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Neural, Cognitive and Abuse-Related Consequences of Chronic THC Exposure during Adolescence in Nonhuman Primates

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: 04/30/2025

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Neural, Cognitive and Abuse-Related Consequences of Chronic THC Exposure during Adolescence in Nonhuman Primates - Cannabis is the most widely self-administered psychoactive substance among adolescents in the U.S., and its use shows no signs of abatement. Studies in humans suggest that heavy cannabis use during this critical period of development can alter brain structure and function and impair cognitive and behavioral processes. However, the extent to which neural changes and neuropsychological deficits produced by cannabis use during adolescence persist into adulthood remains poorly understood, hampering the assessment of long-term health risks. Consequently, there continues to be a pressing need for carefully controlled research on the potential long-term impact of adolescent cannabis exposure on brain development, cognitive competency and addiction. The present research addresses this need with longitudinal studies in nonhuman primates to examine the long-term impact of chronic exposure to the cannabinoid Δ9-THC during adolescence. In this research, groups of adolescent male and female squirrel monkeys will be treated daily with a low active dose or a high active dose of Δ9-THC or with vehicle. Daily treatment will continue throughout adolescence for 6 months, during which time observational and activity data will be collected to assess behavioral status and the any tolerance to the effects of drug treatment. Neuroimaging data will be collected before, during, and after daily treatment to evaluate changes in neural structure or function that may be associated with chronic exposure to Δ9-THC. After the chronic regimens are discontinued, subjects will remain drug-free for 6 weeks to allow for the elimination of the lipophilic cannabinoid. Next, using touchscreen-based tasks, subjects will be studied to determine whether prior exposure to Δ9-THC may have persisting effects on motivation or different types of cognitive function. First, using a behavioral economic demand analysis, motivation will be assessed by comparing the reinforcing strength of sweetened condensed milk, a highly palatable reinforcer, in the different treatment groups. Subsequently, two tasks (stimulus discrimination/reversal and delayed matching to position) will be used to compare learning, response inhibition, and spatial short-term memory across treatment groups. Neuroimaging information will be collected prior to and following the above testing. Finally, the acquisition of Δ9-THC self-administration will be studied to determine whether adolescent exposure to Δ9- THC may have enhanced its reinforcing effects. Lastly, the study will conclude with a final neuroimaging scan. Overall, these longitudinal studies will provide information regarding the persistence of neural abnormalities that may be produced by Δ9-THC exposure during adolescence, their association with cognitive impairments or changes in sensitivity to abuse-related effects of Δ9-THC, and whether such sequelae and associations can be related to the chronic dosage Δ9-THC or differ in males and females.


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 = $1,178,464 )
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
2025	2023	THE MCLEAN HOSPITAL CORPORATION	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	5	8/19/2025	NON-COMPETING CONTINUATION	-$1,185
														Subtotal = $1,178,464

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 = $4,484,106

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Neural, Cognitive and Abuse-Related Consequences of Chronic THC Exposure during Adolescence in Nonhuman Primates

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: 04/30/2025

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