“Background: Osteosarcoma remains a therapeutic challenge due to its aggressive behavior and high metastatic potential, necessitating exploration of novel treatment modalities. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with emerging anticancer properties, has shown promise in preclinical cancer models. However, its mechanisms of action in osteosarcoma remain incompletely understood. This study systematically investigates the antitumor effects of CBD on osteosarcoma and elucidates its molecular targets within the TNF-α/NF-κB/CCL5 signaling axis.
Methods: The effective concentration of CBD was determined using the CCK-8 assay. Functional assays (EdU proliferation, Transwell migration/invasion, and scratch wound healing) evaluated its impact on osteosarcoma cell malignancy. A mouse xenograft model assessed in vivo efficacy. Network pharmacology and RNA-seq identified key pathways, which were validated via ELISA, qRT-PCR, and western blot. Molecular interactions were confirmed through CETSA, SPR, ITC, and molecular docking analyses targeting p65 (NF-κB subunit).
Results: CBD potently suppressed osteosarcoma cell proliferation, migration, and invasion while inhibiting xenograft tumor growth in vivo. Mechanistically, CBD disrupted the TNF-α/NF-κB/CCL5 axis by directly binding p65, thereby attenuating NF-κB-mediated transcriptional activation of CCL5. Notably, CBD abrogated a p65-CCL5 positive feedback loop that perpetuates inflammatory signaling, a novel finding linking CBD’s effects to inflammatory cascade disruption in osteosarcoma.
Conclusion: This study provides the first evidence that CBD inhibits osteosarcoma progression by targeting the TNF-α/NF-κB/CCL5 axis, disrupting a coordinated inflammatory-proliferative cascade. These findings position CBD as a promising therapeutic candidate for osteosarcoma, warranting further clinical investigation.”
“Background: The efficacy of medical cannabis in alleviating pain has been demonstrated in clinical trials, yet questions remain regarding the extent to which specific chemical compounds contribute to analgesia versus expectation-based (placebo) responses. Effective blinding is notoriously difficult in cannabis trials, complicating the identification of compound-specific effects.
Methods: In a prospective study of 329 chronic pain patients (40% females; aged 48.9 ± 15.5) prescribed medical cannabis, we examined whether the chemical composition of cannabis cultivars could predict treatment outcomes. We used a Random Forest classifier with nested cross-validation to assess the predictive value of demographics, clinical features, and approximately 200 chemical compounds. Model robustness was evaluated using six additional machine learning algorithms.
Results: Here we show that incorporating chemical composition markedly improves the prediction of pain relief (AUC = 0.63 ± 0.10) compared to models using only demographic and clinical features (AUC = 0.52 ± 0.09; p < 0.001). This result is consistent across all models tested. While well-known cannabinoids such as THC and CBD provide limited predictive value, specific terpenoids, particularly α-Bisabolol and eucalyptol, emerge as key predictors of treatment response.
Conclusions: Our findings demonstrate that pain relief can be predicted from cannabis chemical profiles that are unknown to patients, providing evidence for compound-specific therapeutic effects. These results highlight the importance of considering the full range of cannabis compounds when developing more precise and effective cannabis-based therapies for pain management.”
“Chronic pain affects millions of people, and many turn to medical cannabis for relief. However, scientists debate whether cannabis truly reduces pain or if patients feel better simply because they expect it to work (placebo effect). In this study, we looked at 329 people who used medical cannabis and analyzed the chemical makeup of their treatments. Using machine learning, we tested whether the specific chemicals in cannabis could predict who would get pain relief.
We found that patients’ pain improvement could be predicted from the chemical content of their cannabis, even though patients didn’t know what chemicals they were receiving. This suggests that cannabis provides real pain relief beyond just patient expectations.
These findings show that medical cannabis has genuine therapeutic effects for pain management.”
“In conclusion, to the best of our knowledge, our study provides compelling evidence that the efficacy of MC in pain relief is not merely a placebo response but is strongly influenced by its diverse chemical composition. Our findings challenge the traditional focus on THC and CBD as the primary therapeutic agents in cannabis and highlight the importance of considering the full spectrum of chemical compounds present in MC. By embracing a more comprehensive approach to understanding MC’s therapeutic potential, we can work towards developing safer, more effective, and more precisely targeted treatments for the millions of individuals suffering from chronic pain worldwide.”
“Classical cisplatin-based chemotherapeutic drugs are widely used in clinical practice. In recent years, novel platinum-based antitumor drugs have focused on replacing classical cisplatin-like Pt(II) complexes with relatively inert Pt(IV) prodrugs to overcome drug resistance and reduce toxic side effects.
Based on the excellent physiological and pharmacological activities of cannabidiol (CBD), this study designed and synthesized novel Pt(IV) prodrugs W1-W6, which are axial conjugates of cisplatin with CBD and specific active small molecules.
These prodrugs demonstrated more significant antitumor activity against tested tumor cell lines. Among them, the multifunctional Pt(IV) prodrug W5, conjugated with CBD and the PDK inhibitor DCA, exhibited excellent activity against both platinum-sensitive and cisplatin-resistant tumor strains.
The IC50 value of W5 for the A549R tumor strain was 8.53 ± 0.76 μM, significantly higher than that of the cisplatin group and 3.64 times the activity of CBD alone, demonstrating strong synergistic antitumor activity and potential to overcome cisplatin resistance. W5 is reduced by GSH in A549R cells, releasing CBD and Pt(II). Pt(II) binds to DNA, inducing damage and inhibiting repair, while CBD activates pro-apoptotic proteins, leading to mitochondrial dysfunction. Simultaneously, W5 reduces the levels of ROS scavengers, triggering endoplasmic reticulum dysfunction. These three mechanisms synergistically promote tumor cell apoptosis and overcome drug resistance.
This design integrates multiple mechanisms through axial functionalization, breaking through the limitation of traditional platinum drugs targeting DNA alone, and achieves synergistic effects by regulating metabolism and intervening in the immune microenvironment.”
“Cannabidiol (CBD) is another high-content non-psychoactive component in cannabis extracts, possessing functions such as antitumor, antiepileptic, anticonvulsant, anxiolytic, and anti-inflammatory properties [[12], [13], [14]]. Research indicates that cannabidiol, as a hydrophobic molecule, can easily cross the blood-brain barrier to reach brain tumor sites [15], enhancing interactions with the endocannabinoid system (ECS) to alleviate pain and promote immune cell regulation [16], thereby increasing the expression of complexes that help the immune system recognize cancer.”
“Objective: This descriptive, real-world, multicenter study aimed to evaluate the efficacy, safety, and tolerability of purified cannabidiol (CBD) as an add-on therapy in children with treatment-resistant developmental and epileptic encephalopathies (DEE).
Methods: Children aged 0.5 to 16 years who met the International League against Epilepsy (ILAE) criteria for drug-resistant DEE and were treated with purified CBD at 10 different centers between March 2021 and December 2024 were included.
Results: A total of 551 patients were enrolled. The mean age at CBD initiation was 8.5 years (SD 5 years; range 0.5-18). Median follow-up duration was 22 months (range 13-32). Etiologies were structural in 249 (45 %), genetic in 160 (28.8 %), immune-mediated in five (0.9 %), infectious in three (0.5 %), and unknown in 134 (24.3 %). After 12-32 months of follow-up, 279 patients (50.6 %) had a > 50 % reduction in seizure frequency, including 78 (14.2 %) who became seizure-free. A reduction of < 50 % was observed in 106 (19.1 %), and 34 (6.2 %) experienced no change. Adverse events occurred in 32.7 %, mostly mild and transient, improving with dose adjustments. At the last visit, 389 patients (70.6 %) continued CBD, with 173 (31.4 %) maintaining a > 50 % reduction in seizures and 56 (10.2 %) remaining seizure-free.
Conclusions: This study supports the use of purified CBD as an effective, safe, and well-tolerated treatment option for children with drug-resistant DEEs of diverse etiologies.”
“Purpose: Cystic echinococcosis is a parasitic zoonosis caused by the larval stage of Echinococcus granulosus sensu lato. Albendazole (ABZ) is the drug of choice, although its efficacy is variable. The present research aimed to assess the in vitro and in vivo efficacy of a full-spectrum extract of Cannabis sativa inflorescences against E. granulosus sensu stricto (s.s.).
Methods: Protoscoleces and cysts were incubated in vitro with the C. sativa extract, achieving final CBD concentrations of 1, 5, 10, and 50 µg/ml. Viability was evaluated periodically. Structural and ultrastructural alterations were also recorded. For the clinical efficacy study, female CF-1 mice were infected. Six months later, mice were divided into groups (n = 10): (a) water control; (b) ABZ; (c) C. sativa extract, and (d) ABZ + C. sativa extract. Treatments were administered every 24 h for 30 days. The efficacy of the treatments was evaluated according to the weight of the cysts collected and the ultrastructural alterations observed.
Results: The C. sativa extract caused a significant decrease in the viability of protoscoleces and cysts in vitro. The greatest effect was observed with 50 µg/ml, which generated the reduction in protoscoleces viability to 0% between 6 and 24 h post-incubation (pi) and the collapse of 92 ± 13% of the cysts after 24 h pi. All the in vivo treatments reduced the weight of the cysts and caused ultrastructural alterations, especially the combination of ABZ + C. sativa extract.
Conclusion: We demonstrated the in vitro and in vivo efficacy of a full-spectrum extract of C. sativa inflorescences against E. granulosus s.s.”
“Echinococcus granulosus sensu stricto (s.s.) refers to a specific species within the Echinococcus granulosus complex, a group of tapeworms that cause cystic echinococcosis (CE) in humans and other animals. This species, also known as the “sheep strain,” is the most prevalent cause of human CE globally.”
“Cystic echinococcosis in cattle and sheep caused by Echinococcus granulosus sensu stricto genotypes G1 and G3 in the USA”
“Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder caused by oxidative stress and dysregulation of lipid metabolism. The endocannabinoid system (ECS), particularly the type 1 cannabinoid (CB1) receptor, plays a crucial role in NAFLD progression. Cannabinoids, such as cannabidiol (CBD) and tetrahydrocannabinol (THC), along with terpenes, such as beta-myrcene and d-limonene, have shown potential therapeutic effects on liver health, particularly in reducing oxidative stress and modulating lipid metabolism.
This study aimed to analyse the effects of five cannabis oils (COs), each with different CBD:THC ratios and terpenes content, on hypertension, dyslipidemia, hepatic steatosis, oxidative stress, and CB1 receptor expression in an experimental model of NAFLD induced by a sucrose-rich diet (SRD) in Wistar rats for 3 weeks.
Methods: Male Wistar rats were fed either a: (1) reference diet (RD; standard commercial laboratory diet) or a: (2) sucrose-rich diet (SRD) for 3 weeks. 3 to 7 SRD + CO as following: (3) SRD + THC; (4) SRD + CBD; (5) SRD + CBD:THC 1:1; (6) SRD + CBD:THC 2:1; and (7) SRD + CBD:THC 3:1. The COs were administered orally at a dose of 1.5 mg total cannabinoids/kg body weight daily. The cannabinoid and terpenes content of all COs used in the study was determined. The terpenes found in COs were beta-myrcene, d-limonene, terpinolene, linalool, beta-caryophyllene, alpha-humulene, (-)-guaiol, (-)-alpha-bisabolol. During the experimental period, body weight, food intake and blood pressure were measured. Serum glucose, triglyceride, total cholesterol, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) levels were evaluated. Liver tissue histology, NAFLD activity score (NAS), triglyceride and cholesterol content, lipogenic enzyme activities, enzyme related to mitochondrial fatty acid oxidation, reactive oxygen species (ROS), thiobarbituric acid reactive substance (TBARS), and antioxidant enzyme activities were also evaluated. The CB1 receptor expression was also determined.
Results: The results showed that SRD-fed rats developed hypertension, dyslipidemia, liver damage, hepatic steatosis, lipid peroxidation, and oxidative stress. This was accompanied by upregulation of liver CB1 receptor expression. CBD-rich CO, CBD:THC 1:1 ratio CO; CBD:THC 2:1 ratio CO and CBD:THC 3:1 ratio CO showed antihypertensive properties. THC-rich CO, CBD:THC 1:1 ratio CO; CBD:THC 2:1 ratio CO showed the greatest beneficial effects against hepatic steatosis and liver damage. All COs exhibited antioxidant effects in liver tissue. This was associated with normal liver CB1 receptor expression.
Conclusions: This study demonstrated that COs, particularly THC-rich CO, CBD:THC ratio 1:1 CO, CBD:THC ratio 2:1 CO and terpenes, can effectively reduce dyslipidemia, liver damage and hepatic steatosis in SRD-induced NAFLD. COs with a higher proportion of CBD in their composition showed antihypertensive properties. All the COs exhibited antioxidant properties. These findings suggest that COs, especially those with CBD:THC ratios of 1:1 and 2:1 and terpenes, may represent a promising therapeutic approach for managing NAFLD and preventing its progression to more severe liver disease.”
“This study demonstrated that COs, particularly THC-rich formulations, and those with CBD:THC ratios of 1:1 and 2:1, effectively reduced dyslipidemia, hepatic steatosis, and liver damage in SRD-induced NAFLD. All COs exhibited significant antioxidant properties, which contributed to the attenuation of oxidative stress. Notably, oils containing CBD also displayed antihypertensive effects, likely due to their vasodilatory properties. The modulation of CB1 receptor is closely linked to the improvement in hepatic steatosis and oxidative stress. These results underscore the synergistic role of cannabinoids and terpenes in targeting key mechanisms involved in NAFLD pathophysiology.”
“These findings suggest that COs, especially those with balanced CBD: THC ratios (1:1 and 2:1) and with meaningful terpenes content, represent a promising therapeutic approach for managing NAFLD and preventing its progression to more severe liver diseases.”
“The endocannabinoid system (eCBS) plays a crucial role in pain modulation through its components, including endocannabinoids, cannabinoid receptors (CB1 and CB2), and metabolic enzymes.
Recent research highlights the interaction between the eCBS and non-opioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and pyrazolones. These agents may enhance endogenous endocannabinoid levels or influence eCBS signaling pathways, providing a multifaceted approach to pain relief.
This review examines the pharmacological mechanisms underlying these interactions, focusing on the potential of non-opioid eCBS interactions, detailing synergistic effects that could improve analgesic efficacy while minimizing side effects. Additionally, we explore the therapeutic implications of co-administering non-opioid analgesics with eCBS modulators to create more effective pain management strategies.
The combined modulation of non-opioid pathways and the eCBS represents a promising treatment for acute and chronic pain, warranting further clinical investigation and translational research in this evolving field.”
“Emerging Therapeutic Strategies: The integration of non-opioid medications with eCBS modulators represents a novel approach in pain management strategies, aiming to minimize opioid use while maximizing therapeutic efficacy and safety profiles during chronic pain management.”
“Background: Medical cannabis consumption is rising, but limited evidence informs the safety and efficacy of cannabis use in cancer patients. A national survey of oncology trainees found that most fellows felt insufficiently informed to make clinical recommendations about cannabis.
Aim: In this secondary analysis, we aimed to measure how frequently trainees recommend in favor of cannabis and determine factors influencing this clinical practice.
Methods: In this cross-sectional survey study for fellows enrolled in oncology training programs across the United States, an online survey assessing trainee practices regarding medical cannabis was sent to 155 oncology fellowship program directors from January – March 2021; who were asked to distribute it to their fellows. The primary outcome was the frequency with which oncology fellows recommended cannabis in the prior year.
Results: Nationally, 40 programs from 25 states participated, with 189 of 462 trainees across these programs responding (40.9% response rate). 22% (95% CI: 16.3-29.0%) of participants reported recommending medical cannabis to > 5 patients in the past year. 24% (95% CI: 18.4-30.5%) of participants had prior training in medical cannabis. Regarding participant characteristics, only prior training in medical cannabis was significantly associated with recommending cannabis to > 5 patients (RR: 2.4; 95% CI: 1.4-4.2).
Conclusions: With increasing cannabis use among patients with cancer and given that a substantial number of oncology fellows recommend its use, it is crucial that fellowship training incorporate evidence-based curricula regarding medical cannabis use to guide informed decision-making between patients and their fellow providers.”
“1 in 5 oncology fellows participating in our study recommended it to > 5 patients in the past year. Prior training in medical cannabis was the sole factor associated with higher rates of discussing and recommending its use to patients. Personalized, patient-centered care for cancer patients—and all patients—is mandatorily founded on understanding and articulating the best available evidence regarding treatment options.
Accordingly, as medical cannabis gains more widespread legal status and is increasingly considered and used by our patients, it will be of critical importance that contemporary fellowship training programs incorporate rigorous, up-to-date curricula on this subject so as to prepare their trainees to engage in well-informed discussions and shared decision-making with those for whom they care.”
“Innovative topical drug delivery systems, such as film forming systems, aim, among other objectives, to offer new application possibilities, enhance patient compliance, and provide prolonged therapeutic effects.
This study presents the development and comprehensive characterization of a novel chitosan-based film-forming system incorporating cannabidiol for antimicrobial topical treatment.
While chitosan and cannabidiol have been separately explored for their pharmaceutical properties, their combination within an in situ film-forming matrix remains largely unreported. Chitosan was chosen for its film-forming, mucoadhesive, and inherent antimicrobial properties. Ethanol-water ratios enabling optimal solubilization of chitosan were determined, and a suitable cannabidiol solubilizer was identified to ensure its homogeneous incorporation into the polymer matrix. The resulting films were characterized using differential scanning calorimetry, rheological analysis, Raman spectroscopy, optical microscopy, and scanning electron microscopy.
In vitro studies demonstrated sustained cannabidiol release, favorable mechanical properties, and excellent antimicrobial efficacy against both Gram-positive and Gram-negative bacteria, as well as fungi.
These results highlight the developed film-forming system as a novel and promising platform for the localized treatment of bacterial and fungal skin infections.”
“Wound healing in old mice is characterized by disturbed tissue homeostasis, manifested by delayed immune cell infiltration and reduced growth factor secretion, leading to a delayed onset and prolonged duration of the inflammatory phase.
The endocannabinoid system (ECS) is an important regulator of tissue homeostasis and cell migration and is also considered to be subject to aging processes, which may contribute to observable aging phenomena. Therefore, stimulating the aged ECS could represent a therapeutic option to support tissue regeneration in aging.
Female old mice received a low-dose of medical THC daily for 3 weeks, before four excisional full skin wounds were created. At day 1, 3 and 7 post-surgery, the wound closure rate was analyzed and wound samples were examined immunohistochemically for the numbers of granulocytes, M1-macrophages and mesenchymal stem cells (MSCs). The concentrations of inflammatory cytokines and regenerative growth factors were determined by ELISA.
Administration of THC improved the wound healing rate of old mice between day 1 and 7, which was associated with an altered timing and quantity of infiltrating immune cells and decreased levels of inflammatory cytokines in wound tissue on days 1 and 3 post-injury.
THC treatment significantly increased MSC infiltration but had no effect on the growth factor release.
The present study confirmed the anti-inflammatory activity of THC in vivo.
The THC-treatment improved wound healing in old mice by coordinating the temporal sequence of immune cell infiltration and cytokine release. Thus, restoration of ECS signaling could be an effective strategy to support age-related skin regeneration.”
