Targeting cannabinoid receptors in gastrointestinal cancers for therapeutic uses: current status and future perspectives

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“A number of studies have consistently shown that cannabinoids are able to prevent or reduce carcinogenesis in different animal models of colon cancer.

Cannabinoids, via CB1 and possibly CB2 receptors, suppress proliferation and migration and stimulate apoptosis in colorectal cancer cells.

Convincing scientific evidence suggests that cannabinoids, in addition to their well-known use in palliative care in oncology (e.g. improvement of appetite, attenuation of nausea associated to antitumoral medicines, alleviation of moderate neuropathic pain) can reduce, via antiproliferative and proapoptotic as well as by inhibiting angiogenesis, invasion and metastasis or by attenuating inflammation, the growth of cancer cells and hinder the development of experimental colon carcinogenesis in vivo.”

https://www.tandfonline.com/doi/full/10.1080/17474124.2017.1367663?src=recsys

Endocannabinoid system and anticancer properties of cannabinoids

Folia Biologica et Oecologica

“Cannabinoids impact human body by binding to cannabinoids receptors (CB1 and CB2).

The two main phytocannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

THC interacts with CB1 receptors occurring in central nervous system and is responsible for psychoactive properties of marijuana. CBD has low affinity to CB1 receptor, has no psychoactive characteristics and its medical applications can be wider.

CB receptors are part of a complex machinery involved in regulation of many physiological processes – endocannabinoid system.

Cannabinoids have found some applications in palliative medicine, but there are many reports concerning their anticancer affects.

Agonists of CB1 receptors stimulate accumulation of ceramides in cancer cells, stress of endoplasmic reticulum (ER stress) and, in turn, apoptosis. Effects of cannabinoids showing low affinity to CB receptors is mediated probably by induction of reactive oxygen species production.

Knowledge of antitumor activity of cannabinoids is still based only on preclinical studies and there is a necessity to conduct more experiments to assess the real potential of these compounds.”

https://content.sciendo.com/view/journals/fobio/12/1/article-p11.xml

Cannabis in End-of-Life Care: Examining Attitudes and Practices of Palliative Care Providers.

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“Medical cannabis research has become quite extensive, with indications ranging from glaucoma to chemotherapy-induced nausea.

Despite increased interest in cannabis‘ potential medical uses, research barriers, cannabis legislation, stigma, and lack of dissemination of data contribute to low adoption for some medical populations.

Of interest, cannabis use appears low in palliative care settings, with few guidelines available to palliative care providers. The present study sought to examine the attitudes, beliefs, and practices of palliative care providers regarding the use of cannabis for terminally ill patients.

Results demonstrated that palliative care providers endorse cannabis for a wide range of palliative care symptoms, end-of-life care generally, and as an adjuvant medication.

Nevertheless, the gap between these beliefs and actual recommendation or prescription appears vast. Many who support the use of cannabis in palliative care do not recommend it as a treatment. These data suggest recommendations for healthcare providers and palliative care organizations.”

https://www.ncbi.nlm.nih.gov/pubmed/29714640

https://www.tandfonline.com/doi/abs/10.1080/02791072.2018.1462543?journalCode=ujpd20

The use of cannabis in supportive care and treatment of brain tumor

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“Anticancer Effects of Cannabinoids may be able to Prolong Life.

Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC.

Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive.

Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today’s scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients.

THC, a partial CB1, CB2 agonist, has the stigma of psychotropic effects that are mediated by CB1 stimulation. However, CB1 stimulation is necessary for improving mood and appetite and many other effects. At present, it is hard to imagine a better approach than adjusting THC doses individually to balance wanted versus unwanted effects. Generally, higher doses are needed to achieve analgesic and antiemetic effects. Even much higher, supraphysiologic oral doses would be needed to combat tumors.

Combinations were synergistic under many circumstances such as in pain and antitumor studies. Cannabinoids differ in their antitumor activities and probably in their mechanisms and targets, which is a rationale for combinations. However, for many pharmacological effects (except against tumors) roughly 10-times higher daily doses are needed for CBD compared to THC.

In summary, the endocannabinoid system is likely playing a crucial role in palliative care. The future will show whether an optimized treatment strategy with cannabinoids can also prolong life of brain tumor patients by their virtue to combat cancer cells.”

https://academic.oup.com/nop/article/4/3/151/2918616

“Cannabinoid Drug Prolongs the Life of Brain Tumor Patients in Phase II Trials”  https://labiotech.eu/gw-pharmaceuticals-brain-tumor/

Prospective analysis of safety and efficacy of medical cannabis in large unselected population of patients with cancer

Cover image volume 49, Issue

“Cancer is a major public health problem as the leading cause of death. Palliative treatment aimed to alleviate pain and nausea in patients with advanced disease is a cornerstone of oncology.

In 2007, the Israeli Ministry of Health began providing approvals for medical cannabis for the palliation of cancer symptoms. The aim of this study is to characterize the epidemiology of cancer patients receiving medical cannabis treatment and describe the safety and efficacy of this therapy.

Methods

We analyzed the data routinely collected as part of the treatment program of 2970 cancer patients treated with medical cannabis between 2015 and 2017.

Results

The average age was 59.5 ± 16.3 years, 54.6% women and 26.7% of the patients reported previous experience with cannabis. The most frequent types of cancer were: breast (20.7%), lung (13.6%), pancreatic (8.1%) and colorectal (7.9%) with 51.2% being at stage 4. The main symptoms requiring therapy were: sleep problems (78.4%), pain (77.7%, median intensity 8/10), weakness (72.7%), nausea (64.6%) and lack of appetite (48.9%). After six months of follow up, 902 patients (24.9%) died and 682 (18.8%) stopped the treatment. Of the remaining, 1211 (60.6%) responded; 95.9% reported an improvement in their condition, 45 patients (3.7%) reported no change and four patients (0.3%) reported deterioration in their medical condition.

Conclusions

Cannabis as a palliative treatment for cancer patients seems to be well tolerated, effective and safe option to help patients cope with the malignancy related symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/29482741

http://www.ejinme.com/article/S0953-6205(18)30023-2/pdf

“Cannabis to be a “Safe,” “Effective” Medical Treatment in First-of-its-Kind, Peer-Reviewed Study of Thousands of Cancer Patients Using Tikun Olam™ Strains”  http://markets.businessinsider.com/news/stocks/cannabis-to-be-a-safe-effective-medical-treatment-in-first-of-its-kind-peer-reviewed-study-of-thousands-of-cancer-patients-using-tikun-olam-strains-1017297749

“For the first time, a major scientific study has confirmed what cannabis advocates have known for decades: that cannabis can be a safe and effective palliative treatment in patients suffering from the debilitating effects of cancer.”  https://www.prnewswire.com/news-releases/cannabis-to-be-a-safe-effective-medical-treatment-in-first-of-its-kind-peer-reviewed-study-of-thousands-of-cancer-patients-using-tikun-olam-strains-300604361.html

The current state and future perspectives of cannabinoids in cancer biology.

Cancer Medicine

“To date, cannabinoids have been allowed in the palliative medicine due to their analgesic and antiemetic effects, but increasing number of preclinical studies indicates their anticancer properties. Cannabinoids exhibit their action by a modulation of the signaling pathways crucial in the control of cell proliferation and survival. Many in vitro and in vivo experiments have shown that cannabinoids inhibit proliferation of cancer cells, stimulate autophagy and apoptosis, and have also a potential to inhibit angiogenesis and metastasis. In this review, we present an actual state of knowledge regarding molecular mechanisms of cannabinoids’ anticancer action, but we discuss also aspects that are still not fully understood such as the role of the endocannabinoid system in a carcinogenesis, the impact of cannabinoids on the immune system in the context of cancer development, or the cases of a stimulation of cancer cells’ proliferation by cannabinoids. The review includes also a summary of currently ongoing clinical trials evaluating the safety and efficacy of cannabinoids as anticancer agents.”

https://www.ncbi.nlm.nih.gov/pubmed/29473338

http://onlinelibrary.wiley.com/doi/10.1002/cam4.1312/abstract

Phytochemical Aspects and Therapeutic Perspective of Cannabinoids in Cancer Treatment

Cannabis sativa L. – dried pistillate inflorescences and trichomes on their surface. (a) dried pistillate inflorescences (50% of the size); (b) non‐cystolithic trichome; (c) cystolithic trichome; (d) capitate‐sessile trichome; (e) simple bulbous trichome; (f) capitate‐stalked trichome (400×).

“Cannabis sativa L. (Cannabaceae) is one of the first plants cultivated by man and one of the oldest plant sources of fibre, food and remedies.

Cannabinoids comprise the plant‐derived compounds and their synthetic derivatives as well as endogenously produced lipophilic mediators. Phytocannabinoids are terpenophenolic secondary metabolites predominantly produced in CannabissativaL.

The principal active constituent is delta‐9‐tetrahydrocannabinol (THC), which binds to endocannabinoid receptors to exert its pharmacological activity, including psychoactive effect. The other important molecule of current interest is non‐psychotropic cannabidiol (CBD).

Since 1970s, phytocannabinoids have been known for their palliative effects on some cancer‐associated symptoms such as nausea and vomiting reduction, appetite stimulation and pain relief. More recently, these molecules have gained special attention for their role in cancer cell proliferation and death.

A large body of evidence suggests that cannabinoids affect multiple signalling pathways involved in the development of cancer, displaying an anti‐proliferative, proapoptotic, anti‐angiogenic and anti‐metastatic activity on a wide range of cell lines and animal models of cancer.”

https://www.intechopen.com/books/natural-products-and-cancer-drug-discovery/phytochemical-aspects-and-therapeutic-perspective-of-cannabinoids-in-cancer-treatment

Medical Cannabis: The Oncology Nurse’s Role in Patient Education About the Effects of Marijuana on Cancer Palliation

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“Cannabis, also known as marijuana, is legal either medicinally or recreationally in 29 states and the District of Columbia, with a majority of the U.S. adult population now living in states where cannabis is legal for medicinal use. As an advocate for patient autonomy and informed choice, the oncology nurse has an ethical responsibility to educate patients about and support their use of cannabis for palliation.

OBJECTIVES:

This article aims to discuss the human endocannabinoid system as a basis for better understanding the palliative and curative nature of cannabis as a medicine, as well as review cannabis delivery methods and the emerging role of the oncology nurse in this realm.

FINDINGS:

The oncology nurse can play a pivotal role in supporting patients’ use of cannabis for palliation”

https://www.ncbi.nlm.nih.gov/pubmed/29350699

https://cjon.ons.org/cjon/22/1/medical-cannabis-oncology-nurse-s-role-patient-education-about-effects-marijuana-cancer

Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

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“Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. These nanoparticle drones can be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy.

In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous (“sea”) routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

As discussed earlier, nanoparticle drones are particularly attractive because they can also be loaded with drugs payload like cannabinoids. Cannabinoids, which are the bioactive components of Cannabis sativa and their derivatives, may exert palliative effects in cancer patients by preventing nausea, vomiting, and pain and by stimulating appetite .

Furthermore, studies indicate that cannabinoids can inhibit cancer cell growth in in vitro and in vivo. A Nature Reviews Cancer article and other recently published work highlight the potential of cannabinoids for treating cancer, working in synergy with radiotherapy and serving as radiosensitzers to enhance damage to lung tumor cells in particular. Consistent with this, our own experiments have confirmed the potential of cannabinoids in treating lung cancer, with results confirming that cannabinoids can enhance damage to cancer cells.

Overall, the use of nanoparticle drones administered via INH to enhance NRT, as highlighted in this article, may provide a good strategy for maximizing therapeutic efficacy in external beam NRT for lung cancer. Also there is growing evidence that cannabinoids can serve as radiosensitizers, enhance damage to tumor cells, slow tumor growth, and work synergistically with radiotherapy in cancer treatment.”

http://journal.frontiersin.org/article/10.3389/fonc.2017.00208/full

“Cannabis Science Announces Publication of Initial Research Results Using Nanoparticle Drones to Target Lung Cancer With Radiosensitizers and Cannabinoids in the Renowned Journal Frontiers in Oncology” https://ca.finance.yahoo.com/news/cannabis-science-announces-publication-initial-120522920.html

“Cannabis Science “Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids” Full Publication Released Today In Frontiers In Oncology” http://www.marketwired.com/press-release/cannabis-science-nanoparticle-drones-target-lung-cancer-with-radiosensitizers-cannabinoids-2234167.htm

Confirmed marijuana use and lymphocyte count in black people living with HIV

Drug and Alcohol Dependence Home

“Marijuana is a commonly used recreational substance with purported analgesic and mood enhancing properties. Many people living with HIV identify marijuana as a palliative substance.

However, through its main psychoactive component, tetrahydrocannabinol (THC), is known to influence the immune system. The effects of marijuana use in people with HIV are still controversial, with very scant literature in Black adults.

The current study determined the differences in the lymphocyte count, specifically the number cluster differentiation 4 and 8 (CD4+ and CD8+), among patients who urine drug tested negative for THC (n = 70) and those who tested positive for THC (n = 25).”  HTTP://WWW.SCIENCEDIRECT.COM/SCIENCE/ARTICLE/PII/S037687161730412X

“After adjusting for demographic and HIV-related covariates, THC-positive patients had significantly higher CD4+ and CD8+ counts than their THC-negative counterparts.”  http://www.drugandalcoholdependence.com/article/S0376-8716(17)30412-X/fulltext

“These results extend previous HIV-related immunity findings in an underrepresented group, and suggest that THC use does not reduce immune function as measured by CD count. Further research is warranted on the overall effects of THC on immune function in HIV positive patients.”  https://www.ncbi.nlm.nih.gov/pubmed/28850903