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Endocannabinoid Active Sites as Therapeutic Targets

Award Number: P01DA009158
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/1994
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Endocannabinoid Active Sites as Therapeutic Targets - RESEARCH & RELATED - OTHER PROJECT INFORMATION - PROJECT SUMMARY/ABSTRACT In this Program Project renewal application, we propose to fundamentally expand current understanding of the variable potentially functional modulations of the CB1 and CB2 cannabinoid receptors. During this current period, our work has resulted in the development of a number of key pharmacologically diverse and selective agonists and antagonists for CB1 and CB2 cannabinoid receptors. We also produced detailed information on the structures of these two receptors. Based upon the strengths of this foundational work, we now propose to develop new functionally selective tools for fine tuning CB1 function and for selectively enhancing CB2 actions in vivo. Our work will generate early candidates for the discovery and development of new therapeutic medications. In this renewal, we will elucidate the functional selectivity aspect of CB1 agonists and develop positive allosteric modulators at CB1 that selectively enhance endocannabinoid signaling. We also propose to develop highly selective CB2 agonists to enable studies of CB2 in vivo while limiting the contributions of CB1 that have been associated with undesirable side effects. Additionally, we propose to develop ligands that act as activators of CB2 while also acting as CB1 antagonists. Using such compounds in vivo may lay the groundwork for the development of medications for inflammatory and fibrotic disorders. Our goals will be accomplished through the synthesis of druggable analogs. The design of these ligands will be based on existing structures of the CB1 and CB2 receptors that were developed during the current funding period and by utilizing computational approaches. The work will require detailed molecular pharmacology aimed at studying the signaling of novel compounds accompanied by targeted mutations in CB1 and CB2 to confirm mechanistic underpinnings of pharmacological divergences in signaling. The most efficient novel compounds will be assayed using in vivo approaches aimed at exploring potential therapeutic value. The overall project will provide foundational information on cannabinoid receptor signaling and serve as a basis for the future development of rationally designed, mechanism-based therapeutic medications.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $1,444,077 )
2024	2024	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	22	7/1/2024	NON-COMPETING CONTINUATION	$1,444,077
														Subtotal = $1,444,077

Issue Date FY: 2023 ( Subtotal = $1,434,681 )
2023	2023	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	002	21	5/23/2023	NON-COMPETING CONTINUATION	$1,434,681
2023	2022	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	20	10/28/2022	COMPETING CONTINUATION	$0
2023	2022	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	001	20	12/27/2022	COMPETING CONTINUATION	$0
														Subtotal = $1,434,681

Issue Date FY: 2022 ( Subtotal = $1,477,010 )
2022	2022	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	001	20	8/9/2022	COMPETING CONTINUATION	$1,477,010
2022	2018	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	19	12/13/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,477,010

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	19	7/27/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $1,266,254 )
2018	2018	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	19	6/26/2018	NON-COMPETING CONTINUATION	$1,266,254
														Subtotal = $1,266,254

Issue Date FY: 2017 ( Subtotal = $1,266,254 )
2017	2017	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	18	7/3/2017	NON-COMPETING CONTINUATION	$1,266,254
														Subtotal = $1,266,254

Issue Date FY: 2016 ( Subtotal = $1,253,591 )
2016	2016	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	17	7/26/2016	NON-COMPETING CONTINUATION	$1,253,591
														Subtotal = $1,253,591

Issue Date FY: 2015 ( Subtotal = $1,251,775 )
2015	2015	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	16	6/11/2015	NON-COMPETING CONTINUATION	$1,251,775
														Subtotal = $1,251,775

Issue Date FY: 2014 ( Subtotal = $1,281,665 )
2014	2014	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	002	15	9/8/2014	COMPETING CONTINUATION	$1,281,665
2014	2011	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	14	5/12/2014	NON-COMPETING CONTINUATION	$0
2014	2011	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	001	14	9/5/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,281,665

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2011	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	14	5/31/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $1,051,850 )
2011	2011	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	14	5/2/2011	NON-COMPETING CONTINUATION	$1,051,850
														Subtotal = $1,051,850

Issue Date FY: 2010 ( Subtotal = $1,053,894 )
2010	2010	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	13	5/5/2010	NON-COMPETING CONTINUATION	$1,053,894
														Subtotal = $1,053,894

Issue Date FY: 2009 ( Subtotal = $1,097,826 )
2009	2009	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	12	4/17/2009	NON-COMPETING CONTINUATION	$1,097,826
														Subtotal = $1,097,826

Issue Date FY: 2008 ( Subtotal = $1,134,867 )
2008	2008	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	002	10	1/4/2008	SUPPLEMENT FOR EXPANSION	$32,447
2008	2008	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	11	5/21/2008	NON-COMPETING CONTINUATION	$1,102,420
														Subtotal = $1,134,867

Issue Date FY: 2007 ( Subtotal = $1,074,178 )
2007	2007	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	10	5/11/2007	COMPETING CONTINUATION	$1,027,528
2007	2007	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	001	10	9/7/2007	SUPPLEMENT FOR EXPANSION	$46,650
														Subtotal = $1,074,178

Issue Date FY: 2005 ( Subtotal = $1,256,605 )
2005	2005	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	9	4/1/2005	NON-COMPETING CONTINUATION	$1,256,605
														Subtotal = $1,256,605

Issue Date FY: 2004 ( Subtotal = $1,161,249 )
2004	2004	UNIVERSITY OF CONNECTICUT, GRANTS & CONTRACTS	ADMINISTRATION BUILDING	STORRS	CT	06268	CAPITOL	USA	Drug Use and Addiction Research Programs	000	7	9/28/2004	NON-COMPETING CONTINUATION	$1,161,249
														Subtotal = $1,161,249

Issue Date FY: 2003 ( Subtotal = $1,125,457 )
2003	2003	UNIVERSITY OF CONNECTICUT, GRANTS & CONTRACTS	ADMINISTRATION BUILDING	STORRS	CT	06268	CAPITOL	USA	Drug Use and Addiction Research Programs	001	6	7/28/2003	SUPPLEMENT FOR EXPANSION	$72,410
2003	2003	UNIVERSITY OF CONNECTICUT, GRANTS & CONTRACTS	ADMINISTRATION BUILDING	STORRS	CT	06268	CAPITOL	USA	Drug Use and Addiction Research Programs	000	6	5/21/2003	NON-COMPETING CONTINUATION	$906,091
2003	2003	UNIVERSITY OF CONNECTICUT, GRANTS & CONTRACTS	ADMINISTRATION BUILDING	STORRS	CT	06268	CAPITOL	USA	Drug Use and Addiction Research Programs	002	6	9/1/2003	SUPPLEMENT FOR EXPANSION	$146,956
														Subtotal = $1,125,457

Issue Date FY: 2002 ( Subtotal = $972,428 )
2002	2002	UNIVERSITY OF CONNECTICUT, GRANTS & CONTRACTS	ADMINISTRATION BUILDING	STORRS	CT	06268	CAPITOL	USA	Drug Use and Addiction Research Programs	000	5	5/20/2002	NON-COMPETING CONTINUATION	$972,428
														Subtotal = $972,428

Issue Date FY: 2001 ( Subtotal = $1,045,433 )
2001	2001	UNIVERSITY OF CONNECTICUT, GRANTS & CONTRACTS	ADMINISTRATION BUILDING	STORRS	CT	06268	CAPITOL	USA	Drug Use and Addiction Research Programs	000	4	4/20/2001	COMPETING CONTINUATION	$1,045,433
														Subtotal = $1,045,433

Grand Total All Awards = $21,649,094

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Endocannabinoid Active Sites as Therapeutic Targets

Award Number: P01DA009158

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/1994

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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