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Effect on CBD on Exosome release from CNS infected cells

Award Number: R21DA050176
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 10/31/2023

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Effect on CBD on Exosome release from CNS infected cells - HIV-1 remains an incurable disease and as of 2017 over 30 million people were estimated to be living with HIV-1 with an average of 1.8 million new infections occurring annually. Up to 50% of people with HIV (PWH) suffer from HIV-associated neurocognitive disorders (HAND) despite effective combination anti-retroviral therapy (cART). HAND therefore represents a significant cause of morbidity in PWH. The inability of cART to prevent viral transcription and neurocognitive dysfunction confirms the need for adjunct therapies that target underlying mechanisms that contribute to HAND. In this context, mechanisms that may contribute to HAND include delivery of selective cargo in extracellular vesicles (EVs) released from HIV-infected macrophages/microglia. The long-term goal of this proposal is to mitigate virally-mediated pathogenesis within the CNS. The short term goals including elucidating the role of the cannabinoids in the inhibition of viral transcription and the reduction in the release of extracellular vesicles containing viral RNAs and proteins which cause CNS dysfunction. Our preliminary data suggests that the cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), may be effective in reducing HIV-1 transcription of both short, non-coding RNA such as trans-activating response (TAR) RNA and full- length genomic RNA, thereby resulting in a decreased production of infectious virus. Additional data indicates that the reduction in transcription results in a decreased incorporation of HIV-1 RNA into EVs released from infected cells, which has been previously shown to contribute to dysfunction in recipient cells including activation of the NF- kB pathway through TLR3 and increased susceptibility to infection. The data suggests this therapeutic effect is further amplified as treatment with cannabinoids results in a significant reduction in the number of EVs released from HIV-1 infected cells. We hypothesize that cannabinoid treatment may affect host cell pathways, including autophagy and the endosomal sorting complexes required for transport (ESCRT) pathways, to alter EV release which can potentially mitigate EV-related dysfunction during viral infection of the CNS. Our Aim include: 1) To define the mechanisms of cannabinoid-mediated decreased EV production and release in HIV-1 infected cells, and 2) Effect of CBD and THC on HIV-1 expression using 3D neurospheres. The overall positive impact of these two aims are to highlight the role of cannabinoids in EV release and dampening of the neuroinflammation.


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 = -$17 )
2024	2021	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Drug Use and Addiction Research Programs	000	2	3/11/2024	NON-COMPETING CONTINUATION	-$17
														Subtotal = -$17

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Drug Use and Addiction Research Programs	000	2	6/22/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $236,054 )
2021	2021	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Drug Use and Addiction Research Programs	000	2	4/15/2021	NON-COMPETING CONTINUATION	$236,054
														Subtotal = $236,054

Issue Date FY: 2020 ( Subtotal = $211,049 )
2020	2020	GEORGE MASON UNIVERSITY	4400 UNIVERSITY DR	FAIRFAX	VA	22030	FAIRFAX CITY	USA	Drug Use and Addiction Research Programs	000	1	4/16/2020	NEW	$211,049
														Subtotal = $211,049

Grand Total All Awards = $447,086

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Effect on CBD on Exosome release from CNS infected cells

Award Number: R21DA050176

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 10/31/2023

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