Dr. Lile's graduate and post-doctoral research focused on the neuropharmacological basis of stimulant addiction and how the neurotransmitter systems that mediate the effects of stimulants could be targeted for medications development. The career development and research plan proposed in this application outlines the training that will enable him to apply his previous experience, along with new methodolgies, to an emerging area of research, the treatment of cannabis-related disorders. Despite the fact that cannabis use is more prevalent than for any other illicit drug and can progress to abuse and dependence, there are no pharmacotherapies for these disorders and little clinical research has been conducted to this end. The experiments described here were designed to identify the neurotransmitter systems that are involved in the effects of the primary active constituent of cannabis, delta 9-THC, in humans. The primary outcome variable for these experiments is the interoceptive cue produced by delta 9-THC. The interoceptive effects of delta 9- THC will be measured using the drug-discrimination procedure, which is a pharmacologically specific and sensitive means to characterize the profile of a drug. Because cannabis-related disorders are associated with maladaptive changes in behavior and cognition, additional experimental measures to assess reinforcement, subjective ratings, impulsivity, psychomotor performance, learning and memory will also be taken. The role of the cannabinoid, opioid, GABA and dopamine systems will be investigated, which will reveal targets for future research efforts. Dr. Lile will be sponsored by Dr. Kelly, an expert in cannabis research in humans. The conduct of these experiments and the training described in this proposal will occur at the University of Kentucky, which has an extensive community of scientists engaged in basic and clinical research related to drug addiction. This award will allow Dr. Lile to develop as an independent investigator and to establish a program of human research concentrated on cannabis-related disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DA018772-02
Application #
7071854
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Aigner, Thomas G
Project Start
2005-06-01
Project End
2010-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
2
Fiscal Year
2006
Total Cost
$149,880
Indirect Cost
Name
University of Kentucky
Department
Psychology
Type
Schools of Medicine
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Fogel, Jessica S; Kelly, Thomas H; Westgate, Philip M et al. (2017) Sex differences in the subjective effects of oral ?9-THC in cannabis users. Pharmacol Biochem Behav 152:44-51
Lile, Joshua A; Kelly, Thomas H; Charnigo, Richard J et al. (2013) Pharmacokinetic and pharmacodynamic profile of supratherapeutic oral doses of ?(9) -THC in cannabis users. J Clin Pharmacol 53:680-90
Lile, Joshua A; Kelly, Thomas H; Hays, Lon R (2012) Separate and combined effects of the GABA reuptake inhibitor tiagabine and ?9-THC in humans discriminating ?9-THC. Drug Alcohol Depend 122:61-9
Lile, Joshua A; Stoops, William W; Glaser, Paul E A et al. (2011) Discriminative stimulus, subject-rated and cardiovascular effects of cocaine alone and in combination with aripiprazole in humans. J Psychopharmacol 25:1469-79
Lile, Joshua A; Babalonis, Shanna; Emurian, Cleeve et al. (2011) Comparison of the behavioral and cardiovascular effects of intranasal and oral d-amphetamine in healthy human subjects. J Clin Pharmacol 51:888-98
Rush, Craig R; Stoops, William W; Lile, Joshua A et al. (2011) Physiological and subjective effects of acute intranasal methamphetamine during atomoxetine maintenance. Pharmacol Biochem Behav 100:40-7
Lile, Joshua A; Kelly, Thomas H; Hays, Lon R (2011) Separate and combined effects of the cannabinoid agonists nabilone and ??-THC in humans discriminating ??-THC. Drug Alcohol Depend 116:86-92
Lile, Joshua A; Stoops, William W; Glaser, Paul E A et al. (2011) Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance. Drug Alcohol Depend 119:187-93
Rush, Craig R; Stoops, William W; Lile, Joshua A et al. (2011) Subjective and physiological effects of acute intranasal methamphetamine during d-amphetamine maintenance. Psychopharmacology (Berl) 214:665-74
Lile, Joshua A; Kelly, Thomas H; Hays, Lon R (2010) Substitution profile of the cannabinoid agonist nabilone in human subjects discriminating ?9-tetrahydrocannabinol. Clin Neuropharmacol 33:235-42

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