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Prenatal Cannabis Exposure (PreCE) and Immune-Endocannabinoid Pathways to Development of Offspring Brain and Behavior up to Age 6

Award Number: R01DA046224
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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Prenatal Cannabis Exposure (PreCE) and Immune-Endocannabinoid Pathways to Development of Offspring Brain and Behavior up to Age 6 - PROJECT SUMMARY/ABSTRACT Recent estimates from the United States suggest that 8% of pregnant women used cannabis in the past month. While evidence remains mixed, emerging research documents an association between prenatal cannabis exposure (PreCE) and offspring birthweight, brain development (e.g., white matter microstructure), and behavior, especially inattention, impulsivity and broader externalizing symptoms. The Cannabis Use During Development and Early Life (CUDDEL; DA046224) study collected data on pregnant women who reported cannabis use during pregnancy (validated using self-report and urine screens; PreCE, n=200) and women who used cannabis prior to but never during pregnancy (NPreCE, n=200). Of these women, 150 PreCE and 100 NPreCE mother- child dyads were recruited to participate in the postpartum arm of the project where neonatal brain imaging was conducted soon after birth, and children were followed up with behavioral assessments at ages 6, 12 and 18 months. In this renewal application, we propose to longitudinally follow this cohort of mother-child dyads until the children are 7 years of age. Children will participate in brain imaging and behavioral assessments at ages 4-5 and 6-7 years providing data that will outline whether PreCE exerts an enduring effect into childhood. As cannabis use becomes more common and rates of second hand exposure increase, second hand cannabis exposure (SCE) will be assessed using maternal self-report and quantification of THC-COOH in biospecimens from mother and child. In addition to studying the longitudinal associations between PreCE, SCE and brain and behavioral development, placental and offspring blood signatures of endogenous cannabinoid (eCB) signaling and immune markers (cytokines, transcriptomics, brain imaging derived) will allow for a comprehensive examination of the role of eCB- mediated immune mechanisms in PreCE and SCE effects on child health. The specific aims of the CUDDELup renewal project are to: (i) examine enduring effects of PreCE (N=150; with N=100 NPreCE) and postnatal second-hand cannabis exposure (SCE) on offspring behavior; (ii) assess contributions of PreCE and SCE to longitudinal alterations in brain structure and resting state functional connectivity and test whether these neural phenotypes shape trajectories of early childhood cognition and behavior; (iii) evaluate whether PreCE and SCE are associated with eCB and immune function; and (iv) identify the multifaceted nature through which biomarkers and neural phenotypes are associated with child behavior. With these data, CUDDELup will be uniquely poised to disarticulate cannabis-specific sequelae and test a plausible eCB-immune mechanism of PreCE effects, thus contributing to our understanding of how cannabis affects the developing child, and adding to knowledge regarding prevention and interventions. CUDDELup is highly aligned with NIH priorities (study of neurodevelopmental conditions, child health, nutrition and exposures, actionable and measurable health outcomes, reproducible science) and with NIDA’s focus on substance-exposure related immune mechanisms.


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: 2026 ( Subtotal = $1,636,390 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Drug Use and Addiction Research Programs	000	7	4/17/2026	NON-COMPETING CONTINUATION	$1,636,390
														Subtotal = $1,636,390

Issue Date FY: 2025 ( Subtotal = $1,532,611 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Drug Use and Addiction Research Programs	001	6	6/26/2025	COMPETING CONTINUATION	$1,532,611
2025	2023	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Drug Use and Addiction Research Programs	000	5	6/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,532,611

Issue Date FY: 2023 ( Subtotal = $515,712 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Drug Use and Addiction Research Programs	000	5	1/19/2023	NON-COMPETING CONTINUATION	$515,712
														Subtotal = $515,712

Issue Date FY: 2022 ( Subtotal = $573,588 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Drug Use and Addiction Research Programs	000	4	1/26/2022	NON-COMPETING CONTINUATION	$516,230
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Drug Use and Addiction Research Programs	001	4	3/18/2022	NON-COMPETING CONTINUATION	$57,358
														Subtotal = $573,588

Issue Date FY: 2021 ( Subtotal = $623,706 )
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Drug Use and Addiction Research Programs	000	3	2/8/2021	NON-COMPETING CONTINUATION	$623,706
														Subtotal = $623,706

Issue Date FY: 2020 ( Subtotal = $640,331 )
2020	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Drug Use and Addiction Research Programs	000	2	1/31/2020	NON-COMPETING CONTINUATION	$640,331
														Subtotal = $640,331

Issue Date FY: 2019 ( Subtotal = $642,018 )
2019	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Drug Use and Addiction Research Programs	000	1	3/29/2019	NEW	$642,018
														Subtotal = $642,018

Grand Total All Awards = $6,164,356

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Prenatal Cannabis Exposure (PreCE) and Immune-Endocannabinoid Pathways to Development of Offspring Brain and Behavior up to Age 6

Award Number: R01DA046224

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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