THC Total Health Care

A comprehensive encyclopedia of THC related medical research articles

CBD Enhances the Anticancer Effects of THC

Posted on February 5, 2018 by David Worrell

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“Δ9-Tetrahydrocannabinol (Δ9-THC) and other cannabinoids can act as direct anticancer agents in multiple types of cancer in culture and in vivo.

Cannabidiol Enhances the Inhibitory Effects of Δ9-Tetrahydrocannabinol on Human GlioblastomaCell Proliferation and Survival.

Δ9-THC and Cannabidiol Inhibit the Growth of Multiple Glioblastoma Cell Lines.

Cannabidiol Enhances the Inhibitory Effects of Δ9-THC on Glioblastoma Cell Growth.

Combination treatments with cannabinoids may improve overall efficacy”

https://www.scribd.com/document/50154001/CBD-Enhances-the-Anticancer-Effects-of-THC-Journal-MCT-Marcu

“Cannabidiol Enhances the Inhibitory Effects of Δ⁹-Tetrahydrocannabinol on Human Glioblastoma Cell Proliferation and Survival” http://mct.aacrjournals.org/content/9/1/180.full

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Hypoxia-induced inhibition of the endocannabinoid system in glioblastoma cells.

Posted on November 14, 2017 by David Worrell

Journal Cover

“The endocannabinoid system plays an important role in the regulation of physiological and pathological conditions, including inflammation and cancer.

Hypoxia is a fundamental phenomenon for the establishment and maintenance of the microenvironments in various physiological and pathological conditions. However, the influence of hypoxia on the endocannabinoid system is not fully understood. In the present study, we investigated the effects of hypoxia on the endocannabinoid system in malignant brain tumors.

Although cannabinoid receptor (CB) engagement induces cell death in U-87 MG cells in normoxic conditions, CB agonist-induced death was attenuated in hypoxic conditions. These results suggest that hypoxia modifies the endocannabinoid system in glioblastoma cells.

Hypoxia-induced inhibition of the endocannabinoid system may aid the development of glioblastoma.”

https://www.ncbi.nlm.nih.gov/pubmed/29130103

https://www.spandidos-publications.com/10.3892/or.2017.6048

A Review of the Therapeutic Antitumor Potential of Cannabinoids.

Posted on August 12, 2017 by David Worrell

“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.”

https://www.ncbi.nlm.nih.gov/pubmed/28799775

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Regulation of human glioblastoma cell death by combined treatment of cannabidiol, γ-radiation and small molecule inhibitors of cell signaling pathways.

Posted on June 10, 2017 by David Worrell

“Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. The challenging problem in cancer treatment is to find a way to upregulate radiosensitivity of GBM while protecting neurons and neural stem/progenitor cells in the brain. The goal of the present study was upregulation of the cytotoxic effect of γ-irradiation in GBM by non-psychotropic and non-toxic cannabinoid, cannabidiol (CBD). We emphasized three main aspects of signaling mechanisms induced by CBD treatment (alone or in combination with γ-irradiation) in human GBM that govern cell death: 1) CBD significantly upregulated the active (phosphorylated) JNK1/2 and MAPK p38 levels with the subsequent downregulation of the active phospho-ERK1/2 and phospho-AKT1 levels. MAPK p38 was one of the main drivers of CBD-induced cell death, while death levels after combined treatment of CBD and radiation were dependent on both MAPK p38 and JNK. Both MAPK p38 and JNK regulate the endogenous TRAIL expression. 2) NF-κB p65-P(Ser536) was not the main target of CBD treatment and this transcription factor was found at high levels in CBD-treated GBM cells. Additional suppression of p65-P(Ser536) levels using specific small molecule inhibitors significantly increased CBD-induced apoptosis. 3) CBD treatment substantially upregulated TNF/TNFR1 and TRAIL/TRAIL-R2 signaling by modulation of both ligand and receptor levels followed by apoptosis. Our results demonstrate that radiation-induced death in GBM could be enhanced by CBD-mediated signaling in concert with its marginal effects for neural stem/progenitor cells and astrocytes. It will allow selecting efficient targets for sensitization of GBM and overcoming cancer therapy-induced severe adverse sequelae.”

https://www.ncbi.nlm.nih.gov/pubmed/28599319

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=18240&path[]=58479

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Pharmacogenetics of Cannabinoids.

Posted on May 26, 2017 by David Worrell

European Journal of Drug Metabolism and Pharmacokinetics

“Although the application of medical marijuana and cannabinoid drugs is controversial, it is a part of modern-day medicine. The list of diseases in which cannabinoids are promoted as a treatment is constantly expanding. Cases of significant improvement in patients with a very poor prognosis of glioma or epilepsy have already been described. However, the occurrence of side effects is still difficult to estimate, and the current knowledge of the therapeutic effects of cannabinoids is still insufficient. In our opinion, the answers to many questions and concerns regarding the medical use of cannabis can be provided by pharmacogenetics. Knowledge based on proteins and molecules involved in the transport, action, and metabolism of cannabinoids in the human organism leads us to predict candidate genes which variations are responsible for the presence of the therapeutic and side effects of medical marijuana and cannabinoid-based drugs. We can divide them into: receptor genes-CNR1, CNR2, TRPV1, and GPR55, transporters-ABCB1, ABCG2, SLC6A, biotransformation, biosynthesis, and bioactivation proteins encoded by CYP3A4, CYP2C19, CYP2C9, CYP2A6, CYP1A1, COMT, FAAH, COX2, ABHD6, ABHD12 genes, and also MAPK14. This review organizes the current knowledge in the context of cannabinoids pharmacogenetics according to individualized medicine and cannabinoid drugs therapy.” https://www.ncbi.nlm.nih.gov/pubmed/28534260

“There is a feeling that the next milestone, after legal acceptance of medical marijuana, will be intensive pharmacogenetic-oriented study of individual populations, which hopefully explain the previous contradictory results and identify in the future genetic markers to personalize cannabinoids treatment.” https://link.springer.com/article/10.1007%2Fs13318-017-0416-z

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

Posted on April 21, 2017 by David Worrell

Image result for Rev Physiol Biochem Pharmacol.

“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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Can Marijuana Cure Cancer? Pharmaceutical Company Developing Cannabis Medicine To Treat Brain Cancer

Posted on February 10, 2017 by David Worrell

“Can Marijuana Cure Cancer? Pharmaceutical Company Developing Cannabis Medicine To Treat Brain Cancer” http://www.ibtimes.com/can-marijuana-cure-cancer-pharmaceutical-company-developing-cannabis-medicine-treat-2489282

“GW Pharmaceuticals Achieves Positive Results in Phase 2 Proof of Concept Study in Glioma” http://ir.gwpharm.com/releasedetail.cfm?ReleaseID=1010672

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

“Drug Company Claims to Have Marijuana Treatment That Could Increase Lifespan of Brain Cancer Patients” http://www.complex.com/life/2017/02/gw-pharmaceuticals-claims-to-have-treatment-that-could-increase-lifespan-of-brain-cancer-patients

“GW Pharma’s cannabis-derived combo med helps brain cancer patients” http://www.fiercebiotech.com/biotech/gw-pharma-s-cannabis-derived-combo-med-helps-brain-cancer-patients

“GW pharmaceuticals to develop oncology portfolio after cannabis medication shows promising results” http://www.telegraph.co.uk/business/2017/02/07/gw-pharmaceuticals-develop-oncology-portfolio-cannabis-medication/

“GW Pharma is touting claims that a combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) produced positive survival benefits in a small study of 21 patients with recurrent glioblastoma multiforme, a common form of brain cancer.” https://endpts.com/gw-touts-positive-survival-benefit-in-small-brain-cancer-study-ablynx-files-for-ultra-rare-disease-drug-ok/

“GW Pharmaceuticals Is Set to Benefit as Cannabis Takes on Cancer” https://www.thestreet.com/story/13996559/1/gw-pharmaceuticals-is-set-to-benefit-as-cannabis-takes-on-cancer.html

“GW Pharmaceuticals Achieves Positive Results In Phase 2 Proof Of Concept Study In Glioma” https://www.clinicalleader.com/doc/gw-pharmaceuticals-phase-proof-of-concept-study-in-glioma-0001

“Here’s How Marijuana May Help Brain Cancer Patients Live Longer” http://www.menshealth.com/health/marijuana-drug-treats-brain-cancer?utm_source=facebook.com&utm_medium=social&utm_campaign=sharebutton

“New pharmaceutical drug uses marijuana to treat brain cancer” http://blog.sfgate.com/smellthetruth/2017/02/09/new-pharmaceutical-drug-uses-marijuana-to-treat-brain-cancer/

“Medicine’s Secret Weapon Against Brain Cancer Is Weed” https://www.inverse.com/article/27578-cancer-treatment-marijuana-gw-pharmaceuticals?utm_source=facebook.com&utm_medium=on_site&utm_campaign=desktop

“The Next Big Brain Cancer Drug Could Come from Marijuana” http://fortune.com/2017/02/07/gw-pharmaceuticals-marijuana-brain-cancer/

“Can Weed Cure Cancer? Marijuana Helps Fight Glioblastoma Multiforme, One Of The Deadliest Forms Of Brain Cancer” http://www.medicaldaily.com/marijuana-just-might-help-cure-one-deadliest-forms-brain-cancer-410947 http://www.thctotalhealthcare.com/category/brain-cancer/

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A Science Based Evaluation of Cannabis and Cancer

Posted on November 18, 2016 by David Worrell

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“The irritant properties of all smoke will naturally tend to promote a pro-inflammatory immune response with the corresponding production of potentially carcinogenic free radicals. However, cannabis promotes immune deviation to an anti-inflammatory Th2 response via immune-system specific CB2 receptors. Thus, the natural pharmacological properties of marijuana’s cannabinoids, that are not present in tobacco smoke, would minimize potential irritant initiated carcinogenesis. In contrast, the pharmacological activities of tobacco smoke would tend to amplify its carcinogenic potential by inhibiting the death of genetically damaged cells. Together these observations support the epidemiological study of the Kaiser Foundation that did not find cannabis smoking to be associated with cancer incidence. Additionally, the demonstrated cancer killing activities of cannabinoids has been ignored. Cannabinoids have been shown to kill some leukemia and lymphoma, breast and prostate, pheochromocytoma, glioma and skin cancer cells in cell culture and in animals.” http://www.bmj.com/rapid-response/2011/10/29/science-based-evaluation-cannabis-and-cancer

Novel indole-based compounds that differentiate alkylindole-sensitive receptors from cannabinoid receptors and microtubules: Characterization of their activity on glioma cell migration.

Posted on November 13, 2016 by David Worrell

Image result for Pharmacol Res.

“Indole-based compounds, such as the alkyl-indole (AI) compound WIN55212-2, activate the cannabinoid receptors, CB₁ and CB₂, two well-characterized G protein-coupled receptors (GPCR). Reports indicate that several indole-based cannabinoid agonists, including WIN55212-2, lack selectivity and interact with at least two additional targets: AI-sensitive GPCRs and microtubules. Studying how indole-based compounds modulate the activity of these 4 targets has been difficult as selective chemical tools were not available. Here we report the pharmacological characterization of six newly-developed indole-based compounds (ST-11, ST-23, ST-25, ST-29, ST-47 and ST-48) that exhibit distinct binding affinities at AI-sensitive receptors, cannabinoid CB₁ and CB₂ receptors and the colchicine site of tubulin. Several compounds exhibit some level of selectivity for AI-sensitive receptors, including ST-11 that binds AI-sensitive receptors with a K_d of 52nM and appears to have a weaker affinity for the colchicine site of tubulin (K_d=3.2μM) and does not bind CB₁/CB₂ receptors. Leveraging these characteristics, we show that activation of AI-sensitive receptors with ST-11 inhibits both the basal and stimulated migration of the Delayed Brain Tumor (DBT) mouse glioma cell line. Our study describes a new series of indole-based compounds that enable the pharmacological and functional differentiation of alkylindole-sensitive receptors from cannabinoidreceptors and microtubules.”

https://www.ncbi.nlm.nih.gov/pubmed/27832960

Quantitative analyses of synergistic responses between cannabidiol and DNA-damaging agents on the proliferation and viability of glioblastoma and neural progenitor cells in culture.

Posted on November 10, 2016 by David Worrell

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“Evidence suggests that the non-psychotropic cannabis-derived compound, cannabidiol (CBD), has anti-neoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM).

DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM.

Here we studied the anti-proliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures.

This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system (CNS) toxicity.

We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells.

Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells.

Co-treatment regiments combining CBD and DNA-damaging agents produced synergistic anti-proliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs.

Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells.

Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little-to-no therapeutic window when considering NPCs.”

https://www.ncbi.nlm.nih.gov/pubmed/27821713

“Definition of antineoplastic: inhibiting or preventing the growth and spread of tumors or malignant cells” http://www.merriam-webster.com/dictionary/antineoplastic

“Cannabidiol Enhances the Inhibitory Effects of Δ9-Tetrahydrocannabinol on Human Glioblastoma Cell Proliferation and Survival” http://mct.aacrjournals.org/content/9/1/180.full