Marijuana dependence and withdrawal are increasingly reported, yet adequate treatment options have not been identified. This R01 will expand upon a compelling line of investigation demonstrating that drug discrimination can be used to quantify the behavioral effects of the cannabinoid antagonist SR 141716A in monkeys receiving delta9-THC. Dependence will be established with delta9-THC and withdrawal characterized by directly observable signs, drug discrimination, and neuroendocrine response.
Aim 1 will examine a role for cannabinoid and monoamines in the discriminative stimulus effects of delta9-THC withdrawal, induced both by SR 141716A and by temporary discontinuation of A9-THC treatment. Studies will examine a role for cannabinoids and monoamines in the directly observable signs of withdrawal induced by SR 141716A. Collectively, studies in Aim 1 will examine the relative contribution of cannabinoids and monoamines across different indices of withdrawal and will test the hypothesis that monoamines attenuate discriminative measures and not other indices of withdrawal.
Aim 2 will examine a role for hypothalamic pituitary adrenal activity (indexed by cortisol and ACTH) in the acute and chronic effects of delta9-THC and will examine a role for CRH antagonists in modifying delta9-THC withdrawal. Drug discrimination will be used in Aim 3 to characterize the subjective effects of inhaled marijuana smoke which represents the predominant route of administration in humans. Studies will examine modification of the discriminative stimulus effects of inhaled marijuana smoke by cannabidiol and cannabinol and blockade of these discriminative stimulus effects by cannabinoid antagonists. A likely future direction will be to characterize dependence that occurs to inhaled marijuana smoke. This application will address a need for understanding the behavioral, pharmacologic, and neuroendocrine determinants of cannabinoid dependence and will examine test compounds for modification of cannabinoid withdrawal and acute marijuana action.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA019222-04
Application #
7284371
Study Section
Special Emphasis Panel (ZDA1-KXA-N (14))
Program Officer
Acri, Jane
Project Start
2004-09-30
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
4
Fiscal Year
2007
Total Cost
$346,086
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Pharmacology
Type
Other Domestic Higher Education
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Hruba, Lenka; McMahon, Lance R (2017) Apparent Affinity Estimates and Reversal of the Effects of Synthetic Cannabinoids AM-2201, CP-47,497, JWH-122, and JWH-250 by Rimonabant in Rhesus Monkeys. J Pharmacol Exp Ther 362:278-286
McMahon, Lance R (2016) Enhanced discriminative stimulus effects of ?(9)-THC in the presence of cannabidiol and 8-OH-DPAT in rhesus monkeys. Drug Alcohol Depend 165:87-93
Hruba, Lenka; Seillier, Alexandre; Zaki, Armia et al. (2015) Simultaneous inhibition of fatty acid amide hydrolase and monoacylglycerol lipase shares discriminative stimulus effects with ?9-tetrahydrocannabinol in mice. J Pharmacol Exp Ther 353:261-8
Ghosh, Sudeshna; Kinsey, Steven G; Liu, Qing-Song et al. (2015) Full Fatty Acid Amide Hydrolase Inhibition Combined with Partial Monoacylglycerol Lipase Inhibition: Augmented and Sustained Antinociceptive Effects with Reduced Cannabimimetic Side Effects in Mice. J Pharmacol Exp Ther 354:111-20
Rodriguez, Jesse S; McMahon, Lance R (2014) JWH-018 in rhesus monkeys: differential antagonism of discriminative stimulus, rate-decreasing, and hypothermic effects. Eur J Pharmacol 740:151-9
Hruba, Lenka; McMahon, Lance R (2014) The cannabinoid agonist HU-210: pseudo-irreversible discriminative stimulus effects in rhesus monkeys. Eur J Pharmacol 727:35-42
Ginsburg, Brett C; Hruba, Lenka; Zaki, Armia et al. (2014) Blood levels do not predict behavioral or physiological effects of ??-tetrahydrocannabinol in rhesus monkeys with different patterns of exposure. Drug Alcohol Depend 139:1-8
Gould, Georgianna G; Seillier, Alexandre; Weiss, Gabriela et al. (2012) Acetaminophen differentially enhances social behavior and cortical cannabinoid levels in inbred mice. Prog Neuropsychopharmacol Biol Psychiatry 38:260-9
Ginsburg, Brett C; McMahon, Lance R; Sanchez, Jesus J et al. (2012) Purity of synthetic cannabinoids sold online for recreational use. J Anal Toxicol 36:66-8
Ginsburg, Brett C; Schulze, David R; Hruba, Lenka et al. (2012) JWH-018 and JWH-073: ??-tetrahydrocannabinol-like discriminative stimulus effects in monkeys. J Pharmacol Exp Ther 340:37-45

Showing the most recent 10 out of 25 publications