Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment

pharmaceutics-logo“Cannabidiol (CBD), a primary bioactive phytocannabinoid extracted from hemp, is reported to possess potent anti-tumorigenic activity in multiple cancers.

However, the effects of CBD on bladder cancer (BC) and the underlying molecular mechanisms are rarely reported.

Here, several experiments proved that CBD promoted BC cells (T24, 5637, and UM-UC-3) death.

In summary, this work demonstrates that CBD may become a novel reliable anticancer drug and the developed intravesical adhesion system is expected to turn into a potential means of BC chemotherapy drug delivery.

We believe that our study makes a significant contribution to the field because these results can be developed as a promising strategy for a safer and more efficient anticancer therapy.”

https://www.mdpi.com/1999-4923/13/9/1415/htm

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A Novel Mechanism of Cannabidiol in Suppressing Hepatocellular Carcinoma by Inducing GSDME Dependent Pyroptosis

Frontiers in Cell and Developmental Biology - Institut de Myologie“Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been demonstrated to exhibit promising anti-tumor properties in multiple cancer types. However, the effects of CBD on hepatocellular carcinoma (HCC) cells remain unknown. We have shown that CBD effectively suppresses HCC cell growth in vivo and in vitro, and induced HCC cell pyroptosis in a caspase-3/GSDME-dependent manner. We further demonstrated that accumulation of integrative stress response (ISR) and mitochondrial stress may contribute to the initiation of pyroptotic signaling by CBD. Simultaneously, CBD can repress aerobic glycolysis through modulation of the ATF4-IGFBP1-Akt axis, due to the depletion of ATP and crucial intermediate metabolites. Collectively, these observations indicate that CBD could be considered as a potential compound for HCC therapy.”

https://pubmed.ncbi.nlm.nih.gov/34350183/

“Hepatocellular carcinoma (HCC) is an extremely malignant cancer, accounting for almost 95% of primary liver cancer cases. Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been shown to have anti-tumor activity and to be a potential compound for tumor therapy. Previous studies have demonstrated that CBD treatment could effectively induce cell apoptosis in tumor cells. In this study, we have shown that CBD can effectively suppress HCC cell growth both in vitro and in vivo, which was similar to the anti-tumor activity of CBD observed in other cancer types. In summary, a mechanistic model of CBD anti-tumor activity in HCC cell pyroptosis and growth was demonstrated. All the observations described herein reveal a novel mechanism of the anti-tumor activity of CBD in HCC cells, suggesting that CBD could be considered as a promising compound for HCC therapy.”

https://www.frontiersin.org/articles/10.3389/fcell.2021.697832/full

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Combination therapy with cannabidiol and chemotherapeutics in canine urothelial carcinoma cells

“Background: Canine urothelial carcinoma is the most common form of canine bladder cancer. Treatment with chemotherapy has variable response rates leading to most dogs succumbing to their disease within a year. Cannabidiol is an emerging treatment within the field of oncology. In reported in vivo studies, cannabidiol has induced apoptosis, reduced cell migration, and acted as a chemotherapy sensitizer in various human tumor types. The aim of this study was to characterize the effects of cannabidiol on canine urothelial carcinoma cell viability and apoptosis as both a single agent and in combination with chemotherapy in vitro.

Results: Cannabidiol reduced cell viability and induced apoptosis in canine urothelial cells as determined by crystal violet viability assay and annexin V/propidium iodide flow cytometry. Furthermore, combinations of cannabidiol with mitoxantrone and vinblastine chemotherapy yielded significantly reduced cell viability and increased apoptosis compared to single agent treatment alone. The drug interactions were deemed synergistic based on combination index calculations. Conversely, the combination of cannabidiol and carboplatin did not result in decreased cell viability and increased apoptosis compared to single agent treatment. Combination index calculations suggested an antagonistic interaction between these drugs. Finally, the combination of the non-steroidal anti-inflammatory drug piroxicam with cannabidiol did not significantly affect cell viability, although, some cell lines demonstrated decreased cell viability when mitoxantrone was combined with piroxicam.

Conclusions: Cannabidiol showed promising results as a single agent or in combination with mitoxantrone and vinblastine for treatment of canine urothelial carcinoma cells. Further studies are justified to investigate whether these results are translatable in vivo.”

https://pubmed.ncbi.nlm.nih.gov/34352013/

“Cannabidiol (CBD) is a phytocannabinoid derived from the Cannabis sativa plant with well-documented analgesic, anti-inflammatory, and anxiolytic effects. This study determined that CBD treatment reduced viability and induced cell death in canine urothelial carcinoma cells in vitro. Taken together, these results suggest that CBD may be a potential treatment for use in combination with chemotherapeutic agents to improve canine UC carcinoma response rates and survival.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255591

 

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Cannabis Improves Stuttering: Case Report and Interview with the Patient

View details for Cannabis and Cannabinoid Research cover image“Introduction: Speech dysfluency, often referred to as stuttering, is a frequent speech disorder encountered in about 5% of children. Although in the majority of people affected, symptoms improve in adulthood, in some patients, stuttering persists and significantly impairs everyday functioning and quality of life. Treatment for stuttering includes speech therapy, cognitive behavioral therapy, and relaxation techniques. However, a substantial number of patients do not benefit sufficiently from these treatment strategies or are even treatment resistant. 

Methods: We present the case of a 20-year-old male with treatment-resistant stuttering, who markedly improved after treatment with medicinal cannabis. 

Results: Besides improved speech fluency as assessed by several phoniatric tests, we observed remission of (social) anxiety, improved mood, and reduced stress, resulting in an overall improvement of quality of life after cannabis therapy. The patient, in addition, reported improved attention, concentration, and sleep, increased self-confidence, and better social life. No side effects occurred. Over a time period of more than a year, treatment was equally effective. In an interview, the patient describes his personal view and the influence of cannabis-based treatment on his life. 

Conclusions: Medicinal cannabis could be effective in treatment of refractory stuttering, but these preliminary data have to be confirmed in controlled studies.”

https://pubmed.ncbi.nlm.nih.gov/34314602/

https://www.liebertpub.com/doi/10.1089/can.2021.0060

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Use and caregiver-reported efficacy of medical cannabis in children and adolescents in Switzerland

SpringerLink“Evidence on the use and efficacy of medical cannabis for children is limited. We examined clinical and epidemiological characteristics of medical cannabis treatment and caregiver-reported effects in children and adolescents in Switzerland.

We collected clinical data from children and adolescents (< 18 years) who received Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of the two between 2008 and 2019 in Switzerland. Out of 205 contacted families, 90 agreed to participate. The median age at the first prescription was 11.5 years (interquartile range (IQR) 6-16), and 32 patients were female (36%). Fifty-one (57%) patients received CBD only and 39 (43%) THC. Patients were more likely to receive THC therapy if one of the following symptoms or signs were present: spasticity, pain, lack of weight gain, vomiting, or nausea, whereas seizures were the dominant indication for CBD therapy.

Improvements were reported in 59 (66%) study participants.

The largest treatment effects were reported for pain, spasticity, and frequency of seizures in participants treated with THC, and for those treated with pure CBD, the frequency of seizures. However, 43% of caregivers reported treatment interruptions, mainly because of lack of improvement (56%), side effects (46%), the need for a gastric tube (44%), and cost considerations (23%).

Conclusions: The effects of medical cannabis in children and adolescents with chronic conditions are unknown except for rare seizure disorders, but the caregiver-reported data analysed here may justify trials of medical cannabis with standardized concentrations of THC or CBD to assess its efficacy in the young.

What is Known: • The use of medical cannabis (THC and CBD) to treat a variety of diseases among children and adolescents is increasing. • In contrast to adults, there is no evidence to support the use of medical cannabis to treat chronic pain and spasticity in children, but substantial evidence to support the use of CBD in children with rare seizure disorders.

What is New: • This study provides important insights into prescription practices, dosages, and treatment outcomes in children and adolescents using medical cannabis data from a real-life setting.

• The effects of medical cannabis in children and adolescents with chronic conditions shown in our study support trials of medical cannabis for chronic conditions.”

https://pubmed.ncbi.nlm.nih.gov/34309706/

“For two thirds of participants treated with standardized THC or CBD preparations, the caregiver reported an improvement in their condition and well-being. Medical cannabis could be a promising and useful therapy for children and adolescents with neurological conditions.”

https://link.springer.com/article/10.1007%2Fs00431-021-04202-z

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Cannabinoids and their derivatives in struggle against melanoma

SpringerLink“Melanoma is one of the most aggressive malignances in human. Recently developed therapies improved overall survival rate, however, the treatment of melanoma still remains a challenging issue.

This review attempts to summarize recent advances in studies on cannabinoids used in the setting of melanoma treatment.

Conclusions after analysis of available data suggest that cannabinoids limit number of metastasis, and reduce growth of melanoma. The findings indicate that cannabinoids induce apoptosis, necrosis, autophagy, cell cycle arrest and exert significant interactions with tumor microenvironment.

Cannabinoids should be rather considered as a part of multi-targeted anti-tumor therapy instead of being standalone agent. Moreover, cannabinoids are likely to improve quality of life in patients with cancer, due to different supportive effects, like analgesia and/or anti-emetic effects.

In this review, it was pointed out that cannabinoids may be potentially useful in the melanoma therapy. Nevertheless, due to limited amount of data, great variety of cannabinoids available and lack of clinical trials, further studies are required to determine an exact role of cannabinoids in the treatment of melanoma.”

https://pubmed.ncbi.nlm.nih.gov/34264513/

“The endocannabinoid system is dysregulated in numerous pathological conditions, including malignancies. Recently, cannabinoids have received increasing amount of interest in the setting of treatment of various cancers.  Cannabinoids seem to be promising agents in the setting of melanoma treatment. In the case of melanoma, most important actions of cannabinoids described so far are decrease of cells viability by increase of apoptosis, necrosis and cell cycle arrest. Moreover, cannabinoids slow down disease progress by reduction of metastasis and tumor vascularization. Due to large variety of cannabinoids, there are many potential derivatives, which may be found useful in the therapy of melanoma.”

https://link.springer.com/article/10.1007%2Fs43440-021-00308-1

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Effects of tetrahydrocannabinols on human oral cancer cell proliferation, apoptosis, autophagy, oxidative stress, and DNA damage

Archives of Oral Biology“Cannabinoids, including delta-8- and delta-9-tetrahydrocannabinol (THC) have a palliative care impact and may therefore be beneficial against cancer.

The aim of this study was to investigate the effect of Δ9-THC and Δ8-THC on oral cancer cell behaviors.

Results: Both cannabinoids were found to decrease cell viability/proliferation by blocking the cell cycle progression from the S to the G2/M phase and enhancing their apoptosis and autophagy. Δ9-THC and Δ8-THC also suppressed the migration/invasion by inhibiting epithelial-mesenchymal transition markers, such as E-cadherin, in addition to decreasing reactive oxygen species (ROS) production and increasing glutathione (GSH) and the expression of mtMP. Δ9-THC and Δ8-THC also downregulated cyclin D1, p53, NOXA, PUMAα, and DRAM expressions but increased p21 and H2AX expression.

Conclusion: We demonstrated that cannabinoids (Δ9-THC and Δ8-THC) were able to decrease oral cancer cell growth through various mechanisms, including apoptosis, autophagy, and oxidative stress. These results suggest a potential use of these molecules as a therapy against oral cancer.”

https://pubmed.ncbi.nlm.nih.gov/34146926/

Cannabinoids (Δ9-THC and Δ8-THC) decrease oral cancer cell viability/ proliferation.”

https://www.sciencedirect.com/science/article/abs/pii/S0003996921001631?via%3Dihub

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Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB 2 receptor in the arthritis progression and pain: an updated review

“Over the last several decades, the percentage of patients suffering from different forms of arthritis has increased due to the ageing population and the increasing risk of civilization diseases, e.g. obesity, which contributes to arthritis development. Osteoarthritis and rheumatoid arthritis are estimated to affect 50-60% of people over 65 years old and cause serious health and economic problems. Currently, therapeutic strategies are limited and focus mainly on pain attenuation and maintaining joint functionality. First-line therapies are nonsteroidal anti-inflammatory drugs; in more advanced stages, stronger analgesics, such as opioids, are required, and in the most severe cases, joint arthroplasty is the only option to ensure joint mobility.

Cannabinoids, both endocannabinoids and synthetic cannabinoid receptor (CB) agonists, are novel therapeutic options for the treatment of arthritis-associated pain. CB1 receptors are mainly located in the nervous system; thus, CB1 agonists induce many side effects, which limit their therapeutic efficacy. On the other hand, CB2 receptors are mainly located in the periphery on immune cells, and CB2 modulators exert analgesic and anti-inflammatory effects in vitro and in vivo. In the current review, novel research on the cannabinoid-mediated analgesic effect on arthritis is presented, with particular emphasis on the role of the CB2 receptor in arthritis-related pain and the suppression of inflammation.”

https://pubmed.ncbi.nlm.nih.gov/34050525/

“Cannabinoids not only alleviate joint hyperalgesia but also may help to prevent joint damage, chronic pain development and disease progression.”

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Anticancer property of Hemp Bioactive Peptides in Hep3B liver cancer cells through Akt/GSK3β/β-catenin signaling pathway

Food Science & Nutrition“Foodborne protein hydrolysates exhibit biological activity that may be therapeutic in a number of human disease settings. Hemp peptides (HP) generated by controlled hydrolysis of hemp proteins have a number of health benefits and are of pharmaceutical value. In the present study, we produce small molecular weight HP from hemp seed and investigate its anticancer properties in Hep3B human liver cancer cells. We demonstrate that HP treatment increased apoptosis, reduced cell viability, and reduced cell migration in Hep3B human liver cancer cells without affecting the normal liver cell line L02. We correlate these phenotypes with increased cellular ROS levels, upregulation of cleaved caspase 3 and Bad, and downregulation of antiapoptotic Bcl-2. HP treatment led to increased Akt and GSK-3β phosphorylation, with subsequent downregulation of β-catenin, suggesting β-catenin signaling modulation as a critical mechanism by which HP exhibits anticancer properties. Our findings suggest HP are of potential therapeutic interest for liver cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/33841802/

“Together, these data demonstrate that HP from hemp seed protein hydrolysates display anticancer properties. Increase in cellular ROS levels represents a crucial mechanism by which HP exerts its antiproliferative and proapoptotic activity and HP treatment modulates activity of the Akt/GSK/β‐catenin signaling pathway. Our findings suggest that HP represents a promising anticancer therapy in the context of liver cancer; further investigation of the anticancer properties of foodborne protein hydrolysates is warranted.”

https://onlinelibrary.wiley.com/doi/10.1002/fsn3.1976

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Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies

biomolecules-logo“In recent years, evidence has accumulated that cannabinoids-especially the non-psychoactive compound, cannabidiol (CBD)-possess promising medical and pharmacological activities that might qualify them as potential anti-tumor drugs. This review is based on multiple studies summarizing different mechanisms for how CBD can target tumor cells including cannabinoid receptors or other constituents of the endocannabinoid system, and their complex activation of biological systems that results in the inhibition of tumor growth. CBD also participates in anti-inflammatory activities which are related to tumor progression, as demonstrated in preclinical models. Although the numbers of clinical trials and tested tumor entities are limited, there is clear evidence that CBD has anti-tumor efficacy and is well tolerated in human cancer patients. In summary, it appears that CBD has potential as a neoadjuvant and/or adjuvant drug in therapy for cancer.”

https://pubmed.ncbi.nlm.nih.gov/33921049/

“It has been shown that CBD, either alone or in combination with other therapies, has the potential to act as a novel anti-tumor, anti-inflammatory and anti-pain drug in preclinical studies and first clinical trials. A few clinical trials have now demonstrated beneficial pharmacokinetic and pharmacodynamic characteristics of the drug, and some anti-tumor activities at well-tolerated doses. Therefore, it can be assumed that CBD might be considered a potential candidate for neoadjuvant and/or adjuvant interventions in oncology.”

https://www.mdpi.com/2218-273X/11/4/582/htm

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