Leaf Boutique

25/04/2025

Exosomal formulation of cannabidiol (CBD) inhibits lung cancer proliferation and enhances uptake and tumor targeting

Lung cancer remains a leading cause of cancer-related deaths, with treatment specificity posing a major challenge. Thus, we aim to repurpose cannabidiol (CBD) as an antitumor agent, delivered via tumor-targeted exosomes (Exo). We demonstrated that oral CBD administration inhibited orthotopic lung tumor growth by ∼60% (p < 0.01), with enhanced efficacy (∼80%; p < 0.001) achieved using folic acid-functionalized exosomes loaded with CBD. We hypothesized that the enhanced antitumor efficacy is due to 1) increased accumulation at the tumor site due to FA-targeting; 2) improved cellular uptake of CBD via exosomal delivery; and 3) modulation of mechanistic pathways by CBD. To evaluate tumor targeting, FA-Exo labeled with Alexa Fluor-750 (AF750) were administered orally to tumor-bearing mice. Single doses of free AF750, Exo-AF750, and FA-Exo-AF750 were compared (n=3 per group). After 12 hr, mice were euthanized and imaged ex vivo using Odyssey LiCor Imager. For bioavailability studies, female C57BL/6 mice were given a single oral dose of 40 mg/kg CBD or ExoCBD, and tissue CBD levels were quantified 4 hr post-administration. Additionally, ER stress modulation by CBD was assessed in A549 lung cancer cells through analysis of key markers. FA-Exo-AF750 exhibited 3-fold higher signal in tumor tissues compared to non-functionalized exosomes (p

25/04/2025

Exploring the apoptosis-inducing potential of Cannabis sativa and cannabidiol in pancreatic cancer in vitro

Pancreatic cancer is deemed one of the most aggressive types of cancer, with a high mortality rate and poor prognosis. It is ranked the 12th most prevalent cancer globally, with 510,992 new cases and 467,409 deaths reported in 2022. In South Africa, it is ranked the 9th most common cancer, with a mortality rate of approximately 84%. Pancreatic cancer is often diagnosed in advanced stages when the disease is too aggressive to manage, rendering the available treatments ineffective. Cannabis sativa (C. sativa) is a medicinal plant that has been used for centuries based on its health benefits; more recently, it has been explored for its anti-cancer properties. However, knowledge of the impact of C. sativa on pancreatic cancer is still limited. This study aimed to explore the apoptosis-inducing potential of C. sativa and cannabidiol (CBD) in pancreatic cancer cells. Crude C. sativa extracts were obtained by dissolving dried C. sativa leaves in absolute ethanol; CBD was isolated from the crude extract using column chromatography. The cytotoxic effects of the crude extract and CBD on pancreatic cancer cells (Mia-PaCa2) and normal lung cells (MRC-5) were determined using the AlamarBlue reagent. Apoptosis was investigated by analysing morphological changes using light microscopy. This was followed by an evaluation of phosphatidylserine externalisation and nuclear condensation, hallmarks of apoptosis, using Annexin V staining and Hoechst staining, respectively. Furthermore, levels of ATP and activation of caspase-3 and -7, key executioners of apoptosis, were measured. DNA fragmentation was analysed using agarose gel electrophoresis. Lastly, gene expression of apoptosis-related genes was assessed using quantitative polymerase chain reaction (qPCR). The results show that the crude and CBD induced substantial cytotoxic effects on Mia-PaCa2 cells but not MRC-5. C. sativa and CBD caused significant morphological changes in Mia-PaCa2 cells, including cell detachment and rounding, phosphatidylserine externalisation, and nuclear condensation as seen through light microscopy, Annexin V staining, and Hoechst staining. Furthermore, the crude and CBD extracts reduced ATP levels and activated caspase-3 and -7, with more pronounced effects in the crude extract. DNA fragmentation was also more distinct in cells treated with the crude extract, validating that crude C. sativa and CBD induced apoptosis in Mia-PaCa2. This was further supported by the upregulation of BAX, BAK-1, and p53 and the downregulation of BCL-2, indicating the activation of the intrinsic apoptotic pathway. In conclusion, both crude and CBD have apoptosis-inducing potential in pancreatic cancer cells.

01/04/2025

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.

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. Addition...

24/02/2025

In this study, Lumbriculus variegatus are exposed to CBD, and its metabolites 7-hydroxy-cannabidiol (7-OH-CBD) and 7-carboxy-cannabidiol (7-COOH-CBD). In this study, toxicity, tactile stimulation to elicit stereotypical behaviours and locomotor activity are measured after 24-hour exposure of L. variegatus to CBD and its metabolites. We also describe the impacts on dorsal blood vessel pulsation and oxygen consumption after 24-hour exposure to CBD and 7-OH-CBD, and the effects on regenerative capacity and total energy reserves after 72 hours of exposure to CBD and 7-OH-CBD. We observe CBD, 7-OH-CBD and 7-COOH-CBD display toxicity in 50% of test populations at 14.12 µM, 11.29 µM and 15.36 µM, respectively. 24-hour exposure to CBD decreases tactile stimulation response to elicit body reversal at ≥ 2.5 µM and helical swimming at ≥ 0.5 µM and reduces locomotor activity. L. variegatus oxygen consumption was not affected by CBD but ≥2.5 µM significantly reduced dorsal blood vessel pulse rate. We observe that exposure to 7-OH-CBD does not affect the regenerative capacity of L. variegatus while CBD is shown to reduce regeneration. Exposure to CBD also results in a significant decrease in carbohydrates, increased lipid, and no effect on protein levels in L. variegatus. We determined that CBD can reduce L. variegatus behaviours, decrease pulse rates and regenerative capacity, and disrupt energy reserves. Our findings show that CBD is toxic to this common aquatic organism and the increased availability and use of CBD, and related substances, warrants further study of their environmental impact.

Abstract. Cannabidiol (CBD) is a major non-psychoactive cannabinoid that has been detected in environmental samples, but the ecotoxicological effects remai

24/02/2025

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.

Commonly known as ma*****na or h**p, 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...

05/02/2025

In conclusion, our study investigated the safety and potential bioactivities of CBD at the cellular level and explored its potential mechanisms for cosmeceutical application. Regarding CBD’s safety in the short term and long term, our results indicate that CBD at low concentrations is safe to be used on the skin and promotes the growth of both keratinocytes and fibroblasts. In terms of functional CBD bioactivity studies, we found that CBD showed promising antioxidant activity and anti-aging activity in fibroblasts and keratinocytes. In terms of involved molecular mechanisms, we found that CBD promoted TGF-β1, VEGF, and NF-κB expression in fibroblasts, which are related to proliferative and wound healing processes. In addition, CBD can increase collagen production in fibroblasts through CO1A2 expression. Overall, we suggest that CBD exhibits many potential characteristics that can be used to develop topical cosmeceutical products, such as sun protection products, hair care products, or wound healing products. For future studies, we recommend using 3D skin models, ex vivo skin, or in vivo models to better understand skin processes after CBD application and to confirm the safety and activities of CBD over a longer period of time.

Backgrounds: Cannabidiol (CBD) has been used for the development of extensive cosmeceutical commercial products. However, the safety and unclear bioactivity of CBD are still concerns and need to be examined to assess the impact of CBD on skin cells through cosmeceutical applications, particularly it...

03/02/2025

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

Background: Gardnerella va**nalis is a natural inhabitant of the va**na, but when an imbalance occurs in the va**nal 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....

27/01/2025

Recent cellular and rodent studies highlight that cannabidiol (CBD), the main non-intoxicating cannabinoid in cannabis, has multifaceted mechanisms of action in the brain, encompassing multiple molecular targets and resulting in a range of potential beneficial effects on brain function and behavior.
The promising preclinical findings, combined with preliminary clinical reports of CBD’s efficacy in patients with various psychiatric conditions, have encouraged recent randomized controlled trials to more thoroughly assess its therapeutic potential in psychiatric disorders, including substance-use disorder, anxiety, psychoses, and autism spectrum disorder.
While CBD is generally well tolerated and shows promise for treating neuropsychiatric conditions, current clinical evidence has limitations, requiring well-designed, properly powered controlled trials to address data gaps and optimize its benefits for patients with neuropsychiatric disorders.

Cannabidiol (CBD), the primary non-intoxicating compound in cannabis, is currently approved for treating rare, treatment-resistant seizures. Recent preclinical research suggests that CBD’s multifaceted mechanisms of action in the brain, which involve multiple molecular targets, underlie its neurop...

26/01/2025

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

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) allev...

25/01/2025

Cannabidiol as prophylactic treatment for intestinal ischaemia reperfusion injury in elderly rats

AbstractIntroduction. The deprivation of blood supply to an intestinal segment, followed by its subsequent restoration, triggers the condition known as int

08/01/2025

Cannabidiol Targets Colorectal Cancer Cells via Cannabinoid Receptor 2, Independent of Common Mutations

CBD is a well-known anti-inflammatory agent currently in the limelight for its broad therapeutic window and various pharmacologic effects. The cannabinoid receptor CB2 has previously been thought to be expressed only in the immune cells and therefore not targeted in treating CRC. Our study, using four different CRC cell lines with several common mutations, demonstrated that CBD acts on the CRC cells primarily through the CB2 receptor. This study also demonstrated that CBD could induce ER stress, promote apoptosis, and inhibit cell proliferation, migration, and invasion in a similar fashion in all CRC cells tested. These studies support the role of CBD in CRC treatment; however, further studies are required to identify the precise mechanisms of action of CBD in different CRC cell types and its clinical efficacy/applicability. This will require understanding the relationship of potency, IC50 to dose, and concomitant chemotherapy. Achieving therapeutic effects in human and in vivo models remains a significant challenge in CBD research due to its hydrophobic nature and low bioavailability. Therefore, the development of novel delivery methods would be required to achieve the targeted pharmacokinetic profile of CBD. Despite these challenges, this study provides a strong foundation for future research on CBD’s potential in the treatment of CRC.

Cannabidiol (CBD) is a non-neurotoxic, phytocannabinoid from cannabis with reported medicinal properties, including antiepileptic and anti-inflammatory activity. Several in vitro and in vivo studies have shown that CBD has antitumor potential against colorectal cancer (CRC), the third deadliest canc...

03/01/2025

Twenty controls and 29 patients with CKD completed the study. The area under the curve (AUC) for THC (median (IQR)) was 2.76 (1.77-3.48), 4.16 (3.35-5.28), and 4.31 (3.16-5.42) h*ng/ml for controls, eGFR ≤30 & >15, and eGFR ≤15, respectively, with significant differences between patients with CKD and controls. AUC for CBD and metabolites, and other pharmacokinetic parameters such as maximum concentration (Cmax) and excretion of metabolites in urine were also significantly different between patients with CKD and controls. After 1.5 hours numeric rating scores (NRS) for dizziness were significantly higher for each CKD group compared to controls (mean NRS-scores: 0.7 and 1.5 vs 0.1).
Conclusion
Total exposure to THC, CBD, and metabolites was higher in patients with CKD stages 4 and 5 compared to controls, and side effects may be more pronounced; however, the inter-subject variability was high. If cannabis products are administered to patients with severe CKD, caution is needed.