The drug abuse problem in general and the widespread use of marijuana in particular have focused attention on the chemistry and pharmacology of the plant Cannabis sativa. In the decade since the discovery of the cannabinoid receptors, much progress has been made in the cannabinoid field. It has been established that there are at least two types of cannabinoid receptors: CB1 receptors which are present both inside and outside the central nervous system (CMS) and CB2 receptors which are found mainly in the periphery. Two main endogenous ligands have been discovered, anandamide (AEA) and 2-arachidonyl-glycerol (2-Ara-GI). Also known as endocannabinoids, they are both present in central as well as peripheral tissues. Several chemically distinct and diverse structural classes of compounds which have no chemical/ structural relationships have been discovered as ligands for the cannabinoid receptors. The goal of the proposed synthetic research is to generate chemical probes which will help in understanding the mechanisms involved and the role of endocannabinoids in the CMS and the periphery.
Our Specific Aims are (1) development of allosteric modulators of the cannabinoids CB1 receptors, (2) development of DAGL-a inhibitors, (3) development of selective inhibitors of enzymes involved in endocannabinoid metabolism and (4) supply AEA, 2-Ara-GI and ligands of interest to investigators for the other projects for further biological testing. The synthesis of the analogs will provide endocannabinoid probes for the in vitro and in vivo studies and the results could point us in the direction of other cannabinoid receptor subtypes, reveal mechanisms involved in brain function and lead to therapeutic drugs in the areas of inflammation, pain, immune response, neuroprotection in head injury and other CMS related diseases. The proposed study will help our understanding of the pharmacological action of this important class of compounds and provide drugs in the health care field.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDA1-RXL-E)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Virginia Commonwealth University
United States
Zip Code
Yun, Bogeon; Lee, HeeJung; Ghosh, Moumita et al. (2014) Serine hydrolase inhibitors block necrotic cell death by preventing calcium overload of the mitochondria and permeability transition pore formation. J Biol Chem 289:1491-504
Galdino, Giovane; Romero, Thiago; Silva, José Felippe Pinho da et al. (2014) Acute resistance exercise induces antinociception by activation of the endocannabinoid system in rats. Anesth Analg 119:702-15
Pertwee, Roger G (2014) Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications. Proc Nutr Soc 73:96-105
Vallée, Monique; Vitiello, Sergio; Bellocchio, Luigi et al. (2014) Pregnenolone can protect the brain from cannabis intoxication. Science 343:94-8
Ignatowska-Jankowska, B M; Ghosh, S; Crowe, M S et al. (2014) In vivo characterization of the highly selective monoacylglycerol lipase inhibitor KML29: antinociceptive activity without cannabimimetic side effects. Br J Pharmacol 171:1392-407
Abdulnour, Joseph; Yasari, Siham; Rabasa-Lhoret, Remi et al. (2014) Circulating endocannabinoids in insulin sensitive vs. insulin resistant obese postmenopausal women. A MONET group study. Obesity (Silver Spring) 22:211-6
Grim, Travis W; Ghosh, Sudeshna; Hsu, Ku-Lung et al. (2014) Combined inhibition of FAAH and COX produces enhanced anti-allodynic effects in mouse neuropathic and inflammatory pain models. Pharmacol Biochem Behav 124:405-11
Wiley, Jenny L; Walentiny, D Matthew; Wright Jr, M Jerry et al. (2014) Endocannabinoid contribution to ?9-tetrahydrocannabinol discrimination in rodents. Eur J Pharmacol 737:97-105
Schlosburg, Joel E; Kinsey, Steven G; Ignatowska-Jankowska, Bogna et al. (2014) Prolonged monoacylglycerol lipase blockade causes equivalent cannabinoid receptor type 1 receptor-mediated adaptations in fatty acid amide hydrolase wild-type and knockout mice. J Pharmacol Exp Ther 350:196-204
Murase, Ryuichi; Kawamura, Rumi; Singer, Eric et al. (2014) Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer. Br J Pharmacol 171:4464-77

Showing the most recent 10 out of 231 publications