Anti-inflammatory effects of cannabidiol in the treatment of type 1 diabetes: A mini review

Table 1 Anti-inflammatory and immunomodulatory effects of cannabidiol in type 1 diabetes models

Ref.	Experimental model	Dose/route of administration	Treatment duration	Inflammatory markers evaluated	Main findings	Quality assessment
Li et al[13]	Male C57BL/6 mice (6-8 weeks old) with STZ-induced T1D	Cannabidiol at doses of 5 mg/kg and 10 mg/kg, administered intraperitoneally	Once daily for 28 consecutive days	CCL2 (monocyte chemoattractant protein-1), IL-1β, AGEs, RAGE	Significantly reduced immunomodulator levels in the liver and spleen, and decreased expression of AGEs and RAGE in mouse tissues	High
González-Mariscal et al[18]	NOD and C57BL/6J mice with STZ-induced diabetes (150 mg/kg)	Abn-CBD (abnormal cannabidiol); intraperitoneal injection at doses of 0.1 mg/kg and 1 mg/kg	NOD mice: Once daily for 12 weeks; STZ-induced mice: 7 consecutive days	Inflammatory cytokines (IL-6, TNF-α), NF-κB and TXNIP activation, CD4+ and CD8+ T cell infiltration in pancreatic islets	Reduction in insulitis and β-cell apoptosis, decreased pancreatic inflammation, and improved glucose tolerance	High
Lehmann et al[19]	Female NOD mice (6 weeks old)	5 mg/kg, intraperitoneally	10 weeks (5 times per week)	Leukocyte rolling and adhesion (intravital microscopy); functional capillary density; plasma cytokines; ICAM-1 and 1P-selectin	CBD delayed the onset of T1DM, reduced leukocyte activation, and increased pancreatic capillary perfusion	High
Weiss et al[30]	Female NOD mice (6-12 weeks old)	5 mg/kg, intraperitoneally	2 to 4 weeks (10-20 applications)	IFN-γ, TNF-α, IL-12, IL-10, IL-4 (in plasma, splenocytes, and macrophages); pancreatic histology (insulitis)	Reduction in T1DM incidence (from 86% to 30%), delayed disease onset, reduced insulitis, suppression of Th1 cytokines, and increased IL-10 and IL-4	High
Weiss et al[31]	Female NOD mice (11-14 weeks old)	5 mg/kg, intraperitoneally	4 weeks (5 times per week)	IL-6, IL-12, TNF-α, IL-10, IL-4 (from splenocyte and macrophage cultures); islet infiltration (pancreatic histology)	Significant reduction in T1DM incidence [32% vs (86%-100%)], decreased insulitis, increased Th2 cytokines (IL-10, IL-4), and reduced IL-6 and IL-12 Levels	High
González-Mariscal et al[36]	Male C57BL/6J mice with T1D mellitus induced by streptozotocin (150mg/kg)	Synthetic cannabidiol derivative: (+)-CBD-HPE, 10 mg/kg, administered intraperitoneally	7 consecutive days, starting before diabetes induction	Phospho-NF-κB, cleaved caspase-3, CD3+ (T lymphocyte infiltration), plasma cytokines (interferon-gamma, IL-5, TNF-α, IL-18)	Inhibited NF-κB transcription factor activation, reduced T-cell infiltration in pancreatic islets and kidneys, prevented β-cell apoptosis, and lowered interferon-gamma levels	High
Aseer et al[37]	Female NOD mice with β-cell-specific genetic deletion of the CB1	Genetic deletion (β-cell-specific knockout); JD-5037 (CB1 inverse agonist) also tested separately	26-week follow-up; JD-5037 administered for 4 weeks	Inflammatory cytokines: Interferon-gamma, IL-1β, IL-12p70, TNF-α; chemokines: CXCL9, CXCL10, CCL5; adhesion molecules	Reduced islet inflammation, with lower expression of proinflammatory cytokines, increased frequency of regulatory T cells, and reduced insulitis score	High

¹P-selectin: A cell adhesion molecule involved in leukocyte interactions.

Abn-CBD: Abnormal cannabidiol; AGEs: Advanced glycation end products; CB1: Cannabinoid receptor type 1; CBD: Cannabidiol; (+)-CBD-HPE: Synthetic cannabidiol derivative; CCL: C-C motif chemokine ligand; CXCL: C-X-C motif chemokine ligand; ICAM-1: Intercellular adhesion molecule-1; IFN: Interferon; IL: Interleukin; JD-5037: Cannabinoid receptor type 1 inverse agonist; NF-κB: Nuclear factor kappa B; NOD: Non-obese diabetic; RAGE: Receptor for advanced glycation end product; STZ: Streptozotocin; T1D: Type 1 diabetes; T1DM: Type 1 diabetes mellitus; TXNIP: Thioredoxin-interacting protein.