Category Archives: THC (Delta-9-Tetrahydrocannabinol)

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.”

https://pubmed.ncbi.nlm.nih.gov/40303989/

“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

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

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

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

Multifunctional cosmetic potential of extracellular vesicle‑like nanoparticles derived from the stem of Cannabis sativa in treating pigmentation disorders

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“While natural products and synthetic chemicals are used in functional cosmetics, their potential side effects remain a concern.

This has driven the need safer and more effective agents to treat skin disorders. Therefore, the present study aimed to explore the functional properties of Cannabis sativa stem‑derived nanoparticles (CSS‑NPs) and evaluate their potential as a cosmetic ingredient.

Using nanoparticle analysis, CSS‑NPs, with a mean diameter of ~120 nm exhibited notable resistance to external stress conditions, including pH fluctuation and enzymatic degradation by DNase, RNase and proteinase K. They also contained 48 distinct biochemical components. In vitro assays revealed that CSS‑NPs significantly downregulated the expression of genes and proteins associated with melanin synthesis in mouse B16F10 melanoma cells under α‑melanocyte stimulating hormone (α‑MSH)‑induced hyperpigmentation. These inhibitory effects were mediated by the activation of ERK and Akt signaling pathways. Furthermore, CSS‑NPs improved the viability of α‑MSH‑treated B16F10 cells; this was accompanied by the upregulation of antioxidant‑associated enzymes and a decrease in α‑MSH‑induced reactive oxygen species levels.

Collectively, these findings suggested that CSS‑NPs carry out a key role in mitigating skin pigmentation and enhancing antioxidant defenses by modulating the ERK/Akt axis during excessive melanin synthesis. Thus, CSS‑NPs represent a promising multifunctional cosmetic ingredient with potential in treating pigmentation disorders and protecting skin cells.”

https://pubmed.ncbi.nlm.nih.gov/40183388/

https://www.spandidos-publications.com/10.3892/mmr.2025.13512

Characterizing the Population of a Medical Cannabis Clinic in a Pediatric Hospital

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“Background: Medical cannabis (MC) is increasingly in use due to recent cultural and political changes. Other than patients with Lennox-Gastaut and Dravet syndrome, there is inadequate literature to provide evidence-based support for prescribing MC in pediatric patients. 

Objectives: Characterize the population receiving an MC recommendation in an ambulatory pediatric palliative care setting and quantify patient/family-reported outcomes. 

Design: Retrospective chart review of electronic medical record (EMR) data. Setting/Subjects: Total n = 46 consecutive patients receiving medical advice regarding MC (n = 42) in a specialized ambulatory clinic embedded in a palliative care division and n = 4 inpatient in a midwestern U.S. hospital between 2019 and 2022. Measurements: Demographics, diagnosis, symptoms, adverse reactions, patient-reported outcomes, and barriers abstracted from EMR. 

Results: Our sample included 46 palliative care patients with a mean age of 11.7 years (SD 5.4); 50% had a neurological diagnosis (n = 25); 37% (n = 14) hematological/oncologic; and 13% (n = 6), chronic pain. The most common type of MC recommended was 1:1 Cannabidiol (CBD): tetrahydrocannabinol (THC) tincture. There was a statistically significant decrease in inpatient floor days and cost. Totally, 35% of patients were able to decrease or discontinue other medications. Thematic analysis identified four barriers to use (product unavailable, difficulty obtaining state MC card, cost, and organizational) and subjective symptom improvement. 

Conclusions: These data characterize the palliative care MC clinic population at our pediatric hospital. Positive outcomes were noted across several symptom domains. MC seems to be associated with lower health care utilization, reduced polypharmacy, and increased quality of life and was used without significant adverse events. In a value-conscious health care environment, the data warrant further exploration.”

https://pubmed.ncbi.nlm.nih.gov/40180570/

https://www.liebertpub.com/doi/10.1089/jpm.2024.0533

Cannabinoid receptor deficiencies drive immune response dynamics in Salmonella infection

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“This study investigated the roles of cannabinoid receptors 1 and 2 (CB1R and CB2R) in regulating host responses to Salmonella Typhimurium in C57BL/6 mice.

The absence of both receptors significantly impaired host resilience, as evidenced by increased weight loss, deteriorated body condition, and reduced survival following infection.

Notably, CB1R deficiency resulted in more pronounced weight loss and heightened susceptibility to bacterial proliferation, as demonstrated by increased Salmonella dissemination to organs. In addition, both CB1R and CB2R knockout mice exhibited alterations in immune cell recruitment and cytokine production. CB1R-KO mice displayed increased T cell and macrophage populations, whereas CB2R-KO mice showed a reduction in NK cells, indicating receptor-specific effects on immune cell mobilization.

Cytokine profiling of macrophages post-infection revealed that CB1R-KO mice had reduced IL-10 levels, along with increased IL-6 and TGF-β, suggesting a dysregulated polarization state that combines pro-inflammatory and regulatory elements. In contrast, CB2R-KO mice exhibited a profile consistent with a more straightforward pro-inflammatory shift.

Furthermore, microbiota analysis demonstrated that CB2R-KO mice experienced significant gut dysbiosis, including reduced levels of beneficial Lactobacillus and Bifidobacterium species and an increase in pro-inflammatory Alistipes species post-infection. Functional microbiome analysis further indicated declines in key metabolic pathways, such as the Bifidobacterium shunt, L-glutamine biosynthesis, and L-lysine biosynthesis, suggesting microbiota-driven immune dysregulation.

Together, these findings highlight the distinct, non-redundant roles of CB1R and CB2R in modulating innate immunity, host defense, and microbiota composition during bacterial infections.

Significance statement: Understanding the role of cannabinoid receptors in immune regulation is important for identifying new therapeutic targets for bacterial infections. Our study demonstrates that CB1R and CB2R play distinct, non-redundant roles in host defense against Salmonella Typhimurium. The absence of these receptors impairs host resilience, increases bacterial dissemination, and alters immune cell recruitment and cytokine production. Notably, CB1R deficiency leads to enhanced weight loss, increased bacterial spread, and a dysregulated macrophage cytokine profile-characterized by reduced IL-10 and elevated IL-6 and TGF-β-while CB2R deficiency is associated with reduced NK cell numbers and a more pronounced pro-inflammatory cytokine profile. These findings reveal a receptor-specific balance in immune responses, suggesting that cannabinoid signaling modulates infection outcomes.

Targeting CB1R and CB2R pathways may offer novel strategies to enhance host immunity and improve treatments for bacterial infections in the future.”

https://pubmed.ncbi.nlm.nih.gov/40161677/

https://www.biorxiv.org/content/10.1101/2025.03.10.642352v1

Cannabinoids in Chronic Pain Management: A Review of the History, Efficacy, Applications, and Risks

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“Background/Objectives: Chronic pain remains a pervasive and challenging public health issue, often resistant to conventional treatments such as opioids, which carry substantial risks of dependency and adverse effects. Cannabinoids, bioactive compounds derived from the Cannabis sativa plant and their synthetic analogs, have emerged as a potential alternative for pain management, leveraging their interaction with the endocannabinoid system to modulate pain and inflammation. 

Methods: The current, evolving literature regarding the history, efficacy, applications, and safety of cannabinoids in the treatment of chronic pain was reviewed and summarized to provide the most current review of cannabinoids. 

Results: Evidence suggests that cannabinoids provide moderate efficacy in managing neuropathic pain, fibromyalgia, cancer-related pain, and multiple sclerosis-related spasticity. Patient-reported outcomes further indicate widespread perceptions of cannabinoids as a safer alternative to opioids, with potential opioid-sparing effects. However, the quality of existing evidence is limited by small sample sizes and methodological inconsistencies. Regulatory barriers, including the classification of cannabis as a Schedule I substance in the United States, continue to hinder robust research and clinical integration. Moreover, the risks associated with cannabinoids, such as psychiatric effects, addiction potential, and drug interactions, necessitate cautious application. 

Conclusions: Cannabinoids represent a promising, albeit complex, alternative for chronic pain management, particularly given the limitations and risks of traditional therapies such as opioids. However, significant deficiencies remain in the research. While smaller trials and systematic reviews indicate therapeutic potential, the quality of evidence is often low due to limited sample sizes, short study durations, and methodological inconsistencies. Large-scale, randomized controlled trials with long-term follow-up are urgently needed to confirm efficacy and safety across diverse patient populations and pain etiologies.”

https://pubmed.ncbi.nlm.nih.gov/40149508/

“The future for cannabis research is bright, and as regulatory frameworks adapt to balance access and oversight, cannabinoids may transition from an experimental adjunct to a well-established option in chronic pain care, provided scientific rigor and evidence-based policymaking remain at the forefront.”

https://www.mdpi.com/2227-9059/13/3/530

Parthanatos and apoptosis: unraveling their roles in cancer cell death and therapy resistance

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“Cell death is a fundamental process that needs to be maintained to balance cellular functions and prevent disease. There are several cell death pathways; however, apoptosis and parthanatos are the most prominent and have important roles in cancer biology. As an extremely well-regulated process, apoptosis removes damaged or abnormal cells via caspase activation and mitochondrial involvement.

Unlike in the healthy cells, the loss of ability to induce apoptosis in cancer permits tumor cells to survive and multiply out of control and contribute to tumor progression and therapy resistance. On the contrary, parthanatos is a caspase-independent metabolic collapse driven by poly (ADP-ribose) polymerase 1 (PARP1) overactivation, translocation of apoptosis-inducing factor (AIF), and complete DNA damage. Several cancer models are involved with parthanatos. Deoxypodophyllotoxin (DPT) induces parthanatos in glioma cells by excessive ROS generation, PARP1 upregulation, and AIF nuclear translocation.

Like in acute myeloid leukemia (AML), the cannabinoid derivative WIN-55 triggers parthanatos, and the effects can be reversed by PARP inhibitors such as olaparib.

Developing cancer treatment strategies involving advanced cancer treatment strategies relies on the interplay between apoptosis and parthanatos. However, such apoptosis-based cancer therapies tend to develop resistance, so there is an urgent need to look into alternative pathways like parthanatos, which may not always trigger apoptosis.

In overcoming apoptosis resistance, there is evidence that combining apoptosis-inducing agents, such as BH3 mimetics, with PARP inhibitors synergistically enhances cell death.

Oxidative stress modulators have been found to promote the execution of parthanatic and apoptotic pathways and allow treatment. In this review, apoptosis and parthanatos are thoroughly compared at the molecular level, and their roles in cancer pathogenesis as related to cancer therapeutic potential are discussed.

We incorporate recent findings to demonstrate that not only can parthanatos be used to manage therapy resistance and enhance cancer treatment via the combination of parthanatos and apoptosis but also that immunity and bone deposition can feasibly be employed against long-circulating cancer stem cells to treat diverse forms of metastatic cancers.”

https://pubmed.ncbi.nlm.nih.gov/40166425/

“Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions.”

https://pubmed.ncbi.nlm.nih.gov/38461169/