Does tetrahydrocannabinol (THC) elevate white blood cell (leukocyte) counts?

Does THC Elevate Leukocytes?

No, THC does not elevate leukocyte counts; instead, it suppresses and modulates immune cell function, particularly reducing activated monocyte populations and shifting immune responses toward an immunosuppressive state. 1, 2, 3

Mechanism of Immunosuppression

THC acts as a partial agonist at CB1 and CB2 cannabinoid receptors, which are key modulators of immune system activity. 1 The CB2 receptor is primarily located on immune and inflammatory cells, making it the principal target for THC's immunomodulatory effects. 1 Through these receptors, THC:

• Suppresses T-cell proliferation, activation, and cytotoxic activity 1
• Reduces granulocyte cytokine production 1
• Impairs dendritic and natural killer cell function 1
• Decreases neutrophil chemotactic capacity 1
• Promotes rapid expansion and recruitment of immunosuppressive myeloid-derived suppressor cells 2

Clinical Evidence of Leukocyte Reduction

The most robust clinical evidence demonstrates that THC reduces, rather than elevates, specific leukocyte populations:

• HIV-infected cannabis users have significantly lower circulating CD16+ monocytes (activated inflammatory monocytes) compared to non-cannabis-using HIV patients 3
• Plasma levels of IFN-γ-inducible protein 10 (IP-10), a key inflammatory marker, are lower in cannabis users 3
• In vitro THC treatment (0.625-5 μg/ml) impairs the transition of monocytes to the CD16+ activated state and reduces monocyte-derived IP-10 production 3
• Monocytes from cannabis users are unable to induce CD16 expression when stimulated with IFNα, whereas non-users show pronounced CD16 induction, confirming THC's anti-inflammatory effects 3

Effects on Specific Leukocyte Populations

T Lymphocytes

• THC suppresses T-cell proliferation in a dose-dependent manner 4
• Reduces interferon-gamma production and shifts the Th1/Th2 cytokine balance toward Th2 dominance (an immunosuppressive shift) 4
• Decreases both the percentage and intensity of activated T cells capable of producing interferon-gamma 4
• These effects are mediated through CB2 receptors, as demonstrated by abrogation with CB2 antagonist SR144528 4

Polymorphonuclear Leukocytes (Neutrophils)

• No direct modulatory effects on human neutrophil migration or phagocytosis were detected at THC concentrations between 10⁻¹⁰ and 10⁻⁵ M 5
• Circulating human neutrophils from healthy individuals remain functionally unaffected by THC due to absence of functional CB2 receptor expression 5

Comprehensive Transcriptomic Effects

Single-cell RNA sequencing reveals that THC acutely alters gene expression in 15,973 blood cells across eight cell types, identifying 294 transcriptome-wide significant genes. 6 These include:

• 69 common genes affected across all cell types 6
• 225 cell-type-specific genes, involving immune response, cytokine production, cell proliferation, and apoptosis pathways 6
• Distinct transcriptomic sub-clusters perturbed by THC in major immune cell types 6

Critical Clinical Implications

Cancer Immunotherapy

Cannabis consumption must be avoided during cancer immunotherapy treatment. 2 The American Society of Clinical Oncology reports that:

• THC decreases response rates to nivolumab 1
• Significantly decreases time to tumor progression and overall survival in patients receiving immunotherapy 1, 2
• THC directly reduces the therapeutic effect of PD-1 blockade by suppressing T-cell antitumor immunity through inhibition of JAK/STAT signaling via CB2 receptors 1

Context-Dependent Effects

The immunosuppressive properties of THC create a paradox:

• In conditions requiring active immune surveillance (e.g., cancer, infections), THC's immunosuppression is dangerous 1, 2
• In conditions characterized by excessive inflammation without need for immune activation, THC's anti-inflammatory properties could theoretically provide benefit 1

Common Pitfalls to Avoid

• Do not confuse anti-inflammatory effects with leukocyte elevation: THC reduces inflammatory cell activation and numbers, not increases them 3
• Do not assume all leukocyte populations respond identically: Neutrophils lack functional CB2 receptors and remain unaffected, while monocytes and T cells are significantly suppressed 5, 3, 4
• Do not overlook the clinical significance in immunocompromised patients: The immunosuppressive effects have real consequences for treatment outcomes in cancer and HIV 1, 2, 3