THC may suppress a type of inflammatory immune response implicated in HIV-associated cognitive decline, according to a study published this week in the Journal of Pharmacology and Experimental Therapeutics.
Researchers from Michigan State University examined how delta-9 THC affects CD8+ T cells, immune cells that help eliminate infected or abnormal cells but can also contribute to chronic inflammation.
The study focused partly on HIV-associated neurocognitive disorder, or HAND, a group of cognitive problems that can occur among people living with HIV even when antiretroviral therapy successfully suppresses the virus.
Researchers note that interferon gamma-producing CD8+ T cells can enter the central nervous system and contribute to persistent neuroinflammation, with higher levels of these cells previously associated with worse cognitive outcomes.
The researchers analyzed CD8+ T cells obtained from people with and without HIV. Participants with HIV were receiving combination antiretroviral therapy and were also separated based on reported marijuana use.
HIV status itself did not significantly alter interferon gamma responses. Among participants with HIV, however, marijuana consumers showed modestly lower average interferon gamma secretion, although the difference was not statistically significant.
The researchers then directly exposed isolated human CD8+ T cells to THC.
THC significantly reduced secretion of interferon gamma and other inflammatory cytokines, including interleukin-2 and tumor necrosis factor alpha. THC produced greater suppression than CBD.
A selective cannabinoid receptor 2 agonist known as JWH-015 also reduced cytokine secretion, suggesting that CB2 signaling may play a role in THC’s effects.
Further experiments indicated that THC was not simply preventing individual T cells from producing interferon gamma. Instead, THC interfered with the process through which naïve CD8+ T cells differentiated into CD45RO+ cells capable of producing and secreting the inflammatory cytokine.
In other words, THC reduced the number of cells developing into the inflammatory state rather than directly shutting down interferon gamma production within cells that had already reached that state.
The researchers said the findings could have relevance for HIV-associated neuroinflammation because reducing interferon gamma-producing CD8+ T cells in the central nervous system may potentially improve cognitive outcomes.
They also said the mechanism could have implications outside HIV, since the same inflammatory T-cell responses have been implicated in other inflammatory diseases.
The findings do not demonstrate that marijuana or THC can treat HIV-associated neurocognitive disorder in patients. Rather, the study identifies a potential mechanism through which THC can alter inflammatory activity in human immune cells and provides a basis for further research.
The study was authored by Joel R. Marty, Robert B. Crawford, Lance K. Blevins II, Peter Gulick and Norbert E. Kaminski.
