Author Archives: David Worrell

The Effects of Cannabis sativa L. Extract on Oxidative Stress Markers In Vivo

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life-logo“In recent decades, a lot of attention has been paid to Cannabis sativa L. due to its useful applications, including in fibers, oil, food for humans and animals, and therapeutics.

The present study aimed to determine antioxidant activity of cannabinoids in Cannabis sativa L. in vivo, evaluating the possible antioxidative effect of Cannabis sativa L. extract (CE) on malondialdehyde (MDA) and glutathione (GSH) concentrations as well as on catalase (CAT) activity in BALB/c mice.

The findings in vivo indicate that Cannabis sativa L. is a good source of natural antioxidants and can be used in the management of oxidative stress.”

https://pubmed.ncbi.nlm.nih.gov/34357019/

https://www.mdpi.com/2075-1729/11/7/647

Association Between Smoking Cannabis and Quitting Cigarettes in a Large American Cancer Society Cohort

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Cancer Epidemiology, Biomarkers & Prevention“Background: Cannabis use is increasing, including among smokers, an at-risk population for cancer. Research is equivocal on whether using cannabis inhibits quitting cigarettes. The current longitudinal study investigated associations between smoking cannabis and subsequently quitting cigarettes.

Results: Adjusted cigarette quitting rates at follow-up did not differ significantly by baseline cannabis smoking status [never 36.2%, 95% confidence interval (CI), 34.5%-37.8%; former 34.1%, CI, 31.4%-37.0%; recent 33.6%, CI, 30.1%-37.3%], nor by frequency of cannabis smoking (low 31.4%, CI, 25.6%-37.3%; moderate 36.7%, CI, 30.7%-42.3%; high 34.4%, CI, 28.3%-40.2%) among recent baseline cannabis smokers. In cross-sectional analyses conducted at follow-up the proportion of cigarette smokers intending to quit smoking cigarettes in the next 30 days did not differ by cannabis smoking status (p=0.83).

Conclusions: Results do not support the hypothesis that cannabis smoking inhibits quitting cigarette smoking among adults.”

https://pubmed.ncbi.nlm.nih.gov/34348959/

“Results do not support the hypothesis that cannabis smoking inhibits quitting cigarette smoking among adults.” https://cebp.aacrjournals.org/content/early/2021/08/04/1055-9965.EPI-20-1810

Risk and benefit of cannabis prescription for chronic non-cancer pain

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Taylor and Francis Online“Objectives: We investigated whether cannabis usage was associated with reduced opioid usage, and the rates of opioid and cannabis use disorders among chronic pain patients who had been prescribed medical cannabis.

Results: Of the 100 participants aged 18-70 years (compliance 67% (aged >40) and 33% (aged ≤ 40y)), 76 ever used opioids. Of them, 93% decreased or stopped opioids following cannabis initiation. Ten patients (10%), 17.4% of the ≤40 y age group, met the criteria for cannabis use disorder. Compared to those who did not meet the criteria, their lifetime depression was higher (80% vs. 43.2%, respectively, P=.042), and they were less educated (12.2 ± 0.6y vs. 13.5 ± 2.1y, p = 0.05).

Conclusions: Cannabis usage was associated with reduced opioid usage. The prevalence of cannabis use disorder was high among the younger participants who also had a lower study compliance rate, suggesting the higher actual prevalence of cannabis use disorder. While medical cannabis may help reduce opioid use in chronic non-cancer pain patients, younger age, depression, and other risk factors should be carefully evaluated before cannabis is prescribed.”

https://pubmed.ncbi.nlm.nih.gov/34338621/

“Cannabis usage was associated with reduced opioid usage.”

https://www.tandfonline.com/doi/abs/10.1080/10550887.2021.1956673?journalCode=wjad20

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

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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

Combination therapy with cannabidiol and chemotherapeutics in canine urothelial carcinoma cells

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“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

 

The Pharmacological Effects of Plant-Derived versus Synthetic Cannabidiol in Human Cell Lines

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/WebMaterial/ShowPic/1344608“Introduction: Cannabidiol (CBD) can be isolated from Cannabis sativa L. or synthetically produced. The aim of this study was to compare the in vitro effects of purified natural and synthetic CBD to establish any pharmacological differences or superiority between sources. 

Conclusion: Our results suggest that there is no pharmacological difference in vitro in the antiproliferative, anti-inflammatory, or permeability effects of purified natural versus synthetic CBD. The purity and reliability of CBD samples, as well as the ultimate pharmaceutical preparation, should all be considered above the starting source of CBD in the development of new CBD medicines.

This study demonstrates for the first time that the anticancer, neuroprotective, and intestinal barrier protective properties of purified CBD are similar regardless of the source from which CBD is derived. From a pharmacological perspective, where a molecular target is implicated (i.e., 5HT1A in stroke and CB1 in gut permeability), the effects of CBD were similar. This suggests that any beneficial effects that could be achieved in a clinical setting for purified CBD are likely to be similar at a pharmacodynamic level.”

https://www.karger.com/Article/FullText/517120

“Study finds no in-vitro pharmacological difference in the antiproliferative, anti-inflammatory, or permeability effects of purified natural versus synthetic CBD”

https://www.streetinsider.com/Globe+Newswire/Artelo+Biosciences+Announces+Publication+of+Study+Results+Comparing+the+Pharmacological+Effects+of+Plant-Derived+Versus+Synthetic+Cannabidiol+in+Human+Cell+Lines/18767297.html

An overview on plants cannabinoids endorsed with cardiovascular effects

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Biomedicine & Pharmacotherapy“Nowadays cardiovascular diseases (CVDs) are the major causes for the reduction of the quality of life.

The endocannabinoid system is an attractive therapeutic target for the treatment of cardiovascular disorders due to its involvement in vasomotor control, cardiac contractility, blood pressure and vascular inflammation. Alteration in cannabinoid signalling can be often related to cardiotoxicity, circulatory shock, hypertension, and atherosclerosis.

Plants have been the major sources of medicines until modern eras in which researchers are experiencing a rediscovery of natural compounds as novel therapeutics.

One of the most versatile plant is Cannabis sativa L., containing phytocannabinoids that may play a role in the treatment of CVDs.

The aim of this review is to collect and investigate several less studied plants rich in cannabinoid-like active compounds able to interact with cannabinoid system; these plants may play a pivotal role in the treatment of disorders related to the cardiovascular system.”

https://pubmed.ncbi.nlm.nih.gov/34332376/

“Cannabis sativa L. is the most investigated source of phytocannabinoids. Other plants are a rich source of cannabinoid-like compounds. Cannabinoid-like compounds may interact with cannabinoid system. Most of them may exhibit a protective role on cardiovascular system.” 

https://www.sciencedirect.com/science/article/pii/S0753332221007459?via%3Dihub

 

Cannabidiol Loaded Extracellular Vesicles Sensitize Triple-Negative Breast Cancer to Doxorubicin in both in-vitro and in vivo Models Running Title: Formulation and anti-cancer potential of CBD loaded hUCMSC-derived Extracellular Vesicles in TNBC

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International Journal of Pharmaceutics“Extracellular Vesicles (EVs) were isolated from human umbilical cord mesenchymal stem cells (hUCMSCs) and were further encapsulated with cannabidiol (CBD) through sonication method (CBD EVs). CBD EVs displayed an average particle size of 114.1±1.02 nm, zeta potential of -30.26±0.12 mV, entrapment efficiency of 92.3±2.21% and stability for several months at 4 °C. CBD release from the EVs was observed as 50.74±2.44% and 53.99±1.4% at pH 6.8 and pH 7.4, respectively after 48 h. Ourin-vitrostudies demonstrated that CBD either alone or in EVs form significantly sensitized MDA-MB-231 cells to doxorubicin (DOX) (*P<0.05). Flow cytometry and migration studies revealed that CBD EVs either alone or in combination with DOX induced G1 phase cell cycle arrest and decreased migration of MDA-MB-231 cells, respectively. CBD EVs and DOX combination significantly reduced tumor burden (***P<0.001) in MDA-MB-231 xenograft tumor model. Western blotting and immunocytochemical analysis demonstrated that CBD EVs and DOX combination decreased the expression of proteins involved in inflammation, metastasis and increased the expression of proteins involved in apoptosis. CBD EVs and DOX combination will have profound clinical significance in not only decreasing the side effects but also increasing the therapeutic efficacy of DOX in TNBC.”

https://pubmed.ncbi.nlm.nih.gov/34324983/

https://www.sciencedirect.com/science/article/abs/pii/S0378517321007493?via%3Dihub

KY Hemp-induced Modulation of Ovarian Cancer Cell Metastasis

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“Our laboratory is interested in searching for a new plant-based therapeutics to treat ovarian cancer.

We are interested in studying anti-cancer effects of KY grown hemp as a potential candidate drug.

Marijuana and hemp belong to the same genus and species. However, they are different in cannabidiol (CBD) and tetrahydrocannabinol (THC) content.

Both CBD and THC are therapeutically beneficial. Hemp is harmless and non-addictive.

Major objective of this study is to investigate whether KY hemp extract can modulate the metastasis of ovarian cancer.

Based on the data here we conclude that KY hemp has significant anti-metastatic properties against ovarian cancer.”

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2018.32.1_supplement.667.7

Searching for a New Anti-Cancer Drug: Investigation of KY Hemp-Induced Apoptosis in Ovarian Cancer Cells

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“Marijuana (cannabis sativa) is a schedule 1 drug that has been recently approved by some states in the US for its therapeutic benefit.

Although there are a few reports about its anti-cancer potential, currently it has been used mainly for treatment-resistant epilepsy and to alleviate pain.

Hemp, which belongs to the same genus and species as marijuana, shows similar therapeutic benefits without addictive potential.

Our laboratory is interested in examining for unconventional therapies for ovarian cancer.

The main objective of the current study is to investigate hemp-induced modulation of A2780 ovarian cancer cell apoptosis.

Based on the data here we conclude that KY hemp has anti-cancer potential against ovarian cancer.”

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2018.32.1_supplement.616.1