Author Archives: David

Cannabidiol from Conventional to Advanced Nanomedicines for the Management of Cancer-Associated Pain

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“Chemotherapy-induced pain is one of the major challenges that hamper the patient’s quality of life. Several cases of insufficient pain management were reported globally, especially in the case of patients who do not respond well to conventional pain management regimes and opioid analgesics. Additionally, conventional pain management has several shortcomings, and evidence suggests that cannabidiol has the potential to overcome those shortcomings.

Cannabidiol (CBD) is a non-psychoactive compound of the Cannabis plant that shows an effective outcome in chemotherapy- induced pain as well as in cancer treatment, as it possesses anti-inflammatory and analgesic properties.

The mechanism of pain and its management by cannabidiol, with all possible evidence, is well summarised in the paper. This article concludes the types of pain experienced by cancer patients, the effectiveness of CBD in the management of pain, and challenges faced by patients after using Cannabidiol with various case studies.

Later, antitumor efficacy studies of CBD were disclosed, and its various types of formulations and nano-formulations were summarized in the paper. Overall, the paper establishes the role of cannabidiol in Chemotherapy-induced pain.”

https://pubmed.ncbi.nlm.nih.gov/40151084/

https://www.eurekaselect.com/article/147414

The protective role of cannabidiol in stress-induced liver injury: modulating oxidative stress and mitochondrial damage

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“Background: Stress-induced liver injury, resulting from acute or chronic stress, is associated with oxidative stress and inflammation. The endocannabinoid system, particularly cannabinoid receptor 2 (CB2R), plays a crucial role in liver damage. However, there are currently no clinical drugs targeting CB2R for liver diseases. Cannabidiol (CBD), a CB2R agonist, possesses anti-inflammatory and antioxidant properties. This study aims to investigate the pharmacological effects of CBD in a mouse model of stress-induced liver injury.

Methods: We employed a mouse model of stress-induced liver injury to evaluate the protective effects of CBD. Assessments included histopathological analysis, cytokine detection via ELISA, protein expression analysis using immunohistochemistry and Western blot, and gene transcription differential analysis. Transmission electron microscopy was utilized to observe mitochondrial morphology. Additionally, we examined the expression levels of CB2R, SLC7A11, α-SMA, and ACSL4 proteins to elucidate the mechanisms underlying CBD’s effects.

Results: CBD exhibited significant protective effects against stress-induced liver injury in mice. Decreases in liver function indicators (including Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) and inflammatory cytokines (such as IL-1β and Tumor Necrosis Factor-alpha (TNF-α)) were observed. CBD enhanced CB2R expression and reduced α-SMA levels, mitigating liver fibrosis. It also decreased ACSL4 levels, increased SOD and GSH-Px activities, and upregulated SLC7A11 protein expression. Furthermore, CBD improved mitochondrial morphology, indicating a reduction in oxidative cell death.

Conclusion: CBD activates the CB2R/α-SMA pathway to modulate liver inflammation and fibrosis. Through the SLC7A11/ACSL4 signaling pathway, CBD alleviates oxidative stress in stress-induced liver injury, enhances mitochondrial morphology, and reduces liver damage. These findings provide a theoretical basis for the potential application of CBD in the prevention and treatment of stress-induced liver injury.”

https://pubmed.ncbi.nlm.nih.gov/40160456/

“The cold-water immersion restraint method effectively simulates a stress-induced liver injury model caused by conditions such as hunger, cold exposure, and the fear of death. CBD demonstrates protective effects against stress-induced liver injury, and its protective mechanism may be associated with the activation of CB2R and mitochondrial metabolism. Specifically, CBD appears to exert its anti-liver fibrosis and antioxidative effects by activating CB2R, inhibiting the expression of α-SMA and ACSL4 proteins, and enhancing the expression of SLC7A11 protein, thereby alleviating liver damage.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1567210/full

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

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

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

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

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

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

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

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

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

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

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

Early oral administration of THC:CBD formulations prevent pain-related behaviors without exacerbating paclitaxel-induced changes in weight, locomotion, and anxiety in a rat model of chemotherapy-induced neuropathy

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“Rationale: Paclitaxel-induced neuropathy stands out as the primary, dose-limiting side effect of this extensively used chemotherapy agent. Prolonged hypersensitivity and pain represent the most severe clinical manifestations. Effective preventive and therapeutic strategies are currently lacking.

Objectives: Our study aimed to assess the impact of early oral administration of pharmaceutical-grade formulations containing the phytocannabinoids THC and CBD in a rat model of paclitaxel-induced neuropathy.

Methods: The experimental design involved the co-administration of paclitaxel and cannabinoid formulations with different THC to CBD ratios (THC:CBD 1:1 and THC:CBD 1:20) to adult male rats. Mechanical and thermal sensitivity, locomotor activity, vertical exploratory behaviors, anxiety-related parameters, weight gain, food and water consumption, and liver functionality were assessed.

Results: Daily administration of THC:CBD 1:1 successfully prevented paclitaxel-induced cold allodynia, while THC:CBD 1:20 effectively prevented both thermal and mechanical hypersensitivities. Additionally, THC:CBD 1:1 formulation restored rearing behavior, significantly reduced by paclitaxel. Conversely, neither cannabinoid formulation was able to counteract paclitaxel-induced hypo-locomotion, reduced vertical exploratory activity, increased anxiety-like behaviors, attenuated weight gain, or decreased food and water intakes. However, the formulations employed did not induce further alterations or toxicity in animals receiving paclitaxel, and no signs of liver damage were detected.

Conclusions: Our results suggest a differential therapeutic effect of two THC:CBD formulations on pain-related behaviors and spontaneous activities, particularly in the context of peripheral neuropathy. These formulations represent a promising therapeutic strategy not only to managing pain but also for enhancing daily activities and improving the quality of life for cancer patients.”

https://pubmed.ncbi.nlm.nih.gov/40163146/

Cannabidiol/tetrahydrocannabinol-enrich extract decreases neuroinfalmmation and improves locomotor outcome following spinal cord injury

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“Neuroinflammation is one of the main players in lesion expansion and locomotor deficits after spinal cord injury (SCI), thus treatments to control the inflammatory process emerge as novel therapeutic strategies. In this context, the anti-inflammatory effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), the main phytocannabinoids of Cannabis sativa, are increasingly recognized.

The aim of this work was to investigate the effects of a standardized Cannabis sativa extract (CSE), which is mainly composed by THC/CBD in equimolar concentration, on neuroinflammation, secondary damage and locomotor outcome after SCI in rats.

After acute SCI, CSE therapy increased the number of non-inflammatory (arginase-1 positive) microglial cells in the epicenter of the lesion and decreased the number of pro-inflammatory ones (arginase-1 negative) in the epicenter and in the rostral and caudal regions of the lesion. CSE also reduced the number of reactive astrocytes in the grey matter of the rostral and caudal regions.

These results are consistent with the downregulation of mRNAs of inflammatory mediators (IL-1β, TNFα, IL-6, C3) and the upregulation of anti-inflammatory markers (ARG-1, MRC). In the chronic phase, CSE treatment prevented cyst expansion and also increased the volume of spared grey and white matter. Regarding locomotor outcome, CSE-treated rats showed better locomotor scores (open field test), higher latency to fall (Rotarod test) and lower number of hindlimb foot misplacements (horizontal ladder walking test) than untreated injured rats.

These results suggest that this standardized CSE offers a promising perspective for reducing acute neuroinflammation and promoting functional recovery after SCI.”

https://pubmed.ncbi.nlm.nih.gov/40157632/

https://www.ibroneuroscience.org/article/S0306-4522(25)00258-1/abstract

Evaluation of the antibacterial activity and mechanism of cannabigerol against drug-resistant Streptococcus iniae in vitro

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“This study aimed to investigate the antibacterial effects and mechanism of cannabigerol against drug-resistant Streptococcus iniae.

The determination of antibacterial activity was based on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), growth curve analysis, time-kill assay, biofilm inhibition and eradication assessments.

The antibacterial mechanism was explored by DNA leakage assay, assessment of cell membrane permeability, evaluation of cell membrane integrity, measurement of membrane potential, determination of respiratory chain dehydrogenase activity, and examination by using scanning electron microscopy (SEM) and transmission electron microscopy (TEM).

The results demonstrated that cannabigerol effectively inhibited the growth and biofilm formation of Streptococcus iniae in vitro.

Mechanistically, cannabigerol induced DNA leakage, impaired cell membrane integrity, hyperpolarized membrane potential, and reduced respiratory chain dehydrogenase activity in S. iniae.

In conclusion, these findings suggest that cannabigerol inhibited the growth of S. iniae by disrupting the cell membrane.”

https://pubmed.ncbi.nlm.nih.gov/40146372/

Extraction of Cannabinoids and Terpenes from Hemp Flowers and Leaves (Cannabis sativa L., Futura 75): Chemical Profiling and Evaluation of Anticancer Properties

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“This study investigated efficient extraction methods for cannabinoids and terpenes from the above-ground parts of Futura 75, focusing on two techniques: pressurized extraction and magnetic stirrer-assisted extraction. The effects of solvent type, temperature, time, and pressure were evaluated using five organic solvents and two binary solvent systems.

Cannabinoid profiles of obtained extracts were analyzed using gas chromatography coupled with mass spectrometry (GC-MS), while terpene profiles were characterized through solid-phase microextraction (SPME) combined with GC-MS. Next, two selected extracts with the highest content of cannabinoid and terpene fractions (Futu1 and Futu2) were tested for antiproliferative activity toward cancer cell lines (MV4-11, AGS, HT-29, MDA-MB-468, MCF-7) and their cytotoxicity was evaluated on non-tumorigenic MCF-10A cells. Extract Futu1 contained 51.57% cannabinoids, 9.8% monoterpenes, and 90.2% sesquiterpenes in the terpene fraction. Futu2 exhibited a higher proportion of monoterpenes in the terpene fraction (19.6% monoterpenes and 80.4% sesquiterpenes) and consisted of 49.49% cannabinoids.

Both extracts exhibited higher selectivity for cancer cells over non-tumorigenic cells, with Futu2 demonstrating stronger antiproliferative properties.”

https://pubmed.ncbi.nlm.nih.gov/40142100/

“Cannabis sativa L., commonly known as hemp, belongs to the Cannabaceae family, which includes two primary cannabis varieties: hemp (Cannabis sativa L. var. sativa) and marijuana (Cannabis sativa L. var. indica).”

“The effects of two selected extracts from the Futura 75 hemp variety—containing cannabinoids and terpene fractions with differing monoterpene-to-sesquiterpene ratios—were investigated for their potential to inhibit cancer cell growth and their safety concerning healthy breast cells. The results indicate that while the extracts are less active than the tested individual cannabinoids, they exhibit significantly higher selectivity toward cancer cells compared to non-tumorigenic cells. Furthermore, the extract with a higher monoterpene content (Futu 2) demonstrated slightly stronger antiproliferative activity.”

https://www.mdpi.com/1420-3049/30/6/1325

Anti-Inflammatory Activity of Cannabis sativa L. Extract in 2,4-Dinitrochlorobenzene-Induced Dermatitis in Rats

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“Background:Cannabis sativa L. and its products are becoming popular for the treatment of inflammatory diseases. One of the main phytocannabinoids contained in cannabis is cannabidiol (CBD), which is a component of numerous cosmetic preparations used to treat inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. However, current data regarding the efficacy and safety of CBD for dermatological indications are limited. Therefore, the aim of the present study was to evaluate the anti-inflammatory effect of high-CBD Cannabis sativa L. extract (eCBD) in a model of AD. 

Methods: Dermatitis was induced by repeated application of 2,4-dinitrochlorobenzene (DNCB) to the skin of the rats’ ears. The therapeutic effect of eCBD was evaluated in behavioral, histopathological, and hematological studies following topical application as an ointment containing 2% CBD. 

Results: Application of the ointment containing eCBD resulted in attenuation of DNCB-induced inflammation. Interestingly, an anti-edematous effect was more pronounced in rats treated with the eCBD than in rats treated with 1% hydrocortisone ointment. However, eCBD did not reduce the frequency of DNCB-induced scratching, while there was a visible antipruritic effect of 1% hydrocortisone application. Histopathological analysis revealed that both eCBD and 1% hydrocortisone ointments significantly decreased mast cell count compared with the Vaseline control group. Furthermore, treatment with an ointment containing eCBD resulted in a decrease in the number of leukocytes in the blood. 

Conclusions: Topically administered eCBD had a stronger anti-edematous effect than glucocorticosteroid and differently affected hematological parameters. It is suggested that eCBD has therapeutic potential for the treatment of AD.”

https://pubmed.ncbi.nlm.nih.gov/40143146/

“Taken together, the results of this study demonstrate that Cannabis sativa L. extract containing a high concentration of CBD (eCBD), applied topically in the form of an ointment, showed anti-inflammatory effects, as manifested in a reduction in ear edema in rats with DNCB-induced dermatitis. Interestingly, the anti-edematous effect of eCBD was more pronounced than that observed after hydrocortisone treatment at the concentrations of the substance used. Furthermore, eCBD caused a decrease in the number of mast cells in the inflamed skin and changes in the parameters of the white blood cell system. Therefore, it seems that eCBD may be a valuable addition to therapy in AD patients, but further research is needed.”

https://www.mdpi.com/1424-8247/18/3/370

Evaluating Vaporized Cannabinoid Therapy in Multiple Sclerosis: Findings from a Prospective Single-Center Clinical Study

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“Introduction: Multiple Sclerosis (MS) is associated with a wide range of debilitating symptoms, and conventional therapies often fail to adequately address the disease’s multifaceted challenges. Cannabidiol (CBD) 13.0% + Delta9-tetrahydrocannabinol (THC) 9.0% (CBD13/THC9), a vaporized cannabis-based medicinal product, presents a novel therapeutic option for managing MS symptoms. 

Methods: This single-center longitudinal study followed 69 MS patients over a six-month period. Participants were assessed at treatment initiation and at three- and six-month intervals. Key measures included muscle spasticity, urine bladder dysfunction, and the evaluation of disability progression rate. The evaluation included the Modified Ashworth Scale (MAS), the Post Void Residual (PVR) volume, and the Expanded Disability Status Scale (EDSS). 

Results: Significant improvement was observed across all outcome assessments. The EDSS score was decreased over time (p = 0.009), indicating a slight reduction in disability progression rate, while MAS scores showed substantial improvement in muscle spasticity (p < 0.001). Urine bladder function improved significantly, with PVR volume showing notable improvement between baseline and the six-month assessment (p < 0.001). Correlation analyses revealed that a gradual increase in vaporized CBD13/THC9 dose was correlated with slightly lower EDSS scores, while the adverse effects were negatively associated with the frequency of cannabinoid use. Finally, patients who were smokers used CBD13/THC9 more frequently. 

Conclusions: The vaporized CBD13/THC9 formulation demonstrated notable efficacy in slightly improving disability progression rate via reduction in muscle spasticity and urine bladder dysfunction in MS patients. This highlights its addon therapeutic value during rehabilitation in MS patients with debilitating disability symptoms.”

https://pubmed.ncbi.nlm.nih.gov/40142928/

https://www.mdpi.com/2077-0383/14/6/2121

The Therapeutic Potential of Cannabidiol in the Management of Temporomandibular Disorders and Orofacial Pain

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“Background: Temporomandibular disorders (TMDs) are a group of conditions affecting the temporomandibular joint (TMJ) and associated muscles, leading to pain, restricted jaw movement, and impaired quality of life. Conventional treatments, including physical therapy, medications, and surgical interventions, have varying degrees of success and potential side effects. Cannabidiol (CBD), a non-psychoactive component of cannabis, has gained attention for its anti-inflammatory, analgesic, and anxiolytic properties. This study explores the potential role of CBD in TMD management. 

Methods: A review of existing literature was conducted (2007-2024), focusing on preclinical and clinical studies assessing the efficacy of CBD in pain modulation, inflammation reduction, and muscle relaxation. Relevant studies were sourced from PubMed, Scopus, and Web of Science databases. Additionally, potential mechanisms of action, including interactions with the endocannabinoid system, were analyzed. 

Results: Studies suggest that CBD exerts analgesic and anti-inflammatory effects by modulating CB1 and CB2 receptors, reducing cytokine release, and influencing neurotransmitter pathways. Preliminary clinical evidence indicates that CBD may alleviate TMD-related pain and muscle tension with minimal adverse effects. However, high-quality randomized controlled trials are limited. 

Conclusions: CBD demonstrates promise as a potential adjunctive treatment for TMD. Further research, including well-designed clinical trials, is necessary to establish its efficacy, optimal dosage, and long-term safety.”

https://pubmed.ncbi.nlm.nih.gov/40142992/

“Within the limitations of this review, current evidence suggests that cannabidiol (CBD) holds promise as a therapeutic adjunct for managing temporomandibular disorders (TMD). Multiple preclinical and preliminary clinical studies highlight that CBD may reduce muscle hyperactivity, alleviate inflammatory pain, and potentially improve patient-reported outcomes such as sleep and anxiety. These findings align with the review’s primary objective, which was to assess whether CBD could mitigate TMD symptoms and serve as a viable treatment option.”

https://www.mdpi.com/1999-4923/17/3/328