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High-probability grants
According to our matching algorithm, Torbjorn Jarbe is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2001 — 2006 |
Jarbe, Torbjorn U |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Exogenous/Endogenous Cannabinoids--a Comparison @ Northeastern University
DESCRIPTION (provided by applicant): The recent advances in our understanding of the neurochemical/physiological basis of cannabinoid action provide exciting background material for continuing efforts to further delineate the mechanism of action of cannabimimetic agents. Cannabinoids and cannabimimetics induce their receptor-based effects by modulating the functions of one or more of four known "cannabinoid target proteins": CB1, CB2, anandamide amidase, and the anandarnide transporter. The overall purpose of the proposed studies is to compare the structure-activity relationships of the subjective effects of delta-9-tetrahydrocannabinol (delta-9-THC) and other cannabimimetics with analogs such as [(R)-methanandamide] and AM-1346 of the putative endogenous cannabinoid receptor ligand anandamide as well as representatives from a second endocannabinoid family discovered in brain, i.e., 2-arachidonyiglycerol (2-AG). Other targets for examination concern the enzymes responsible for the synthesis and degradation of anandamide and the anandamide transporter system involved in reuptake of endocannabinoids. The SAR between chemical structure and drug action reveals the structural requirements for a given drug effect or drug action. Though some studies suggest that delta-9-THC and anandamide as well as (R)-methanandamide share many similar properties, a one-on-one relationship has not been demonstrated. Studies from our own and other laboratories have shown the THC-like properties of synthetic cannabinoids and cannabimimetics are highly dependent on particular structural configurations. The proposed studies investigate structural requirements of anandamide- and 2-AG analogs in comparison to known cannabimimetic compounds. These studies also focus on identifying useful pharmacotherapies for cannabis abuse by effectively blocking the psychoactive, cannabimimetic properties. The present project will utilize drug discrimination procedures with rats as an animal model for assessing the psychoactive properties of delta-9-THC, (R)-methanandamide, and related compounds. Drug discrimination is the most commonly used paradigm for studying the subjective, intoxicating effects of drugs in preclinical psychopharmacology. A special feature of this proposal is the use of different training doses of THC to create different efficacy demands. Additionally, food maintained responding and open-field activity studies will also be conducted. By providing important information on the SAR of endogenous anandamide and exogenous delta-9-THC, as well as potential cannabimimetic antagonists, these studies will not only add to our understanding of the behavioral neurobiology of cannabis abuse and dependence, but may also lead to the development of effective pharmacological treatments.
|
0.958 |
2007 — 2016 |
Jarbe, Torbjorn U |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Endogenous/Exogenous Cannabinoids: a Comparison @ Northeastern University
DESCRIPTION (provided by applicant): Research on cannabinoids has progressed tremendously since the discovery of specific recognition sites (receptors) for chemicals like ?9-tetrahydrocannabinol (THC), the main active ingredient in marijuana. The endocannabinoid signaling system (ECS) thus likely serves as the biological substrate for the marijuana high. This subjective state presumably underlies human marijuana consumption that may lead to compulsive cannabis intake and dependence disorders. Drug discrimination is a powerful, pharmacologically selective model for assessing subjectively experienced drug effects in animals (and man) and is the major in vivo behavioral technique in this application. Cannabinoid receptor CB1 (CB1R) agonists and antagonists will be trained in drug discrimination using different doses, providing for in vivo assays with different sensitivity levels. This is complemented by observational studies and schedule controlled responding allowing for an in depth characterization of ligands. A major aim of this research is to identify new medications that will translate into better pharmacotherapies for combating marijuana addiction. Alleviation of withdrawal-related effects in physically dependent individuals likely is an important motivational factor in addiction processes. New molecules are designed and synthesized by on site expertise. One focus is to identify and refine in vivo neutral CB1R antagonists. Most current CB1R antagonists also display intrinsic activity (inverse agonism) that may hamper patient compliance in treatment settings. Thus, the studies will expand our understanding of the ECS, comprised of two major endogenous signaling molecules, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) acting on two known receptors, CB1 and CB2, in normal body function and pathophysiology. Additional therapeutic targets for the application concern ligands selectively affecting the enzymes involved in the deactivation of the endocannabinoids, thus potentially avoiding direct receptor activation. The behavioral studies are aided by neuro/biochemical procedures provided by collaborating faculty in pursuing these goals. In addition to AEA, recent developments regarding 2-AG allow for a much more comprehensive understanding of this major endocannabinoid in ECS signaling. By obtaining information on the functions of the endogenous substances (AEA and 2-AG) and the exogenous THC, as well as in vivo neutral blocking agents, these studies will not only further our understanding of ECS signaling in the behavioral neurobiology of cannabis abuse / dependence, but may also lead to the development of effective medications for treating disorders involving cannabis / marijuana, and designer THC-like cannabimimetics.
|
0.958 |