Tag Archives: cannabinoid

Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization

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molecules-logo“Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer.

An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR).

The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity.

Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.”

https://pubmed.ncbi.nlm.nih.gov/33477303/

https://www.mdpi.com/1420-3049/26/2/465

Effects of cannabidiol (CBD) on the inhibition of melanoma cells in vitro

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Journal of Immunoassay and Immunochemistry: Vol 41, No 5 “Cannabidiol (CBD) is one of the most popular emerging plant extracts that is being investigated for its wide range of potential health benefits.

This experiment tests how B16 mice melanoma cells, are affected by four different concentrations (0.2 mg/mL, 0.04 mg/mL, 0.008 mg/mL and 0.0016 mg/mL) of 99% CBD oil.

The results of this experiment demonstrate that CBD significantly inhibited melanoma cell growth in-vitro at 0.2 mg/mL and 0.04 mg/mL.

This shows that CBD has the potential to inhibit melanoma cell growth in vertebrates, namely mice.”

https://pubmed.ncbi.nlm.nih.gov/33428525/

 

A Survey on the Effect That Medical Cannabis Has on Prescription Opioid Medication Usage for the Treatment of Chronic Pain at Three Medical Cannabis Practice Sites

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Cureus | LinkedIn“Objective: The opioid epidemic continues to claim thousands of lives every year without an effective strategy useful in mitigating mortality. The use of medical cannabis has been proposed as a potential strategy to decrease opioid usage. The objective of this study was to determine how the use of medical cannabis affects prescribed opioid usage in chronic pain patients.

Methods: We conducted an online convenience sample survey of patients from three medical cannabis practice sites who had reported using opioids. A total of 1181 patients responded, 656 were excluded for not using medical cannabis in combination with opioid use or not meeting the definition of chronic pain, leaving 525 patients who had used prescription opioid medications continuously for at least three months to treat chronic pain and were using medical cannabis in combination with their prescribed opioid use.

Results: Overall, 40.4% (n=204) reported that they stopped all opioids, 45.2% (n=228) reported some decrease in their opioid usage, 13.3% (n=67) reported no change in opioid usage, and 1.1% (n=6) reported an increase in opioid usage. The majority (65.3%, n=299) reported that they sustained the opioid change for over a year. Almost half (48.2%, n=241) reported a 40-100% decrease in pain while 8.6% (n=43) had no change in pain and 2.6% (n=13) had worsening pain. The majority reported improved ability to function (80.0%, n=420) and improved quality of life (87.0%, n=457) with medical cannabis. The majority (62.8%, n=323) did not want to take opioids in the future. While the change in pain level was not affected by age and gender, the younger age group had improved ability to function compared with the middle and older age groups.

Conclusions: Patients in this study reported that cannabis was a useful adjunct and substitute for prescription opioids in treating their chronic pain and had the added benefit of improving the ability to function and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/33409086/

“Our results show a remarkable percentage of patients both reporting complete cessation of opioids and decreasing opioid usage by the addition of medical cannabis, with results lasting for over a year for the majority. Additional benefits of medical cannabis included improved ability to function and improved quality of life, especially for the younger age group. We believe our results lend further support that medical cannabis provided in a standardized protocol can lead to decreased pain and opioid usage, improved function, and quality of life measures, and even complete cessation of opioids in patients with chronic pain treated by opioids.”

https://www.cureus.com/articles/41928-a-survey-on-the-effect-that-medical-cannabis-has-on-prescription-opioid-medication-usage-for-the-treatment-of-chronic-pain-at-three-medical-cannabis-practice-sites

Association Between Marijuana Use and Cardiovascular Disease in US Adults

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Cureus | LinkedIn “This study aims to add evidence regarding the impact marijuana use has on the prevalence of cardiovascular disease.

Our study lends support to the notion that marijuana use does not have an association with cardiovascular disease.

Although previous literature has shown that marijuana use has a negative impact on cardiovascular health, our study suggests that users and non-users of marijuana did not have an association with the prevalence of cardiovascular disease.”

https://pubmed.ncbi.nlm.nih.gov/33409101/

“The primary aim of this study was to evaluate the relationship between marijuana use and cardiovascular disease. After controlling for several confounding variables, we found that there was a decrease in the prevalence of cardiovascular events with marijuana use. In conclusion, our study found that there is no link to marijuana use and an increase in cardiovascular disease. Furthermore, there may be a link between marijuana use and lowered risk of cardiovascular disease”

https://www.cureus.com/articles/45502-association-between-marijuana-use-and-cardiovascular-disease-in-us-adults

Cannabis use is associated with reduced risk of exposure to fentanyl among people on opioid agonist therapy during a community-wide overdose crisis

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Drug and Alcohol Dependence “Background: The ongoing opioid overdose crisis is driven largely by exposure to illicitly-manufactured fentanyl. Preliminary observational and experimental research suggests that cannabis could potentially play a role in reducing use of prescription opioids among individuals with chronic pain. However, there is limited data on the effects of cannabis on illicit opioid consumption, particularly fentanyl, especially among individuals on opioid agonist therapy (OAT). We sought to assess the longitudinal association between cannabis use and exposure to fentanyl among people on OAT.

Results: Among the 819 participants on OAT who contributed 1989 observations over the study period, fentanyl exposure was common. At the baseline interview, fentanyl was detected in a majority of participants (431, 53 %), with lower prevalence among individuals with urine drug tests positive for tetrahydrocannabinol (47 vs. 56 %, p = 0.028). Over all study interviews, cannabis use was independently associated with reduced likelihood of being recently exposed to fentanyl (Adjusted Prevalence Ratio = 0.91, 95 % Confidence Interval: 0.83 – 0.99).

Conclusions: Participants on OAT using cannabis had significantly lower risk of being exposed to fentanyl. Our findings reinforce the need for experimental trials to investigate the potential benefits and risks of controlled cannabinoid administration for people on OAT.”

https://pubmed.ncbi.nlm.nih.gov/33342591/

“Opioid agonist therapies (OAT) are the primary treatments for opioid use disorder. Exposure to fentanyl is driving mortality risk in the overdose crisis. Among 819 participants on OAT, cannabis was negatively associated with fentanyl. Experimental trials are needed to evaluate cannabis use during OAT.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871620305858?via%3Dihub

“Cannabis could reduce fentanyl use, reduce overdose risk: study” https://www.bccsu.ca/blog/news-release/cannabis-could-reduce-fentanyl-use-reduce-overdose-risk-study/

“Cannabis could reduce fentanyl use, reduce overdose risk” https://www.med.ubc.ca/news/cannabis-could-reduce-fentanyl-use-reduce-overdose-risk/

(Endo)Cannabinoids and Gynaecological Cancers

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cancers-logo“Gynaecological cancers can be primary neoplasms, originating either from the reproductive tract or the products of conception, or secondary neoplasms, representative of metastatic disease. For some of these cancers, the exact causes are unknown; however, it is recognised that the precise aetiopathogeneses for most are multifactorial and include exogenous (such as diet) and endogenous factors (such as genetic predisposition), which mutually interact in a complex manner.

One factor that has been recognised to be involved in the pathogenesis and progression of gynaecological cancers is the endocannabinoid system (ECS). The ECS consists of endocannabinoids (bioactive lipids), their receptors, and metabolic enzymes responsible for their synthesis and degradation. In this review, the impact of plant-derived (Cannabis species) cannabinoids and endocannabinoids on gynaecological cancers will be discussed within the context of the complexity of the proteins that bind, transport, and metabolise these compounds in reproductive and other tissues. In particular, the potential of endocannabinoids, their receptors, and metabolic enzymes as biomarkers of specific cancers, such as those of the endometrium, will be addressed. Additionally, the therapeutic potential of targeting selected elements of the ECS as new action points for the development of innovative drugs will be presented.”

https://pubmed.ncbi.nlm.nih.gov/33375539/

“Cancers of the female reproductive system are common and are responsible for a large number of deaths in women. The exact reasons why some of these cancers occur are unknown. It is, however, known that for most of these cancers, several factors interact for them to happen. These interactions involve factors external and internal to the woman. An understanding of some of the internal factors involved in how these cancers arise will not only help drive preventive strategies, but will speed the development of new treatment approaches.

The endocannabinoid system is a family including chemicals (known as endocannabinoids) produced in the body that are similar to those derived from the cannabis plant. This system, which is widely distributed in the body, has been shown to be involved in various functions. Its disruption has been shown to lead to various diseases, one of which is cancer. In this review, we summarise current knowledge of this system, its various constituents, and how they are involved in reproductive events and their pathologies, especially cancers. Furthermore, we discuss the role of the endocannabinoid system in these cancers and how targeting it could lead to new approaches to diagnosis and treatment of cancers of the female reproductive system.”

https://www.mdpi.com/2072-6694/13/1/37

Phytocannabinoid Pharmacology: Medicinal Properties of Cannabis sativa Constituents Aside from the “Big Two”

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 Go to Volume 0, Issue 0“Plant-based therapies date back centuries. Cannabis sativa is one such plant that was used medicinally up until the early part of the 20th century.

Although rich in diverse and interesting phytochemicals, cannabis was largely ignored by the modern scientific community due to its designation as a schedule 1 narcotic and restrictions on access for research purposes. There was renewed interest in the early 1990s when the endocannabinoid system (ECS) was discovered, a complex network of signaling pathways responsible for physiological homeostasis. Two key components of the ECS, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), were identified as the molecular targets of the phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC).

Restrictions on access to cannabis have eased worldwide, leading to a resurgence in interest in the therapeutic potential of cannabis. Much of the focus has been on the two major constituents, Δ9-THC and cannabidiol (CBD). Cannabis contains over 140 phytocannabinoids, although only a handful have been tested for pharmacological activity. Many of these minor cannabinoids potently modulate receptors, ionotropic channels, and enzymes associated with the ECS and show therapeutic potential individually or synergistically with other phytocannabinoids.

The following review will focus on the pharmacological developments of the next generation of phytocannabinoid therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/33356248/

https://pubs.acs.org/doi/10.1021/acs.jnatprod.0c00965

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Phenolic Compounds Cannabidiol, Curcumin and Quercetin Cause Mitochondrial Dysfunction and Suppress Acute Lymphoblastic Leukemia Cells

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ijms-logo“Anticancer activity of different phenols is documented, but underlying mechanisms remain elusive. Recently, we have shown that cannabidiol kills the cells of acute lymphoblastic leukemia (ALL) by a direct interaction with mitochondria, with their consequent dysfunction.

In the present study, cytotoxic effects of several phenolic compounds against human the T-ALL cell line Jurkat were tested by means of resazurin-based metabolic assay. To unravel underlying mechanisms, mitochondrial membrane potential (∆Ψm) and [Ca2+]m measurements were undertaken, and reactive oxygen species generation and cell death were evaluated by flow cytometry.

Three out of eight tested phenolics, cannabidiol, curcumin and quercetin, which displayed a significant cytotoxic effect, also dissipated the ∆Ψm and induced a significant [Ca2+]m increase, whereas inefficient phenols did not.

Dissipation of the ∆Ψm by cannabidiol was prevented by cyclosporine A and reverted by Ru360, inhibitors of the permeation transition pore and mitochondrial Ca2+ uniporter, respectively. Ru360 prevented the phenol-induced [Ca2+]m rise, but neither cyclosporine A nor Ru360 affected the curcumin- and quercetin-induced ∆Ψm depolarization. Ru360 impeded the curcumin- and cannabidiol-induced cell death.

Thus, all three phenols exert their antileukemic activity via mitochondrial Ca2+ overload, whereas curcumin and quercetin suppress the metabolism of leukemic cells by direct mitochondrial uncoupling.”

https://pubmed.ncbi.nlm.nih.gov/33379175/

https://www.mdpi.com/1422-0067/22/1/204

Cannabinoid receptor activation on hematopoietic cells and enterocytes protects against colitis

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Oxford University Press“Cannabinoid receptor (CB) activation can attenuate inflammatory bowel disease (IBD) in experimental models and human cohorts. However, the role of the microbiome, metabolome, or the respective contributions of hematopoietic and non-hematopoietic cells in the anti-colitic effects of cannabinoids has yet to be determined.

Methods: Female C57BL/6 mice were treated with either cannabidiol (CBD), Δ 9-tetrahydrocannabinol (THC), a combination of CBD and THC or vehicle, in several models of chemically induced colitis. Clinical parameters of colitis were assessed by colonoscopy, histology, flow cytometry and detection of serum biomarkers; single-cell RNA sequencing and qRT-PCR were used to evaluate the effects of cannabinoids on enterocytes. Immune cell transfer from CB2 knockout mice was used to evaluate the contribution of hematopoietic and non-hematopoietic cells to colitis protection.

Results: We found that THC prevented colitis, and that CBD, at the dose tested, provided little benefit to the amelioration of colitis, or when added synergistically with THC. THC increased colonic barrier integrity by stimulating mucus, tight junction and antimicrobial peptide production, and these effects were specific to the large intestine. THC increased colonic gram-negative bacteria, but the anti-colitic effects of THC were independent of the microbiome. THC acted on both immune cells via CB2 and on enterocytes to attenuate colitis.

Conclusions: Our findings demonstrate how cannabinoid receptor activation on both immune cells and colonocytes is critical to prevent colonic inflammation. These studies also suggest how cannabinoid receptor activation can be used as a preventive and therapeutic modality against colitis.”

https://pubmed.ncbi.nlm.nih.gov/33331878/

https://academic.oup.com/ecco-jcc/advance-article-abstract/doi/10.1093/ecco-jcc/jjaa253/6040793?redirectedFrom=fulltext

In vivo and in vitro anti-inflammatory activity evaluation of Lebanese Cannabis sativa L. ssp. indica (Lam.)

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Journal of Ethnopharmacology “Cannabis sativa L. is an aromatic annual herb belonging to the family Cannabaceae and it is widely distributed worldwide. Cultivation, selling, and consumption of cannabis and cannabis related products, regardless of its use, was prohibited in Lebanon until April 22, 2020. Nevertheless, cannabis oil has been traditionally used unlawfully for many years in Lebanon to treat diseases such as arthritis, diabetes, cancer and few neurological disorders.

Aim of the study: The present study aims to evaluate the phytochemical and anti-inflammatory properties of a cannabis oil preparation that is analogous to the illegally used cannabis oil in Lebanon.

Results: Chemical analysis of COE revealed that cannabidiol (CBD; 59.1%) and tetrahydrocannabinol (THC; 20.2%) were found to be the most abundant cannabinoids.Various monoterpenes (α-Pinene, Camphene, β-Myrecene and D-Limonene) and sesquiterpenes (β-Caryophyllene, α-Bergamotene, α-Humelene, Humulene epoxide II, and Caryophyllene oxide) were identified in the extract. Results showed that COE markedly suppressed the release of TNF-α in LPS-stimulated rat monocytes. Western blot analysis revealed that COE significantly inhibited LPS-induced COX-2 and i-NOS protein expressions and blocked the phosphorylation of MAPKs, specifically that of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 MAPK. COE displayed a significant inhibition of paw edema in both rat models. Histopathological examination revealed that COE reduced inflammation and edema in chronic paw edema model.

Conclusion: The current findings demonstrate that COE possesses remarkable in vivo and in vitro anti-inflammatory activities which support the traditional use of the Lebanese cannabis oil extract in the treatment of various inflammatory diseases including arthritis.”

https://pubmed.ncbi.nlm.nih.gov/33359187/

https://www.sciencedirect.com/science/article/abs/pii/S037887412033631X?via%3Dihub

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