Marijuana's Acute Effects on Risk Taking, Sexual/HIV risk, and Impulsivity

描述（由申请人提供）：尽管大麻使用与鲁莽驾驶、性传播疾病和HIV等冒险行为存在关联，但大麻对冒险和冲动的急性效应的对照研究有限，大麻增加这些行为的机制尚未建立。delta-9-四氢大麻酚（THC）的药理作用和大麻损害判断力或使人去抑制的预期都可能导致受控认知加工的缺陷，对负面后果的低估，以及随后在大麻影响下的风险承担增加。平衡安慰剂设计（BPD）是确定药物效应的最佳方法，独立于被告知药物被消耗的预期效应。与酒精和尼古丁的BPD研究相比，大麻对药物预期对行为的影响的研究很少。这个新研究者R01的主要假设是，药物效应和大麻预期操纵都将独立地a)增加冒险的计算机测量倾向，b)增加延迟奖励的折扣，c)降低抑制冲动的能力，d)在行为和自我报告测量中增加性风险的预期参与。在一个2（教学组：被告知THC vs.不被告知THC） X 2（药物管理：大麻含THC vs.安慰剂）受试者之间的BPD中，我们将对124名非依赖性18-25岁大麻吸烟者进行中等（2.5%）剂量的THC独立于大麻预期对这些措施的药理学作用进行研究。受试者将在基线/不吸烟条件下进行测试，并随机分配到4种BPD条件中的一种，一周后在大麻/安慰剂下进行测试。将收集DMA样本进行CNR1基因的候选基因分型，这可能会获得关于四氢大麻酚药理作用的额外信息。本研究首次评估了大麻的药理学和预期的独立作用，这可能有助于理解大麻与高危行为的关联。Lay description：我们需要理解为什么人们在使用大麻时更愿意冒诸如毒品驾驶或不安全性行为等风险。这项研究通过将药物的实际效果与安慰剂和对大麻的看法区分开来，可能有助于理解冒险和冲动决策的过程。

DESCRIPTION (provided by applicant): 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.