Antiproliferative Effects of Cannabinoids and Cisplatin in Cervical Cancer Cells

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“Introduction: Cervical cancer remains a leading cause of cancer-related mortality among women globally, particularly in low- and middle-income countries. Cisplatin, a standard chemotherapeutic agent, is limited by severe toxicities and chemoresistance. This study aimed to assess the effects of cisplatin in combination with phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on cell proliferation, morphology, cell cycle progression, cell death, and DNA damage.

Methods: Synergistic interactions between THC, CBD, and cisplatin were assessed in HeLa, SiHa, and MCF-12A cells using the checkerboard assay and SRB assay. Cell morphology, cell cycle progression, apoptosis induction, autophagic activity, and DNA repair gene expression were evaluated using various techniques.

Results: The THC-CBD-cisplatin combination exhibited the strongest apoptotic response in cancer cells (HeLa 53%, SiHa 58%), while minimally affecting MCF-12A cells (32%). Cannabinoid co-treatment amplified the antiproliferative and pro-apoptotic effects of cisplatin in HeLa and SiHa cells. The triple combination induced a G2/M arrest in HeLa cells and sub-G1 accumulation in SiHa cells. Autophagic activity, indicated by LC3B puncta formation, increased in HeLa and SiHa cells following THC and CBD exposure. DNA repair genes XRCC1 and RAD51 were downregulated by the cannabinoid-cisplatin combination.

Conclusion: These findings demonstrate that combining THC and CBD with cisplatin results in enhanced and mechanistically diverse anticancer effects, with a higher degree of selectivity for cervical cancer cells compared to non-cancerous MCF-12A cells by inducing apoptosis and autophagy while inhibiting DNA repair capacity. This study highlights the potential of cannabinoid-based combination therapies as a promising approach for cervical cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/42055476

“Cannabinoids, a diverse group of bioactive compounds from the cannabis plant, have been shown to inhibit cancer cell proliferation through mechanisms such as inducing apoptosis, arresting the cell cycle, and inhibiting angiogenesis.”

“This study demonstrates that the combination of cannabinoids, specifically THC and CBD, with cisplatin results in enhanced, selective, and mechanistically diverse anticancer effects in cervical cancer cells. The combined treatment induces apoptosis and autophagy while inhibiting DNA repair capacity, leading to significant cytotoxicity against cancer cells and minimizing damage to normal cells. These findings underscore the potential of cannabinoid-based combination therapies as a promising and safer approach for cervical cancer treatment.”

https://onlinelibrary.wiley.com/doi/10.1002/cnr2.70561

Immunohistochemical analysis and distribution of lymphocytes and Kupffer cells in the liver of rats with long-term experimental use of hemp seed oil

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“Objective: Aim: To conduct histological and immunohistochemical analysis and distribution of lymphocytes and Kupffer cells in the liver of rats with long-term experimental use of hemp seed oil (HSO).

Patients and methods: Materials and Methods: 26 sexually mature male rats (180-230 g, 5-7 months old) were divided into three groups: experimental (n=14, 0.5 ml/kg/day HSO orally for 10 weeks), control (n=6, 0.1 ml/kg/day HSO orally for 10 weeks), and intact (n=6). Histological and immunohistochemical (CD3, CD20, CD56, CD68) studies, alongside quantitative analysis of lymphocyte and macrophage distribution in hepatic lobules, were performed. Statistical significance was assessed using Mann-Whitney and Pearson tests, with p<0.05 considered significant.

Results: Results: After 10 weeks of 0.5 ml/kg/day HSO, 71.43% of experimental rats developed mild fatty liver disease (Kleiner grade S1 steatosis), a significant difference from the control group (p<0.0001). No histological inflammation or necrotic changes in hepatocytes were observed. Small numbers of CD3 lymphocytes were present in portal tracts, without extending into or damaging the adjacent parenchyma. CD20 and NK resident lymphocytes were sparse. Aggregates of CD68-positive Kupffer cells were most common near liver lobule triads. The average number of Kupffer cells (5.79±0.06 per 0.01 mm2) in the experimental group significantly (p<0.001) exceeded the control by 1.49 times, suggesting hyperplasia of specialized macrophages and their increased role in liver immune function.

Conclusion: Conclusions: Ten weeks of experimental use indicates that hemp seed oil is safe to consume at a dose of 0.5 ml/kg/day.”

https://pubmed.ncbi.nlm.nih.gov/42048501

Evaluation of Dronabinol to Decrease Opioid Use for Cancer-Induced Bone Pain

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“Background: Bone metastases (BM) from breast cancer cause significant cancer-induced bone pain (CIBP). Management of CIBP is primarily with opioids, which have notable side effects. In preclinical models, cannabinoid receptor (CB)2 and CB1 agonists were shown to decrease CIBP and bone degradation. We hypothesized that the addition of CB2/CB1 agonists would decrease opioid requirements in patients with BM.

Methods: We conducted a single-arm study among breast cancer patients with BM on opioid therapy. Patients were treated with 10 mg dronabinol BID for 8 weeks. Our primary objective was to determine the proportion who decreased their opioid use by ≥ 20%. Participants completed the Brief Pain Inventory and the European Organization for Research and Treatment of Cancer quality of life questionnaires before and after treatment. Pre- and post-treatment blood and urine were collected for analysis of biomarkers of bone remodeling.

Results: We enrolled 14 evaluable patients, and 4 decreased opioid use by ≥ 20%, meeting the primary endpoint. Patients reported significant improvements in pain severity, interference scores, quality of life, and insomnia. There was one grade 3 adverse event (dizziness) related to the study drug. A significant decrease was noted in serum C-terminal telopeptide levels with therapy.

Conclusion: Our pilot study shows that the addition of dronabinol resulted in decreased opioid requirements for CIBP. Patient-reported outcomes also demonstrated improved pain and QOL with addition of dronabinol. Our results are promising and warrant further investigation into novel analgesics for CIBP to decrease opioid use.”

https://pubmed.ncbi.nlm.nih.gov/42050177

https://academic.oup.com/oncolo/advance-article/doi/10.1093/oncolo/oyag163/8664403

“Dronabinol, sold under the brand names Marinol and Syndros, is the generic name for the molecule of (−)-trans-Δ9-tetrahydrocannabinol (THC) in the pharmaceutical context. It has indications as an appetite stimulant and antiemetic and is approved by the US Food and Drug Administration (FDA) as safe and effective for HIV/AIDS-induced anorexia and chemotherapy-induced nausea and vomiting.”

Cannabidiol modulates spontaneous recovery through distinct and conserved transcriptomic signatures in mPFC subregions

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“Cannabidiol (CBD) has shown therapeutic potential for post-traumatic stress disorder (PTSD) by reducing spontaneous recovery (SR), yet the underlying mechanisms remain unclear.

We examined the effects of CBD on SR in male and female mice and found greater behavioral efficacy in males. To uncover the molecular basis of these effects, we performed transcriptomic profiling of the prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC).

We identified distinct and overlapping SR-associated gene sets in each subregion, and CBD shifted the expression of a significant subset of these genes toward non-stressed control levels, including genes involved in retrograde endocannabinoid signaling. Cross-species comparisons with human PTSD transcriptomic datasets revealed conserved gene alterations within each subregion, suggesting shared molecular signatures between mouse SR and human PTSD.

These findings highlight region-specific and conserved pathways through which CBD may exert therapeutic effects and provide mechanistic insight to advance CBD-based interventions for PTSD-associated spontaneous recovery.”

https://pubmed.ncbi.nlm.nih.gov/42050066

https://www.nature.com/articles/s42003-026-10111-4

Cannabidiol potentiates olaparib-induced cytotoxicity through cell cycle arrest and DNA damage modulation in breast cancer cells

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“Triple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive nature and limited treatment options, while therapeutic resistance in estrogen receptor-positive (ER+) breast cancer continues to limit treatment efficacy.

Although olaparib is primarily effective in BRCA-mutated cancers, its activity in BRCA-wild type (BRCA-wt) tumors is limited. Therefore, this study aimed to investigate whether cannabidiol (CBD) can enhance the response of BRCA-wt breast cancer cells to PARP inhibition.

The effects of olaparib (OLAP) and CBD, alone and in combination, were evaluated in MDA-MB-231 (TNBC) and MCF-7 (ER+) cell lines using comprehensive two-dimensional (2D) mechanistic analyses and three-dimensional (3D) spheroid models, including HCC-70 cells to extend TNBC validation.

The results demonstrate that combined OLAP and CBD treatment enhanced cytotoxic effects compared to single treatments, with more pronounced responses observed in 3D spheroid models, particularly in TNBC models. Flow cytometry and caspase 3/7 assays indicated increased apoptosis and G2​/M phase arrest following combination treatment. Gene expression analysis revealed downregulation of key DNA damage response and cell cycle-related genes (ATM, ATR, BRCA1/2, RAD51, and CDK1/2/4/6), supporting a role for cell cycle arrest and DNA damage modulation in mediating these effects. Functional assays showed reduced colony formation and migratory capacity, although these effects may reflect both cytotoxic and cytostatic responses under the selected experimental conditions.

Overall, these findings suggest that CBD may enhance the efficacy of olaparib in BRCA-wt breast cancer models and highlight its potential as a combinational therapeutic strategy in breast cancer treatment.”

“Cannabinoids have been reported to enhance the effects of conventional cancer treatments, including chemotherapy and radiotherapy, thereby improving therapeutic efficacy while potentially reducing treatment-related toxicity.”

“CBD, in particular, has shown promising antitumor activity in triple-negative breast cancer (TNBC) by inducing apoptosis, autophagy, and oxidative stress through modulation of signaling pathways such as AKT/mTOR.”

https://link.springer.com/article/10.1007/s11010-026-05550-w

Decoding the antihypertensive mechanism of cannabidiol through integrative bioinformatics and machine learning

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“Hypertension (HTN) results from intricate molecular mechanisms, making clinical remission difficult to achieve. This study explores the molecular pathways through which cannabidiol (CBD) may influence HTN.

Methods

Several RNA sequencing datasets related to HTN were retrieved from the GEO database and divided into training and validation sets. Candidate genes potentially associated with HTN were screened through differential expression analysis and weighted gene co-expression network analysis. The interactions and binding potential between CBD and key target proteins were then systematically investigated using bioinformatics, machine learning, immune cell infiltration analysis, and molecular dynamics simulation.

Result

Seventy genes were identified as potential targets for CBD intervention in HTN. Machine learning analysis refined this list to five core genes: pyruvate kinase PKM (PKM), thyroid hormone receptor beta (THRB), aldo–keto reductase family 1 member B1 (AKR1B1), TGF-beta receptor type-1 (TGFBR1), and proto-oncogene tyrosine-protein kinase Src (SRC). Among these, PKM, THRB, AKR1B1, and SRC were significantly upregulated in HTN, while TGFBR1 was downregulated (P < 0.05). These genes formed a regulatory network, showing direct or indirect interactions, and were associated with infiltration levels of neutrophils and resting mast cells. Molecular dynamics simulation revealed that CBD exhibits strong binding specificity to these target proteins.

Conclusion

This integrated analysis prioritized PKM, THRB, AKR1B1, TGFBR1, and SRC as candidate genes potentially associated with HTN progression. Molecular dynamics simulation suggested a favorable binding potential between CBD and these targets. These findings may provide supportive evidence for future studies exploring the potential mechanisms by which CBD may act in HTN.”

Associations of Low-Level Prenatal Alcohol and Cannabis Exposure With Adolescent Cognitive Trajectories

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“Background: No studies have examined the differential and combined effects of prenatal alcohol and cannabis exposure (PAE/PCE) on longitudinal trajectories of adolescent cognitive development. Further, previous alcohol research is mixed, with some evidence for negative PAE effects on cognition and other studies reporting null or positive associations. This study examined associations between PAE, PCE, and growth trajectories of adolescent cognition in a large, diverse sample.

Methods: N = 11,029 adolescents from the Adolescent Brain Cognitive Development℠ Study completed the NIH Toolbox cognitive battery at baseline (Mage = 9.95), two-year follow-up (Mage = 11.95), and four-year follow-up (Mage = 14.07). Retrospective parent report of PAE and PCE was assessed at baseline. Univariate growth trajectories were estimated for cognitive measures: Pattern Comparison, Picture Sequence Memory, Oral Reading, Flanker Task, and Picture Vocabulary. Cross-product terms for PAE and PCE tested combined use.

Results: Most mothers reported no prenatal alcohol (n = 8257; 74%) or cannabis (n = 10,812; 94%) use. Overall, use was low: across pregnancy, women reporting any alcohol use averaged 33.31 drinks, and those reporting any cannabis use averaged 33.00 use occasions. Before including covariates, there were negative main effects of PCE and positive main effects of PAE on intercepts for all five cognitive domains. There was little evidence for PCE/PAE effects on slopes for cognition. After adding covariates, no negative effects of PCE remained. Small positive PAE effects on intercepts for multiple domains persisted. Cross-product terms for combined exposure were not significant.

Conclusions: Little evidence emerged for negative effects of low PAE, PCE, or combined exposure on adolescents’ cognitive development after accounting for sociodemographic factors. Light drinking in families with social features positively associated with cognitive ability may result in few negative consequences. This study is the first to demonstrate weak evidence for adverse differential and combined low-level PAE and PCE effects on the development of adolescent cognition.”

https://pubmed.ncbi.nlm.nih.gov/41947378

“Little evidence emerged for negative effects of low level prenatal alcohol, cannabis, or combined exposure on adolescents’ cognitive development after accounting for sociodemographic factors.”

https://onlinelibrary.wiley.com/doi/10.1111/acer.70297

Inhibitory effect of cannabidiol on infectious bronchitis virus in chickens in vitro and in vivo

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“Avian infectious bronchitis virus (IBV), a gamma coronavirus, remains the predominant pathogen affecting poultry worldwide, posing a significant threat to the poultry industry.

Cannabidiol (CBD), the primary non-psychoactive constituent of Cannabis sativa, has demonstrated diverse pharmacological properties.

This study investigated the inhibitory effects of CBD against IBV infection both in vitro and in vivo. Chicken embryo kidney (CEK) cells infected with IBV were treated with CBD at various concentrations (2–20 µM).

Our results demonstrated that CBD significantly suppressed IBV replication in a dose-dependent manner without affecting cell viability. Furthermore, in SPF chickens, CBD treatment markedly alleviated clinical symptoms, reduced tracheal and renal histopathological lesions, and significantly decreased viral loads in tissues. Transcriptomic analysis of tracheal tissue suggested that CBD may inhibit IBV infection through modulation of immune-related signaling pathways, particularly the JAK-STAT pathway and interferon-stimulated gene expression.

These findings indicate that CBD represents a promising candidate for therapeutic intervention against IBV infection.”

https://link.springer.com/article/10.1007/s00203-026-04886-7

Exploring the therapeutic potential of cannabidiol in soft tissue wound healing: Delivery strategies and anti-inflammatory pathways

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“This review explores the molecular and cellular pathways of soft tissue wound healing and the potential therapeutic use of the non-psychotropic cannabinoid cannabidiol (CBD), integrating findings from in vitro and in vivo preclinical studies as well as completed and ongoing clinical trials.

It provides a comprehensive summary of the next steps in new CBD-based product development by analyzing current trends in dosage optimization, treatment guidance, delivery systems, ranging from liposomes, microemulsions to hydrogels. Additionally, the review examines clinical trials related to CBD formulations, delivery routes, and participant outcomes, offering a deeper understanding of the mechanisms guiding the activity beyond binding to cannabinoid 1 (CB1) and CB2 receptors. Furthermore, it highlights challenges and future perspectives in CBD formulation studies, presenting both currently studied approaches and emerging possibilities for innovation.

Therapeutic potential of CBD has proved itself in the recent years and only regulatory issues and clarity in treatment and delivery routes will limit its widespread use in soft tissue healing.”

https://pubmed.ncbi.nlm.nih.gov/42039297

“The therapeutic properties of Cannabis sativa have been recognized for over five millennia, with it use as a medical substance dating back to the Christian era in Central and Northeast Asia, particularly in India. However, despite its potential, this plant has undergone limited scientific exploration of its chemical and biological properties, and its medical use has remained restricted, particularly following its classification as a substance with no medical value under the United Nations Single Convention on Narcotic Drugs.”

“The historical use of cannabinoids in ancient medicine, coupled with modern preclinical investigations into their various components, unveils a broad spectrum of its potential clinical applications for soft tissue regeneration.”

“The unique therapeutic properties of CBD hold great promise for the treatment of different diseases and disorders, including alleviating pain associated with various soft tissue injuries or conditions, fibrosis, inflammation, and addressing muscle disorders.”

https://www.sciencedirect.com/science/article/pii/S2211383525006744?via%3Dihub

Preliminary Prospective Study of Pharmaceutical-Grade Cannabidiol for Seizure Frequency, Anxiety, and Comorbid Symptoms in Pediatric Epilepsy: Associations With Circulating Endocannabinoids and Lipid Biomarkers

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“Anxiety commonly co-occurs with childhood epilepsy, yet treatments targeting both are limited.

Epidiolex (cannabidiol, CBD) is an FDA-approved treatment for seizures associated with rare pediatric epilepsies and may have anxiolytic effects. We evaluated its effects on seizures and anxiety in pediatric patients with refractory epilepsy, representing diverse seizure etiologies and circulating endocannabinoids and related biomarkers.

Twelve participants (12.17 ± 5.17 years; 6 female) initiated Epidiolex for 4-6 weeks. Caregivers completed pre- and post-treatment seizure diaries; validated anxiety and quality-of-life assessments; and plasma endocannabinoids, related lipids, and CBD metabolites-including 7-hydroxycannabidiol (7-OH-CBD)-were measured.

Post-treatment, 73% of caregivers reported improvements in anxiety and seizure frequency with minimal side effects and improved sleep. Plasma 2-arachidonoylglycerol increased from baseline to study end, with greater elevations in those with lower baseline concentrations. Plasma 7-OH-CBD increased from baseline to study end, confirming systemic CBD exposure.

Epidiolex may provide anxiolytic benefits across pediatric epilepsy, potentially involving endocannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/42033397

https://journals.sagepub.com/doi/10.1177/08830738261439213