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)
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Special Emphasis Panel (ZDA1-RXL-E)
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Virginia Commonwealth University
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Donvito, Giulia; Nass, Sara R; Wilkerson, Jenny L et al. (2018) The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain. Neuropsychopharmacology 43:52-79
Wilkerson, Jenny L; Curry, Zachary A; Kinlow, Pamela D et al. (2018) Evaluation of different drug classes on transient sciatic nerve injury-depressed marble burying in mice. Pain 159:1155-1165
Mitjavila, Jose; Yin, Danielle; Kulkarni, Pushkar M et al. (2018) Enantiomer-specific positive allosteric modulation of CB1 signaling in autaptic hippocampal neurons. Pharmacol Res 129:475-481
Wilkerson, Jenny L; Ghosh, Sudeshna; Mustafa, Mohammed et al. (2017) The endocannabinoid hydrolysis inhibitor SA-57: Intrinsic antinociceptive effects, augmented morphine-induced antinociception, and attenuated heroin seeking behavior in mice. Neuropharmacology 114:156-167
Wilkerson, Jenny L; Niphakis, Micah J; Grim, Travis W et al. (2016) The Selective Monoacylglycerol Lipase Inhibitor MJN110 Produces Opioid-Sparing Effects in a Mouse Neuropathic Pain Model. J Pharmacol Exp Ther 357:145-56
Buczynski, Matthew W; Herman, Melissa A; Hsu, Ku-Lung et al. (2016) Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure. Proc Natl Acad Sci U S A 113:1086-91
Staiano, Rosaria I; Loffredo, Stefania; Borriello, Francesco et al. (2016) Human lung-resident macrophages express CB1 and CB2 receptors whose activation inhibits the release of angiogenic and lymphangiogenic factors. J Leukoc Biol 99:531-40
Tessaris, Daniele; Matarazzo, Patrizia; Lala, Roberto et al. (2016) Odontoiatric perspectives and osteonecrosis of the jaw as a possible adverse effect of bisphosphonates therapy in fibrous dysplasia and McCune-Albright syndrome. J Pediatr Endocrinol Metab 29:333-6
Kocova, Mirjana; Zdraveska, Nikolina; Kacarska, Rozana et al. (2016) Diagnostic approach in children with unusual symptoms of acquired hypothyroidism. When to look for pituitary hyperplasia? J Pediatr Endocrinol Metab 29:297-303
Anavi-Goffer, Sharon; Ross, Ruth A (2016) A Functional Assay for GPR55: Envision Protocol. Methods Mol Biol 1412:77-83

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