Wednesday, January 15, 2025 1/15/2025

Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

Award Number: R21AT010763
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Background: Converging lines of evidence from preclinical studies, treatment studies in animals, and anecdotal reports suggest that cannabidiol (CBD) may have a therapeutic role in chronic pain disorders. Emerging neurobiological evidence suggests that the transition from acute to chronic pain is mediated by a) the biological mechanism of increased brain microglial activation and b) the physiological mechanism of increased central pain-sensitization. However, whether CBD modulates brain microglial activation and central pain-sensitization in humans has not been examined to-date. Intradermal capsaicin-induced secondary hyperalgesia (ICSH) is a validated measure of central pain-sensitization related to activation of specific brain regions. We have demonstrated, in pilot data, that ICSH is sensitive to the effects of cannabinoids (such as THC) in a laboratory paradigm. Low-dose lipopolysaccharide (LPS) has been shown to increase brain microglial activation. The combination of LPS and intradermal capsaicin provides a unique experimental paradigm to examine the relationship between brain microglial activation and central pain-sensitization. Harnessing the high sensitivity and molecular specificity of positron emission tomography (PET) imaging, we have demonstrated in vivo evidence of increased brain microglial activation following LPS, using [11C]PBR28. Additionally, LPS has been shown to result in a 2-fold increase in capsaicin-induced secondary hyperalgesia (ICSH). The combination of LPS with intradermal capsaicin (pLPS-IC) thus provides a validated and reliable model to examine the effects of CBD on a) the biological mechanism of increased brain microglial activation and b) the physiological mechanism of increased central pain-sensitization. Hypothesis #1: CBD pretreatment will result in lower brain microglial activation (specifically in the thalamus) compared to placebo in healthy individuals. Aim#1: To examine the effect of CBD pretreatment on brain microglial activation in vivo in humans using a LPS-challenge paradigm and [11C]PBR28 PET imaging. Hypothesis #2: The degree of reduction in brain microglial activation with CBD pretreatment will correlate with the degree of reduction in central pain-sensitization. Aim#2: To examine the relationship between microglial activation and central pain-sensitization with CBD pretreatment, measured using [11C]PRB28 and ICSH in a pLPS-IC paradigm.


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 = $0 )
2024	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	001	2	11/2/2023	SUPPLEMENT FOR EXPANSION	$0
2024	2023	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	005	2	9/24/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2023	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	003	2	7/5/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2020	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	002	2	7/3/2024	NON-COMPETING CONTINUATION	$0
2024	2020	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	004	2	9/23/2024	NON-COMPETING CONTINUATION	$0
2024	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	000	2	11/1/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $51,979 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	002	2	6/28/2023	SUPPLEMENT FOR EXPANSION	$51,979
2023	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	001	2	6/27/2023	NON-COMPETING CONTINUATION	$0
2023	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	000	2	10/19/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $51,979

Issue Date FY: 2020 ( Subtotal = $430,626 )
2020	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	003	2	8/6/2020	NON-COMPETING CONTINUATION	$209,375
2020	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	001	1	12/20/2019	SUPPLEMENT FOR EXPANSION	$221,251
2020	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	000	1	12/19/2019	NEW	$0
2020	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	002	1	8/6/2020	NEW	$0
														Subtotal = $430,626

Issue Date FY: 2019 ( Subtotal = $29,999 )
2019	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research and Training in Complementary and Integrative Health	000	1	9/27/2019	NEW	$29,999
														Subtotal = $29,999

Grand Total All Awards = $512,604

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Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

Award Number: R21AT010763

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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