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

Area of Science:

• Immunology
• Pharmacology
• Nephrology

Background:

• Cannabidiol (CBD) is a common pain management option.
• Patients with kidney disease or renal allografts have limited pain relief choices.
• The immunomodulatory effects of CBD in this population are not well understood.

Purpose of the Study:

• To investigate the effects of oral cannabidiol (CBD) on peripheral immune cell distribution and function in individuals with kidney disease.
• To compare immune cell profiles before and after CBD exposure at steady-state concentrations.
• To assess the interaction of CBD with tacrolimus, an immunosuppressant.

Main Methods:

• Phase 1 human study involving 23 participants receiving oral CBD (up to 5 mg/kg twice daily for 11 days).
• Ex vivo analysis of lymphocytes stimulated with anti-CD3/CD28 antibodies, with or without tacrolimus.
• Assays included CellTiter-Glo® proliferation, single-cell RNA sequencing (scRNA-seq), cytokine analysis, and flow cytometry.
• Quantification of steady-state plasma CBD concentrations using tandem mass spectrometry.

Main Results:

• Significant increase in T effector memory (TEM) cells post-CBD (22% increase, P < 3.2 x 10^-32), correlating with CBD plasma levels (r=0.77, P < 0.01).
• Elevated proinflammatory IL-6 and anti-inflammatory IL-10 cytokine levels observed post-CBD (adjusted P < 0.0001).
• CBD reduced T and B lymphocyte proliferation, showing additive immunosuppression with tacrolimus.
• Increased TEM and TEMRA cell proportions noted post-CBD with tacrolimus (P < 0.05).

Conclusions:

• Cannabidiol (CBD) demonstrates mixed immunomodulatory effects, including pro-inflammatory and anti-inflammatory signals.
• CBD increases TEM cells and alters cytokine profiles in patients with kidney disease.
• Further research into the clinical safety of CBD is crucial for immunocompromised transplant populations with limited pain management options.