Research mapping of cannabinoids and endocannabinoid system in cancer over the past three decades: insights from bibliometric analysis

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“Background: The cannabinoids and endocannabinoid system are thought to play critical roles in multiple signaling pathways in organisms, and extensive evidence from preclinical studies indicated that cannabinoids and endocannabinoids displayed anticancer potential. This study aimed to summarize the research of cannabinoids and endocannabinoid system in cancer through bibliometric analysis.

Methods: Relevant literature in the field of cannabinoids and endocannabinoid system in cancer published during 1995-2024 were collected from the Web of Science Core Collection database. VOSviewer and SCImago Graphica were applied to perform bibliometric analysis of countries, institutions, authors, journals, documents, and keywords.

Results: A total of 3,052 publications were identified, and the global output exhibited a generally upward trend over the past 3 decades. The USA had the greatest number of publications and citations in this research field. Italian National Research Council led in terms of publication, while Complutense University of Madrid had the highest total citations. Vincenzo Di Marzo was the leading author in this field with the greatest number of publications and citations. The co-occurrence of keywords revealed that the research frontiers mainly included “cannabinoids”, “endocannabinoid system”, “cancer”, “anandamide”, “cannabidiol”, “cannabinoid receptor”, “apoptosis”, and “proliferation”.

Conclusion: Our results revealed that the research of cannabinoids and endocannabinoid system in cancer would receive continuous attention. The USA and Italy have made remarkable contributions to this field, supported by their influential institutions and prolific scholars. The research emphasis has evolved from basic functional characterization to mechanistic exploration of disease pathways and translational applications within multidisciplinary framework.”

https://pubmed.ncbi.nlm.nih.gov/40242437/

“In this study, we conducted a comprehensive bibliometric analysis on the research of cannabinoids and endocannabinoid system in cancer over the past 3 decades. Our results would provide referable guidance for the understanding of research emphasis on this topic, offering insights for clinical interventions and scientific inquiries.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1540619/full

Cannabinoids as Multitarget Drugs for the Treatment of Autoimmunity in Glaucoma

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“Diseases of multifactorial origin like neurodegenerative and autoimmune diseases require a multitargeted approach.

The discovery of the role of autoimmunity in glaucoma and retinal ganglionic cell (RGC) death has led to a paradigm shift in our understanding of the etiopathology of glaucoma. Glaucoma can cause irreversible vision loss that affects up to an estimated 3% of the population over 40 years of age. The current pharmacotherapy primarily aims to manage only intraocular pressure (IOP), a modifiable risk factor in the glaucomatous neurodegeneration of RGCs. However, neurodegeneration continues to happen in normotensive patients (where the IOP is below a reference value), and the silent nature of the disease can cause significant visual impairment and take a massive toll on the healthcare system.

Cannabinoids, although known to reduce IOP since the 1970s, have received renewed interest due to their neuroprotective, anti-inflammatory, and immunosuppressive effects on autoimmunity. Additionally, the role of the gut-retina axis and abnormal Wnt signaling in glaucoma makes cannabinoids even more relevant because of their action on multiple targets, all converging in the pathogenesis of glaucomatous neurodegeneration. Cannabinoids also cause epigenetic changes in immune cells associated with autoimmunity.

In this Review, we are proposing the use of cannabinoids as a multitargeted approach for treating autoimmunity associated with glaucomatous neurodegeneration, especially for the silent nature of glaucomatous neurodegeneration in normotensive patients.”

https://pubmed.ncbi.nlm.nih.gov/40242585/

https://pubs.acs.org/doi/10.1021/acsptsci.4c00583

Meta-analysis of medical cannabis outcomes and associations with cancer

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“Background: Growing bodies of evidence suggest that cannabis may play a significant role in both oncological palliative care and as a direct anticarcinogenic agent, but classification as a Schedule I substance has complicated research into its therapeutic potential, leaving the state of research scattered and heterogeneous. This meta-analysis was conducted to determine the scientific consensus on medical cannabis’ viability in cancer treatment.

Objective: The aim of this meta-analysis was to systematically assess the existing literature on medical cannabis, focusing on its therapeutic potential, safety profiles, and role in cancer treatment.

Methods: This study synthesized data from over 10,000 peer-reviewed research papers, encompassing 39,767 data points related to cannabis and various health outcomes. Using sentiment analysis, the study identified correlations between cannabis use and supported, not supported, and unclear sentiments across multiple categories, including cancer dynamics, health metrics, and cancer treatments. A sensitivity analysis was conducted to validate the reliability of the findings.

Results: The meta-analysis revealed a significant consensus supporting the use of medical cannabis in the categories of health metrics, cancer treatments, and cancer dynamics. The aggregated correlation strength of cannabis across all cancer topics indicates that support for medical cannabis is 31.38× stronger than opposition to it. The analysis highlighted the anti-inflammatory potential of cannabis, its use in managing cancer-related symptoms such as pain, nausea, and appetite loss, and explored the consensus on its use as an anticarcinogenic agent.

Discussion: The findings indicate a strong and growing consensus within the scientific community regarding the therapeutic benefits of cannabis, particularly in the context of cancer. The consistent correlation strengths for cannabis as both a palliative adjunct and a potential anticarcinogenic agent redefine the consensus around cannabis as a medical intervention.

Conclusion: The consistency of positive sentiments across a wide range of studies suggests that cannabis should be re-evaluated within the medical community as a treatment option. The findings have implications for public health research, clinical practice, and discussions surrounding the legal status of medical cannabis. These results suggest a need for further research to explore the full therapeutic potential of cannabis and address knowledge gaps.”

“The data presented here indicate that cannabis has a well-established role in managing symptoms related to cancer and may have both direct and indirect anticancer properties, which challenges the notion that it has no accepted medical use.”

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1490621/full

Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1G93 A) mouse model of amyotrophic lateral sclerosis

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“Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting voluntary muscle movement as well as cognitive and other behavioural domains at later disease stages. No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the copper-zinc superoxide dismutase 1 (SOD1) mouse model of ALS that carries a G93A mutation (SOD1G93A).

Methods: Male and female SOD1G93A and wild type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.

Results: CBD treatment ameliorated the bodyweight loss in female SOD1G93A mice, tended to reinstate sociability in SOD1G93A males, strengthened social recognition memory in SOD1G93A females, and improved the PPI response in younger SOD1G93A females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male SOD1G93A mice and decreased the acoustic startle response and strengthened cue freezing in male mice.

Conclusion: Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of SOD1G93A mice in a sex specific manner without altering the motor phenotype.”

https://pubmed.ncbi.nlm.nih.gov/40229540/

“In conclusion, the study discovered beneficial effects of oral CBD on the bodyweight deficit in both male and female SOD1G93 A mice as well as improving social recognition memory and the PPI response in female SOD1G93 A mice. CBD also reduced the ASR and increased the freezing response to a conditioned cue in both SOD1G93 A transgenic and WT male mice. However, CBD treatment did not reverse motor impairments or sensorimotor gating deficits. Thus, chronic oral CBD treatment at the dose administered here may be therapeutically useful for only particular ALS symptoms including bodyweight decline, which is an indicator of disease progression and declining survival rate (Dharmadasa et al. 2017). Further investigations should consider additional CBD dosing and beginning treatment at an earlier age prior to the onset of motor deficits. This could be followed by combination treatments of CBD and e.g. cannabinoid receptor antagonists to explore potential mechanisms behind observed CBD effects.”

https://link.springer.com/article/10.1007/s00213-025-06785-z

Antibacterial properties of silver and gold nanoparticles synthesized using Cannabis sativa waste extract against Pseudomonas aeruginosa

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“Aims: The study aimed to explore the sustainable synthesis of metal nanoparticles using a green and eco-friendly resource. Specifically, it investigated the utilization of Cannabis sativa waste extract for the production of gold and silver nanoparticles, focusing on their antimicrobial activity against gram-negative bacteria, particularly Pseudomonas aeruginosa strains, which are significant in nosocomial infections.

Methods: Cannabis sativa waste extract was employed to synthesize gold and silver nanoparticles through a green synthesis approach. The produced nanoparticles were characterized using transmission electron microscopy (TEM), atomic absorption spectrometry (AAS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The antimicrobial efficacy of the synthesized nanoparticles was assessed through their minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimal biofilm inhibitory concentration (MBIC) against Pseudomonas aeruginosa, utilizing a microcultivation device, solid medium cultivation, and a metabolic activity assay in a polystyrene microtiter plate, respectively.

Results: The TEM analysis revealed the size and morphology of the nanoparticles, while AAS confirmed their concentration. XRD provided insights into the crystalline structure, and FTIR analysis identified the molecular structure of the nanoparticle’s stabilizing layer. The synthesized nanoparticles showed significant antimicrobial activity against Pseudomonas aeruginosa, with determined MIC, MBC, and MBIC values of produced silver nanoparticles, showcasing their potential as effective antimicrobial agents.

Conclusions: This study successfully demonstrated the synthesis of silver and gold nanoparticles using Cannabis sativa waste extract and highlighted their potent antimicrobial properties. It underscores the potential of utilizing plant waste extracts in sustainable nanomaterial synthesis and contributes to the fields of green nanotechnology and waste valorization within the circular economy. The findings also offer valuable insights into developing natural waste source-based antimicrobial agents.”

https://pubmed.ncbi.nlm.nih.gov/40221737/

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00272-0

Evaluation of Cannabis sativa L. Callus Extract as a Novel Cosmetic Ingredient with Dual Anti-Inflammatory and Antioxidant Effects

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“The plant callus culture technique is an emerging source of bioactive compounds with potential applications in cosmetics and pharmaceuticals. Callus-derived extracts contain high concentrations of secondary metabolites with significant antioxidant and anti-inflammatory properties when elicited.

Cannabis sativa L. has been used for its medicinal effects; however, the potential of its C. sativa callus extract (CCE) for cosmetic applications remains unexplored.

Callus from C. sativa was induced in vitro using a Murashige and Skoog (MS) medium supplemented with Thidiazuron (TDZ) and naphthalene acetic acid (NAA). The extract was analyzed for its bioactive composition using high-performance liquid chromatography (HPLC). The antioxidant activity was assessed using the DPPH radical scavenging assay. The anti-inflammatory effects were evaluated in lipopolysaccharides (LPS)-stimulated RAW264.7 macrophages by measuring nitric oxide (NO) production, DAF-2 fluorescence intensity, released cytokine levels, and protein expression of inflammatory mediators via ELISA, Western blot, and immunofluorescence assays.

CCE demonstrated significant radical scavenging activity. CCE effectively suppressed LPS-induced NO production and reduced pro-inflammatory cytokine levels. Western blot analysis revealed that CCE inhibited NF-κB nuclear translocation while upregulating NRF2-mediated antioxidant responses. Furthermore, HPLC analysis confirmed the presence of cannabinoids, which could potentially be associated with the modulation of inflammatory pathways through the endocannabinoid system.

This study provides evidence that CCE possesses notable antioxidant and anti-inflammatory properties, making it a promising ingredient for cosmetic formulations targeting oxidative stress and inflammatory skin conditions.”

https://pubmed.ncbi.nlm.nih.gov/40219215/

Effect of cannabinoids on the efficacy and side effects of anticancer therapeutic strategies – Current status of preclinical and clinical research

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“Cannabinoids have attracted increasing attention in cancer research in recent decades. A major focus of current preclinical and clinical studies is on the interactions and potential risks when combined with chemotherapeutic agents, targeted therapies and other anticancer strategies.

Given the extensive preclinical data on additive, synergistic and, in some cases, antagonistic tumor cell killing effects of chemotherapeutic agents and cannabinoids when co-administered, a critical analysis of these data seems essential. The available data mainly relate to combination treatments for glioblastoma, hematological malignancies and breast cancer, but also for other cancer types.

Such an analysis also appears necessary because cannabinoids are used as an option to treat nausea and vomiting caused by chemotherapy, as well as tumor-related pain, and cancer patients sometimes take cannabinoids without a medical prescription. In addition, numerous recent preclinical studies also suggest cannabinoid-mediated relief of other chemotherapy-related side effects such as peripheral neuropathy, nephrotoxicity, cardiotoxicity, cystitis, bladder complications and mucositis.

To summarize, the data available to date raise the prospect that cannabinoids may increase the efficacy of chemotherapeutic agents while reducing their side effects. However, studies on interactions are mostly limited to cytotoxicity analyses. An equally thorough investigation of the effects of such combinations on the immune system and on the tumorigenic levels of angiogenesis, invasion and metastasis is still pending. On this basis, a comprehensive understanding for the evaluation of a targeted additional treatment of various cancers with cannabinoids could be established.”

https://pubmed.ncbi.nlm.nih.gov/40221102/

“The anticancer effect of various phytocannabinoids, including Δ9-tetrahydrocannabinol (THC), was first demonstrated in animal experiments in 1975 (Munson, Harris, Friedman, Dewey, & Carchman, 1975). After the discovery of the endocannabinoid system in the early 1990s, these effects were confirmed in numerous preclinical studies in a variety of different neoplastic entities. Based on these findings and studies demonstrating the anticancer effects of cannabinoids on various hallmarks of tumorigenesis, cannabinoids have increasingly become the focus of scientific discussions as systemic tumor therapies in recent years (for an overview, see Ramer & Hinz, 2015; Hinz & Ramer, 2019). From a preclinical point of view, the systemic antitumor effects of cannabinoids thus represent the basis for combining cannabinoids with chemotherapies, which can increase the effectiveness of chemotherapeutic agents and overcome resistance.”

https://www.sciencedirect.com/science/article/abs/pii/S0163725825000634?via%3Dihub

The efficacy of cannabidiol for seizures reduction in pharmacoresistant epilepsy: a systematic review and meta-analysis

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“Background: Epilepsy is a neurological syndrome caused by excessive neuronal discharges, with a part of the patients being pharmacoresistant to the traditional treatment. Cannabidiol, a non-psychoactive component of Cannabis Sativa, shows promise as an alternative, but further research is needed to quantify its efficacy.

Methods: This literature systematic review was made following the PRISMA protocol guidelines. The Google Scholar, Scielo, and PubMed/MEDLINE databases were included using the descriptors “Cannabidiol”, “Epilepsy”, and “Drug Resistant Epilepsy”. This research was registered in the Prospero platform with the identification (CRD42024479643).

Results: A total of 1448 results were identified from the PubMed, Virtual Health Library, and Google Scholar databases. After applying exclusion criteria, six studies met the criteria for full-text evaluation and eligibility. The compiled analysis showed that the patients who received cannabidiol experienced a 41.0875% reduction in the total number of seizures, compared to an average reduction of 18.1% in placebo groups. This represents a 127% higher response rate for patients who received the intervention.

Conclusions: Given these results, it is possible to conclude that the therapeutic response of cannabidiol is worthy of consideration in new protocols and of being added to public healthcare systems for its antiepileptic potential. However, the high efficacy rate observed in the placebo group suggests that other methods of data collection analysis may be employed.”

https://pubmed.ncbi.nlm.nih.gov/40217555/

“Based on the results from the analyzed studies, it can be concluded that the addition of CBD to the treatment regimen for patients with pharmacoresistant epilepsy is beneficial in most cases. The doses of 10 mg/kg/day and 20 mg/kg/day were compared in 5 out of 6 studies, with a higher dose demonstrating superior seizure control. However, the lower dose also showed significant efficacy, making it a viable option for inclusion in treatment and guidelines as well.”

https://aepi.biomedcentral.com/articles/10.1186/s42494-024-00191-2

Cannabidiol-Rich Cannabis sativa L. Extract Alleviates LPS-Induced Neuroinflammation Behavioral Alterations, and Astrocytic Bioenergetic Impairment in Male Mice

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“Neuroinflammation is a hallmark of various neurodegenerative disorders, yet effective treatments remain limited.

This study investigates the neuroprotective potential of a cannabidiol (CBD)-Rich Cannabis sativa L. (CS) extract in a lipopolysaccharide (LPS)-induced neuroinflammation mouse model.

The effects on anxiety-like behavior, cognitive function, and locomotor activity were assessed using behavioral tests (open field, elevated plus maze, novel object recognition, and Morris water maze). Antioxidant activity was measured by assaying glutathione (GSH) levels and lipid peroxidation by-products (TBARs). Anti-inflammatory properties were evaluated using quantitative reverse transcription polymerase chain reaction (QRt-PCR) for proinflammatory cytokines (IL-6 and TNF-α), glial fibrillary acidic protein (GFAP), and cannabinoid receptor 1 (CB1) mRNAs in the prefrontal cortex (PFC). Astrocytic bioenergetics were analyzed using extracellular flux assays. Additionally, computational inference with a deep learning approach was conducted to evaluate the synergistic interactions among CS phytocompounds on the CB1 receptors.

Compared with synthetic CBD, the CS extract (20.0 mg/kg) demonstrated superior efficacy in mitigating LPS-induced anxiety-like behavior, cognitive deficits, and locomotor impairments. It also significantly mitigated oxidative stress (increased GSH, reduced TBARs) and suppressed proinflammatory cytokines and GFAP mRNAs, indicating potent anti-inflammatory properties.

The extract modulated CB1 receptor expression and preserved metabolic homeostasis in cortical astrocytes, preventing their shift from glycolysis to oxidative phosphorylation under neuroinflammatory conditions. Computational modeling highlighted conformational changes in CB1 receptor residues induced by Delta-9-THC that enhanced CBD binding.

These findings underscore the potential of CS extract as a therapeutic candidate for managing neuroinflammation and its associated neurodegenerative consequences, warranting further clinical exploration.”

https://pubmed.ncbi.nlm.nih.gov/40195769/

https://onlinelibrary.wiley.com/doi/10.1002/jnr.70035

Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data

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“Background: Immune checkpoint inhibitors (ICIs) benefit patients across various tumor types. ICIs block cancer and T-cell interactions whereas cannabinoids may inhibit T-cell activation, reducing lysis of tumor cells. Interactions between cannabinoid use and dual ICI treatment remain unknown.

Methods: Individual patient data from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (n = 684) were pooled. Cochran – Mantel – Haenszel and log-rank tests (stratified by trial/treatment arms) correlated cannabinoid use with clinicopathologic characteristics, Best Overall Response (BOR)/iBOR per RECIST 1.1/iRECIST, Progression-Free Survival (PFS)/iPFS, Overall Survival (OS) and immune-related adverse events (irAEs).

Results: Sixty-five (9.5%) patients took cannabinoids at any time on trial, 32 (4.7%) of which were using cannabinoids at baseline. By multivariate analysis, cannabinoid use at baseline was significantly associated with improved iPFS (0.05), but not iBOR (p = 0.15), PFS (p = 0.12), OS (p = 0.35) or incidence of grade 1/2 or 3/4 irAEs (p = 0.96 and 0.65 respectively). Results were not significantly different with cannabinoid use at any time on trial.

Conclusion: Improved iPFS with cannabinoid use in patients treated with durvalumab plus tremelimumab ± chemotherapy did not translate into OS benefits. This study supports the safe use of cannabinoids in the context of combination ICI therapy.”

https://pubmed.ncbi.nlm.nih.gov/40184324/

“Plain Language Summary

Immune checkpoint inhibitors (ICI) have become an important treatment option for cancer patients and has been associated with improved survival outcomes across various tumor types. Cannabinoids are active components of cannabis and include tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabis use has increased in Canadian cancer patients and is often used for symptom management. Some studies have suggested that cannabinoids can alter the function of the immune system, which could impact the effectiveness of immune checkpoint inhibitors. Therefore, we aimed to evaluate whether cannabinoid use might impact the effectiveness of combination ICI treatment with durvalumab plus tremelimumab (with/without chemotherapy) using data from four clinical trials completed through the Canadian Cancer Trials Group (CCTG). We found no significant difference in response, survival outcomes or adverse events in patients who used cannabinoids with combination ICI treatment compared to cannabinoid non-users. This study supports the safe use of cannabinoids in the context of combination ICI therapy.”

https://www.tandfonline.com/doi/full/10.1080/1750743X.2025.2485012