Category Archives: Cancer

Future Aspects for Cannabinoids in Breast Cancer Therapy.

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“Cannabinoids (CBs) from Cannabis sativa provide relief for tumor-associated symptoms (including nausea, anorexia, and neuropathic pain) in the palliative treatment of cancer patients.

Additionally, they may decelerate tumor progression in breast cancer patients.

Indeed, the psychoactive delta-9-tetrahydrocannabinol (THC), non-psychoactive cannabidiol (CBD) and other CBs inhibited disease progression in breast cancer models.

The effects of CBs on signaling pathways in cancer cells are conferred via G-protein coupled CB-receptors (CB-Rs), CB1-R and CB2-R, but also via other receptors, and in a receptor-independent way.

THC is a partial agonist for CB1-R and CB2-R; CBD is an inverse agonist for both.

In breast cancer, CB1-R expression is moderate, but CB2-R expression is high, which is related to tumor aggressiveness. CBs block cell cycle progression and cell growth and induce cancer cell apoptosis by inhibiting constitutive active pro-oncogenic signaling pathways, such as the extracellular-signal-regulated kinase pathway.

They reduce angiogenesis and tumor metastasis in animal breast cancer models. CBs are not only active against estrogen receptor-positive, but also against estrogen-resistant breast cancer cells. In human epidermal growth factor receptor 2-positive and triple-negative breast cancer cells, blocking protein kinase B- and cyclooxygenase-2 signaling via CB2-R prevents tumor progression and metastasis.

Furthermore, selective estrogen receptor modulators (SERMs), including tamoxifen, bind to CB-Rs; this process may contribute to the growth inhibitory effect of SERMs in cancer cells lacking the estrogen receptor.

In summary, CBs are already administered to breast cancer patients at advanced stages of the disease, but they might also be effective at earlier stages to decelerate tumor progression.”

 https://www.ncbi.nlm.nih.gov/pubmed/30987191
https://www.mdpi.com/1422-0067/20/7/1673

The onus of cannabinoids in interrupting the molecular odyssey of breast cancer: A critical perspective on UPRER and beyond.

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Saudi Pharmaceutical Journal

“Cannabinoids, commonly used for medicinal and recreational purposes, consist of various complex hydrophobic molecules obtained from Cannabis sativa L. Acting as an inhibitory molecule; they have been investigated for their antineoplastic effect in various breast tumor models. Lately, it was found that cannabinoid treatment not only stimulates autophagy-mediated apoptotic death of tumor cells through unfolded protein response (UPRER) activated downstream effectors, but also imposes cell cycle arrest. The exploitation of UPRER tumors as such is believed to be a major molecular event and is therefore employed in understanding the development and progression of breast tumor. Simultaneously, the data on clinical trials following administration of cannabinoid is currently being explored to find its role not only in palliation but also in the treatment of breast cancer. The present study summarizes new achievements in understanding the extent of therapeutic progress and highlights recent developments in cannabinoid biology towards achieving a better cure of breast cancer through the exploitation of different cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/30976189

https://www.sciencedirect.com/science/article/pii/S1319016419300064?via%3Dihub

Impact of Medical Cannabis on Patient-Reported Symptoms for Patients With Cancer Enrolled in Minnesota’s Medical Cannabis Program.

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Journal of Oncology Practice

“Minnesota’s medical cannabis program is unique, in that it routinely collects patient-reported scores on symptoms. This article focuses on changes in symptom severity reported by patients with cancer during their first 4 months of program participation.

MATERIALS AND METHODS::

Patients with cancer in Minnesota’s medical cannabis program reported symptoms (anxiety, lack of appetite, depression, disturbed sleep, fatigue, nausea, pain, and vomiting) at their worst over the last 24 hours before each medical cannabis purchase. Baseline scores on each of the eight symptoms were statistically compared with the average symptom scores reported in the first 4 months of program participation. Symptom scores were also calculated as percent change from baseline, with patients achieving and maintaining at least a 30% reduction in symptoms reported in this article. Patients also reported intensity of adverse effects.

RESULTS::

A significant reduction in scores was found across all symptoms when comparing baseline scores with the average score submitted within the first 4 months of program participation (all Ps < .001). The proportion of patients achieving 30% or greater symptom reduction within the first 4 months of program participation varied from 27% (fatigue) to 50% (vomiting), with a smaller proportion both achieving and maintaining those improvements. Adverse effects were reported in a small proportion of patients (10.5%).

CONCLUSION::

Patients with cancer enrolled in Minnesota’s medical cannabis program showed significant reduction across all eight symptoms assessed within 4 months of program participation. Medical cannabis was well tolerated, and some patients attained clinically meaningful and lasting levels of improvement.”

https://www.ncbi.nlm.nih.gov/pubmed/30860938

http://ascopubs.org/doi/10.1200/JOP.18.00562

“Medical cannabis reduces severity of symptoms for some patients with cancer, according to new study”

https://www.health.state.mn.us/news/pressrel/2019/cannabis040819.html

Members of the endocannabinoid system are distinctly regulated in inflammatory bowel disease and colorectal cancer.

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Scientific Reports

“Preclinical studies have demonstrated that the endocannabinoid system (ECS) plays an important role in the protection against intestinal inflammation and colorectal cancer (CRC); however, human data are scarce. We determined members of the ECS and related components of the ‘endocannabinoidome’ in patients with inflammatory bowel disease (IBD) and CRC, and compared them to control subjects. Anandamide (AEA) and oleoylethanolamide (OEA) were increased in plasma of ulcerative colitis (UC) and Crohn’s disease (CD) patients while 2-arachidonoylglycerol (2-AG) was elevated in patients with CD, but not UC. 2-AG, but not AEA, PEA and OEA, was elevated in CRC patients. Lysophosphatidylinositol (LPI) 18:0 showed higher levels in patients with IBD than in control subjects whereas LPI 20:4 was elevated in both CRC and IBD. Gene expression in intestinal mucosal biopsies revealed different profiles in CD and UC. CD, but not UC patients, showed increased gene expression for the 2-AG synthesizing enzyme diacylglycerol lipase alpha. Transcripts of CNR1 and GPR119 were predominantly decreased in CD. Our data show altered plasma levels of endocannabinoids and endocannabinoid-like lipids in IBD and CRC and distinct transcript profiles in UC and CD. We also report alterations for less known components in intestinal inflammation, such as GPR119, OEA and LPI.”

 https://www.ncbi.nlm.nih.gov/pubmed/30787385
https://www.nature.com/articles/s41598-019-38865-4

Characterization of Cancer-Induced Nociception in a Murine Model of Breast Carcinoma.

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“Severe and poorly treated pain often accompanies breast cancer. Thus, novel mechanisms involved in breast cancer-induced pain should be investigated. Then, it is necessary to characterize animal models that are reliable with the symptoms and progression of the disease as observed in humans. Explaining cancer-induced nociception in a murine model of breast carcinoma was the aim of this study. 4T1 (104) lineage cells were inoculated in the right fourth mammary fat pad of female BALB/c mice; after this, mechanical and cold allodynia, or mouse grimace scale (MGS) were observed for 30 days. To determine the presence of bone metastasis, we performed the metastatic clonogenic test and measure calcium serum levels. At 20 days after tumor induction, the antinociceptive effect of analgesics used to relieve pain in cancer patients (acetaminophen, naproxen, codeine or morphine) or a cannabinoid agonist (WIN 55,212-2) was tested. Mice inoculated with 4T1 cells developed mechanical and cold allodynia and increased MGS. Bone metastasis was confirmed using the clonogenic assay, and hypercalcemia was observed 20 days after cells inoculation. All analgesic drugs reduced the mechanical and cold allodynia, while the MGS was decreased only by the administration of naproxen, codeine, or morphine. Also, WIN 55,212-2 improved all nociceptive measures. This pain model could be a reliable form to observe the mechanisms of breast cancer-induced pain or to observe the efficacy of novel analgesic compounds.”

https://www.ncbi.nlm.nih.gov/pubmed/30850915

https://link.springer.com/article/10.1007%2Fs10571-019-00666-8

Striking lung cancer response to self-administration of cannabidiol: A case report and literature review.

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SAGE Journals

“In spite of new drugs, lung cancer is associated with a very poor prognosis. While targeted therapies are improving outcomes, it is not uncommon for many patients to have only a partial response, and relapse during follow-up. Thus, new drugs or re-evaluation of existing therapies used to treat other non-malignant diseases (drug repurposing) are still needed. While this research both in vitroand in vivo is being carried out, it is important to be attentive to patients where the disease responds to treatments not considered standard in clinical practice.

We report here a patient with adenocarcinoma of the lung who, after declining chemotherapy and radiotherapy, presented with tumour response following self-administration of cannabidiol, a non-psychoactive compound present in Cannabis sativa. Prior work has shown that cannabidiol may have anti-neoplastic properties and enhance the immune response to cancer.

The data presented here indicate that cannabidiol might have led to a striking response in a patient with lung cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/30815264

https://journals.sagepub.com/doi/10.1177/2050313X19832160

CBN: The cancer fighting Cannabinoid

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“CBN, cannabinol, is a mildly psychoactive cannabinoid found within the cannabis plant. We examine the very complex mechanisms that give allowance for this cannabinoids entrance into the cell membrane and its effect on cannabinoid receptors and the inhibition of the enzyme adenylate cyclase that is responsible for phosphate production. Prior study bears weight accordingly; we examine this phosphate as a potent energy source, the enzymes responsible for cell replication cycle and inhibition thereof. Moreover, how IL-2, (Interleukin-2), a type of cytokine signaling molecule in the immune system stops being produced when immune T cells are exposed to cannabinoids. How IL-2 stimulates the cell cycle via promotion of the c-Fos protein and is responsible for modulation of the immune response. This is shown by Faubert and Kaminski, that administration of CBN can slow cell replication and endure cell death (apoptosis).”

http://www.imedpub.com/proceedings/cbn-the-cancer-fighting-cannabinoid-5528.html

“Programmed Cell Death (Apoptosis)” http://www.ncbi.nlm.nih.gov/books/NBK26873/

The Endocannabinoid System, Our Universal Regulator

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“The endocannabinoid system (ECS) plays a very important role in the human body for our survival. This is due to its ability to play a critical role in maintaining the homeostasis of the human body, which encompasses the brain, endocrine, and immune system, to name a few. ECS is a unique system in multiple dimensions.

To begin with, it is a retrograde system functioning post- to pre-synapse, allowing it to be a “master regulator” in the body. Secondly, it has a very wide scope of influence due to an abundance of cannabinoid receptors located anywhere from immune cells to neurons. Finally, cannabinoids are rapidly synthesized and degraded, so they do not stay in the body for very long in high amounts, possibly enabling cannabinoid therapy to be a safer alternative to opioids or benzodiazepines. This paper will discuss how ECS functions through the regulation of neurotransmitter function, apoptosis, mitochondrial function, and ion-gated channels. The practical applications of the ECS, as well as the avenues for diseases such as epilepsy, cancer, amyotrophic lateral sclerosis (ALS), and autism, which have no known cure as of now, will be explored.

The ECS is one of the, if not the most, important systems in our body. Its role in the homeostatic function of our body is undeniable, and its sphere of influence is incredible. Additionally, it also plays a major role in apoptotic diseases, mitochondrial function, and brain function.

Its contribution is more than maintaining homeostasis; it also has a profound ability in regulation. Working in a retrograde fashion and with a generally inhibitory nature, ECS can act as a “kill switch.” However, it has been shown to play an inhibitory or stimulatory role based on the size of the influx of cannabinoids, resulting in a bimodal regulation. Furthermore, due to the nature of the rate of degradation of cannabinoids, it does not have as many long-term side effects as most of the current drugs on the market.

The ECS may not only provide answers for diseases with no known cures, but it could change the way we approach medicine. This system would allow us to change our focus from invasive pharmacological interventions (i.e. SSRIs for depression, benzodiazepines for anxiety, chemotherapies for cancer) to uncovering the mystery of why the body is failing to maintain homeostasis. Understanding the roles of ECS in these diseases confers a new direction for medicine which may eradicate the use of some of the less tolerable therapeutics.”

https://www.jyi.org/2018-june/2018/6/1/the-endocannabinoid-system-our-universal-regulator

Inhibition of ATM kinase upregulates levels of cell death induced by cannabidiol and γ-irradiation in human glioblastoma cells.

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Related image“Despite advances in glioblastoma (GBM) therapy, prognosis of the disease remains poor with a low survival rate.

Cannabidiol (CBD) can induce cell death and enhance radiosensitivity of GBM but not normal astrocytes.

Inhibition of ATM kinase is an alternative mechanism for radiosensitization of cancer cells.

In this study, we increased the cytotoxic effects of the combination of CBD and γ-irradiation in GBM cells through additional inhibition of ATM kinase with KU60019, a small molecule inhibitor of ATM kinase.

We observed in GBM cells treated by CBD, γ-irradiation and KU60019 high levels of apoptosis together with strong upregulation of the percentage of G2/M-arrested cells, blockade of cell proliferation and a massive production of pro-inflammatory cytokines.

Overall, these changes caused both apoptotic and non-apoptotic inflammation-linked cell death. Furthermore, via JNK-AP1 activation in concert with active NF-κB, CBD upregulated gene and protein expression of DR5/TRAIL-R2 and sensitize GBM cells to TRAIL-induced apoptosis. In contrast, CBD notably decreased in GBM surface levels of PD-L1, a critical immune checkpoint agent for T-lymphocytes. We also used in the present study TS543 human proneural glioma cells that were grown as spheroid culture. TS543 neurospheres exhibited dramatic sensitivity to CBD-mediated killing that was additionally increased in combination with γ-irradiation and KU60019.

In conclusion, treatment of human GBM by the triple combination (CBD, γ-irradiation and KU60019) could significantly increase cell death levels in vitro and potentially improve the therapeutic ratio of GBM.”

https://www.ncbi.nlm.nih.gov/pubmed/30783513

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=26582&path[]=82682

Cannabinoids: a new approach for pain control?

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“To analyze available data related to the use of cannabinoids in medicine, with a special focus on pain management in cancer. The use of cannabis for medical purposes is growing but there are still numerous questions to be solved: effectiveness, safety, and specific indications.

RECENT FINDINGS:

There is considerable variation between countries in the approaches taken, reflecting a variety of historical and cultural factors and despite few randomized controlled studies using natural cannabinoids, there is a trend to state that the use of cannabis should be taken seriously as a potential treatment of cancer-related pain. Cannabidiol, a nontoxic phytocannabinoid with few side-effects is promising in various indications in medicine.

SUMMARY:

The endocannabinoid system is a potential therapeutic target. Cannabinoids may be considered as potential adjuvant in cancer-related pain management. Cannabidiol appears to be the drug of choice. Analgesic trial designs should evolve to get closer to real-life practice and to avoid biases.”

https://www.ncbi.nlm.nih.gov/pubmed/30789867

https://insights.ovid.com/crossref?an=00001622-900000000-00002