Cannabidiol exerts antiinflammatory effects but maintains T effector memory cell differentiation in humans

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 healthy volunteer study to compare the peripheral immune cell distribution before (pre-cannabidiol) and after exposure to cannabidiol at steady state (post-cannabidiol). This study included specimens from 12 participants who received oral cannabidiol (up to 5 mg/kg twice daily) for 12 days. Lymphocytes were isolated and stimulated with anti-CD3/CD28 antibodies, with or without tacrolimus. Understanding the clinical safety of cannabidiol use is important given the paucity of pain control options available for immunocompromised transplant populations. Each individual has three conditions that are sequenced for the phase No CD3/CD28, CD3/CD28 and CD3/CD28 +Tacrolimus across two phases: pre-CBD and post-CBD. Overall design: PBMCs were collected from each participant at Day 1 (pre-CBD) and Day 12 (post-CBD). Cells were cultured ex vivo for 72 h under six conditions that combine T-cell stimulation (±CD3/CD28), cannabidiol (±CBD), and tacrolimus (±TAC). After culture, cells were processed for single-cell RNA-seq using the 10x Genomics Chromium 3' v3.1 workflow and sequenced on an Illumina NovaSeq 6000. In total, 59 libraries (6 conditions × 2 time-points × participants) capture transcriptomic effects of CBD, TAC, and T-cell activation: 1 - No CD3/CD28, No CBD, No Tacrolimus; 2 - CD3/CD28, No CBD; No Tacrolimus; 3 - CD3/CD28, No CBD, Tacrolimus; 4 - No CD3/CD28, CBD; No Tacrolimus; 5 - CD3/CD28, CBD; No Tacrolimus; 6 - CD3/CD28, CBD; Tacrolimus;