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The neural bases of placebo effects and their relation to regulatory processes

Award Number: R01MH076136
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Placebo treatments can induce clinically significant benefits, compared with no-treatment controls, across a variety of disorders. But placebo treatments themselves are pharmacologically and physically inert: Their benefits result from active brain and psychological responses to the treatment context. Neuroscientific studies have established that placebo treatments influence cortical-subcortical brain pathways and neurochemical systems relevant for expectation, appraisals of personal and social meaning, and value-driven learning. These systems are also related to symptom progression across mental health disorders and several other neurological and substance use disorders. Understanding the brain and psychological mechanisms of placebo effects will help improve psychological and neurological (e.g., neuromodulation-based) treatments across disorders. This R01 renewal funds an ongoing program of research that has made fundamental contributions to this literature. It has also identified several significant gaps that are particularly important for connecting placebo research to mental health. One gap is that our understanding of the brain mechanisms underlying placebo effects comes almost purely from studies of pain. The proposed studies extend previous work to study the brain pathways underlying placebo effects in anxiety and social rejection, negative affective processes directly relevant for multiple mental health disorders. Pattern-recognition (machine learning) analyses identify the most symptom-relevant pathways, and test effects of placebo and other context interventions on these pathways. In Aim 1 (Experiments 1-3), we develop models across multiple affective symptoms, parsing affective pathways into those that are symptom-specific and those that generalize across multiple symptoms and outcomes. We also address the role of endogenous opioids, strongly linked to placebo analgesia, in other negative affective experiences. Another gap is that most previous studies of the context variables that drive strong placebo effects—including social influences, treatment history—have not been studied extensively at the brain level. In Aim 2, we study the brain pathways underlying several promising context interventions that enhance the strength of placebo effects, including social modeling of successful or unsuccessful treatment response, initial experiences of treatment success or failure, and the match between placebo suggestions and a person’s predisposition to be receptive to them.


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: 2025 ( Subtotal = -$30,454 )
2025	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	16	11/14/2024	NON-COMPETING CONTINUATION	-$30,454
														Subtotal = -$30,454

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	16	7/9/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $700,570 )
2023	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	001	16	3/6/2023	NON-COMPETING CONTINUATION	$70,057
2023	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	16	11/15/2022	NON-COMPETING CONTINUATION	$630,513
														Subtotal = $700,570

Issue Date FY: 2022 ( Subtotal = $714,646 )
2022	2022	TRUSTEES OF DARTMOUTH COLLEGE	6001 PARKHURST HALL STE 207	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	15	12/10/2021	NON-COMPETING CONTINUATION	$643,181
2022	2022	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	001	15	5/10/2022	NON-COMPETING CONTINUATION	$71,465
														Subtotal = $714,646

Issue Date FY: 2021 ( Subtotal = $740,565 )
2021	2021	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	14	2/23/2021	NON-COMPETING CONTINUATION	$740,565
														Subtotal = $740,565

Issue Date FY: 2020 ( Subtotal = $797,673 )
2020	2020	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	001	13	2/3/2020	NON-COMPETING CONTINUATION	$79,768
2020	2020	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	13	11/14/2019	NON-COMPETING CONTINUATION	$717,905
2020	2020	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	003	13	3/26/2020	NON-COMPETING CONTINUATION	$6
2020	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	002	11	3/26/2020	COMPETING CONTINUATION	-$6
														Subtotal = $797,673

Issue Date FY: 2019 ( Subtotal = $804,458 )
2019	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	11	12/21/2018	COMPETING CONTINUATION	$757,781
2019	2019	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	004	12	9/21/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$769,982
2019	2019	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	005	12	9/26/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2019	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	003	11	9/21/2019	COMPETING CONTINUATION	-$723,305
2019	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	002	11	4/3/2019	COMPETING CONTINUATION	$7
2019	2017	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	001	10	4/3/2019	NON-COMPETING CONTINUATION	-$7
														Subtotal = $804,458

Issue Date FY: 2017 ( Subtotal = $641,810 )
2017	2017	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST., RM 479 572 UCB	BOULDER	CO	80303	BOULDER	USA	Mental Health Research Grants	000	10	11/15/2016	NON-COMPETING CONTINUATION	$577,629
2017	2017	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST., RM 479 572 UCB	BOULDER	CO	80303	BOULDER	USA	Mental Health Research Grants	001	10	5/9/2017	NON-COMPETING CONTINUATION	$64,181
														Subtotal = $641,810

Issue Date FY: 2016 ( Subtotal = $644,555 )
2016	2016	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	001	9	3/8/2016	EXTENSION WITH OR WITHOUT FUNDS	$64,456
2016	2016	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	9	11/18/2015	EXTENSION WITH OR WITHOUT FUNDS	$580,099
														Subtotal = $644,555

Issue Date FY: 2015 ( Subtotal = $648,290 )
2015	2015	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	001	8	2/23/2015	NON-COMPETING CONTINUATION	$64,830
2015	2015	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	8	11/24/2014	NON-COMPETING CONTINUATION	$583,460
														Subtotal = $648,290

Issue Date FY: 2014 ( Subtotal = $650,172 )
2014	2014	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	001	7	2/27/2014	NON-COMPETING CONTINUATION	$65,017
2014	2014	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	7	11/26/2013	NON-COMPETING CONTINUATION	$585,155
														Subtotal = $650,172

Issue Date FY: 2013 ( Subtotal = $748,295 )
2013	2013	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	6	1/25/2013	COMPETING CONTINUATION	$748,295
														Subtotal = $748,295

Issue Date FY: 2010 ( Subtotal = $316,289 )
2010	2010	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Mental Health Research Grants	001	4	2/2/2010	NON-COMPETING CONTINUATION	$35,669
2010	2010	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Mental Health Research Grants	000	4	12/18/2009	NON-COMPETING CONTINUATION	$321,025
2010	2010	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Mental Health Research Grants	002	4	5/20/2010	NON-COMPETING CONTINUATION	-$318,407
2010	2010	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	003	5	5/20/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$278,002
														Subtotal = $316,289

Issue Date FY: 2009 ( Subtotal = $356,908 )
2009	2009	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Mental Health Research Grants	001	3	4/15/2009	NON-COMPETING CONTINUATION	$35,691
2009	2009	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Mental Health Research Grants	000	3	12/23/2008	NON-COMPETING CONTINUATION	$321,217
														Subtotal = $356,908

Issue Date FY: 2008 ( Subtotal = $357,113 )
2008	2008	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Mental Health Research Grants	000	2	2/6/2008	NON-COMPETING CONTINUATION	$357,113
														Subtotal = $357,113

Issue Date FY: 2007 ( Subtotal = $357,311 )
2007	2007	COLUMBIA UNIVERSITY	2960 BROADWAY, MAIL CODE 7409	NEW YORK NEW YORK	NY	10027		USA	Mental Health Research Grants	000	1	12/27/2006	NEW	$357,311
														Subtotal = $357,311

Grand Total All Awards = $8,448,201

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The neural bases of placebo effects and their relation to regulatory processes

Award Number: R01MH076136

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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