Category Archives: Cancer

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Cannabis and Anti-Cancer Drugs: Societal Usage and Expected Pharmacological Interactions – A Review.

Category : Cancer

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Cannabis and Anti-Cancer Drugs: Societal Usage and Expected Pharmacological Interactions – A Review.

Fundam Clin Pharmacol. 2018 Apr 16;:

Authors: Bouquié R, Deslandes G, Mazaré H, Cogné M, Mahé J, Grégoire M, Jolliet P

Abstract
Cannabis is a plant that has been used for centuries to relieve a wide range of symptoms. Since the 1960s, interest in medical research into this plant has grown steadily. Already very popular for recreational use, a growing number of consumers not accustomed to using cannabis for psychoactive purposes, have begun to use it as an alternative or complement to mainstream pharmaceutical medicines. The principal unsubstantiated or “social” uses of cannabis are based mainly on data that is at best controversial, but usually not scientifically proven. The aim of this review is to identify the scientific basis and reasons that lead patients with cancer to consume cannabis, and also to identify whether there is a risk of interaction between cannabis and anti-cancer medicines through drug transporters (P-glycoprotein and other ABC-superfamily members) Cytochromes P450 (3A, 1A, 2B, 2C 2D families…) and glucuronyl-transferases. This article is protected by copyright. All rights reserved.

PMID: 29660159 [PubMed – as supplied by publisher]

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[Cannabinoid therapy in practice].

Category : Cancer

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[Cannabinoid therapy in practice].

Urologe A. 2018 Apr 12;:

Authors: Rasche T, Emmert D, Stieber C, Mücke M, Conrad R

Abstract
BACKGROUND: In recent years, the media and scientists have shown increased interest in cannabis-based drugs.
OBJECTIVES: Background information about cannabis-based drugs and their mechanism of action as well as discussion of possible applications as supportive therapy or in palliative medicine, respectively, are presented.
MATERIALS AND METHODS: The recent literature was examined and evaluated.
RESULTS: In many medical fields, we do not have sufficient evidence for the efficacy of cannabinoids. In German pharmaceutical legislation, the use of nabiximols for the treatment of intermediate to severe, therapy-resistant spasticity in multiple sclerosis is the only approved indication for cannabis-based drugs. Furthermore, in view of the current evidence cannabinoids, combined with established treatments and as part of an individual therapeutic attempt, can be used for neuropathic pain, cancer-associated pain and human immunodeficiency virus (HIV)-related cachexia.
CONCLUSIONS: In most cases, today’s assessment of cannabinoids relies on studies that are classified as low evidence. Therefore, further studies which involve more participants and evaluate long-term effects are needed.

PMID: 29651709 [PubMed – as supplied by publisher]

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

Category : Cancer

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

Cancer Med. 2018 Feb 23;:

Authors: Śledziński P, Zeyland J, Słomski R, Nowak A

Abstract
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.

PMID: 29473338 [PubMed – as supplied by publisher]

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Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis.

Category : Cancer

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Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis.

J Physiol Biochem. 2018 Feb 13;:

Authors: Fonseca BM, Correia-da-Silva G, Teixeira NA

Abstract
Among a variety of phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most promising therapeutic compounds. Besides the well-known palliative effects in cancer patients, cannabinoids have been shown to inhibit in vitro growth of tumor cells. Likewise, the major endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), induce tumor cell death. The purpose of the present study was to characterize cannabinoid elements and evaluate the effect of cannabinoids in endometrial cancer cell viability. The presence of cannabinoid receptors, transient receptor potential vanilloid 1 (TRPV1), and endocannabinoid-metabolizing enzymes were determined by qRT-PCR and Western blot. We also examined the effects and the underlying mechanisms induced by eCBs and phytocannabinoids in endometrial cancer cell viability. Besides TRPV1, both EC cell lines express all the constituents of the endocannabinoid system. We observed that at concentrations higher than 5 μM, eCBs and CBD induced a significant reduction in cell viability in both Ishikawa and Hec50co cells, whereas THC did not cause any effect. In Ishikawa cells, contrary to Hec50co, treatment with AEA and CBD resulted in an increase in the levels of activated caspase -3/-7, in cleaved PARP, and in reactive oxygen species generation, confirming that the reduction in cell viability observed in the MTT assay was caused by the activation of the apoptotic pathway. Finally, these effects were dependent on TRPV1 activation and intracellular calcium levels. These data indicate that cannabinoids modulate endometrial cancer cell death. Selective targeting of TPRV1 by AEA, CBD, or other stable analogues may be an attractive research area for the treatment of estrogen-dependent endometrial carcinoma. Our data further support the evaluation of CBD and CBD-rich extracts for the potential treatment of endometrial cancer, particularly, that has become non-responsive to common therapies.

PMID: 29441458 [PubMed – as supplied by publisher]

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Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol.

Category : Cancer

Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol.

Fitoterapia. 2018 Feb 07;:

Authors: Smeriglio A, Giofrè SV, Galati EM, Monforte MT, Cicero N, D’Angelo V, Grassi G, Circosta C

Abstract
Aldose reductase (ALR2) is a key enzyme involved in diabetic complications and the search for new aldose reductase inhibitors (ARIs) is currently very important. The synthetic ARIs are often associated with deleterious side effects and medicinal and edible plants, containing compounds with aldose reductase inhibitory activity, could be useful for prevention and therapy of diabetic complications. Non-psychotropic phytocannabinoids exert multiple pharmacological effects with therapeutic potential in many diseases such as inflammation, cancer, diabetes. Here, we have investigated the inhibitory effects of extracts and their fractions from two Cannabis sativa L. chemotypes with high content of cannabidiol (CBD)/cannabidiolic acid (CBDA) and cannabigerol (CBG)/cannabigerolic acid (CBGA), respectively, on human recombinant and pig kidney aldose reductase activity in vitro. A molecular docking study was performed to evaluate the interaction of these cannabinoids with the active site of ALR2 compared to known ARIs. The extracts showed significant dose-dependent aldose reductase inhibitory activity (>70%) and higher than fractions. The inhibitory activity of the fractions was greater for acidic cannabinoid-rich fractions. Comparative molecular docking results have shown a higher stability of the ALR2-cannabinoid acids complex than the other inhibitors. The extracts of Cannabis with high content of non-psychotropic cannabinoids CBD/CBDA or CBG/CBGA significantly inhibit aldose reductase activity. These results may have some relevance for the possible use of C. sativa chemotypes based preparations as aldose reductase inhibitors.

PMID: 29427593 [PubMed – as supplied by publisher]

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Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation.

Category : Cancer

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Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation.

Sci Rep. 2017 Nov 06;7(1):14542

Authors: Zgair A, Lee JB, Wong JCM, Taha DA, Aram J, Di Virgilio D, McArthur JW, Cheng YK, Hennig IM, Barrett DA, Fischer PM, Constantinescu CS, Gershkovich P

Abstract
Cannabidiol (CBD) and ∆(9)-tetrahydrocannabinol (THC) have well documented immunomodulatory effects in vitro, but not following oral administration in humans. Here we show that oral co-administration of cannabinoids with lipids can substantially increase their intestinal lymphatic transport in rats. CBD concentrations in the lymph were 250-fold higher than in plasma, while THC concentrations in the lymph were 100-fold higher than in plasma. Since cannabinoids are currently in clinical use for the treatment of spasticity in multiple sclerosis (MS) patients and to alleviate nausea and vomiting associated with chemotherapy in cancer patients, lymphocytes from those patients were used to assess the immunomodulatory effects of cannabinoids. The levels of cannabinoids recovered in the intestinal lymphatic system, but not in plasma, were substantially above the immunomodulatory threshold in murine and human lymphocytes. CBD showed higher immunosuppressive effects than THC. Moreover, immune cells from MS patients were more susceptible to the immunosuppressive effects of cannabinoids than those from healthy volunteers or cancer patients. Therefore, administering cannabinoids with a high-fat meal or in lipid-based formulations has the potential to be a therapeutic approach to improve the treatment of MS, or indeed other autoimmune disorders. However, intestinal lymphatic transport of cannabinoids in immunocompromised patients requires caution.

PMID: 29109461 [PubMed – in process]

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Cannabidiol and Palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon.

Category : Cancer

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Cannabidiol and Palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon.

Clin Sci (Lond). 2017 Sep 27;:

Authors: Couch DG, Tasker C, Theophilidou E, Lund JN, O’Sullivan SE

Abstract
Objective: We sought to quantify the anti-inflammatory effects of two cannabinoid drugs: cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue.  These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants. Design: Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of IFNγ and TNFα (10 ng/ml), inflammation and PEA (10µM), inflammation and CBD (10µM), & PEA or CBD alone.  PEA, CBD or vehicle were added simultaneously with IFNγ. Nine intracellular signalling phosphoproteins were determined by multiplex.  Inflammatory cytokine secretion was determined using ELISA.  Receptor mechanisms were investigated using antagonists for CB1, CB2, PPARα, PPARγ, TRPV1 and GPR55. Results:   IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants.  Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants.  CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB2antagonist AM630 and TRPV1 antagonist SB366791.  PEA effects were blocked by the PPARα antagonist GW6471.  PEA and CBD were anti-inflammatory in IBD and appendicitis explants. Conclusion: PEA and CBD are anti-inflammatory in the human colon.  This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy.

PMID: 28954820 [PubMed – as supplied by publisher]

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Medical marijuana for the treatment of vismodegib-related muscle spasm.

Category : Cancer

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Medical marijuana for the treatment of vismodegib-related muscle spasm.

JAAD Case Rep. 2017 Sep;3(5):438-440

Authors: Yuan JT, Tello TL, Hultman C, Barker CA, Arron ST, Yom SS

PMID: 28932790 [PubMed]

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Cannabidiol, a novel inverse agonist for GPR12.

Category : Cancer

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Cannabidiol, a novel inverse agonist for GPR12.

Biochem Biophys Res Commun. 2017 Sep 06;:

Authors: Brown KJ, Laun AS, Song ZH

Abstract
GPR12 is a constitutively active, Gs protein-coupled receptor that currently has no confirmed endogenous ligands. GPR12 may be involved in physiological processes such as maintenance of oocyte meiotic arrest and brain development, as well as pathological conditions such as metastatic cancer. In this study, the potential effects of various classes of cannabinoids on GPR12 were tested using a cAMP accumulation assay. Our data demonstrate that cannabidiol (CBD), a major non-psychoactive phytocannabinoid, acted as an inverse agonist to inhibit cAMP accumulation stimulated by the constitutively active GPR12. Thus, GPR12 is a novel molecular target for CBD. The structure-activity relationship studies of CBD indicate that both the free hydroxyl and the pentyl side chain are crucial for the effects of CBD on GPR12. Furthermore, studies using cholera toxin, which blocks Gs protein and pertussis toxin, which blocks Gi protein, revealed that Gs, but not Gi is involved in the inverse agonism of CBD on GPR12. CBD is a promising novel therapeutic agent for cancer, and GPR12 has been shown to alter viscoelasticity of metastatic cancer cells. Since we have demonstrated that CBD is an inverse agonist for GPR12, this provides novel mechanism of action for CBD, and an initial chemical scaffold upon which highly potent and efficacious agents acting on GPR12 may be developed with the ultimate goal of blocking cancer metastasis.

PMID: 28888984 [PubMed – as supplied by publisher]

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Cannabinoids as Anticancer Drugs.

Category : Cancer

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Cannabinoids as Anticancer Drugs.

Adv Pharmacol. 2017;80:397-436

Authors: Ramer R, Hinz B

Abstract
The endocannabinoid system encompassing cannabinoid receptors, endogenous receptor ligands (endocannabinoids), as well as enzymes conferring the synthesis and degradation of endocannabinoids has emerged as a considerable target for pharmacotherapeutical approaches of numerous diseases. Besides palliative effects of cannabinoids used in cancer treatment, phytocannabinoids, synthetic agonists, as well as substances that increase endogenous endocannabinoid levels have gained interest as potential agents for systemic cancer treatment. Accordingly, cannabinoid compounds have been reported to inhibit tumor growth and spreading in numerous rodent models. The underlying mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor cells as well as inhibition of tumor cell invasion and angiogenic features of endothelial cells. In addition, cannabinoids have been shown to suppress epithelial-to-mesenchymal transition, to enhance tumor immune surveillance, and to support chemotherapeutics’ effects on drug-resistant cancer cells. However, unwanted side effects include psychoactivity and possibly pathogenic effects on liver health. Other cannabinoids such as the nonpsychoactive cannabidiol exert a comparatively good safety profile while exhibiting considerable anticancer properties. So far experience with anticarcinogenic effects of cannabinoids is confined to in vitro studies and animal models. Although a bench-to-bedside conversion remains to be established, the current knowledge suggests cannabinoid compounds to serve as a group of drugs that may offer significant advantages for patients suffering from cancer diseases. The present review summarizes the role of the endocannabinoid system and cannabinoid compounds in tumor progression.

PMID: 28826542 [PubMed – in process]

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