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- W402214138 abstract "DIFFERENTIAL ROLES OF THE TWO MAJOR ENDOCANNABINOID HYDROLYZING ENZYMES IN CANNABINOID RECEPTOR TOLERANCE AND SOMATIC WITHDRAWAL By Joel E. Schlosburg, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2010. Major Director: Dr. Aron Lichtman, Professor, Department of Pharmaco logy & Toxicology While there is currently active debate over possible therapeutic applications of marijuana and cannabis-based compounds, consistently their primary drawbacks have been the psychoactive properties, dependence, and abuse potential. Pro longed administration of ∆tetrahydrocannabinol (THC), the primary psychoactive constituent in marijuana, demonstrates both tolerance and physical withdrawal in both preclinical and clinical studies. Repeated THC administration also produces CB1 receptor adaptations in the form of reduced activation of receptors, along with a downregulation of membrane surface receptors, in many brain regions involved in THC-associated behaviors. The increased need for drug to maintain therapeutic effects, and a withdrawal syndrome following discontinuation of use, are common risk factors in drugs of abuse. Recently, compounds have been developed that prolong the availability of the major naturally occurring endogenous cannabinoids, anandamide (AEA) and 2arachidonoylglycerol (2-AG), through inhibition of their catabolic breakdown by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. The overall objectives of this research are to elucidate the physiologic roles of these two endogenous ligands" @default.
- W402214138 created "2016-06-24" @default.
- W402214138 creator A5055122999 @default.
- W402214138 date "2010-01-01" @default.
- W402214138 modified "2023-09-23" @default.
- W402214138 title "Differential roles of the two major endocannabinoid hydrolyzing enzymes in cannabinoid receptor tolerance and somatic withdrawal" @default.
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