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Neural and Behavioral Consequences of Chronic THC Exposure During Adolescence

Award Number: R01DA047575
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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Neural and Behavioral Consequences of Chronic THC Exposure During Adolescence - Abstract Studies in humans suggest that frequent cannabis use during adolescence can alter brain structure and function and impair motivational and cognitive processes. However, the extent to which such neural changes and neurocognitive deficits persist into adulthood remains poorly understood, hampering the assessment of long- term health risks. Consequently, there is a pressing need for prospective research to investigate the potential long-term impact of adolescent cannabis exposure on brain development and dynamic behavioral processes. In ongoing work under R01-DA047575 to address this need, we have conducted longitudinal studies in nonhuman primates to examine the long-term impact of chronic exposure during adolescence to Δ9-THC, the most prominent cannabinoid in cannabis products. In male and female squirrel monkeys, neuroimaging data show that moderate and high levels of Δ9-THC exposure for 6 months during late adolescence interfered with normal age-related changes in functional connectivity and produced changes in brain structure and function that persisted into adulthood. Exposure to Δ9-THC during adolescence also had persisting effects on motivation, assessed with an economic demand analysis of both reward processing and the reinforcing strength of a highly palatable food, and on reward-based learning and cognitive flexibility, assessed with a stimulus discrimination/reversal task. Moreover, brain regions implicated in motivated behavior and cognitive function were among those in which resting state functional connectivity was altered. In conjunction, our findings thus far are striking. To further advance our understanding of the long-term consequences of chronic exposure to Δ9- THC during adolescence, we plan to continue our studies along three lines of investigation. First, to assess the unique vulnerability of adolescence to the effects of daily exposure to Δ9-THC, we will conduct longitudinal studies in adult monkeys identical to those already conducted in adolescent monkeys. This will permit direct comparison of long-lasting neural and behavioral effects of adolescent and adult Δ9-THC exposure. Second, to explore the generality of the reward devaluation revealed in economic demand studies of food reinforcement, neuroimaging (BOLD) data and exponential demand functions from studies of drug (cocaine, fentanyl) reinforcement during awake 9.4T scan sessions will be collected and analyzed. Third, we plan to further examine the disruption of reward-based learning mechanisms by adolescent Δ9-THC exposure. In these studies, we will investigate the effects of such exposure on the dynamics of Pavlovian conditioning of neutral stimuli with appetitive or aversive events (acquisition and extinction of conditioned stimulus properties) and on associated patterns of neural activity revealed with BOLD imaging during awake 9.4T scan sessions. Overall, these studies will significantly extend our understanding of selectivity and persistence of neural and behavioral abnormalities following chronic Δ9-THC exposure during adolescence. The overall impact of this research will lie in increasing awareness of long-term health risks that can follow exposure to Δ9-THC-containing cannabis products.


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 = $1,179,649 )
2025	2025	THE MCLEAN HOSPITAL CORPORATION	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	6	5/27/2025	COMPETING CONTINUATION	$1,179,649
														Subtotal = $1,179,649

Issue Date FY: 2023 ( Subtotal = $556,272 )
2023	2023	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	5	4/27/2023	NON-COMPETING CONTINUATION	$556,272
														Subtotal = $556,272

Issue Date FY: 2022 ( Subtotal = $718,402 )
2022	2022	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	4	4/14/2022	NON-COMPETING CONTINUATION	$718,402
														Subtotal = $718,402

Issue Date FY: 2021 ( Subtotal = $719,019 )
2021	2021	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	3	4/29/2021	NON-COMPETING CONTINUATION	$719,019
														Subtotal = $719,019

Issue Date FY: 2020 ( Subtotal = $710,343 )
2020	2020	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	2	8/31/2020	NON-COMPETING CONTINUATION	$0
2020	2020	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	2	4/29/2020	NON-COMPETING CONTINUATION	$710,343
														Subtotal = $710,343

Issue Date FY: 2019 ( Subtotal = $601,606 )
2019	2019	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	1	6/17/2019	NEW	$601,606
														Subtotal = $601,606

Grand Total All Awards = $4,485,291

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Neural and Behavioral Consequences of Chronic THC Exposure During Adolescence

Award Number: R01DA047575

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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