Two weeks of daily CBD decreased immune cell counts in the spleens of healthy rats without affecting their ability to kill infected cells | Research

The takeaway

Repeated CBD administration at 5 mg/kg/day for 14 days reduced T cell and non-T/NK lymphocyte counts in rat spleens, mirroring effects previously seen in blood, but did not affect natural killer cell numbers or cytotoxicity.

Immunologists, people taking CBD long-term, and researchers studying CBD safety and immunomodulation.

CBD depleted T cells and B cells in spleen; NK cells unaffected

What the researchers found

CBD at 5 mg/kg/day for 14 days decreased splenic T cells and non-T/NK CD45RA+ lymphocytes but not NK cells. Natural killer cell cytotoxicity was unaffected in both blood and spleen. A CB2 receptor antagonist showed a significant interaction with CBD, suggesting partial CB2 involvement.

Why it matters

CBD is widely marketed as safe and anti-inflammatory, but this study shows it can deplete specific immune cell populations in a major immune organ. This has implications for people taking CBD long-term, particularly those with compromised immune systems.

The numbers in context

63 rats. 14 days of daily CBD. 5 mg/kg dose effective; 2.5 mg/kg not significant. T cells and non-T/NK CD45RA+ lymphocytes decreased in spleen. NK cells unaffected. NK cytotoxicity unchanged. CB2 antagonist interaction significant.

How the study worked

63 adult male Wistar rats received intraperitoneal CBD (2.5 or 5 mg/kg/day) or vehicle for 14 consecutive days. Splenic lymphocyte subsets counted by flow cytometry. NK cell cytotoxicity measured by Chromium-51 release assay in both blood and spleen. CB2 antagonist AM630 co-administered in some groups.

What this study cannot tell us

Male rats only. Intraperitoneal administration does not reflect typical human oral use. Healthy animals may respond differently than diseased ones. CBD doses may not be equivalent to human doses. Fourteen-day exposure is relatively short.

How to read the evidence

Preliminary: well-designed animal study with mechanistic CB2 receptor investigation, but limited to male rats with intraperitoneal dosing.

When this study was published

Published 2026.

The bigger picture

The selective depletion of T cells and B cells while sparing NK cells is an interesting pattern. It suggests CBD's immunomodulatory effects are cell-type specific, which could be therapeutically useful for autoimmune conditions but concerning for long-term immunosuppression.

Questions still open

Do these splenic immune changes translate to increased infection susceptibility? Would oral CBD produce similar effects at equivalent doses? Are these effects reversible after CBD cessation? How do these findings apply to people using CBD for autoimmune conditions?

Common questions

Does CBD affect the immune system?

In this rat study, 14 days of daily CBD reduced specific immune cell populations (T cells and B cells) in the spleen without affecting natural killer cells or their ability to kill target cells.

Is long-term CBD use safe for the immune system?

This study raises questions about chronic CBD use and immune function. While the immune cell reductions could be therapeutic for autoimmune conditions, they could also reduce immune surveillance. Human studies are needed.

Read the original research

Repeated administration of cannabidiol decreases splenic lymphocyte subset numbers in rats.

International journal of immunopathology and pharmacology, 40, 3946320251411441

View on PubMed ↗Publisher’s paper ↗

Citation

Turkki, Tara H; Jankowski, Maciej M; Glac, Wojciech; Badtke, Piotr; Saito, Viviane M; Swiergiel, Artur H; Ignatowska-Jankowska, Bogna M. (2026). Repeated administration of cannabidiol decreases splenic lymphocyte subset numbers in rats.. International journal of immunopathology and pharmacology, 40, 3946320251411441. https://doi.org/10.1177/03946320251411441