Cannabidiol exerts anti-inflammatory effects but maintains T effector memory cell differentiation: A Single-Cell Study in Humans

Le résumé fourni par la source

Abstract Cannabidiol is widely available and often used for pain management. Individuals with kidney disease or renal allografts have limited analgesia options. We conducted a Phase 1 human study to compare the peripheral immune cell distribution before (pre-cannabidiol) and after exposure to cannabidiol at steady state (post-cannabidiol). This ex vivo study included specimens from 23 participants who received oral cannabidiol (up to 5 mg/kg twice daily) for 11 days. Lymphocytes were isolated and stimulated with anti-CD3/CD28 antibodies, with or without tacrolimus. Pharmacodynamic responses were assessed via CellTiter-Glo® proliferation, scRNA-seq, cytokine assays, and flow cytometry. Steady-state plasma concentrations of CBD were quantified via tandem mass spectrometry. We identified an increased proportion of T effector memory (TEM) cells post-cannabidiol (22% increase, P-value of 3.2 x 10 -32 ), which correlated with CBD plasma concentrations ( Pearson Corr= 0.77, P-value < 0.01 ). Post-cannabidiol cytokine assays revealed elevated proinflammatory IL-6 protein levels and anti-inflammatory IL-10 levels ( adjusted P-values < 0.0001 ). Cannabidiol reduced overall T and B lymphocyte proliferation with additive immunosuppressive effects to tacrolimus. In flow cytometry, the proportion of TEM and TEMRA increased post-cannabidiol with tacrolimus ( P-values < 0.05 ). Cannabidiol exhibits mixed immunomodulatory effects with pro- and anti-inflammatory signals. Understanding the clinical safety of cannabidiol use is important given the paucity of pain control options available for immunocompromised transplant populations.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.