Development of Rodent Self-Administration Vapor Inhalation Chambers for THC



 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.