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Translational Studies of Cannabis Administration, Cognition, and the Endocannabinoid System in HIV

Award Number: R01DA051295
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Translational Studies of Cannabis Administration, Cognition, and the Endocannabinoid System in HIV - PROJECT SUMMARY Understanding how co-morbidities in persons with HIV (PWH) such as substance use affect risk-taking, decision- making, and other cognitive behaviors is important given implications for everyday functioning and transmission risk. The high prevalence of cannabis use in PWH, medicinally and recreationally, may indicate disease severity, impart therapeutic benefits, or adverse consequences. In fact, cannabis is recommended to those with HIV to alleviate nausea, improve appetite, relieve pain, and lift mood. To-date, the consequences of cannabis use in PWH remain unclear as do potential interactions with HIV treatments. In healthy participants, heavy cannabis use is associated with cognitive deficits e.g., risky decision-making, response disinhibition and inattention, but pro-cognitive effects in PWH may exist at mild use levels due to its anti-inflammatory and anti-excitotoxic properties. Furthermore, little has been done to determine the effects of cannabis use on the endocannabinoid (EC) system in general or in PWH. This area of study is especially germane to cognition since the virus affects brain regions rich in ECs. CNS relevance is of particular importance given that the EC system exerts regulatory effects over the dopaminergic system, critical for these cognitive processes. This application will utilize a cross- species approach to delineate the effects EC system activation has on HIV-relevant cognitive and motivational domains. Animal studies enable mechanistic insights on chronic and withdrawal effects in this system. Both behavioral and mechanistic overlap will occur between the human and animal studies. Specific Aim 1 will determine the effects of the two primary cannabis constituents (Δ9-tetrahydrocannabinol [THC], cannabidiol [CBD]) vs. placebo on risky decision-making, response inhibition, reward learning, temporal perception, and motivation, plus EC and homovanillic acid (HVA; a surrogate for dopamine activity) levels in HIV+ and HIV- subjects. Participants with infrequent cannabis use will undergo baseline cognitive testing and biomarker assays with antiretrovirals (ART) use quantified. They will be randomized to a 5-day course of either THC, CBD, or placebo and return for follow-up testing and re-assaying of ECs and HVA levels. Specific Aim 2 will conduct parallel experiments in a rodent model of HIV on acute, chronic, and withdrawal effects of 2 doses of THC vs. 2 doses of CBD, plus combined THC/CBD/ART (dolutegravir) on the same cognitive and motivational tests, plus EC and HVA levels to provide directionality and potential interaction of drug effects. Each experiment will train and test HIV-1 transgenic and wildtype littermate rats on cross-species versions of tasks used in Aim 1. Rats will be tested at baseline, immediately after acute, then chronic treatment, then during withdrawal. The brains of rats will be harvested and assessed for EC and dopamine receptor levels to determine potential mechanisms of the beneficial/negative effects of cannabinoid treatments on symptoms related to HIV. Disentangling the cognitive and biological effects of THC and CBD and their relation with ART is a much-needed advance in the HIV field and will inform development of therapeutics and policy advice for co-morbid substance use.


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 = $0 )
2026	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	5	3/3/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $812,158 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	5	6/26/2025	NON-COMPETING CONTINUATION	$812,158
														Subtotal = $812,158

Issue Date FY: 2024 ( Subtotal = $944,197 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	004	4	5/1/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	003	4	4/26/2024	SUPPLEMENT FOR EXPANSION	$13,204
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	002	4	4/25/2024	NON-COMPETING CONTINUATION	$81,214
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	001	4	3/4/2024	SUPPLEMENT FOR EXPANSION	$118,835
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	4	3/1/2024	NON-COMPETING CONTINUATION	$730,944
														Subtotal = $944,197

Issue Date FY: 2023 ( Subtotal = $944,197 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	3	1/19/2023	NON-COMPETING CONTINUATION	$812,158
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	001	3	1/24/2023	SUPPLEMENT FOR EXPANSION	$132,039
														Subtotal = $944,197

Issue Date FY: 2022 ( Subtotal = $812,158 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	001	2	3/29/2022	NON-COMPETING CONTINUATION	$81,215
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	2	1/28/2022	NON-COMPETING CONTINUATION	$730,943
														Subtotal = $812,158

Issue Date FY: 2021 ( Subtotal = $811,729 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	1	4/29/2021	NEW	$811,729
														Subtotal = $811,729

Grand Total All Awards = $4,324,439

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Translational Studies of Cannabis Administration, Cognition, and the Endocannabinoid System in HIV

Award Number: R01DA051295

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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