Binge alcoholism is a growing problem worldwide. Young adults (16-24 years of age) are particularly prone to the adverse effects of alcoholic binging, which is often consumed with secondary drugs of abuse including marijuana. Previous research has suggested that alcohol may share pharmacological effects with cannabinoid agonists such as D9-tetrahydrocannabinol (THC), the primary psychoactive substituent of marijuana. Further, previous work has found that these effects may be modulated by alcohol's effects on the endocannabinoid system. Although much of the preclinical work on both alcohol and cannabinoids has been conducted in male rodents, results of sparse studies in female rodents have suggested sex-selective differences, with females often exhibiting enhanced sensitivity to the pharmacological effects of ethanol as well as THC. In the parent grant, our goals are to characterize some of these differences for THC and to investigate potential mechanisms. In this supplement, we propose to incorporate examination of ethanol/ cannabinoid co-abuse into our overall research strategy. As with the parent grant, integrated in vivo and in vitro measures will be used. To take advantage of local expertise on the hepatic effects of alcohol, we have expanded the dual brain and behavior focus present in the parent grant to incorporate research on the effects of alcohol and THC on the liver. In the proposed project, we will investigate sex differences in the acute in vivo pharmacological effects of alcoho and THC co-administration, as well as their rewarding / aversive effects following repeated intermittent co-administration (Aim 1). These behavioral effects will be correlated with in vitro measures of endocannabinoid system functioning in the brain and the liver and with determination of the extent of liver injury induced by co-abuse of both substances (Aim 2). Understanding the sex-selective effects of co-abuse of alcohol and marijuana is particularly critical at this time since the recent loosening of legal restrictions on marijuana use in the U.S. will likely be associated with increased rates of alcohol-marijuana co-abuse in both sexes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA016644-08S1
Application #
8739924
Study Section
Special Emphasis Panel (ZDA1-SXC-E (16))
Program Officer
Lynch, Minda
Project Start
2003-07-01
Project End
2017-08-31
Budget Start
2014-04-01
Budget End
2014-08-31
Support Year
8
Fiscal Year
2014
Total Cost
$106,855
Indirect Cost
$54,772
Name
Research Triangle Institute
Department
Type
DUNS #
004868105
City
Research Triangle
State
NC
Country
United States
Zip Code
27709
Marusich, Julie A; Lefever, Timothy W; Antonazzo, Kateland R et al. (2014) Evaluation of sex differences in cannabinoid dependence. Drug Alcohol Depend 137:20-8
Wiley, Jenny L; Burston, James J (2014) Sex differences in ?(9)-tetrahydrocannabinol metabolism and in vivo pharmacology following acute and repeated dosing in adolescent rats. Neurosci Lett 576:51-5
Wakley, Alexa A; Wiley, Jenny L; Craft, Rebecca M (2014) Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat. Drug Alcohol Depend 143:22-8
Marusich, Julie A; Wiley, Jenny L (2012) Rimonabant abolishes sensitivity to workload changes in a progressive ratio procedure. Pharmacol Biochem Behav 101:575-80
Wiley, Jenny L; Evans, Rhys L; Grainger, Darren B et al. (2011) Locomotor activity changes in female adolescent and adult rats during repeated treatment with a cannabinoid or club drug. Pharmacol Rep 63:1085-92
Wiley, Jenny L; Jones, Amanda R; Wright Jr, M Jerry (2011) Exposure to a high-fat diet decreases sensitivity to ?9-tetrahydrocannabinol-induced motor effects in female rats. Neuropharmacology 60:274-83
Burston, James J; Wiley, Jenny L; Craig, Abimbola A et al. (2010) Regional enhancement of cannabinoid CB₁ receptor desensitization in female adolescent rats following repeated Delta-tetrahydrocannabinol exposure. Br J Pharmacol 161:103-12
Wiley, Jenny L; Burston, James J (2010) Chronic Delta9-tetrahydrocannabinol during adolescence increases sensitivity to subsequent cannabinoid effects in delayed nonmatch-to-position in rats. Pharmacol Biochem Behav 94:516-23
Wiley, Jenny L; Evans, Rhys L (2009) To breed or not to breed? Empirical evaluation of drug effects in adolescent rats. Int J Dev Neurosci 27:9-20
McKinney, Diana L; Cassidy, Michael P; Collier, Lauren M et al. (2008) Dose-related differences in the regional pattern of cannabinoid receptor adaptation and in vivo tolerance development to delta9-tetrahydrocannabinol. J Pharmacol Exp Ther 324:664-73

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