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

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Cannabidiol may enhance the effectiveness of targeted cancer therapies by increasing stress on tumor-cell survival mechanisms. In this breast cancer study, CBD potentiated the cytotoxic effects of olaparib, a PARP inhibitor, by promoting cell-cycle arrest and altering DNA-damage responses. The combination produced stronger anticancer effects than olaparib alone, suggesting that CBD may help sensitize breast cancer cells to PARP-targeted treatment. The findings support cannabinoid-based combination strategies aimed at improving treatment response in breast cancer.

“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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Cannabidiol is increasingly being investigated for its potential to lower blood pressure through multiple interacting biological pathways. In this study, researchers combined bioinformatics and machine-learning approaches to identify the molecular targets most strongly associated with CBD’s antihypertensive effects. The analysis highlighted networks involved in vascular tone, inflammation, oxidative stress, and cardiovascular signaling, providing a systems-level explanation for how CBD may influence blood-pressure regulation. The findings strengthen the case for CBD as a promising cardiovascular therapeutic candidate and identify specific molecular pathways for future drug development.

“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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Questions about prenatal cannabis exposure often center on whether even low levels of exposure are associated with lasting cognitive effects later in childhood. This longitudinal study followed adolescent cognitive development and found that low-level prenatal cannabis exposure was not associated with broad declines in cognitive trajectories across adolescence. The results help add longer-term developmental evidence to a field often dominated by short-term or heavily confounded findings and provide important context for understanding the effects of lower-level prenatal exposure.

“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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Cannabidiol is showing antiviral activity beyond human pathogens. In this study, CBD inhibited infectious bronchitis virus in chickens in both laboratory and live-animal models, reducing viral activity and demonstrating protective effects against infection. The findings suggest that CBD may have practical antiviral potential in poultry health and broaden the evidence that cannabinoids can act directly against viral disease. This study also highlights a possible veterinary and agricultural application for cannabidiol in managing economically important infections.

“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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Cannabidiol is emerging as a promising agent for soft-tissue repair because it can influence several biological processes involved in wound healing at once. This review examines evidence that CBD can reduce inflammation and oxidative stress, support fibroblast activity and tissue remodeling, and promote conditions favorable for wound closure and regeneration. It also highlights advanced delivery systems designed to improve CBD stability, penetration, and localized release at injured tissue. The findings support CBD as a versatile candidate for next-generation wound-care therapies that combine anti-inflammatory activity with regenerative support.

“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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Pharmaceutical-grade cannabidiol is being studied in pediatric epilepsy not only for seizure control, but also for its effects on anxiety and other common comorbid symptoms. In this prospective study, CBD treatment was associated with reductions in seizure frequency together with improvements in anxiety and related behavioral symptoms. Researchers also identified changes in circulating endocannabinoids and lipid mediators, linking the clinical improvements with measurable biological effects on the body’s cannabinoid-related signaling systems. The findings strengthen evidence that CBD may provide benefits across both seizure activity and broader neurological symptoms in children with epilepsy.

“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

Cannabidiol prevents mucosal HIV-1 transmission by targeting Langerhans cells, dendritic cells, macrophages and T-cells

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Cannabidiol may have antiviral effects that extend to the earliest stages of HIV transmission. In this study, CBD reduced mucosal HIV-1 transmission by acting on several immune-cell populations involved in viral entry and spread, including Langerhans cells, dendritic cells, macrophages, and T cells. The findings suggest that CBD can interfere with multiple cellular pathways that HIV exploits during initial infection, highlighting a potentially important role for cannabinoid-based strategies in HIV prevention research.

“HIV-1 transmission depends on the structure and immune cell composition of mucosal epithelia. Transmission mechanisms involve direct infection of CD4+ T-cells or macrophages, and indirect viral transfer to CD4+ T-cells from Langerhans cells (LCs) or dendritic cells (DCs). LCs-mediated HIV-1 transfer is inhibited by the neuropeptide calcitonin gene-related peptide (CGRP), due to upstream activation in LCs of the transient receptor potential vanilloid 1 (TRPV1) ion channel.

Herein, we investigated the potential anti-HIV-1roles of cannabidiol (CBD), the non-psychoactive compound in marijuana, which has well-described immunosuppressive functions and principally activates TRPV1 over its cognate CB1 and CB2 receptors.

We found that via TRPV1 activation, CBDinhibitsin-vitroinfection of mucosal HIV-1 cellular targets. Specifically, CBD inhibits macrophages HIV-1 direct infection, and CD4+ T-cells HIV-1 direct infection or upon viral transfer from LCsand DCs. Moreover, inhibition of macrophages infection and LCs-mediated HIV-1 transfer involves secreted CGRP.Importantly,

CBD also blocks early events of HIV-1 transmission ex-vivo in human inner foreskin tissues, namely formation of epidermal LC-T-cell conjugates and resulting CD4+ T-cells infection.

Altogether, CBD inhibits infection of all HIV-1 cellular targets, and commercial CBD products might be repositioned as novel HIV-1 pre-exposure prophylaxis, namely ‘CBD PrEP’.”

https://pubmed.ncbi.nlm.nih.gov/42014233

“Bases on our results, we propose an alternative that we coin as ‘CBD PrEP’. This would consist of the repositioning of commercially available CBD-containing products as novel microbicides for the purpose of clinical HIV-1 prevention.”

https://www.mucosalimmunology.org/article/S1933-0219(26)00030-9/fulltext

Cannabis Use and the Risk of Incident Venous Thromboembolism Among People With HIV: A Longitudinal Cohort Study in the United States

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People living with HIV already face an elevated risk of venous thromboembolism, making it important to understand whether cannabis use adds to that risk. In this longitudinal U.S. cohort study, cannabis use was not associated with an increased incidence of venous thromboembolism among people with HIV. The findings provide reassuring real-world evidence that cannabis use did not appear to add measurable clotting risk in this population and help clarify an important cardiovascular safety question in HIV care.

“People with HIV (PWH) are at an increased risk of venous thromboembolism (VTE), and cannabis use is common in this population. However, evidence of cannabis impact on VTE risk has been conflicting and not well evaluated in PWH.

Using data from five Centers for AIDS Research Network of Integrated Clinical Systems sites (2009-2020), we assessed the association between cannabis use and VTE risk.

Among 13,646 PWH, 30% reported current cannabis use. In adjusted Cox models, neither former (adjusted hazard ratio [aHR] 0.78, 95% confidence interval (CI) 0.57-1.07) nor current (aHR 0.74, 95% CI 0.51-1.06) cannabis use showed a significant increase in VTE incidence compared with never use. Additionally, no dose-dependent relationship was observed between cannabis use frequency and VTE.

Among PWH, cannabis use does not appear to be associated with an elevated risk of VTE.

Further research is needed to elucidate the relationship between cannabis and VTE risk in this population.”

https://pubmed.ncbi.nlm.nih.gov/42017672

https://journals.lww.com/janac/abstract/9900/cannabis_use_and_the_risk_of_incident_venous.255.aspx

The greater the pleiotropic effects, the greater the benefits – cannabis as a “biopsychosocial” drug: a mixed-methods study on chronic non-cancer pain

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Chronic non-cancer pain affects far more than physical sensation, often disrupting sleep, mood, daily function, and social well-being. In this mixed-methods study, patients using cannabis reported benefits across multiple dimensions of pain, including symptom relief, improved sleep, better emotional well-being, and enhanced day-to-day functioning. The findings support the idea that cannabis may work as a biopsychosocial treatment, with its broader “pleiotropic” effects providing value across several interconnected aspects of chronic pain rather than targeting pain intensity alone.

“Background: Against the background of widely inconsistent data from randomized controlled trials (RCT), the use of cannabis-based medicines (CBM) from the perspective of patients with chronic non-cancer pain (CNCP) was described.

Methods: Based on a purposive/convenient sampling, patients were recruited from the Pain Clinic of Hannover Medical School who had been using CBM prescribed by a doctor for at least 6 months. The patients discussed their experiences with CBM in semi-structured individual interviews. The interview transcripts were coded and analyzed using a modified grounded theory approach with the help of MAXQDA®. In addition, the Treatment Satisfaction Questionnaire with Medication (TSQM) was used.

Results: Theoretical saturation was reached after 32 interviews. Open and selective coding revealed the overarching phenomenon of “subjective pain experience under CBM therapy”, with one of the main themes being the “effect of CBM”. This revealed the categories “effect on pain” and “psychological” and “somatic effect”. The most important concepts were “pain intensity”, “pain management”, “stress management”, “musculoskeletal system”, and “sleep quality.” Constructing a theoretical framework 4 groups of responses to CBM treatment were identified. The focus is either on (I) pain reduction, (II) pain coping, (III) reduced stress or (IV) multidimensional aspects. When this classification was applied to topic of quality of life (QOL), the greatest effectiveness and highest overall satisfaction were found in group (IV). Mixed methods showed a continuous increase in the perceived effectiveness of CBM on pain-centered complaints from group (I) to (IV).

Conclusions: In line with the biopsychosocial understanding of chronic pain, it appears that those CNCP patients who benefit most from CBM are those who show the most far-reaching effects on both a physical and psychological level. The pleiotropic effects of CBM may be responsible for this. Based on these results, interdisciplinary prospective research appears sensible and necessary to further and systematically investigate this clinically relevant topic.”

https://pubmed.ncbi.nlm.nih.gov/42015327

https://link.springer.com/article/10.1186/s42238-026-00440-w

Analgesic Effect of Cannabinoids for Fibromyalgia: A Systematic Review and Meta-Analysis

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Cannabinoids are showing meaningful analgesic potential in fibromyalgia, a condition often marked by widespread pain, sleep disturbance, fatigue, and reduced quality of life. This systematic review and meta-analysis found that cannabinoid-based treatments were associated with significant reductions in pain intensity, supporting their role as a therapeutic option for fibromyalgia symptom management. The findings add higher-level evidence that cannabis-based medicines can provide measurable pain relief in a condition where conventional treatments are often incomplete.

“Background: Fibromyalgia is a kind of complex chronic pain syndrome that exerts a profound impact on patients’ lives. Current pharmacological treatments for fibromyalgia often yield suboptimal results. Cannabinoids have emerged as a potential therapeutic alternative to these treatments.

Objectives: Our study aimed to assess the analgesic efficacy of cannabinoids in treating fibromyalgia.

Study design: A systematic review and meta-analysis.

Methods: We conducted a comprehensive literature search using PubMed (MEDLINE), EMBASE, ISI Web of Knowledge, Cochrane Library, and Clinicaltrials.gov to analyze randomized controlled trials and observational studies that investigated the analgesic efficacy of cannabinoids in individuals diagnosed with fibromyalgia. The primary outcome was the effect of cannabinoids on pain intensity, quantified by the standardized mean difference (SMD) in pain levels before and after the treatment. We registered our review protocol in PROSPERO (CRD42024495525). The quality of the evidence was evaluated using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) method.

Results: Twelve clinical studies, consisting of 2 randomized controlled trials and 10 observational studies, (14 comparisons, 1,248 patients) were selected. Cannabinoids reduced pain intensity with statistical significance (SMD = -1.41, 95% CI = -1.98 to -0.84, P < 0.001), which was associated with a low GRADE rating. Both short-term (< 3 months, SMD = -1.37, 95% CI = -2.32 to -0.43, P = 0.004) and longer-term (≥ 3 months, SMD = -1.43, 95% CI = -2.22 to -0.65, P < 0.001) follow-ups showed statistically significant pain score reduction. Patients also experienced statistically significant improvements in sleep quality, anxiety, depression and quality of life (P-values < 0.05). Common adverse effects included dizziness, dry mouth, and drowsiness, while serious adverse effects were rare.

Limitations: Our analyses revealed that the results demonstrated considerable heterogeneity, which was attributed to variations in study designs, interventions, and outcome measurements across the included studies. These factors could potentially influence the validity of the findings. Thus, the results should be interpreted with these variations in mind.

Conclusion: Cannabinoids may provide analgesic benefits for patients with fibromyalgia. Cannabinoid use was also associated with improvements in sleep, anxiety, depression and quality of life. However, the findings should be interpreted with caution due to the quality of the evidence, heterogeneity, and small amount of available data from randomized controlled trials.”

https://pubmed.ncbi.nlm.nih.gov/42013320