Author Archives: David

Cannabidiol (CBD) Acts as an Antioxidant on Gardnerella vaginalis, Resulting in Reduced Metabolic Activity, Loss of Survivability, and Elimination of Biofilms

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“Background: Gardnerella vaginalis is a natural inhabitant of the vagina, but when an imbalance occurs in the vaginal microbiota, this bacterium can cause vaginosis, a condition that must be treated when symptomatic and prior to a gynecological intervention. Cannabidiol (CBD) is an anti-inflammatory compound that also has antibacterial activities against several Gram-positive and certain Gram-negative bacteria. 

Objectives: Since G. vaginalis is an opportunistic pathogenic Gram-variable bacterium, we investigated its response to CBD. 

Methods: The antibacterial activity of CBD was studied by broth dilution assay, changes in intracellular ATP levels, and the ability of bacteria to recover on chocolate agar plates. The antibiofilm activity was investigated by MTT metabolic assay, crystal violet staining, and HR-SEM. Flow cytometric analyses were performed to measure changes in membrane potential, membrane perforation, and metabolic activity. Reactive oxygen species (ROS) production was analyzed using the nitro blue tetrazolium (NBT) reagent. Gene expression was determined by semi-quantitative real-time PCR, while protein composition was determined by LC-MS/MS analysis. 

Results: We observed that G. vaginalis clinical isolates exhibited high susceptibility to CBD with a minimum inhibitory concentration (MIC) of 2.5 µg/mL CBD. CBD induced rapid membrane hyperpolarization and caused cytoplasmic leakage of ATP without increasing propidium iodide uptake. This was accompanied by reduced metabolic activity and loss of survivability. Proteomic analysis revealed decreased expression of some ribosomal-associated proteins. CBD exhibited antioxidant activity by reducing intracellular ROS levels in a dose-dependent manner. The antibacterial effect was neutralized by the free radical scavenger α-tocopherol, suggesting the involvement of radicals in executing the antibacterial effect. Importantly, CBD not only prevented the biofilm formation of G. vaginalis but also reduced the metabolic activity and biofilm biomass of preformed, mature biofilms. Real-time PCR analysis of G. vaginalis treated with CBD for 6 h showed an increase in the expression of biofilm-associated genes, suggesting that the antibiofilm activity of CBD is mainly due to its antibacterial effect. CBD did not alter the ability of G. vaginalis to adhere to HeLa cervical carcinoma cells and CBD-treated bacteria were still phagocytosed by RAW264.7 macrophages. 

Conclusions: Our study shows that CBD exhibits antibacterial and antibiofilm activities against G. vaginalis clinical isolates and is thus a potential drug for the treatment of vaginosis caused by this bacterium.”

https://pubmed.ncbi.nlm.nih.gov/40001381/

https://www.mdpi.com/2079-6382/14/2/136

Association of Financial Wellness with Patterns of Medical Cannabis Use and Patient-Reported Outcomes in Adults with Cancer

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“Objective: Despite increasing use of medical cannabis to manage cancer-related symptoms, U.S. payers do not reimburse medical cannabis, leaving patients responsible for all associated costs. We assessed how self-reported financial well-being is associated with patterns of cannabis consumption, out-of-pocket costs, and impact on symptoms in patients with cancer.

Method: From December 2021 to January 2022, we surveyed patients with cancer enrolled in the Minnesota Medical Cannabis Program. The mailed survey included cancer history, cannabis use history, symptom changes and sociodemographic questions including income and perceived financial wellness. We conducted descriptive analyses.

Results: Of 797 eligible adults, 220 (28%) responded to the survey. Two hundred eleven answered a question about current household income as living comfortably (LC, 45%; n = 95) or not living comfortably (NLC, 55%; n = 116). The NLC group reported lower incomes (47% vs 8% with annual incomes <$50,000) and were typically younger, unmarried, unemployed, or disabled. NLC group purchased more vaporizers (48% vs 27%), used products high in THC (92% vs 82%), and reported higher cannabis costs (40% vs 21% spending $200+/month). The NLC group more often stopped or used cannabis less frequently than they would like (54% versus 32%), frequently citing costs as a reason (85% vs 39%). Both NLC and LC groups typically used cannabis daily and reported a high degree of symptom improvement.

Conclusions: Patients with cancer using cannabis report significant improvements in cancer-related symptoms. High out-of-pocket costs for cannabis may be especially burdensome among those already financially struggling, raising questions about affordability of and equitable access to this therapy.”

https://pubmed.ncbi.nlm.nih.gov/39968481/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/243

Combination of Cannabidiol with Cisplatin or Paclitaxel Analysis Using the Chou-Talalay Method and Chemo-Sensitization Evaluation in Platinum-Resistant Ovarian Cancer Cells

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“Background/Objectives: Cannabidiol (CBD) is known for its anti-cancer properties in preclinical models and is increasingly used alongside conventional chemotherapy in cancer treatment. This study aims to evaluate the anti-cancer activity of CBD from Lebanese Cannabis sativa as a monotherapy and in combination with cisplatin or paclitaxel on human ovarian adenocarcinoma cells. 

Methods: Cytotoxicity of CBD was tested on OVCAR-3 and SK-OV-3 cell lines using the MTS assay. The Chou-Talalay method and CompuSyn software were used to determine the combination indices (CIs) for predicting interactions between CBD and chemotherapeutic agents. CBD showed dose-dependent tumor growth inhibition at 72 h with comparable IC50 values for both cell lines. 

Results: The combination of CBD with cisplatin or paclitaxel showed significant antagonistic interaction in SK-OV-3 cells (CI > 1), but mild synergism (CI < 1) at high growth inhibition rates (95% and 97%) was observed in SK-OV-3 cells with CBD/cisplatin. Pure antagonism was found in OVCAR-3 cells with CBD/cisplatin. Priming SK-OV-3 cells with CBD reduced the IC50 values of both drugs significantly, with a similar effect seen when cells were primed with cisplatin or paclitaxel before CBD treatment. 

Conclusions: Integrating CBD with chemotherapy could improve cancer therapy and address drug resistance. Sequential administration of CBD and chemotherapeutic agents is more beneficial than simultaneous administration. Further in vivo studies are necessary to validate these findings and understand CBD’s interactions with other drugs fully.”

https://pubmed.ncbi.nlm.nih.gov/40002932/

“This study explores the anti-cancer activity of CBD, as monotherapy and in combination with two commonly used chemotherapeutic agents, cisplatin and paclitaxel, against platinum-resistant ovarian cancer OVCAR-3 and SK-OV-3 cell lines.

CBD monotherapy showed promising and significant tumor growth inhibitory effect against both cell lines. The current study demonstrated that the combination of CBD with cisplatin or paclitaxel displayed diminished inhibition of cell proliferation as compared to individual treatment.

CBD and paclitaxel exhibited an antagonistic interaction on all effect levels. In contrast, although antagonism was prominent over most of the inhibitory effect levels with concurrent treatment of CBD and cisplatin, synergy was detected at the highest effect levels, highlighting the potential benefit of combining the two agents at specific concentrations. However, priming with CBD, cisplatin, or paclitaxel has shown significant sensitization of SK-OV-3 cells to the subsequent treatment, stressing the importance of sequential, rather than simultaneous, administration of the drugs.

These findings offer valuable insights for optimizing current therapeutic options when integrating CBD with conventional chemotherapy by adopting priming regimens to circumvent the antagonism observed during co-treatment. Further investigations are necessary to validate the current results in vivo and elucidate the mechanism underlying the interaction of CBD with various anticancer drugs.”

https://www.mdpi.com/2227-9059/13/2/520

Tailored Iron Oxide Nanoparticles as Potential Cannabinoid Carriers for Anti-Cancer Treatment

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“We present a novel, multicomponent nanoparticulate carrier system based on superparamagnetic iron oxide nanoparticles with a designed hydrophilic/hydrophobic balance based on oleic acid and TWEEN 80 to incorporate hydrophobic cannabinoids-cannabigerol and cannabidiol-as well as the hydrophilic anthracycline drug epirubicin, forming a conjugate anticancer system.

Additionally, the superparamagnetic iron oxide-based nanoparticles formed the core of the system, thus providing it with magnetic hyperthermia capabilities with a specific absorption rate comparable to the corresponding systems in the literature. The interaction of the conjugate with the cell membrane was studied using the Langmuir monolayers at the air/water interface formed of selected lipids modeling the healthy and cancerous cell membranes.

Finally, cytotoxicity tests were carried out against the SKOV-3 cell line in vitro. A synergistic effect was observed when both the cannabinoid and epirubicin were present in the conjugate, as compared to the cannabinoid or epirubicin alone, making our system advantageous for further development for tentative therapeutic use.”

https://pubmed.ncbi.nlm.nih.gov/40001533/

https://www.mdpi.com/2218-273X/15/2/230

Extraction, GC-MS analysis, cytotoxic, anti-inflammatory and anticancer potential of Cannabis sativa female flower; in vitro, in vivo and in silico

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“This work examines the anticancer activity, the anti-inflammatory nature, and the cytotoxicity of the ethanol extract obtained from the female flowers of Cannabis sativa L using molecular methods in vitro, animal testing in vivo, as well as computational methods and simulations in silico.

From the GC-MS analysis, the following bioactive compounds were found: cannabidiol (CBD), tetrahydrocannabinol (THC), and humulene. The antiproliferative activities of the extract were determined on HeLa cells by using MTT, Crystal Violet, and Trypan Blue assays with an IC50 value suggesting 51%-77.6% lethality.

The bioinformatics analysis of molecular docking proved significant ligand-protein interactions of CBD, THC, and humulene with cancer-associated proteins such as PD-1/PD-L1, TNF-α, and MMP-9. In vivo, breast cancer was first established in female Sprague-Dawley rats with 7,12-dimethylbenz(a)anthracene (DMBA) then treated with cannabinoids either singularly or in combination.

Detailed treatment demonstrated that the use of the three cannabinoids simultaneously yielded the best anticancer and anti-inflammatory outcomes together with the best tumor reduction. The concentration of serum biomarkers of inflammation and tumor progression was substantially reduced in treated groups compared to the control group, which proves the synergistic effects of these cannabinoids in breast cancer therapy.

This study emphasizes the importance of medical Cannabis sativa derivatives in cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/40008130/

“Cancer still has no known treatment, and research is being conducted to create lead compounds and precursors that could be used as anticancer medications for 1 day. The goal of this study was to identify natural compounds with anticancer properties.

The MTT assay showed that cannabinoids retain anti-proliferative, anti-invasion, and apoptotic effects. IC50 upregulates 51%–77.6% of carcinoma cell death. The synergistic effects of cannabidiol, tetrahydrocannabinol, and humulene significantly suppressed PD-1/PD-L1 expression and oxidative stress, suggesting a possible approach for targeting breast cancer resistance. The greatest effect was obtained when all three compounds were combined, suggesting that the immunosuppressive and oxidative stress-modulatory effects of the compounds occurred synergistically.

Herein, we report comprehensive findings that may be helpful in designing new combinatory therapeutic strategies for breast cancer via the PD-1/PD-L1 pathway and oxidative stress markers. Further studies and trials are needed to identify more cannabinoid-based treatments and to combine pharmacological and cannabinoid drugs to gain remarkable effects against various cancer treatments.”

“Cannabis sativa is the oldest cultivated plant and contains a lot of naturally useful components used by humans. It is used as a source of fuel, food, herbal body care products, and medicines to cure different diseases. It is a plant of the Cannabaceae family. “

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1546062/full

Mechanisms of Cell Death Induced by Cannabidiol Against Tumor Cells: A Review of Preclinical Studies

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“Commonly known as marijuana or hemp, Cannabis sativa L. (Cannabaceae), contains numerous active compounds, particularly cannabinoids, which have been extensively studied for their biological activities. Among these, cannabidiol (CBD) stands out for its therapeutic potential, especially given its non-psychotropic effects.

This review evaluates the antitumor properties of CBD, highlighting its various mechanisms of action, including the induction of apoptosis, autophagy, and necrosis.

By synthesizing findings from in vitro studies on the cell death mechanisms and signaling pathways activated by CBD in various human tumor cell lines, this literature review emphasizes the therapeutic promise of this natural antineoplastic agent. We conducted a comprehensive search of articles in PubMed, Scopus, Springer, Medline, Lilacs, and Scielo databases from 1984 to February 2022.

Of the forty-three articles included, the majority (68.18%) reported that CBD activates apoptosis, while 18.18% observed simultaneous apoptosis and autophagy, 9.09% focused on autophagy alone, and 4.54% indicated necrosis. The antitumor effects of CBD appear to be mediated by transient receptor potential cation channels (TRPVs) in endometrial cancer, glioma, bladder cancer, and myeloma, with TRPV1, TRPV2, and TRPV4 playing key roles in activating apoptosis.

This knowledge paves the way for innovative therapeutic strategies that may enhance cancer treatment outcomes while minimizing the toxicity and side effects associated with conventional therapies.”

https://pubmed.ncbi.nlm.nih.gov/40006844/

“This review underscores the therapeutic potential of CBD as a promising antitumor agent across various cancer types, particularly through its interaction with transient receptor potential cation channels (TRPVs) and endocannabinoid CB receptors.

Our findings suggest that CBD primarily activates the apoptosis pathway while also engaging autophagy and necrosis, offering a multifaceted strategy for inducing cancer cell death. Moreover, the potential for combination therapies that integrate CBD with established chemotherapeutics highlights the importance of further research to investigate these synergies and optimize therapeutic regimens.

Although regulatory challenges persist, robust scientific evidence demonstrating CBD’s safety and efficacy of CBD will be crucial for advancing its clinical application in oncology.”

https://www.mdpi.com/2223-7747/14/4/585

Pharmacokinetics of Non-Psychotropic Phytocannabinoids

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“Cannabinoids are widely recognized for their potential therapeutic effects, making them significant and valuable candidates for medical research and applications across various fields.

This review aims to analyze the pharmacokinetics of Cannabidiol (CBD), Cannabigerol (CBG), and Cannabichromene (CBC), along with their corresponding acidic forms, Cannabidiolic acid (CBDA), Cannabigerolic acid (CBGA), and Cannabichromenic acid (CBCA).

Among these cannabinoids, CBD is the most extensively studied. Nevertheless, research involving all the mentioned cannabinoids has shown that their pharmacokinetic parameters are highly variable, depending significantly on factors such as dose, formulation, route of administration, and diet. Furthermore, challenges such as brain penetration and first-pass metabolism have been highlighted.

In conclusion, this review demonstrates significant progress in understanding the pharmacokinetics of non-psychotropic cannabinoids. However, it also underscores the need for further research, particularly on CBG, CBC, and their respective acidic forms, with the most significant gap being in clinical investigations. Expanding these studies is essential to facilitate their optimized use in medical treatments.”

https://pubmed.ncbi.nlm.nih.gov/40006604/

https://www.mdpi.com/1999-4923/17/2/236

Enhancing Tetrahydrocannabinol’s Therapeutic Efficacy in Inflammatory Bowel Disease: The Roles of Cannabidiol and the Cannabinoid 1 Receptor Allosteric Modulator ZCZ011

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“Background/Objectives: Current inflammatory bowel disease (IBD) treatments focus on symptomatic relief, highlighting the need for innovative approaches. Dysregulation of the cannabinoid 1 (CB1) receptor, part of the endocannabinoid system, is linked to colitis. While tetrahydrocannabinol (THC) alleviates colitis via CB1 activation, its psychotropic effects limit clinical use. ZCZ011, a CB1R allosteric modulator, and cannabidiol (CBD), a non-psychoactive cannabinoid, offer alternatives. This study investigated combining sub-therapeutic THC doses with ZCZ011 or CBD in a murine model of dextran sodium sulphate (DSS)-induced colitis. 

Methods: Acute colitis was induced with 4% DSS for 7 days, followed by 3 days of water. Chronic colitis was modelled over 24 days with alternating DSS concentrations. The combination of 2.5 mg/kg THC with 20 mg/kg ZCZ011 or 10 mg/kg CBD was evaluated. Key markers were assessed to determine efficacy and safety, including disease activity index (DAI), inflammation, cytokine levels, GLP-1, and organ health. 

Results: DSS-induced colitis resulted in increased DAI scores, cytokines, organ inflammation and dysregulation of GLP-1 and ammonia. THC at 10 mg/kg significantly improved colitis markers but was ineffective at 2.5 and 5 mg/kg. ZCZ011 alone showed transient effects. However, combining 2.5 mg/kg THC with either 20 mg/kg ZCZ011 or 10 mg/kg CBD significantly alleviated colitis markers, restored colon integrity and reestablished GLP-1 homeostasis. This combination also maintained favourable haematological and biochemical profiles, including a notable reduction in colitis-induced elevated ammonia levels. 

Conclusions: This study demonstrates the synergistic potential of low-dose THC combined with CBD or ZCZ011 as a novel, effective and safer therapeutic strategy for ulcerative colitis.”

https://pubmed.ncbi.nlm.nih.gov/40005963/

“This study provides compelling evidence that sub-therapeutic doses of THC combined with ZCZ011 or CBD offer a safe and effective strategy for managing both the inflammatory and metabolic components of IBD. Notably, the normalisation of GLP-1 and ammonia levels underscores the dual benefits of these treatments in alleviating colitis while addressing associated metabolic dysregulation and extraintestinal complications. This dual-action approach addresses key limitations of current therapies and emphasizes ECS modulation as a promising avenue for IBD treatment.”

https://www.mdpi.com/1424-8247/18/2/148

Antimicrobial Potential of Cannabinoids: A Scoping Review of the Past 5 Years

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“In the scenario of fighting bacterial resistance to antibiotics, natural products have been extensively investigated for their potential antibacterial activities. Among these, cannabinoids-bioactive compounds derived from cannabis-have garnered attention for their diverse biological activities, including anxiolytic, anti-inflammatory, analgesic, antioxidant, and neuroprotective properties.

Emerging evidence suggests that cannabinoids may also possess significant antimicrobial properties, with potential applications in enhancing the efficacy of conventional antimicrobial agents. Therefore, this review examines evidence from the past five years on the antimicrobial properties of cannabinoids, focusing on underlying mechanisms such as microbial membrane disruption, immune response modulation, and interference with microbial virulence factors. In addition, their synergistic potential, when used alongside standard therapies, underscores their promise as a novel strategy to address drug resistance, although further research and clinical trials are needed to validate their therapeutic use.

Overall, cannabinoids offer a promising avenue for the development of innovative treatments to combat drug-resistant infections and reduce the reliance on traditional antimicrobial agents.”

https://pubmed.ncbi.nlm.nih.gov/40005695/

“The unique chemical properties of cannabinoids, combined with their interactions with existing therapies, contribute to their antimicrobial effects against a wide range of microorganisms, including bacteria, fungi, and viruses.The data collected support the conclusion that cannabinoids exert their effects through multiple pathways, including the disruption of microbial membranes, modulation of immune responses, and interference with microbial virulence factors.

The use of cannabinoids as alternative therapeutic options has demonstrated their potential to overcome the limitations of conventional antibiotics, offering a potential new approach to combating drug-resistant microorganisms, potentially reducing dependence on traditional antimicrobial agents that have become less effective. It also appears that the use of combinations of cannabinoids with other conventional drugs can potentially lead to a synergistic effect with improved therapeutic capabilities.”

https://www.mdpi.com/2076-2607/13/2/325

Modulation of the endocannabinoid system in chronic conditions: a potential therapeutic intervention yet to be explored in sickle cell disease

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“Introduction: Individuals living with Sickle Cell Disease (SCD) are subject to numerous chronic complications, including disabling chronic pain, often dependent on opioids and with important repercussions on quality of life. The use of Medicinal Cannabis in this scenario may be a promising strategy for mitigating this impact.

Areas covered: This work compiled current knowledge regarding the endocannabinoid system in humans and the role of this system in various organic functions. Articles were retrieved through a comprehensive search of the PubMed NCBI database, covering relevant studies up to 2024. These data bring important speculations on the potential role of the use of medicinal cannabis in modulating SCD chronic complications, and the preliminary results of clinical trials carried out in this condition are discussed.

Expert opinion: The search for understanding the role of cannabis-derived products in the management of chronic complications of sickle cell disease could add resources to the serious challenge of dealing with the multiple aspects of the disease faced by patients. They range from the management of chronic pain itself, the risks of opioid dependence, in addition to other difficult scenarios, such as leg ulcers and chronic inflammation and its consequences.”

https://pubmed.ncbi.nlm.nih.gov/39992131/

https://www.tandfonline.com/doi/full/10.1080/17474086.2025.2471864