Despite associations between marijuana use and risk-taking behaviors including reckless driving, sexually transmitted diseases and HIV, controlled research on marijuana's acute effects on risk taking and impulsivity is limited, and the mechanism whereby marijuana may increase such behaviors has not been established. Both the pharmacologic effect of delta-9-tetrahydrocannabinol (THC) and the expectancy that marijuana impairs judgment or makes one disinhibited may lead to deficits in controlled cognitive processing, discounting of negative consequences, and subsequent increases in risk taking under the influence of marijuana. The balanced-placebo design (BPD) is the optimal method for determining pharmacologic effects independent of the expectancy effects of being told that drug was consumed. In contrast to research with alcohol and nicotine BPD, there is little research with marijuana on effects of drug expectancy on behavior. The primary hypotheses in this new investigator R01 are that both the pharmacologic effect and marijuana expectancy manipulation will independently a) increase propensity to take risks on a computerized measure of risk taking, b) increase discounting of delayed rewards, c) decrease ability to inhibit prepotent responses on two impulsivity measures, and d) increase expected involvement in sexual risk on behavioral and self- report measures. In a 2 (instructional set: told THC vs. told no THC) X 2 (drug administration: marijuana with THC vs. placebo) between-subjects BPD, we will examine the pharmacologic effect of a moderate (2.5%) dose of THC independent of marijuana expectancies on these measures with 124 nondependent 18-25 y.o. marijuana smokers. Individuals will be tested under baseline/no smoking condition and randomly assigned to one of 4 BPD conditions to be tested under marijuana/placebo 1 week later. DMA samples will be collected for candidate genotyping of the CNR1 gene, which may yield additional information on the pharmacologic effect of THC. This study is the first to evaluate the independent effects of marijuana pharmacology and expectancies, which may facilitate the understanding of marijuana's association with high risk behaviors. Lay description: We need to understand why people take more risks such as drug driving or involvement in unsafe sex when using marijuana. This research may help understand the process of risk taking and making impulsive decisions by separating the actual drug effects from those of placebo and beliefs about marijuana. ? ? ? ? ? ?
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