Opportunities for cannabis in supportive care in cancer.

 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

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/

Urgent need for “EBMM” in pediatric oncology: Evidence based medical marijuana.

Publication Cover“Marijuana has been used by many different civilizations for numerous different purposes, including its use for medical indications. Recently, there has been significant media coverage of the efficacy of medical marijuana in the treatment of seizures in children with Dravet syndrome, and this has led many to search for other possible pediatric indications for cannabinoids, including many different indications in pediatric cancer. However, there is very little evidence on safety or efficacy of cannabinoids in children being treated with cancer. This commentary accompanies a recent paper by a group in Israel who have published their experience of medical marijuana in 50 children and adolescents with cancer, showing excellent satisfaction and better symptom control, and without significant adverse drug reactions. This study from Israel is an excellent first step, but prospective well-designed trials of medical marijuana in pediatric oncology are urgently needed.”

Heavy Cannabis Use Associated With Reduction in Activated and Inflammatory Immune Cell Frequencies in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Individuals.

Issue Cover“Heavy cannabis users had decreased frequencies of human leukocyte antigen (HLA)-DR+CD38+CD4+ and CD8+ T-cell frequencies, compared to frequencies of these cells in non-cannabis-using individuals.

Heavy cannabis users had decreased frequencies of intermediate and nonclassical monocyte subsets, as well as decreased frequencies of interleukin 23- and tumor necrosis factor-α-producing antigen-presenting cells.

CONCLUSIONS:

While the clinical implications are unclear, our findings suggest that cannabis use is associated with a potentially beneficial reduction in systemic inflammation and immune activation in the context of antiretroviral-treated HIV infection.”

https://www.ncbi.nlm.nih.gov/pubmed/29471387

“We found that heavy cannabis use was associated with decreased frequencies of activated T cells and inflammatory antigen-presenting cell (APC) subsets, suggesting a potential immunologic benefit of cannabinoids through decreased immune activation in HIV-infected individuals.

In summary, our work demonstrates that heavy cannabis use is associated with lower markers of inflammation and immune activation in HIV-infected, ART-treated individuals.

These findings have clinical implications, as cannabinoids may have an immunological benefit and nonpsychoactive cannabis derivatives could be investigated as novel therapeutics to be used in conjunction with ART to aid in reduction of persistent inflammation.”

https://academic.oup.com/cid/article/66/12/1872/4869752

“Cannabinoids for the treatment of inflammation.” http://www.ncbi.nlm.nih.gov/pubmed/17520866

Cannabinoids and inflammation: Implications for People Living with HIV.

Image result for wolters kluwer “Thanks to the success of modern antiretroviral therapy (ART), people living with HIV (PLWH) have life expectancies which approach that of persons in the general population. However, despite the ability of ART to suppress viral replication, PLWH have high levels of chronic systemic inflammation which drives the development of comorbidities such as cardiovascular disease, diabetes and non-AIDS associated malignancies.

Historically, cannabis has played an important role in alleviating many symptoms experienced by persons with advanced HIV infection in the pre-ART era and continues to be used by many PLWH in the ART era, though for different reasons.

Δ-tetrahydrocannabinol (Δ-THC) and cannabidiol (CBD) are the phytocannabinoids which have received most attention for their medicinal properties. Due to their ability to suppress lymphocyte proliferation and inflammatory cytokine production, there is interest in examining their therapeutic potential as immunomodulators.

CB2 receptor activation has been shown in vitro to reduce CD4 T-cell infection by CXCR4-tropic HIV and to reduce HIV replication.

Studies involving SIV-infected macaques have shown that Δ-THC can reduce morbidity and mortality and has favourable effects on the gut mucosal immunity. Furthermore, ΔTHC administration was associated with reduced lymph node fibrosis and diminished levels of SIV proviral DNA in spleens of rhesus macaques compared with placebo-treated macaques.

In humans, cannabis use does not induce a reduction in peripheral CD4 T-cell count or loss of HIV virological control in cross-sectional studies. Rather, cannabis use in ART-treated PLWH was associated with decreased levels of T-cell activation, inflammatory monocytes and pro-inflammatory cytokines secretion, all of which are related to HIV disease progression and co-morbidities.

Randomized clinical trials should provide further insights into the ability of cannabis and cannabinoid-based medicines to attenuate HIV-associated inflammation. In turn, these findings may provide a novel means to reduce morbidity and mortality in PLWH as adjunctive agents to ART.”

https://www.ncbi.nlm.nih.gov/pubmed/31408029

https://insights.ovid.com/crossref?an=00002030-900000000-96855

Terpenes in Cannabis sativa – From plant genome to humans.

Plant Science“Cannabis sativa (cannabis) produces a resin that is valued for its psychoactive and medicinal properties.

Despite being the foundation of a multi-billion dollar global industry, scientific knowledge and research on cannabis is lagging behind compared to other high-value crops. This is largely due to legal restrictions that have prevented many researchers from studying cannabis, its products, and their effects in humans.

Cannabis resin contains hundreds of different terpene and cannabinoid metabolites.

Our understanding of the genomic and biosynthetic systems of these metabolites in cannabis, and the factors that affect their variability, is rudimentary. As a consequence, there is concern about lack of consistency with regard to the terpene and cannabinoid composition of different cannabis ‘strains’.

Likewise, claims of some of the medicinal properties attributed to cannabis metabolites would benefit from thorough scientific validation.”

https://www.ncbi.nlm.nih.gov/pubmed/31084880

https://www.sciencedirect.com/science/article/pii/S0168945219301190?via%3Dihub

Analysis of Terpenes in Cannabis sativa L. Using GC/MS: Method Development, Validation, and Application.

“Terpenes are the major components of the essential oils present in various Cannabis sativa L. varieties.

These compounds are responsible for the distinctive aromas and flavors. Besides the quantification of the cannabinoids, determination of the terpenes in C. sativa strains could be of importance for the plant selection process.

At the University of Mississippi, a GC-MS method has been developed and validated for the quantification of terpenes in cannabis plant material, viz., α-pinene, β-pinene, β-myrcene, limonene, terpinolene, linalool, α-terpineol, β-caryophyllene, α-humulene, and caryophyllene oxide.”

https://www.ncbi.nlm.nih.gov/pubmed/30646402

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-0828-8387

Flavonoid Derivative of Cannabis Demonstrates Therapeutic Potential in Preclinical Models of Metastatic Pancreatic Cancer.

Image result for frontiers oncology“Pancreatic cancer is particularly refractory to modern therapies, with a 5-year survival rate for patients at a dismal 8%.

One of the significant barriers to effective treatment is the immunosuppressive pancreatic tumor microenvironment and development of resistance to treatment. New treatment options to increase both the survival and quality of life of patients are urgently needed.

This study reports on a new non-cannabinoid, non-psychoactive derivative of cannabis, termed FBL-03G, with the potential to treat pancreatic cancer.

In vitro results show major increase in apoptosis and consequential decrease in survival for two pancreatic cancer models- Panc-02 and KPC pancreatic cancer cells treated with varying concentrations of FBL-03G and radiotherapy.

Meanwhile, in vivo results demonstrate therapeutic efficacy in delaying both local and metastatic tumor progression in animal models with pancreatic cancer when using FBL-03G sustainably delivered from smart radiotherapy biomaterials.

Repeated experiments also showed significant (P < 0.0001) increase in survival for animals with pancreatic cancer compared to control cohorts.

The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer, providing impetus for further studies toward clinical translation.”

https://www.ncbi.nlm.nih.gov/pubmed/31396485

“In this study, a flavonoid derivative of cannabis demonstrates significant therapy potential in the treatment of pancreatic cancer, including radio-sensitizing and cancer metastasis treatment potential. The results justify further studies to optimize therapy outcomes toward clinical translation.”

https://www.frontiersin.org/articles/10.3389/fonc.2019.00660/full

“Flavonoids as anticancer agents: structure-activity relationship study.”  https://www.ncbi.nlm.nih.gov/pubmed/12678721

“The antitumor activities of flavonoids.”  https://www.ncbi.nlm.nih.gov/pubmed/16097445

“Anticancer properties of flavonoids: roles in various stages of carcinogenesis.”  https://www.ncbi.nlm.nih.gov/pubmed/21644918

Association between cannabis use and complications related to ulcerative colitis in hospitalized patients: A propensity matched retrospective cohort study.

 Image result for wolters kluwer“Ulcerative colitis (UC) is a chronic inflammatory process that is occasionally associated with complications that cause significant morbidity and mortality.

Studies in experimental animal models have demonstrated a beneficial effect of cannabis on intestinal inflammation. It is however unknown if this corresponds to fewer complications for patients with Ulcerative Colitis.

We aimed to compare the prevalence of UC related complications and certain key clinical endpoints among cannabis users and nonusers hospitalized with a primary diagnosis of UC, or primary diagnosis of a UC-related complication with a secondary diagnosis of UC. Using data from the Healthcare Cost and Utilization Project-National Inpatient Sample (NIS) during 2010-2014, a total of 298 cannabis users with UC were compared to a propensity score matched group of nonusers with UC. We evaluated several UC-related complications and clinical endpoints.

Within our matched cohort, prevalence of partial or total colectomy was lower in cannabis users compared to nonusers (4.4% vs 9.7%, P = .010) and there was a trend toward a lower prevalence of bowel obstruction (6.4% vs 10.7%, P = .057). 

Cannabis users had shorter hospital length-of-stay (4.5 vs 5.7 days P < .007) compared to their nonuser counterparts.

Cannabis use may mitigate some of the well described complications of UC among hospitalized patients. Our findings need further evaluation, ideally through more rigorous clinical trials.”

https://www.ncbi.nlm.nih.gov/pubmed/31393356

https://insights.ovid.com/crossref?an=00005792-201908090-00016

Bones and Joints: The Effects of Cannabinoids on the Skeleton.

Image result for j clin endocrinol metab“This paper reviews the endocannabinoid system and focuses on the role of endocannabinoids in bone metabolism and their potential use in the management of conditions associated with bone loss.

CONTEXT:

The endocannabinoid system uses tissue-specific lipid ligands and G protein-coupled transmembrane receptors to regulate neurological, metabolic, and immune responses. Recent studies demonstrate that the endocannabinoid system influences bone metabolism. With the increasing use of endocannabinoid mimetics, e.g. tetrahydrocannabinol (THC) and cannabidiol (CBD), endocannabinoids’ involvement in bone growth and remodeling has become clinically relevant.

EVIDENCE ACQUISITION:

This literature review is based upon a search of Pubmed and Google Scholar databases, as of June 2019, for all English-language publications relating to cannabinoids and bone. We evaluated retrieved articles for relevance, experimental design, data acquisition, statistical analysis, and conclusions.

EVIDENCE SYNTHESIS:

Preclinical studies establish a role for endocannabinoids in bone metabolism. These studies yield complex and often contradictory results attributed to differences in the specific experimental model examined. Studies using human cells or subjects are limited.

CONCLUSIONS:

In vitro and animal models document that endocannabinoids participate in bone biology. The relevance of these observations to humans is not clear. The increasing chronic use of medical and recreational cannabis underscores the need to better understand the role of endocannabinoids in human bone metabolism. Moreover, it is important to evaluate the role of endocannabinoids as a therapeutic target to prevent and treat disorders associated with bone loss.”

https://www.ncbi.nlm.nih.gov/pubmed/31393556

“[The endocannabinoid system and bone].”  https://www.ncbi.nlm.nih.gov/pubmed/27734700

“Joint problems arising from lack of repair mechanisms: can cannabinoids help?”  https://www.ncbi.nlm.nih.gov/pubmed/29574720

“Cannabinoids and bone regeneration.”  https://www.ncbi.nlm.nih.gov/pubmed/30702341

“Cannabinoids and the skeleton: from marijuana to reversal of bone loss.”  https://www.ncbi.nlm.nih.gov/pubmed/19634029