Honors Theses

Date of Award

Spring 5-11-2023

Document Type

Undergraduate Thesis

Department

School of Pharmacy

First Advisor

Nicole Ashpole

Second Advisor

Mahmoud ElSohly

Third Advisor

Kristie Willett

Relational Format

Dissertation/Thesis

Abstract

Life expectancies of people living with HIV have significantly lengthened due to the availability of antiretroviral therapies. Despite their ability to increase survival, these treatments do not “cure” HIV, nor do the stop the onset of neurological symptoms associated with infection, termed neuroHIV. NeuroHIV describes a myriad of neurological impairments including mood disorders (depression and anxiety), cognitive impairment, neuropathic pain, and motor disinhibition that reduce quality of life for people living with HIV. Mechanistically, the neurological impairments may involve actions of neurotoxic proteins directly produced by the virus. One of these proteins that has been well-characterized is the HIV trans activator of transcription (Tat). Tat exerts neurotoxic effects via activation of microglia, the first line of immune defense of the central nervous system, to induce a pro-inflammatory state in the brain.

Cannabis is more often smoked by HIV-positive individuals than the general population to reduce neuroinflammation. Cannabinoids or cannabis terpenes can attenuate HIV-induced neuroinflammation, this study was carried out to elucidate the potential anti-inflammatory constituents of cannabis for their efficacy on Tat-mediated activation of human microglia cell lines.

Herein, we exposed human microglia to Tat in the presence of a variety of compounds found in cannabis. Toxicity of the cannabis compounds themselves were also assessed. Several active compounds were then tested in a concentration-response curve to determine efficacy and potency. Two compounds, namely, β- caryophyllene and CBN reduced microglial activation in a concentration- dependent manner such that 1000 nM of β-caryophyllene and CBN significantly reduced activation compared to all other concentrations. In regards to CBN acid, 100nM significantly reduced activation compared to 1000nM. As such, the anti-inflammatory effects of β- caryophyllene, CBN, and CBN acid were observed at 1000 nM and 100 nM.

Further studies are needed to be carried out on cannabis and its individual cannabinoids for better understanding of their potential anti-inflammatory effects that the cannabis constituents can exert over HIV or HIV proteins and their mechanisms of actions.

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Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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