Category Archives: Cancer

Cannabis use in cancer: a survey of the current state at BC Cancer before recreational legalization in Canada.

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Image result for Curr Oncol.“Cancer patients experience multiple symptoms throughout their illness, and some report benefit from the use of cannabis. There are concerns that many patients are accessing products inappropriate for their situation and potentially putting themselves at risk.

In the present study, we aimed to capture the prevalence of cannabis use among cancer patients at BC Cancer before recreational legalization in Canada and to identify the reasons that patients take cannabis, the various routes of administration they use, and the reasons that prior users stopped.

RESULTS:

Of surveys sent to 2998 patients, 821 (27.4%) were returned and included in analysis. Of those respondents, 23% were currently using cannabis-based products, almost exclusively for medical purposes, and an additional 28% had been users in the past (most often recreationally). Of the patients currently using cannabis, 31% had medical authorization. The most common symptoms that the current users were targeting were pain, insomnia, nausea, and anxiety; many were also hoping for anticancer effects.

CONCLUSIONS:

More than half the respondents had tried cannabis at some time, and almost one quarter of respondents were currently taking cannabis to help manage their symptoms or treat their cancer, or both. Many more patients would consider use with appropriate guidance from a health care professional. More research is needed to inform physicians and patients about safe uses and doses and about the potential adverse effects of cannabis use.”

https://www.ncbi.nlm.nih.gov/pubmed/31548810

A Novel Highly Selective Cannabinoid CB2 Agonist Reduces in Vitro Growth and TGF-beta Release of Human Glial Cell Tumors.

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“Cannabinoid receptors have been detected in human gliomas and cannabinoids have been proposed as novel drug candidates in the treatment of brain tumors.

Aim of this study was to test the in vitro antitumor activity of COR167, a novel cannabinoid CB2-selective agonist displaying high binding affinity for human CB2 receptors, on tumor cells isolated from human glioblastoma multiforme and anaplastic astrocytoma.

RESULTS:

COR167 was found to significantly reduce the proliferation of both glioblastoma and anaplastic astrocytoma in a dose-dependent manner at lower doses than other known, less specific CB2 agonists. This activity is independent of apoptosis and is associated with significant reduction of TGF-beta 1 and 2 levels in supernatants of glioma cell cultures.

CONCLUSIONS:

These findings add to the role of cannabinoid CB2 receptor as a possible pharmacological target to counteract glial tumor growth and encourage further work to explore any other pharmacological effect of this novel CB2 agonist useful in the treatment of human gliomas.”

https://www.ncbi.nlm.nih.gov/pubmed/31549596

http://www.eurekaselect.com/175066/article

Antiproliferative and antioxidant effect of polar hemp extracts (Cannabis sativa L., Fedora cv.) in human colorectal cell lines.

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Publication Cover “Total phenolic content and antioxidant activity of polar extracts of edible resources from Fedora hemp cultivar (Cannabis sativa L.), namely seed, flour and oil, were evaluated. The main components in the polar extracts were identified using HPLC-DAD and HPLC-ESI-MS/MS. As expected, the molecular profile of components from seeds and flour was strictly similar, dominated by N-trans-caffeoyltyramine. The profile of oil polar extracts contained hydroxycinnamic acid derivatives and cannabinoids at lower extent. While the extracts from hemp seed and flour did not interfere with growth of Caco-2 and HT-29 cell, the one from oil (150 µg/mL) significantly reduced cell viability after 24 h of treatment. This effect was associated with the activation of apoptotic cell death and was independent from the antioxidant capacity of the oil polar extract. Notably, HT-29 cells differentiated with sodium butyrate were not sensitive to the cytotoxic effect of the oil extract.”

https://www.ncbi.nlm.nih.gov/pubmed/31544542

https://www.tandfonline.com/doi/abs/10.1080/09637486.2019.1666804?journalCode=iijf20

Perception of Benefits and Harms of Medical Cannabis among Seriously Ill Patients in an Outpatient Palliative Care Practice.

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“Patients with serious illness often have pain, uncontrolled symptoms, and poor quality of life. Evidence continues to evolve regarding the role of cannabis to treat chronic pain, nausea, and anorexia. Little is known about how patients with serious illness perceive its benefits and harms. Given that an increasing number of clinicians across the United States are treating patients with medical cannabis, it is important for providers to understand patient beliefs about this modality. We assessed patient perceptions of benefits and harms of cannabis who obtained a medical cannabis card within an ambulatory palliative care (APC) practice.

Results: All 101 patients invited to participate completed the survey. A majority had cancer (76%) and were married (61%), disabled or retired (75%), older than 50 years of age (64%), and men (56%). Most patients ingested (61%) or vaporized (49%) cannabis products. A majority of respondents perceived cannabis to be important for their pain (96%) management. They reported that side effects were minimally bothersome, and drowsiness was the most commonly reported bothersome harm (28%). A minority of patients reported cannabis withdrawal symptoms (19%) and concerns for dependency (14%). The majority of patients were using concurrent prescription opioids (65%). Furthermore, a majority of cancer patients reported cannabis as being important for cancer cure (59%).

Conclusion: Patients living with serious illnesses who use cannabis in the context of a multidisciplinary APC practice use cannabis for curative intent and for pain and symptom control. Patients reported improved pain, other symptoms, and a sense of well-being with few reported harms.”

https://www.ncbi.nlm.nih.gov/pubmed/31539298

https://www.liebertpub.com/doi/10.1089/jpm.2019.0211

Evaluation of the effects of cannabinoids CBD and CBG on human ovarian cancer cells in vitro

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University of Huddersfield“Ovarian cancer, with over a 90% reoccurrence within 18 months of treatment, and approximately a 30% mortality rate after 5 years, is the leading cause of death in cases of gynaecological malignancies. Acquired resistance, and toxic side effects by clinically used agents are major challenges associated with current treatments, indicating the need for new approaches in ovarian cancer treatment.

Increased tumour cell proliferation associated with upregulation of cannabinoid (CB) receptors has been observed in ovarian cancer. As cannabinoids reported to bind to CB receptors, and can potentially modulate their downstream signalling, this raises the possibility of cannabinoids as potential anticancer drugs for ovarian cancer treatment.

Amongst the cannabinoids, non-psychoactive CBD and CBG have been shown to have anticancer activities towards prostate and colon cancer cells through multiple mechanisms of action. However, CBD and CBG have yet to be investigated in relation to ovarian cancer therapy either in vitro or in vivo.

Aim:

The aims of this study were to evaluate the potential cytotoxic effects of CBD and CBG in human ovarian cancer cells, their ability to potentiate existing clinically used agents for ovarian cancer, and to perform initial mode of action studies in vitro.

Conclusions:

Both CBD and CBG showed preferential cytotoxicity against the ovarian cancer cells analysed compared to the non-cancer cells; however, this was less than for carboplatin. Importantly, in contrast to carboplatin, CBD and CBG showed similar activity towards cisplatin sensitive and cisplatin resistant cells indicating distinctive mechanisms of action to platinum drugs.

Preferential cytotoxicity towards cancer cells in vitro and ability to potentiate carboplatin and overcome cisplatin resistance identify CBD and CBG as promising candidates that warrant further investigation, both in terms of detailed mechanism of action studies and also in vivo studies to assess whether this promising activity translates into an in vivo setting and their potential for further progression towards the clinic.”

http://eprints.hud.ac.uk/id/eprint/34866/

Preclinical evidence on the anticancer properties of phytocannabinoids

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Image result for CROSBI“Phytocannabinoids are unique terpenophenolic compounds predominantly produced in the glandular trichomes of the cannabis plant (Cannabis sativa L.). The delta-9- tetrahydrocannabinol (THC) is the main active constituent responsible for the plant’s psychoactive effect and, together with the non- psychoactive cannabidiol (CBD), the most investigated naturally occurring cannabinoid.

The first report on the antitumor properties of cannabis compounds appeared more than forty years ago, but the potential of targeting the endocannabinoid system in cancer has recently attracted increasing interest. Our study aimed to review the last decade’s findings on the anticancer potential of plant- derived cannabinoids and the possible mechanisms of their activity.

A large body of in vitro data has been accumulated demonstrating that phytocannabinoids affect a wide spectrum of tumor cells, including gliomas, neuroblastomas, hepatocarcinoma as well as skin, prostate, breast, cervical, colon, pancreatic, lung and hematological cancer.

It has been found that they can stop the uncontrolled growth of cancer cells through the cell-cycle arrest, inhibition of cell proliferation and induction of autophagy and apoptosis. They can also block all the steps of tumor progression, including tumor cell migration, adhesion and invasion as well as angiogenesis. The observed effects are mainly mediated by the cannabinoid CB1 and/or CB2 receptors, although some other receptors and mechanisms unrelated to receptor stimulation may also be involved.

The majority of available animal studies confirmed that phytocannabinoids are capable of effectively decreasing cancer growth and metastasis in vivo. THC was found to be effective against experimental glioma, liver, pancreatic, breast and lung cancer while CBD showed activity against glioma and neuroblastoma, melanoma, colon, breast, prostate and lung cancer. Further in vitro and in vivo studies also greatly support their use in combination with traditional chemotherapy or radiotherapy, which results in improved efficiency, attenuated toxicity or reduced drug resistance.

Taken together most of available preclinical results emphasize the extensive therapeutic potential of THC and CBD in various types of cancers. The potential clinical interest of cannabinoids is additionally suggested by their selectivity for tumor cells as well as their good tolerance and the absence of normal tissue toxicity, which are still the major limitations of most conventional drugs. The accumulated preclinical evidence strongly suggests the need for clinical testing of cannabinoids in cancer patients.”

 https://www.bib.irb.hr/887811

Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity.

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molecules-logo“Mixtures of different Cannabis sativa phytocannabinoids are more active biologically than single phytocannabinoids. However, cannabis terpenoids as potential instigators of phytocannabinoid activity have not yet been explored in detail.

Terpenoid groups were statistically co-related to certain cannabis strains rich in Δ9-tetrahydrocannabinolic acid (THCA) or cannabidiolic acid (CBDA), and their ability to enhance the activity of decarboxylase phytocannabinoids (i.e., THC or CBD) was determined.

Analytical HPLC and GC/MS were used to identify and quantify the secondary metabolites in 17 strains of C. sativa, and correlations between cannabinoids and terpenoids in each strain were determined. Column separation was used to separate and collect the compounds, and cell viability assay was used to assess biological activity.

We found that in “high THC” or “high CBD” strains, phytocannabinoids are produced alongside certain sets of terpenoids. Only co-related terpenoids enhanced the cytotoxic activity of phytocannabinoids on MDA-MB-231 and HCT-116 cell lines.

This was found to be most effective in natural ratios found in extracts of cannabis inflorescence. The correlation in a particular strain between THCA or CBDA and a certain set of terpenoids, and the partial specificity in interaction may have influenced the cultivation of cannabis and may have implications for therapeutic treatments.”

https://www.ncbi.nlm.nih.gov/pubmed/31438532

https://www.mdpi.com/1420-3049/24/17/3031

“Anticancer Terpenoids” https://link.springer.com/chapter/10.1007/978-3-319-14027-8_5

“Anticancer effects of phytocannabinoids” https://www.ncbi.nlm.nih.gov/pubmed/28560402

Opportunities for cannabis in supportive care in cancer.

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 Related image“Cannabis has the potential to modulate some of the most common and debilitating symptoms of cancer and its treatments, including nausea and vomiting, loss of appetite, and pain.

However, the dearth of scientific evidence for the effectiveness of cannabis in treating these symptoms in patients with cancer poses a challenge to clinicians in discussing this option with their patients. A review was performed using keywords related to cannabis and important symptoms of cancer and its treatments.

Literature was qualitatively reviewed from preclinical models to clinical trials in the fields of cancer, human immunodeficiency virus (HIV), multiple sclerosis, inflammatory bowel disease, post-traumatic stress disorder (PTSD), and others, to prudently inform the use of cannabis in supportive and palliative care in cancer.

There is a reasonable amount of evidence to consider cannabis for nausea and vomiting, loss of appetite, and pain as a supplement to first-line treatments. There is promising evidence to treat chemotherapy-induced peripheral neuropathy, gastrointestinal distress, and sleep disorders, but the literature is thus far too limited to recommend cannabis for these symptoms.

Scant, yet more controversial, evidence exists in regard to cannabis for cancer- and treatment-related cognitive impairment, anxiety, depression, and fatigue. Adverse effects of cannabis are documented but tend to be mild.

Cannabis has multifaceted potential bioactive benefits that appear to outweigh its risks in many situations. Further research is required to elucidate its mechanisms of action and efficacy and to optimize cannabis preparations and doses for specific populations affected by cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/31413731

https://journals.sagepub.com/doi/10.1177/1758835919866362

Emerging role of cannabinoids and synthetic cannabinoid receptor 1/cannabinoid receptor 2 receptor agonists in cancer treatment and chemotherapy-associated cancer management

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Journal of Cancer Research and Therapeutics“Cannabis was extensively utilized for its medicinal properties till the 19th century. A steep decline in its medicinal usage was observed later due to its emergence as an illegal recreational drug.

Advances in technology and scientific findings led to the discovery of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound of cannabis, that further led to the discovery of endogenous cannabinoids system consisting of G-protein-coupled receptors – cannabinoid receptor 1 and cannabinoid receptor 2 along with their ligands, mainly anandamide and 2-arachidonoylglycerol.  Endocannabinoid (EC) is shown to be a modulator not only for physiological functions but also for the immune system, endocrine network, and central nervous system.

Medicinal research and meta-data analysis over the last few decades have shown a significant potential for both THC and cannabidiol (CBD) to exert palliative effects. People suffering from many forms of advanced stages of cancers undergo chemotherapy-induced nausea and vomiting followed by severe and chronic neuropathic pain and weight loss.

THC and CBD exhibit effective analgesic, anxiolytic, and appetite-stimulating effect on patients suffering from cancer. Drugs currently available in the market to treat such chemotherapy-induced cancer-related ailments are Sativex (GW Pharmaceutical), Dronabinol (Unimed Pharmaceuticals), and Nabilone (Valeant Pharmaceuticals).

Apart from exerting palliative effects, THC also shows promising role in the treatment of cancer growth, neurodegenerative diseases (multiple sclerosis and Alzheimer’s disease), and alcohol addiction and hence should be exploited for potential benefits.

The current review discusses the nature and role of CB receptors, specific applications of cannabinoids, and major studies that have assessed the role of cannabinoids in cancer management.

Specific targeting of cannabinoid receptors can be used to manage severe side effects during chemotherapy, palliative care, and overall cancer management. Furthermore, research evidences on cannabinoids have suggested tumor inhibiting and suppressing properties which warrant reconsidering legality of the substance.

Studies on CB1 and CB2 receptors, in case of cancers, have demonstrated the psychoactive constituents of cannabinoids to be potent against tumor growth.

Interestingly, studies have also shown that activation of CB1 and CB2 cannabinoid receptors by their respective synthetic agonists tends to limit human cancer cell growth, suggesting the role of the endocannabinoid system as a novel target for treatment of cancers.

Further explorations are required to exploit cannabinoids for an effective cancer management.”

http://www.cancerjournal.net/preprintarticle.asp?id=263538

“Could Cannabis Kill Cancer Cells? A New Study Looks Promising”  https://www.portlandmercury.com/blogtown/2019/08/15/26977361/could-cannabis-kill-cancer-cells-a-new-study-looks-promising

“Study Reviews How Marijuana Compounds Inhibit Tumor Growth And Kill Cancer Cells” https://www.marijuanamoment.net/study-reviews-how-marijuana-compounds-inhibit-tumor-growth-and-kill-cancer-cells/

New approaches to cancer therapy: combining Fatty Acid Amide Hydrolase (FAAH) inhibition with Peroxisome Proliferator-Activated Receptors (PPARs) activation.

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 Go to Volume 0, Issue ja“Over the course of the last decade, Peroxisome Proliferator-Activated Receptors (PPARs) have been identified as part of the cannabinoid signaling system: both phytocannabinoids and endocannabinoids are capable of binding and activating these nuclear receptors. Fatty Acid Amide Hydrolase (FAAH) hydrolyzes the endocannabinoid Anandamide and other N-Acylethanolamines. These substances have been shown to have numerous anti-cancer effects, and indeed the inhibition of FAAH has multiple beneficial effects that are mediated by PPARα subtype and by PPARγ subtype, especially antiproliferation and activation of apoptosis. The substrates of FAAH are also PPAR agonists, which explains the PPAR-mediated effects of FAAH inhibitors. Much like cannabinoid ligands and FAAH inhibitors, PPARγ agonists show antiproliferative effects on cancer cells, suggesting that additive or synergistic effects may be achieved through the positive modulation of both signaling systems. In this perspective, we discuss the development of novel FAAH inhibitors able to directly act as PPAR agonists and their promising utilization as leads for the discovery of highly effective anti-cancer compounds.”

https://www.ncbi.nlm.nih.gov/pubmed/31407888

https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b00885