ELSEVIER Drug and Alcohol Dependence 36 (1994) 227-236 Effects of marijuana history on the subjective, psychomotor, and reinforcing effects of nitrous oxide in humans Santosh Yajnik”, Pankaj Thapar”, J. Lance Lichtor”, Todd Patterson”, James P. Zacny*b aDepartmenr zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA of zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Anesthesia and Critical Care, MC 4028. University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637. USA bDepartment of Psychiatry, MC 4028, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637. LISA Received 26 June 1994; accepted 28 August 1994 Abstract An experiment using marijuana users and non-users was conducted to assess whether the reinforcing, subjective, or psychomotor effects of nitrous oxide were influenced by a subject’s drug history. Subjects in the first four sessions sampled 40% nitrous oxide in oxygen and 100% oxygen (placebo), and then over the next three sessions, chose which agent they wished to inhale. Choice distri- butions between the two groups did not differ significantly, and nitrous oxide choice rates were less than 50% in both groups. How- ever, a history of marijuana use appeared to intensify some of the subjective effects induced by nitrous oxide inhalation. Keywords: Nitrous oxide; History; Reinforcer; Subjective effects; Human 1. Introduction Nitrous oxide is commonly used by health profession- als for its anxiolytic, anesthetic, amnestic, and analgesic properties. Nitrous oxide has potent, but variable, sub- jective effects, and a number of studies have attempted to characterize these effects. Subjects either self-report negative mood effects such as dysphoria and fatigue (Block et al., 1988) or positive mood effects such as euphoria (Atkinson et al., 1979; Block et al., 1990; Gar- field et al., 1975; Henrie et al., 1961). Other studies have found individual differences in the mood-altering effects of nitrous oxide. Some subjects like the effects and others do not, in the same study with identical pro- cedures (Dohrn et al., 1992; Rosenberg, 1974; Timsit- Berthier et al., 1987). Collectively, these studies suggest that nitrous oxide has effects in some individuals which would counteract its use as a recreational drug and has effects in other individuals which would favor its use as a recreational drug. Nitrous oxide is indeed used recreationally by some * Corresponding author. humans (Gillman, 1992; Layzer, 1985) and serves as a reinforcer in animals (Grubman, 1981; Wood, 1977). In a series of studies in our laboratory, we sought to deter- mine if nitrous oxide serves as a reinforcer in non-drug abusing healthy volunteers. In three studies, 30 min of exposure to nitrous oxide ranging in concentrations from 20-40% did not function as a reinforcer in the ma- jority of healthy volunteers tested (Dohrn et al, 1993a,b). Given that nitrous oxide is used in the dental. setting for its sedative and anxiolytic effects and given that patients appear to find the effects of the gas to be pleasant (Jastak, 1975), we found the low choice rates in these experiments to be puzzling. However, we posited that one of the possible reasons for the low choice rates was the fact that we were using non-drug abusing volunteers. There is certainly evidence from both the infra-human and human behavioral pharmacology laboratory demon- strating that the behavioral and subjective effects of drugs, and the likelihood of using psychoactive drugs, is modulated by a subject’s drug history (Schuster and Johanson, 1981; Young et al., 1981; Barrett et al., 1989; Woolverton and Nader, 1990). In infra-humans, such be- 0376-8716/94/$07.00 0 1994 Elsevier Science Ireland Ltd. All rights reserved SS’DI 0376-8716(94)01052-M