“Cannabis use is prevalent among individuals living with HIV in the United States, but the impact of cannabis exposure on the reservoir of latently infected cells that persists during antiretroviral therapy (ART) remains unclear. To address this gap, we analyzed the effect of Δ-9-tetrahydrocannabinol (THC) on primary CD4 T cells that were latently infected with HIV.

We found that THC had no detectable effect on baseline or latency reversing agent (LRA) stimulated HIV expression, or on expression of an activation marker (CD38). However, using an integrated multiomic single-cell analysis of genome-wide chromatin accessibility and gene expression, we observed altered expression of several hundred genes in HIV infected CD4 T cells after THC exposure, including transcriptional downregulation of genes involved in protein translation and antiviral pathways, indicating that THC suppresses innate immune activation in infected cells. Additionally, chromatin accessibility analysis demonstrated upregulated chromatin binding activity for the transcriptional regulator CTCF, and reduced activity for members of the ETS transcription factor family in infected cells after THC exposure.

These findings provide insights into the mechanisms by which cannabis use could influence the persistence of HIV within cellular reservoirs and the molecular phenotype of latently infected cells. Further elucidation of the underlying mechanisms involved in THC-mediated changes to HIV infected cells, will lead to an improved understanding of the impact of cannabis use on the HIV reservoir.

Importance: Cannabis use is common among individuals living with HIV, but the long-term effects of cannabis use on the HIV reservoir are not yet studied completely. We employed advanced single-cell technologies to reveal how cannabis components, specifically THC, influence HIV-infected immune cells and their pattern of gene expression. We found that, while THC doesn’t reactivate virus in latently infected cells, it alters the molecular characteristics of these infected immune cells. These findings are important because they underscore how cannabis could regulate persistent infection in people living with HIV. Understanding these cellular changes in response to THC could be helpful for successful treatment for people living with HIV.”

https://pubmed.ncbi.nlm.nih.gov/40502036/

https://www.biorxiv.org/content/10.1101/2025.06.02.657468v1

“Yes, there is growing evidence that cannabis could play a role in regulating persistent HIV infection. Studies suggest that cannabinoids, particularly THC, can alter the molecular characteristics of HIV-infected immune cells without reactivating the virus. These changes might be beneficial in reducing inflammation and improving treatment outcomes for people living with HIV.”

“Recent work has shown that people with HIV (PWH) exhibit deficits in cognitive control and altered brain responses in the underlying cortical networks, and that regular cannabis use has a normalizing effect on these neural responses.

However, the impact of regular cannabis use on the neural oscillatory dynamics underlying motor control deficits in PWH remains less understood. Herein, 102 control cannabis users, control nonusers, PWH who regularly use cannabis, and PWH who do not use cannabis performed a motor control task with and without interference during high-density magnetoencephalography. The resulting neural dynamics were examined using whole-brain, voxel-wise statistical analyses that examined the impact of HIV status, cannabis use, and their interaction on the neural oscillations serving motor control, spontaneous activity during the baseline period, and neurobehavioral relationships.

Our key findings revealed cannabis-by-HIV group interactions in oscillatory gamma within the prefrontal cortices, higher-order motor areas, and other regions, with the non-using PWH typically exhibiting the strongest gamma interference responses. Cannabis-by-HIV interactions were also found for oscillatory beta in the dorsal premotor cortex. Spontaneous gamma during the baseline was elevated in PWH and suppressed in cannabis users in all regions exhibiting interaction effects and the left primary motor cortex, with spontaneous levels being correlated with behavioral performance.

These findings suggest that regular cannabis use has a normalizing effect on the neural oscillations serving motor control and the abnormally elevated spontaneous gamma activity that has been widely replicated in PWH, which may suggest that cannabis has at least some therapeutic utility in PWH.”

https://pubmed.ncbi.nlm.nih.gov/40473990/

“Further, these findings corroborate multiple recent studies showing elevated spontaneous gamma activity in PWH, and that regular cannabis use is associated with a marked suppression in such spontaneous activity.”

https://link.springer.com/article/10.1007/s11481-025-10219-0

“The main psychoactive component in cannabis-Δ⁹-tetrahydrocannabinol-is known to have anti-inflammatory properties and to alter gamma oscillations, pointing to its potential as a therapeutic agent for people with HIV (PWH). However, it remains unknown how cannabis use among PWH interacts with the neural circuitry underlying inhibitory processing.

Herein, using a cross-sectional study design, we collected data from 108 cannabis users and non-users with and without HIV. Participants were interviewed regarding their substance use history and completed a paired-pulse somatosensory stimulation paradigm during magnetoencephalography (MEG). MEG data were imaged using a beamformer and peak voxel time series data were extracted to examine neural oscillations in response to the stimulation and the strength of spontaneous activity in the same tissue during the baseline period. Across all participants, we observed robust gamma oscillations following stimulation in the left primary somatosensory cortices, with responses to the second stimulation being strongly attenuated relative to the first, thus demonstrating somatosensory gating.

PWH who used cannabis exhibited stronger oscillatory gamma activity compared with non-users with HIV, while the latter group also exhibited elevated spontaneous gamma activity relative to all other groups. Finally, we found that a longer duration of time since HIV diagnosis was associated with less efficient inhibitory processing among PWH who did not use cannabis, but not among PWH who regularly use cannabis.

These findings provide new evidence that cannabis use may mitigate the harmful effects of HIV on oscillatory and spontaneous gamma activity serving inhibitory processing.”

https://pubmed.ncbi.nlm.nih.gov/40421314/

“Taken together, these findings suggest that regular cannabis use may have a neuroprotective effect on inhibitory processing in PWH by normalising spontaneous gamma activity and enhancing gamma oscillatory responses during sensory gating. This pattern indicates that cannabis use could potentially mitigate some of the neural disruptions associated with HIV, highlighting a promising target for future interventions aimed at preserving cognitive function in this population. Importantly, the capacity of cannabis to influence gamma dynamics underscores the broader role of the endocannabinoid system in shaping neural function in the context of HIV-related neuropathology.”

https://academic.oup.com/braincomms/article/7/3/fcaf190/8132827?login=false

“Given the high prevalence of cannabis use among people with HIV (PWH) and its potential to modulate immune responses and reduce inflammation, this systematic review examines preclinical evidence on how tetrahydrocannabinol (THC), a key compound in cannabis, affects gene and micro-RNA expression in simian immunodeficiency virus (SIV)-infected macaques and HIV-infected human cells.

Through a comprehensive search, 19 studies were identified, primarily involving SIV-infected macaques, with a pooled sample size of 176, though methodological quality varied across the studies. Pathway analysis of differentially expressed genes (DEGs) and miRNAs associated with THC revealed enrichment in pathways related to inflammation, epithelial cell proliferation, and adhesion. Notably, some DEGs were targets of the differentially expressed miRNAs, suggesting that epigenetic regulation may contribute to THC’s effects on gene function.

These findings indicate that THC may help mitigate chronic immune activation in HIV infection by altering gene and miRNA expression, suggesting its potential immunomodulatory role. However, the evidence is constrained by small sample sizes and inconsistencies across studies. Further research employing advanced methodologies and larger cohorts is essential to confirm THC’s potential as a complementary therapy for PWH and fully elucidate the underlying mechanisms, which could inform targeted interventions to harness its immunomodulatory effects.”

https://pubmed.ncbi.nlm.nih.gov/40141240/

https://www.mdpi.com/1422-0067/26/6/2598

“Purpose of review: This review explores how cannabis impacts the gut microbiome, immune system, and ART outcomes in people with HIV (PWH). Given the increasing prevalence of cannabis use among PWH, we investigated its potential to reduce chronic inflammation and enhance gut health, both of which can influence HIV pathogenesis.

Recent findings: Cannabis has immunomodulatory and anti-inflammatory effects, including reducing systemic inflammatory biomarkers (such as MCP-1 and IP-10) and improving gut barrier integrity through increased short-chain fatty acid (SCFA) production.

Studies have shown that cannabis use is associated with increased gut mucosal immunity, decreased immune activation, and a unique microbiome composition. Preliminary evidence indicates that cannabis may influence HIV reservoirs, although the results remain inconclusive.

Cannabis shows promise in managing inflammation, gut dysbiosis, and immune dysfunction in PWH. However, its effects on HIV reservoirs, adherence to antiretroviral therapy, and long-term outcomes need further investigation through rigorous clinical trials using standardized formulations.”

https://pubmed.ncbi.nlm.nih.gov/39984806/

https://link.springer.com/article/10.1007/s11904-025-00729-0