Co-Abuse Cannabis and Tobacco

项目摘要 烟草和大麻是美国最常滥用的两种物质。此外，本发明还 同时使用大麻和烟草多种物质的情况并非不多，而且呈上升趋势 因为大麻的使用在越来越多的国家合法化。这种上升趋势尤其令人关注 因为，与不使用烟草的大麻相比，CT-PSU与更大的大麻有关 依赖、心理社会问题和较差的戒烟结果，以及附加的健康风险， 相对于单独的物质。确定CT-PSU的基本机制将需要协调 流行病学、临床前和人体实验室研究。然而，每个学科中的模型和度量 最常用于检查CT-PSU的方法是为了研究单一药物的使用， 捕捉CT-PSU的独特功能。在拟议的项目中，CT-PSU的模式将通过 制定和实施专门针对CT-PSU（R21阶段）的新调查措施。在 此外，还将建立和验证小鼠吸入尼古丁自我给药的程序 同时收集流行病学数据。随后，这两项努力的结果将指导决策 关于用于研究Δ9-四氢大麻酚（THC; 大麻的主要精神活性替代物）对吸入尼古丁的增强作用（即，“追逐”）和 同时施用的两种药物的增强作用（例如，如在钝头或钝头中）在小鼠和人中 吸烟者和不吸烟者。这一具有指导意义的做法将导致建立 更好的模型，通过它来调查CT-PSU，最终目标是发现其潜在的 机制和发展有针对性的治疗方法。

PROJECT SUMMARY Tobacco and cannabis are two of the most commonly abused substances in the United States. Further, simultaneous cannabis and tobacco polysubstance use (CT-PSU) is not insubstantial and is trending upwards as cannabis use is legalized in an increasing number of states. This upward trend is of particular concern because, compared to use of cannabis without tobacco, CT-PSU is associated with greater cannabis dependence, psychosocial problems, and poorer cessation outcomes, as well as with additive health risks, relative to either substance alone. Determination of mechanisms underlying CT-PSU will require coordinated epidemiological, preclinical, and human laboratory studies. Yet, the models and measures in each discipline that are used most often to examine CT-PSU were developed to investigate single drug use and may not capture unique features of CT-PSU. In the proposed project, patterns of CT-PSU will be characterized through development and implementation of novel survey measures that focus specifically on CT-PSU (R21 phase). In addition, a procedure for inhaled nicotine self-administration in mice will be established and validated simultaneously with epidemiological data collection. Subsequently, results from both efforts will guide decisions regarding experimental parameters to be used to investigate the effects of Δ9-tetrahydrocannabinol (THC; primary psychoactive substituent of cannabis) on inhaled nicotine’s reinforcing effects (i.e., “chasing”) and the reinforcing effects of both drugs administered simultaneously (e.g., as in blunts or spliffs) in mice and in human tobacco smokers and non-smokers. This translationally relevant approach will result in the establishment of better models through which to investigate CT-PSU, with the ultimate goals of discovery of its underlying mechanisms and development of targeted treatment approaches.