subjects who smoked placebo marihuana (data not shown). Fig. 1 depicts the effects of ethanol on plasma THC levels after subjects smoked either the low (left) or the moderate (right) dose marihuana cigarette. An analysis of the ascending phase data (t=0–15 min) revealed an ethanol main effect (F(2,3)=8.19, P<0.02); post hoc paired sample t-test revealed that these increases in plasma THC levels were significant for the placebo versus
Discussion
We reported earlier that marihuana smoking actually slows the absorption of ethanol, and as a result, reduces ethanol's psychoactive effects (Lukas et al., 1992). The present study considered the reverse relationship and provides a pharmacological and pharmacokinetic explanation for why individuals use ethanol/marihuana combinations. In the present study, plasma THC levels were significantly increased when subjects had first consumed ethanol. The reason why significant increases in THC levels
Acknowledgements
The authors thank Craig Bushong, M.D. for medical consultation, Leslie Amass, Ph.D., Michele Sholar, Laurie Sholar, Stephen Whalen, Rosemary Smith and Howard Gelles for technical support, and Eleanor DeRubeis and Carol Buchanan for administrative support. Supported by Grants DA 03994 and DA 00343 from the National Institute on Drug Abuse.
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