Δ9-Tetrahydrocannabinol treatment impairs CD8+ T cell differentiation into interferon gamma-competent CD45RO+ cells.

Marty J.; Crawford R.; Blevins L.; Gulick P.; Kaminski N. · The Journal of pharmacology and experimental therapeutics · 2026

**Background & Methods** This is a review study examining whether cannabis use by people living with HIV (PLWH) affects interferon gamma (IFNγ) secretion by CD8+ T cells. The research specifically investigates THC's immunomodulatory effects on T cell differentiation and cytokine production in both HIV-positive and HIV-negative donors using in vitro cell culture models, polymerase chain reaction, and flow cytometry analysis. **Key Findings** - THC treatment reduces CD8+ T cell IFNγ secretion in both HIV+ and HIV- individuals, with greater suppression observed compared to cannabidiol (CBD). The selective cannabinoid receptor 2 (CB2) agonist JWH-015 also suppressed cytokine secretion, suggesting CB2 receptor involvement in this immunomodulatory effect. - THC impairs CD8+ T cell differentiation into IFNγ-competent CD45RO+ memory cells, thereby reducing the proportion of cells capable of producing IFNγ rather than suppressing gene expression or protein synthesis in individual cells. - HIV serostatus did not significantly influence T cell IFNγ responses, indicating that THC's immunomodulatory effects are generalizable across both infected and uninfected populations. **Dosage & Administration** Not reported. The abstract does not specify THC concentrations, treatment duration, or administration methods used in the in vitro experiments. **Safety & Adverse Effects** Not reported. The study focuses on immunological outcomes rather than adverse effects of THC exposure. No safety data or toxicity profiles are discussed in the provided abstract. **Evidence Quality** This review-type study represents moderate evidence quality with significant limitations. The use of isolated in vitro cell culture systems may not fully replicate complex in vivo immune responses within the central nervous system or peripheral immune compartments. The study lacks information regarding sample sizes, statistical analyses, and control conditions. The findings are preliminary in nature and would require validation through in vivo studies in animal models or clinical trials. While the potential therapeutic benefit of reducing CNS IFNγ-producing CD8+ T cells in HIV-associated neurocognitive disorder is intriguing, the generalizability to clinical practice remains uncertain without human efficacy and safety data.

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