Development of Rodent Self-Administration Vapor Inhalation Chambers for THC

THC 啮齿动物自我管理蒸气吸入室的开发

• 批准号: 9247937
• 负责人: Maury D. Cole
• 金额: $ 48.92万
• 依托单位: LA JOLLA ALCOHOL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9247937
• 关键词: 21 year old; Absence of pain sensation; Adolescent; Adopted; Adult; Air; Alcoholism; Alcohols; Animals; Behavioral; Breathing; Cannabinoids; Cannabis; Catalepsy; Cognitive; Data; Dependence; Development; Devices; Dose; Drug Kinetics; Drug usage; Electronic cigarette; Elements; Exposure to; Extinction (Psychology); Failure; Female; Funding; Future; Genetic; Geographic state; Goals; Heroin; Individual; Inhalation Exposure; Injectable; Intravenous; Investigation; Laboratories; Laws; Legal; Lung; Marijuana; Marijuana Abuse; Marijuana Dependence; Medical; Medical Marijuana; Modeling; Motor Activity; Multiple Sclerosis; National Institute of Drug Abuse; Nicotine; Nose; Oral mucous membrane structure; Pharmaceutical Preparations; Phase; Physiologic Thermoregulation; Physiological; Plasma; Probability; Procedures; Propylene Glycols; Psychotropic Drugs; Rattus; Reporting; Research; Rodent; Rodent Model; Route; Sativex; Self Administration; Self-Administered; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Smoke; System; Technology; Testing; Tetrahydrocannabinol; Therapeutic; Time; Work; alcohol research; cocaine use; commercialization; design; drug seeking behavior; ecstasy; experimental study; improved; innovation; instrumentation; male; marijuana use; member; neurochemistry; prototype; public health relevance; recreational drug use; reinforcer; response; symptomatic improvement; trend; twelfth grade; vaping; vapor

 DESCRIPTION (provided by applicant): This SBIR Phase II proposal will enhance the pace of development and support the eventual commercialization of a self-administration vapor inhalation chamber system for the intrapulmonary delivery to rats of ∆9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis. Cannabis remains the most popular illicit psychoactive drug used in the US. Some 70-80% of 40-50 year olds have tried cannabis at least once in their lifetime and 18-19% of 18-21 year olds have used cannabis in the past month. There are more people in the US who meet criteria for cannabis dependence than have used cocaine in the past month or ever tried heroin. It is of further concern that the use of cannabis under medical marijuana laws continues to expand. Further mechanistic understanding of how dependence of THC develops and the discovery of therapeutics is an increasingly critical goal, yet progress has been slowed by the failure of rats to readily self-administer THC by the traditional intravenous route. The studies in this project seek to further refine our instrumentation to create a reliable rat model of THC self-administration via vapor inhalation. Studies under Specific Aim 1 will assess the pharmacokinetic distribution of THC as well as effects of intrapulmonary exposure on thermoregulation, locomotor activity, catalepsy, and analgesia, to determine necessary exposure parameters. The goal is to achieve well-controlled exposure under a broad range of plasma THC levels which range from threshold of behavioral effects to doses which can produce dependence with repeated exposure. Studies under Aim 2 will establish dependence on THC as well as operant self-administration using delivery of volatilized THC as a reinforcer. Studies under Aim 3 will test specific instrumentation design changes dictated by Aims 1 and 2, as well as by the preliminary data detailed in the Research Strategy.

 描述（由申请人提供）：SBIR第二阶段提案将加快开发步伐，并支持用于向大鼠肺内递送大麻的主要精神活性成分1，9-四氢大麻酚（THC）的自我给药蒸汽吸入室系统的最终商业化。大麻仍然是美国最流行的非法精神活性药物。在40-50岁的人群中，约有70-80%的人一生中至少尝试过一次大麻，18-21奥尔兹中有18-19%在过去一个月内使用过大麻。在美国，符合大麻依赖标准的人比过去一个月使用可卡因或尝试过海洛因的人还要多。令人进一步关切的是，根据医用大麻法使用大麻的情况继续扩大。进一步了解THC依赖性如何发展和发现治疗方法是一个越来越重要的目标，但由于大鼠无法通过传统的静脉注射途径容易地自我施用THC，因此进展缓慢。本项目中的研究旨在进一步完善我们的仪器，以通过蒸汽吸入创建THC自我给药的可靠大鼠模型。具体目标1下的研究将评估THC的药代动力学分布以及肺内暴露对体温调节、自发活动、僵住症和镇痛的影响，以确定必要的暴露参数。目标是在广泛的血浆THC水平范围内实现良好控制的暴露，范围从行为效应的阈值到重复暴露可产生依赖性的剂量。目标2下的研究将确定对THC的依赖性以及使用挥发的THC作为释放剂的操作性自我给药。目标3下的研究将测试特定的仪器 目标1和2以及研究策略中详细说明的初步数据所规定的设计变更。