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.
Public Health Relevance Statement: Public Health Relevance: Use of marijuana (and therefore the main active constituent ?9-tetrahydrocannabinol; THC) for recreational and therapeutic purposes continues to expand as additional US States legalize medical and recreational use. Scientific understanding of compulsive use of, and dependence on, marijuana has been hampered by a failure of rats to self-administer THC intravenously at robust levels. The present study will proposes research to enhance the pace of development and commercialization of our self-administration vapor inhalation chamber system and create an intrapulmonary self- administration model in rats which will support future investigations into THC dependence.
Project Terms: 21 year old; Absence of pain sensation; Adolescent; Adopted; Adult; Air; alcohol research; Alcoholism; Alcohols; Animal Model; Behavioral; Breathing; Cannabinoids; Cannabis; Catalepsy; cocaine use; Cognitive; commercialization; Data; Dependence; design; Development; Devices; Dose; Drug Kinetics; drug seeking behavior; Drug usage; ecstasy; Electronic cigarette; Elements; Exposure to; Extinction (Psychology); Failure (biologic function); Female; Funding; Future; Genetic; Geographic state; Goals; Heating; Heroin; improved; Individual; Inhalation Exposure; innovation; instrumentation; Intravenous; Investigation; Laboratories; Laws; Lung; male; Marijuana; Marijuana Abuse; Marijuana Dependence; Marijuana Smoking; marijuana use; Medical; Medical Marijuana; meetings; member; Modeling; Motor Activity; Multiple Sclerosis; National Institute of Drug Abuse; neurochemistry; Nicotine; Nose; Oral mucous membrane structure; Pharmaceutical Preparations; Phase; Physiologic Thermoregulation; Physiological; Plasma; Probability; Procedures; Propylene Glycols; prototype; Psychotropic Drugs; public health relevance; Rattus; recreational drug use; reinforcer; Reporting; Research; research study; response; Rodent; Rodent Model; Route; Sativex; Self Administration; Self-Administered; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Smoke; Symptoms; System; Technology; Testing; Tetrahydrocannabinol; Therapeutic; Time; trend; twelfth grade; vapor; Work
