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

Abstract

This study reviews the anti-inflammatory potential of cannabidiol (CBD) in the management of type 1 diabetes (T1D). A comprehensive search was conducted across PubMed, Scopus, and ScienceDirect databases using the terms “type 1 diabetes”, “cannabidiol”, “anti-inflammatory effect”, and “CBD”. Articles published between 2005 and 2025 were screened, and studies involving animal models that examined CBD as a therapeutic intervention for T1D and reported on its anti-inflammatory effects were included. Of the 62 retrieved articles, only 6 met the predefined inclusion criteria. Although limited in number, the available studies show promising outcomes. CBD demonstrates potential as an adjuvant therapy for T1D due to its immunomodulatory and anti-inflammatory actions. Nonetheless, further research is required to establish safe and effective clinical application protocols.

Key Words: Cannabidiol; Diabetes Mellitus; Type 1 diabetes; Inflammations; Oxidative stress; Behavior; Behavior mechanisms

Core Tip: This review discusses the potential role of cannabidiol (CBD) in modulating inflammation in type 1 diabetes (T1D). By influencing immune pathways and attenuating inflammatory mediators, CBD may contribute to the preservation of pancreatic β cells and delay disease progression. These findings support further investigation into CBD as a complementary strategy in early-stage T1D management.

INTRODUCTION

Type 1 diabetes (T1D) is an autoimmune disease marked by chronic inflammation and progressive destruction of pancreatic β cells, leading to reduced insulin production and impaired glucose homeostasis[1]. This process can also affect other glands, such as the salivary glands, causing xerostomia and altering carbohydrate metabolism even within the oral cavity[2]. In parallel, progressive tissue degeneration occurs in various glands, which may lead to parenchymal glandular atrophy[2,3]. As a result, carbohydrate metabolism becomes impaired even at the oral level. Insulin deficiency compromises glucose transport into muscle and liver cells, promoting persistent hyperglycemia, which over time can trigger neurological, vascular, and renal complications[4,5]. This autoimmune disease has an early onset and is often diagnosed when approximately 80% of β cells have already been destroyed[6]. It presents with clinical manifestations such as polyuria, polydipsia, polyphagia, fatigue, and blurred vision[7]. Chronic hyperglycemia induces increased production of reactive oxygen species and other oxidative ions, causing an imbalance in the cellular redox system and resulting in severe oxidative stress[8]. This imbalance promotes significant structural damage, particularly in epithelial, connective, and muscle tissues, and is associated with pancreatic degeneration, increased bone resorption, and persistent inflammatory infiltration[9].

In this context, different therapeutic approaches have been proposed to attenuate the inflammatory condition underlying the autoimmune destruction of pancreatic cells. Among them, the use of anti-cluster of differentiation 4 (CD4) and anti-CD8 antibodies has shown promising results by reducing lymphocytic infiltration and delaying disease progression in experimental models[10]. However, the high cost of these therapies limits their broad clinical application. The search for anti-inflammatory molecules capable of modulating immune responses and oxidative stress has led to increasing interest in cannabidiol (CBD), a non-psychoactive compound derived from the Cannabis sativa plant, recognized for its immunomodulatory properties[11,12].

Although type 2 diabetes mellitus (T2DM) is the most prevalent form globally, T1DM is distinguished by its autoimmune pathophysiology that selectively targets pancreatic β cells[13-16]. Given CBD’s recognized immunomodulatory activity, this compound may be particularly relevant in modulating the immune mechanisms underlying T1DM progression. While numerous studies have investigated the effects of CBD in T2DM, especially in metabolic regulation and insulin sensitivity, its application in T1DM remains less explored in the literature. Therefore, this mini-review specifically focuses on the potential of CBD in the context of T1DM, aiming to address a relevant knowledge gap and provide a targeted discussion on its anti-inflammatory effects in autoimmune-mediated diabetes.

CBD shows high affinity for cannabinoid receptor type 1 (CB1) and CB2 (Figure 1), which are found in central and peripheral nervous system tissues, as well as in immune cells, respectively[17]. Activation of the CB2 receptor is associated with inhibition of adenylate cyclase and reduction in the expression of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-1β (Figure 2)[18]. Additionally, studies have shown that CBD can attenuate pancreatic inflammatory infiltration, preserve β-cell function, and improve metabolic parameters such as insulin secretion and glycemic control[19,20]. Although T1D is primarily characterized by pancreatic inflammation, increasing evidence suggests that neuroinflammation may also play a role in the disease’s progression and complications[17]. CB1, which is abundant in the central nervous system, is involved in modulating neuroimmune responses, and its activation by CBD may contribute to attenuating neural oxidative stress and preserving neuronal function in diabetic conditions[17].

Figure 1 Cannabidiol activity on the cannabinoid type 1 receptor in nervous tissue. This figure illustrates how cannabidiol (CBD) interacts with cannabinoid type 1 receptor (CB1) located on neuronal membranes in the nervous system – an interaction relevant to its neuroprotective potential in type 1 diabetes. When CBD binds to the cannabinoid type 1 receptor, it activates associated G proteins that inhibit calcium ion channels, and the enzyme adenylate cyclase. As a result, cyclic adenosine monophosphate (cAMP) levels and protein kinase A activity are reduced, ultimately suppressing neurotransmitter release. Beyond this, CBD may also modulate key inflammatory mediators such as nuclear factor kappa B, interleukin 6, and tumor necrosis factor alpha, all of which are linked to neuroinflammation in type 1 diabetes. These combined effects suggest that CBD may help reduce oxidative stress and protect neuronal integrity.

Figure 2 Cannabidiol activity on the cannabinoid receptor type 2 in leukocytes this figure illustrates the mechanism by which cannabidiol interacts with cannabinoid receptor type 2 Located on leukocyte membranes, emphasizing its role in modulating inflammation in type 1 diabetes mellitus. Upon binding to cannabinoid receptor type 2 (CB2), cannabinoid (CBD) activates G protein-coupled signaling pathways that inhibit adenylate cyclase, without impacting calcium-dependent ion channels. This inhibition lowers intracellular cyclic adenosine monophosphate (cAMP) levels and reduces protein kinase A activity, ultimately leading to decreased production of proinflammatory cytokines (represented by the spiral icon), such as tumor necrosis factor alpha, interleukin 6 (IL-6), and IL-1β. Additionally, CBD may influence other inflammatory mediators, including nuclear factor kappa B and chemokines such as C-C motif chemokine ligand 2 and C-X-C motif chemokine ligand 10, suggesting a broader anti-inflammatory effect. Through these mechanisms, CBD contributes to the attenuation of pancreatic inflammation and the preservation of β-cell function in type 1 diabetes mellitus.

In addition to the pathway shown in the Figure 3, other calcium-independent signaling pathways are observed, such as the G-protein-coupled receptor pathway. G-protein-coupled receptors can activate different pathways depending on the type of G protein involved. While pathways with G proteins often mobilize calcium, pathways with stimulatory G proteins or inhibitory G proteins modulate cyclic adenosine monophosphate levels without directly depending on calcium. These pathways are widely involved in processes such as hormonal regulation and inflammatory responses. Another example is the nuclear factor kappa B pathway, which is a key regulator of inflammation and immune response, activated by stimuli such as cytokines (e.g., TNF-α and IL-1β). It promotes the transcription of pro-inflammatory genes and can operate independently of calcium, being essential in chronic inflammatory conditions. Another pathway would be Janus kinase/signal transducer and activator of transcription, which becomes activated by cytokine receptors, such as those for ILs and interferons. This pathway transmits signals directly to the nucleus via signal transducer and activator of transcription proteins, without the need for calcium as a messenger. It is critical for immune and inflammatory responses. The wingless/integrated pathway involves the stabilization of β-catenin and regulates processes such as cell differentiation and development. It works independently of calcium and can influence the immune response or tissue repair in various contexts. Similar to the transforming growth factor beta pathway, it acts through small mothers against decapentaplegic homolog proteins and controls inflammation, apoptosis, and fibrosis. It does not directly depend on calcium and is relevant in processes such as immune regulation and complications associated with chronic diseases. The phosphoinositide 3-kinase/protein kinase B pathway, in turn, is activated by tyrosine kinase receptors and regulates cell survival, growth and metabolism. It operates without calcium dependence and is often modulated under conditions of cellular or metabolic stress and the endoplasmic reticulum stress response. Activated by the accumulation of misfolded proteins in the endoplasmic reticulum, this pathway triggers cellular responses such as concentration and apoptosis, functioning independently of calcium[21-23].

Figure 3 Overview of calcium-independent signaling pathways activated by external stimuli this diagram summarizes key calcium-independent signaling pathways triggered by external stimuli, including G protein-coupled receptors, nuclear factor kappa B, Janus kinase/signal transducer and activator of transcription, wingless/integrated, transforming growth factor beta, phosphoinositide 3-kinase/protein kinase B, and the unfolded protein response. Each pathway involves specific signaling molecules and culminates in transcriptional regulation, cellular adaptation, or apoptosis. Akt: Protein kinase B; ATF6: Activating transcription factor 6; cAMP: Cyclic adenosine monophosphate; Gi: Inhibitory G proteins; GPCR: G protein-coupled receptor; Gs: Stimulatory G proteins; IκB: Inhibitor of nuclear factor kappa B; IL: Interleukin; IRE1: Inositol-requiring enzyme 1; JAK: Janus kinase; LEF: Lymphoid enhancer-binding factor; NF-κB: Nuclear factor kappa B; PERK: Protein kinase RNA-like endoplasmic reticulum kinase; PI3K: Phosphoinositide 3-kinase; PKA: Protein kinase A; SMAD: Small mothers against decapentaplegic homolog; STAT: Signal transducer and activator of transcription; TCF: T-cell factor; TGF-β: Transforming growth factor beta; TNF: Tumor necrosis factor; Wnt: Wingless/integrated; UPR: Unfolded protein response.

Despite its promising therapeutic potential, the effects of CBD in the context of T1D remain underexplored, particularly regarding its clinical applications in humans and its activity in tissues beyond the pancreas (Figure 4). In this context, this review aims to identify the main molecular mechanisms associated with the use of CBD in T1DM and to evaluate its anti-inflammatory effects in experimental models in order to understand its potential therapeutic applications.

Figure 4 High glucose levels increase mitochondrial activity, leading to the production of reactive oxygen species, which activates the nuclear factor kappa B/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3 inflammasome pathway. This activation raises pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β)], promoting CD4+ and CD8+ T-cell activation and resulting in β-cell death. Cannabidiol (CBD) inhibits nuclear factor kappa B (NF-κB)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) activation, thereby reducing TNF-α and IL-1β levels. This downregulates CD4+ and CD8+ T-cell activity, contributing to β-cell survival.

LITERATURE REVIEW

Search strategy and study selection

A systematic search was conducted using the descriptors “cannabidiol” and “type 1 diabetes mellitus” across PubMed, Web of Science, and EMBASE databases. The query returned a total of 248 articles: 10 from PubMed, 108 from Web of Science, and 130 from EMBASE. During the initial screening phase, 232 studies were excluded. Among these, 16 were duplicates, 40 were review articles or book chapters, and 176 either lacked direct relevance to the research question or employed inadequate methodologies that could compromise data interpretation. Only original studies published between 2005 and 2025 were considered for inclusion. After full-text review, the selected articles were categorized into two thematic groups according to the primary outcomes addressed.

Studies examining the anti-inflammatory and immunomodulatory properties of CBD, particularly its influence on cytokine production, immune cell infiltration in pancreatic tissue, β-cell survival, and the attenuation of autoimmune progression in T1D (Table 1). Table 2 compiles research on the influence of CBD on metabolic and behavioral outcomes, such as mood, anxiety, retinopathy, and dyslipidemia, which are frequently associated with complications of T1D. This organizational approach was adopted to enable a comparative and critical examination of the diverse mechanisms through which CBD modulates disease processes in experimental models of T1D. Both tables organize the studies in chronological order by year of publication, enabling an overview of the evolving scientific evidence on the role of CBD in T1D research.

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.

Table 2 Metabolic, behavioral, and complication-related effects of cannabidiol in type 1 diabetes models.

Ref.	Experimental model	Dose/route of administration	Treatment duration	Evaluated parameters	Main findings	Quality assessment
Rajesh et al[24]	C57BL/6J mice with STZ-induced T1D	Cannabidiol administered intraperitoneally at doses of 1 mg/kg to 20 mg/kg	Once daily for 11 weeks	Cardiac function, inflammation, oxidative stress, fibrosis, apoptosis	Cannabidiol improved cardiac function and reduced inflammation, oxidative stress, fibrosis, and cell death, with effects observed even in advanced stages of the disease	High
Toth et al[25]	Mice with STZ-induced T1DM	CBD (CB2 agonist): 0.1-2 mg/kg intranasally or 1-20 mg/kg intraperitoneally	3 months, administered once per week	Tactile and thermal pain sensitivity, microglial density and activation (Iba-1, p-p38), nerve conduction	CBD reduced the development of neuropathic pain and microglial activation when administered early, but had no effect once pain was already established	High
Chaves et al[26]	Adult male Wistar rats (weighing 180-220 g) with STZ-induced T1DM	Cannabidiol at doses of 3 mg/kg, 10 mg/kg, and 30 mg/kg, administered intraperitoneally once daily	14 consecutive days, starting two weeks after diabetes induction	Blood glucose, plasma insulin levels, body weight gain, anxiety-like and depressive-like behaviors, serotonin, norepinephrine, and dopamine levels in the prefrontal cortex and hippocampus	Promoted weight gain, improved glycemic and behavioral profile, with partial normalization of serotonin and norepinephrine levels in the analyzed brain regions	High
Carmona-Hidalgo et al[27]	C57BL/6J mice with STZ-induced T1D	10 mg/kg of CBD, administered intraperitoneally	Once daily for 14 days	Blood glucose, glucose tolerance, renal histology (glomerular, tubular, and interstitial), fibrosis, creatinine, and urea levels	CBD did not prevent diabetes, worsened β-cell loss, and significantly aggravated diabetic nephropathy, although it slightly reduced CD3+ T cell infiltration	High
Chaves et al[28]	Wistar rats with STZ-induced T1D	30 mg/kg of CBD, administered intraperitoneally	Daily for 14 days, with pretreatment using specific antagonists of 5-HT1A, CB1, and CB2 receptors	Anxiolytic behavior, antidepressant behavior, blood glucose levels	Antidepressant and anxiolytic effects mediated by 5-HT1A and CB1 receptors; blood glucose reduction mediated by CB2 receptor	High
Spyridakos et al[29]	Wistar rats with STZ-induced T1DM	CB1 antagonist and CB2 agonist, both administered as eye drops (20 μL, 10 mg/mL)	Once daily for 14 consecutive days	Retinal thickness, number of amacrine cells, apoptosis, and vascular integrity	Restored retinal thickness, reduced apoptosis, and increased amacrine cell density. Both treatments reduced vascular leakage
Chaves et al[34]	Wistar rats with STZ-induced T1D	60 mg/kg of CBD, administered intraperitoneally	Single dose, immediately after contextual fear conditioning	Contextual fear behavior, Arc protein expression in the dorsal hippocampus, anxiety-related behavior	Impaired consolidation and generalization of contextual fear memory; anxiolytic effect observed in the elevated plus maze
McKillop et al[35]	NIH Swiss mice with T1DM induced by five consecutive doses of STZ	Abn-CBD: 0.1 micromole per kilogram, administered orally	Once daily for 28 consecutive days	Pancreatic insulin secretion and content, glucose tolerance, insulin sensitivity, plasma glucagon levels, lipid profile, pancreatic β-cell proliferation, islet morphology	Reduced blood glucose and glucagon levels, increased insulin secretion and pancreatic content, improved glucose tolerance and insulin sensitivity, decreased triglycerides and total cholesterol, and stimulated β-cell proliferation	High
Zheng et al[38]	Clinical trial with patients diagnosed with idiopathic gastroparesis or gastroparesis associated with T1DM/T2DM (6 patients with T1D)	Epidiolex® (CBD), oral dose titrated up to 20 mg/kg/day	Twice daily for 4 weeks	Gastroparesis symptoms, gastric emptying, and gastric volumes	Reduction in gastroparesis symptoms, increased tolerance to liquids, and positive effects even with delayed gastric emptying	High

5-HT1A: 5-hydroxytryptamine 1A receptor; Abn-CBD: Abnormal cannabidiol; Arc: Activity-regulated cytoskeleton-associated protein; CB1: Cannabinoid receptor type 1; CB2: Cannabinoid receptor type 2; CBD: Cannabidiol; Epidiolex^®: Pharmaceutical-grade cannabidiol oral solution; Iba-1: Ionized calcium-binding adapter molecule 1; NIH: National Institutes of Health; P-p38: Phosphorylated p38 mitogen-activated protein kinase; STZ: Streptozotocin; T1D: Type 1 diabetes; T1DM: Type 1 diabetes mellitus.

T1DM: T1DM develops as a result of inflammatory infiltration in the pancreatic glandular tissue, leading to the autoimmune destruction of β cells by macrophages and CD4+ and CD8+ T lymphocytes[2,5,10]. This immune-mediated damage results in a marked reduction in insulin levels, causing hyperglycemia due to impaired glucose uptake by muscle and liver cells, primarily caused by the absence of insulin (Figure 5). Consequently, the translocation of glucose transporters is compromised (Figure 3)[9,20]. Previous studies have shown that blocking CD4 and CD8 receptors on antigen-presenting cells can delay the programmed death of pancreatic β cells, thereby slowing disease progression[10]. However, this blockade is typically achieved using high-cost monoclonal antibodies, making it an economically unfeasible therapeutic option for many individuals with T1DM. In this review, we found that several authors induced T1DM using streptozotocin (STZ) following standardized protocols that selectively target endocrine pancreatic cells, leading to cytotoxic effects on the islets of Langerhans. The toxic impact of STZ was monitored based on the animal’s glycemic response[24-29]. High doses of STZ (e.g., 150 mg/kg) administered to fasting mice (≥ 4 hours) caused significant pancreatic toxicity, effectively inducing hyperglycemia[18]. Other studies included in this review investigated the disease using animal models genetically predisposed to developing T1D[19,30,31].

Figure 5 Insulin signaling cascade and glucose transporter type 4 translocation in type 1 diabetes. This figure illustrates the effects of healthy vs impaired pancreatic function on glucose metabolism in type 1 diabetes. In the healthy pancreas (panel A, left), functional β cells secrete insulin, which binds to its receptor on the cell membrane and activates a signaling cascade via insulin receptor substrate 1 (IRS-1) and IRS-2. This triggers the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) pathway, promoting the translocation of glucose transporter type 4 (GLUT4) to the membrane and facilitating glucose entry into muscle cells. By contrast, panel B (right) depicts the absence of insulin secretion due to β-cell destruction, which disrupts activation of the IRS-1/IRS-2 and PI3K/PKB pathways. As a result, GLUT4 translocation is impaired, preventing glucose uptake and leading to hyperglycemia. This dysfunction is closely associated with inflammatory and oxidative stress in type 1 diabetes, reinforcing the importance of therapeutic strategies that preserve β-cell function or modulate inflammation.

CBD: CBD is a lipophilic compound derived from the Cannabis sativa plant, currently under investigation for a wide range of therapeutic applications[32,33]. However, its use in diabetic conditions, particularly in T1D, remains largely underexplored, with only three studies identified in this review that evaluated its anti-inflammatory effects in this pathological context[18,19]. Lehmann et al[19] investigated the impact of experimental CBD treatment on early pancreatic inflammation in non-obese diabetic mice, administering 5 mg/kg CBD five times per week over a 10-week period. The effects were assessed via intravital microscopy, enabling real-time observation of tissue responses. The CBD-treated group showed a delayed onset of T1D, and significantly reduced expression of proinflammatory cytokines, including IL-1β, IL-6, C-reactive protein, and TNF-α. Moreover, inflammation in the pancreatic glandular tissue was markedly lower in the CBD-treated mice compared to untreated diabetic controls[19].

Cannabidiol and T1D: Preclinical insights on inflammation

Complementary results were reported by Chaves et al[28], who treated Wistar rats with different doses of CBD over a 14-day period. Animals receiving the higher dose (30 mg/kg) exhibited increased insulin expression, reduced hyperglycemia, and elevated serotonin levels – an effect associated with improved mood. Similarly, González-Mariscal et al[18] demonstrated that administration of abnormal CBD, a synthetic CBD derivative, at a dose of 1 mg/kg for 12 days, also lowered glycemic levels in non-obese diabetic mice. These findings reinforce the therapeutic potential of CBD, particularly within the 5 mg/kg to 30 mg/kg dose range. Regarding treatment duration, the literature indicates that reductions in proinflammatory protein expression can be observed as early as 12 days, and that extended use – up to 10 weeks – did not result in toxic effects, which is an important consideration for future research.

All studies included in this review reported a reduction in inflammatory cytokines and proteins. CBD showed a unique capacity to inhibit the protein cascade of transcription factors responsible for promoting cytokine expression involved in leukocyte chemotaxis, vascular changes associated with inflammation, and local lymphocyte infiltration. This effect is primarily mediated by the inhibition of adenylate cyclase following CBD interaction with the CB2, which disrupts the coupled G protein and reduces the activity of signaling proteins involved in cytokine production. This interaction predominantly occurs in leukocytes located in pancreatic tissue.

CBD and T1D: Preclinical insights on behavior

Due to the growing number of studies investigating the effects of CBD on behavioral parameters in T1D models, such as anxiety, depression, and memory, Table 2 was developed to organize and compare this body of evidence. This classification enabled a focused analysis of the neurological and behavioral effects of CBD, alongside its metabolic and systemic implications. Research evaluating the metabolic and behavioral outcomes of CBD in experimental T1DM models reveals partially convergent findings. Chaves et al[26,28,34] reported anxiolytic and antidepressant effects mediated by 5-hydroxytryptamine 1A receptor and CB1, along with improvements in glycemic control and overall behavior at doses ranging from 30 mg/kg to 60 mg/kg. These findings contrast with those of Carmona-Hidalgo et al[27], who observed worsening of diabetic nephropathy, despite a modest reduction in T-lymphocyte infiltration, suggesting that CBD’s effects may vary depending on the target organ, dose, and duration of treatment. In support of its therapeutic potential, McKillop et al[35] reported enhanced insulin secretion and an improved lipid profile, whereas Rajesh et al[24] demonstrated cardioprotective effects and attenuation of oxidative stress, further underscoring CBD’s promise as an adjuvant therapy for systemic complications associated with T1D.

Final considerations

Although this review highlights the anti-inflammatory and therapeutic potential of CBD in the context of T1DM, it is important to acknowledge that CBD is not without risks. Some studies have reported that prolonged or high-dose use may lead to hepatotoxicity, drug-drug interactions, and a potential for abuse, particularly among individuals predisposed to substance use disorders[1,3,4]. Furthermore, the psychoactive potential of CBD analogues or contaminants in commercially available formulations raises additional safety concerns. Regulatory barriers also pose significant challenges, as CBD-based therapies are subject to inconsistent approval standards, legal restrictions, and quality control issues across different countries. These factors hinder the translation of preclinical evidence into clinical applications. To address these challenges, future research should prioritize the development of standardized, pharmaceutical-grade formulations, long-term safety assessments, and international regulatory harmonization. These aspects represent a substantial gap in the literature and underscore the need for a multidisciplinary approach that integrates pharmacological, clinical, and regulatory perspectives to ensure the safe and effective use of CBD in diabetes care.

CONCLUSION

Based on the findings presented in this review, the results suggest a promising role for CBD in controlling the progression of T1DM. However, several gaps remain. These include the compound’s effects on other glands affected by diabetes, which also experience parenchymal damage but are rarely addressed in the literature. Additionally, the impact of CBD on bone repair in diabetic conditions, which is known to be compromised due to increased osteoclastic activity, warrants further investigation. Future studies should explore these and other unresolved issues as research in this area continues to evolve.