INSIGHT ON THE IMPACT OF ENDOCANNABINOID SYSTEM IN CANCER: A REVIEW.

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“In the last decades, the endocannabinoid system has attracted a great interest in medicine and cancer disease is probably one of its most promising therapeutic areas.

On the one hand, endocannabinoid system expression has been found altered in numerous types of tumours compared to healthy tissue, and this aberrant expression has been related to cancer prognosis and disease outcome, suggesting a role of this system in tumour growth and progression that depends on cancer type.

On the other hand, it has been reported that cannabinoids exert an anticancer activity by inhibiting the proliferation, migration and/or invasion of cancer cells; and also tumour angiogenesis.

The endocannabinoid system may be considered as a new therapeutic target, although further studies to fully establish the effect of cannabinoids on tumour progression remain necessary.”

https://www.ncbi.nlm.nih.gov/pubmed/29663308

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Cannabidiol Induces Cytotoxicity and Cell Death via Apoptotic Pathway in Cancer Cell Lines

“In view of obtaining potential anticancer compounds, we studied the inhibitory activity and the cytotoxic effects of a candidate compound in cancer cells. The cytotoxic effects of cannabidiol (CBD) in vitro were evaluated in NIH3T3 fibroblasts, B16 melanoma cells, A549 lung cancer cells, MDA-MB-231 breast cancer cells, Lenca kidney cells and SNU-C4 colon cancer cells.
The inhibitory activity of CBD was increased in all cancer cells and showed especially strong increment in breast cancer cells. The cytotoxicity of CBD increased in a dose- and time-dependent manner with growth inhibition in all cancer cell lines.
Therefore these results suggest that CBD has a possibility of anticancer agents and anticancer effects against cancer cells by modulation of apoptotic pathway in the range of 5-80 μM concentration.”
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Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line.

Iranian Journal of Basic Medical Sciences

“Metastasis is the main cause of death in patients with melanoma.

Cannabis-based medicines are effective adjunctive drugs in cancer patients.

Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized Cannabis sativa extract on cell migration and Tau and Stathmin gene expression in the melanoma cell line.

RESULTS:

Tau and stathmin gene expression was significantly decreased compared to the control group. Cell migration was also significantly reduced compared to controls.

CONCLUSION:

C. sativa decreased tau and stathmin gene expression and cancer metastasis. The results may have some clinical relevance for the use of cannabis-based medicines in patients with metastatic melanoma.”

https://www.ncbi.nlm.nih.gov/pubmed/29147495

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The Risks and Benefits of Cannabis in the Dermatology Clinic.

SAGE Journals

“Cannabis ( Cannabis sativa/indica), also known as marijuana, has been used for medicinal and recreational purposes for millennia.

There has been a recent trend to legalize the use of cannabis, as illustrated by the recent legalization votes in numerous states in the United States and legislation in Canada to allow recreational cannabis use. With this increasing consumption of cannabis, dermatologists will see increased pressure to prescribe cannabis and will see the side effects of cannabis use with greater frequency.

There are several approved medical indications for cannabis use, including psoriasis, lupus, nail-patella syndrome, and severe pain. In addition, very preliminary studies have suggested cannabis and its derivatives might have use in acne, dermatitis, pruritus, wound healing, and skin cancer.

In this review, we summarize some of the studies and reports regarding the medicinal uses of cannabis in the dermatology clinic and some of the side effects that might present more often to dermatologists as the use of cannabis increases.”

“Cannabinoid system in the skin – a possible target for future therapies in dermatology.” https://www.ncbi.nlm.nih.gov/pubmed/19664006

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Medical marijuana for the treatment of vismodegib-related muscle spasm

JAAD Case Reports

“Basal cell carcinoma (BCC) arises from loss-of-function mutations in tumor suppressor patched homologue 1, which normally inhibits smoothened homologue in the sonic hedgehog signaling pathway. Vismodegib, a smoothened homologue inhibitor, is US Food and Drug Administration (FDA) approved for metastatic or locally advanced BCC that has recurred after surgery or for patients who are not candidates for surgery and radiation. Common adverse effects of vismodegib are muscle spasms, alopecia, dysgeusia, nausea, and weight loss. Muscle spasms worsen with duration of drug administration and may lead to drug discontinuation.

We report a case of vismodegib-related muscle spasm that was successfully treated with medical marijuana (MM).

During the first week of vismodegib and radiation, the patient started MM, having heard of its indication in the treatment of muscle cramps. She smoked 3 to 4 joints daily of Trainwreck strain, containing 18.6% tetrahydrocannabinol (THC), 0.0% cannabidiol (CBD), and 0.0% cannabinol. Her muscle spasms resolved immediately. She continued MM for 3.5 weeks, until the cost of MM became prohibitive. She reported no adverse effects from MM. Complete resolution of muscle spasms was sustained through the remaining 3.5 weeks of vismodegib. Complete blood count, comprehensive metabolic panel, and lactate dehydrogenase level were monitored throughout the study with no significant changes. As of 18 months posttreatment, the patient had a complete clinical response of her BCC.

One marijuana joint contains, on average, 0.66 g of marijuana, although the definition of a joint is highly variable. With any MM formulation, patients should start at a low dose and gradually titrate to effect. Additional studies could confirm safety and efficacy and better specify the optimal cannabinoid subtypes, preparations, and dosages that may be most beneficial for vismodegib-induced muscle spasms.”

http://www.jaadcasereports.org/article/S2352-5126(17)30124-8/fulltext

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A Review of the Therapeutic Antitumor Potential of Cannabinoids.

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“The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment.

RESULTS:

Cannabis sativa is a plant rich in more than 100 types of cannabinoids. Besides exogenous plant cannabinoids, mammalian endocannabinoids and synthetic cannabinoid analogues have been identified. Cannabinoid receptors type 1 (CB1) and type 2 (CB2) have been isolated and characterized from mammalian cells. Through cannabinoid receptor and non-receptor signaling pathways, cannabinoids show specific cytotoxicity against tumor cells, while protecting healthy tissue from apoptosis. The dual antiproliferative and proapoptotic effects of cannabinoids and associated signaling pathways have been investigated on a large panel of cancer cell lines. Cannabinoids also display potent anticancer activity against tumor xenografts, including tumors that express high resistance to standard chemotherapeutics. Few studies have investigated the possible synergistic effects of cannabinoids with standard oncology therapies, and are based on the preclinically confirmed concept of “cannabinoid sensitizers.” Also, clinical trials aimed to confirm the antineoplastic activity of cannabinoids have only been evaluated on a small number of subjects, with no consensus conclusions regarding their effectiveness.

CONCLUSIONS:

A large number of cannabinoid compounds have been discovered, developed, and used to study the effects of cannabinoids on cancers in model systems. However, few clinical trials have been conducted on the use of cannabinoids in the treatment of cancers in humans. Further studies require extensive monitoring of the effects of cannabinoids alone or in combination with standard anticancer strategies. With such knowledge, cannabinoids could become a therapy of choice in contemporary oncology.”

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Cannabinoids as Modulators of Cell Death: Clinical Applications and Future Directions.

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“Endocannabinoids are bioactive lipids that modulate various physiological processes through G-protein-coupled receptors (CB1 and CB2) and other putative targets. By sharing the activation of the same receptors, some phytocannabinoids and a multitude of synthetic cannabinoids mimic the effects of endocannabinoids.

In recent years, a growing interest has been dedicated to the study of cannabinoids properties for their analgesic, antioxidant, anti-inflammatory and neuroprotective effects. In addition to these well-recognized effects, various studies suggest that cannabinoids may affect cell survival, cell proliferation or cell death. These observations indicate that cannabinoids may play an important role in the regulation of cellular homeostasis and, thus, may contribute to tissue remodelling and cancer treatment.

For a long time, the study of cannabinoid receptor signalling has been focused on the classical adenylyl cyclase/cyclic AMP/protein kinase A (PKA) pathway. However, this pathway does not totally explain the wide array of biological responses to cannabinoids. In addition, the diversity of receptors and signalling pathways that endocannabinoids modulate offers an interesting opportunity for the development of specific molecules to disturb selectively the endogenous system.

Moreover, emerging evidences suggest that cannabinoids ability to limit cell proliferation and to induce tumour-selective cell death may offer a novel strategy in cancer treatment.

This review describes the main properties of cannabinoids in cell death and attempts to clarify the different pathways triggered by these compounds that may help to understand the complexity of respective molecular mechanisms and explore the potential clinical benefit of cannabinoids use in cancer therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/28425013

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The role of cannabinoids in dermatology

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“Twenty-eight states currently allow for comprehensive public medical cannabis programs, and this number continues to grow.  Approximately 1 in 10 adult cannabis users in the United States use it for medical purposes. Numerous studies have investigated its uses for chronic pain, spasticity, anorexia, and nausea. In recent years, researchers have also investigated its use for the treatment of dermatologic conditions including pruritus, inflammatory skin disease, and skin cancer.”

http://www.jaad.org/article/S0190-9622(17)30308-0/abstract

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The Inhibitory Effect of S-777469, a Cannabinoid Type 2 Receptor Agonist, on Skin Inflammation in Mice.

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“We investigated the effects of S-777469 (1-[[6-Ethyl-1-[4-fluorobenzyl]-5-methyl-2-oxo-1, 2-dihydropyridine-3-carbonyl]amino]-cyclohexanecarboxylic acid), a novel cannabinoid type 2 receptor (CB2) agonist, on 1-fluoro-2,4-dinitrobenzene (DNFB)-induced ear inflammation and mite antigen-induced dermatitis in mice. The oral administration of S-777469 significantly suppressed DNFB-induced ear swelling in a dose-dependent manner. In addition, S-777469 significantly alleviated mite antigen-induced atopic dermatitis-like skin lesions in NC/Nga mice. A histological analysis revealed that S-777469 significantly reduced the epidermal thickness and the number of mast cells infiltrating skin lesions. We demonstrated that S-777469 inhibited mite antigen-induced eosinophil accumulation in skin lesions and an endogenous CB2 ligand, 2-arachidonoylglycerol (2-AG)-induced eosinophil migration in vitro. Moreover, we confirmed that 2-AG levels significantly increased in skin lesions of mite antigen-induced dermatitis model. Together, these results suggest that S-777469 inhibits skin inflammation in mice by blocking the activities of 2-AG.”

https://www.ncbi.nlm.nih.gov/pubmed/28214870

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