CANCER | +80 articles

[mr peabody]

HuaChanSu

Bufo is a group of over 150 species of toads. Nearly all of these species contain a venom in their skin called bufotoxin, a mild psychedelic, and bufotenin, a tryptamine related to the neurotransmitter serotonin. Similar in chemical structure to 5-MeO-DMT and DMT, bufotenin is also known as 5-HO-DMT.

HuaChanSu is a traditional Chinese medicine extracted from the skin of the Bufo toad that is believed to slow the spread of cancerous cells. The skin of the Bufo toad secretes a venom which is dried and dissolved in water. This solution, HuaChanSu, is injected into a cancerous area and targets specific cancer cells. HuaChanSu had been used in China as a therapy for cancer for over 1000 years, and has over time spread to other Asian countries. In 1991, HuaChanSu was accepted by China as an official cancer treatment.

The molecules in HuaChanSu include the cardiac glycosides bufalin, cinobufagin, cinobufotalin and resibufogenin. These molecules are effective due to their lipid-soluble characteristic, which helps them remain in the body longer; they slow the growth of cancer cells and induce cell cycle arrest. Specifically, these molecules suppress the protein Bcl-2, a cancer-prone lymphoma protein, and induce cell death upon melanoma cells. HuaChanSu combined with chemotherapy is superior to simple chemotherapy treatment, reducing gastrointestinal side effects and leucocytopenia. Meta-analysis suggests that HuaChanSu is a promising supplement to routine chemotherapy in treating advanced Non-Small-Cell Lung Cancer.

Clinical trials held in China have shown between 10% and 16% decrease in lung cancer masses. The toxicity levels of HuaChanSu were also recorded and studied during the various trials. The toad venom was found to have grades 1-2 toxicity levels in the majority of injected areas. No toxicity greater than grade 2 was observed, and the effects subsided within a month.

https://en.wikipedia.org/wiki/HuaChanSu

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Bufadienolides

Bufadienolide is a chemical compound with steroid structure. Its derivatives are collectively known as bufadienolides. In China, toad venom and toad skin are widely used in the treatment of various forms of cancer. Bufadienolides are regarded as the main anti-cancer components in toad venom and toad skin.

The skin of Bufo toads is known to be rich in bufadienolide compounds (a group of cardiac glycosides) that exhibit antitumor activity. For example, HuaChanSu, the aqueous extracts from the dried toad skin of Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, has been widely used in clinical therapy for various cancers in China. Clinical data have indicated that Cinobufacini injection may have significant anticancer activity with low toxicity and few side effects. Data suggests that treatment with Cinobufacini may also enhance the quality of life for patients with cancer. Bufadienolides such as bufalin, cinobufagin, resibufogenin and telocinobufagin are responsible for the anti-cancer properties of HuaChanSu through disruption of the cell cycle and consequent inhibition of cell proliferation, induction of apoptosis, immunomodulation and reversal of multi-drug resistance. The Australian cane toad (Bufo marinus) is also known as a source of bufadienolides, and therefore also considered as a new source of candidate lead compounds for drug development.

https://www120.secure.griffith.edu.a...0244d100171/1/

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Evaluating Bufadienolides as the main anti-tumor component in HuaChanSu

In China, the practice of using toad venom to treat cancer is known as HuaChanSu. Toad venom and toad skin are widely used for treating various cancers in China. Bufadienolides are regarded as the main anti-cancer components in toad venom and toad skin.

Cinobufacin injection, also known as HuaChanSu, is a preparation of Cinobufacini made from Cinobufacin extract liquid. Despite that Cinobufacin injection is shown to shrink liver and gastric tumors, improving patient survival and life quality, the effective components in Cinobufacin remain elusive. In this study, we screen the antitumor components from Cinobufacin injection to elucidate the most effective antitumor components for treatment of liver and gastric cancers.

Bufadienolides are the most effective components in Cinobufacini injection for the treatment of liver and gastric cancers. This discovery greatly facilitates further research into improving the therapeutic effects of Cinobufacin injection, meanwhile reducing its adverse reaction.

Bufadienolides are the main material basis in Cinobufacin injection for treating gastric and liver cancer. Further research may give birth to one or more drugs for the treatment of liver and gastric cancer. This would also enable studies on elucidating the mechanism of Cinobufacin injection for inhibiting tumor growth.

Evaluation of Bufadienolides as the Main Antitumor Components in Cinobufacin Injection for Liver and Gastric Cancer Therapy

 

[mr peabody]

Bufadienolides found to induce apoptosis in ESCC cells in vitro and in vivo

Shaohuan Lin, Junhuong Lv, Panli Peng, Changoing Cai, Jianming Deng, Haihong Deng, Xuejun Li, Xinyue Tang

Bufo is a group of over 150 species of toads. Nearly all of these species contain a venom in their skin called bufotoxin, a mild psychedelic, and bufotenin, a tryptamine related to the neurotransmitter serotonin. The skin of Bufo toads is known to be rich in bufadienolide compounds that exhibit antitumor activity. HuaChanSu, the aqueous extracts from the dried toad skin of Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, has been widely used in clinical therapy for various cancers in China.

Bufadienolides are a type of cardiotonic steroids isolated from the skin and parotid venom glands of the toad Bufo bufo gargarizans Cantor, and exhibit wide-spectrum anticancer activities. However, the effects and mechanisms of bufadienolides on esophageal squamous cell carcinoma (ESCC) cells remain unknown. In the present study, the anticancer activities of two bufadienolides, bufotalin and bufalin, were examined in vitro and in vivo.

The results demonstrated that bufotalin and bufalin effectively inhibited the viability of ESCC cells, with half-maximal inhibitory concentration (IC) values of 0.8-3.6 uM. However, bufotalin and bufalin exhibited lower toxicity towards Het-1A human esophageal squamous cells, indicating their high selectivity towards cancer cells. Mechanistic studies revealed that bufotalin effectively induced ESCC cell apoptosis, as characterized by DNA fragmentation and nuclear condensation, which was primarily mediated through activation of caspase family members. In addition, treatment of ESCC cells with bufotalin markedly activated tumor protein p53 phosphorylation.

Transfection of cells with p53 small interfering RNA markedly inhibited bufotalin-induced p53 phosphorylation and significantly inhibited bufotalin‑induced cell apoptosis. Furthermore, bufotalin demonstrated in vivo anticancer efficacy in a tumor-bearing nude mice model, where bufotalin effectively inhibited Eca-109 xenograft tumor growth in a time-and-dose-dependent manner, through activation of the p53 signaling pathway. Collectively, the results from the present study suggested that bufadienolides exert anticancer effects against ESCC by regulating the p53 signaling pathway.

To conclude, in the present study, the in vitro and in vivo anticancer efficacies of two bufadienolides (bufotalin and bufalin) were examined. The results demonstrated that bufotalin and bufalin effectively suppressed the viability of ESCC cell lines through induction of cell apoptosis occurring through activation of the p53 signaling pathway. In addition, bufotalin demonstrated in vivo anticancer efficacy in a nude mouse model, where bufotalin markedly suppressed tumor growth through activation of the p53 signaling pathway. Collectively, these results illustrated the therapeutic potential of bufadienolides against ESCC by regulating the p53 signaling pathway.​

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774392/

 

[mr peabody]

Cannabinoid receptors a novel target for the treatment of prostate cancer

Cannabinoids, the active components of Cannabis sativa and their derivatives have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects and tumor regression. Here we show that expression levels of both cannabinoid receptors, CB1 and CB2, are significantly higher in CA-human papillomavirus-10 cells. WIN-55,212-2 and time-dependent inhibition of cell growth, blocking of CB1 and CB2 receptors by their antagonists (CB1) and (CB2) significantly prevented this effect. Extending this observation, we found that WIN-55,212-2 treatment with LNCaP resulted in a dose- and time-dependent induction of apoptosis (a), decrease in protein and mRNA expression of androgen receptor (b), decrease in intracellular protein and mRNA expression of prostate-specific antigen (c), decrease in secreted prostate-specific antigen levels (d), and decrease in protein expression of proliferation cell nuclear antigen and vascular endothelial growth factor (e). Our results suggest that WIN-55,212-2 or other non–habit-forming cannabinoid receptor agonists could be developed as novel therapeutic agents for the treatment of prostate cancer.

Because prostate cancer has become the most common cancer diagnosed in men, developing novel targets and mechanism-based agents for its treatment has become a challenging issue. In recent years cannabinoids, the active components of Cannabis sativa and their derivatives have drawn renewed attention because of their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects, and tumor regression. Cannabinoids have been shown to induce apoptosis in gliomas, neuroblastoma, hippocampal neurons in vitro, and most interestingly, regression of C6-cell gliomas in vivo. Further interest in cannabinoid research came from the discovery of specific cannabinoid systems and the cloning of specific cannabinoid receptors. These diversified effects of cannabinoids are now known to be mediated by the activation of specific G protein-coupled receptors that are normally bound by a family of endogenous ligands, the endocannabinoids. Two different cannabinoid receptors have been characterized and cloned from mammalian tissues: the “central” CB1 receptor, and the “peripheral” CB2 receptor.

In the present study, we show for the first time that expression levels of both cannabinoid receptors, CB1 and CB2, are higher in human prostate cancer cells than in normal cells. Importantly, we also show that WIN-55,212-2 (CB1/CB2 agonist) treatment with androgen-responsive LNCaP cells results in a dose- and time-dependent inhibition of cell growth with a concomitant induction of apoptosis, decrease in protein and mRNA expression of androgen receptor and prostate-specific antigen (PSA), decrease in secreted PSA levels, protein expression of proliferating cell nuclear antigen (PCNA), and vascular endothelial growth factor (VEGF). We suggest that cannabinoid receptor agonists may be useful in the treatment of human prostate cancer.

It is now well accepted that uncontrolled cellular growth, which may be a result of defects in cell cycle and apoptotic machinery, is responsible for the development of most of the cancers including prostate cancer. Thus, the agents which can modulate apoptosis in cancer cells may be able to affect the steady-state cell population and may be useful in the management and therapy of cancer. Consistent with this notion, there is a need to develop novel targets and mechanism-based agents for the management of prostate cancer. One of the most exciting and promising areas of current cannabinoid research is the ability of these compounds to control the cell survival/death decision. In this study, we found that compared with PrEC and PZ-HPV-7 cells, the expression levels of both cannabinoid receptors CB1 and CB2 were significantly higher in CA-HPV-10 and other human prostate cells.

These data suggest that CB1 and CB2 receptors could be a target for novel treatment options for prostate cancer. We also found that mixed CB1/CB2 agonist WIN-55,212-2 treatment of LNCaP cells resulted in a decrease of cell viability as determined by MTT assay at varying doses and time points, suggesting the involvement of both CB1 and CB2 in the antiproliferative action of cannabinoids. It is widely recognized that apoptosis is an ideal way of elimination of cancer cells and that selective apoptotic events could provide suitable targets for cancer treatment and prevention. In this study, we also observed an increase in apoptosis of LNCaP cells by treatment with WIN-55,212-2. This observation was confirmed by employing confocal microscopy and flow cytometry. This could be an important observation which might be useful for devising strategies for the management of human prostate cancer because apoptosis is a physiological and discrete way of cell death different from necrotic cell death and is regarded to be an ideal way of cell elimination.

Androgens are essential for the growth, differentiation, and functioning of the prostate as well as in increasing prostate cancer development. Many molecular mechanisms have been suggested for the development of recurrent hormone refractory tumors. Most of these mechanisms postulate an alteration in the function of the androgen receptor and its signaling pathways. The overexpression of androgen receptor in prostate cancer may promote cell growth. Hence, elimination or reducing the androgen receptor in prostate cancer should help in treating this neoplastic disease. As most of the molecular mechanism for the development of prostate cancer involves modulation in the function of androgen receptor and its signaling pathways, we further studied the effect of WIN-55,212-2 on androgen receptor protein and mRNA expression and its subsequent effect on PSA production. Our results indicate that WIN-55,212-2 treatment significantly decreases androgen receptor protein and mRNA expression in LNCaP cells.

PSA belongs to the kallikrein family, is a serine protease with highly prostate-specific expression, and is the most widely employed marker in the detection of early prostate cancer. For these reasons, it is considered that agents which could reduce PSA levels may have important clinical implications for prostate cancer. Earlier studies reported that PSA is primarily regulated by androgens. This observation was based on the fact that the antiandrogen, cyperoterone acetate, had the ability to induce PSA, and that hydroxyflutamide could block androgen and progesterone induction of PSA glycoprotein, thus suggesting that PSA glycoprotein expression is influenced predominantly by androgens via its receptor, and the mutation of the receptor can affect the expression of this gene by steroids other than androgens.

Recent studies have established that androgen receptor functions as a transcriptional regulator via its binding to androgen response elements within promoter and enhancer regions of PSA. PSA is currently the most accepted marker for assessment of prostate cancer progression in humans and is being detected in the serum of patients with prostate diseases including prostatitis, benign prostatic hypertrophy, and prostate cancer. It is reported that in LNCaP cells, androgens regulate PSA glycoprotein expression and mRNA via androgen receptor. Our studies show a significant decrease in intracellular, mRN, as well as secreted levels of PSA by WIN-55,212-2 treatment of cells, suggesting that cannabinoid receptor agonists may be exploited to prevent prostate cancer progression.

PCNA recognizes nuclear antigens and its overexpression is associated with increase in PSA serum levels. PCNA expression has significant prognostic value and it seems to be a significant biomarker in prognosis and treatment of prostate cancer. Our results also suggest that concomitant with the decrease in PCNA protein expression, there was a decrease in PSA serum levels following WIN-55,212-2 treatment.

VEGF is a ubiquitous cytokine that regulates embryonic vasculogenesis and angiogenesis. Normal prostate epithelium expresses low levels of VEGF, whereas premalignant lesions have increased VEGF expression, which is additionally increased in prostate carcinoma. Studies have shown that cannabinoid treatment markedly reduced the expression of VEGF in gliomas, the most potent proangiogenic factor and also of angiopoietin 2, which contributes to the angiogenic process by preventing vessel maturation. Our results showed that treatment of LNCaP with WIN-55,212-2 inhibits growth and VEGF protein expression.

Recently, cannabinoids have received considerable attention due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects, and tumor regression. Our results suggest that treatment of androgen-responsive human prostate carcinoma LNCaP cells resulted in a decrease in intracellular and secreted levels of PSA, with concomitant inhibition of androgen receptor, cell growth, and induction of apoptosis. We conclude that cannabinoids should be considered as agents for the management of prostate cancer. If our hypothesis is supported by in vivo experiments, then the long-term implications of our work could be to develop non–habit-forming cannabinoid agonist(s) for the management of prostate cancer.​

http://cancerres.aacrjournals.org/content/65/5/1635

 

[mr peabody]

Alexander Shulgin

CBD + chemotherapy against pancreatic cancer

One of the largest fields of study for cannabis researchers is cancer research.

Several studies have been carried out investigating the effects of CBD on different types of cancer cells. It has already been found to inhibit carcinoma growth in prostate cancer cell cultures, and induce apoptosis in breast cancer and leukemia cells.

Pancreatic cancer is the 11th most common cancer diagnosis, and is responsible for around 331,000 deaths per year. The average survival rate after diagnosis is currently only 6 percent. With no significant improvements seen in the life expectancy and survival rates of patients with pancreatic cancer over the past few decades, new work from a coalition of researchers in the UK, Italy, and Australia examines the effect of CBD on pancreatic cancer cells to examine whether this could lead to improved outcomes for those people affected by this aggressive cancer.

The effect of cannabidiol treatment on life expectancy

The team studied pancreatic cell cultures as well as mice that had been genetically modified to develop pancreatic cancer. The sample group consisted of 34 mice, which were split into 4 smaller groups for treatment. Ten mice were given CBD and 8 were given the chemotherapy drug Gemcitabine, which is more commonly known by its brand name, Gemzar. A further seven mice were given a combination of both CBD and gemcitabine, and nine were given a placebo.

The mice in the placebo group survived for an average of 19 days. The mice that received CBD only survived for around 25 days, and the mice who were given gemcitabine chemotherapy treatment lived for approximately 28 days. The mice who received a combination of CBD and chemotherapy on average lived for almost 53 days. This is nearly three times as long as the mice given the placebo, and around twice as long as the mice given CBD or chemotherapy alone.

GPR55 Signaling and cancer proliferation

As well as studying the survival rates of the mice, the GPR55 gene was also examined as it has previously been recorded as being involved in many of the cellular functions associated with cancer proliferation. The gene produces proteins inside cell membranes that can act as detectors for various substances, including cannabinoids such as CBD. Immunohistochemistry analysis showed an accumulation of GPR55 in human cancer cell lines compared to healthy human cell lines, which lends further weight to the notion that GPR55 may be involved in the proliferation of cancer cells.

The researchers found that CBD can block the receptors that are produced by the GPR55 gene. This prevents the proteins from interacting synergistically with other compounds to promote the proliferation of pancreatic cancer cells. As a result, this inhibition of the GPR55 signaling pathway slows the growth and multiplication of these typically aggressive cancer cells.

Additional considerations for CBD use

In the past, there have been recorded cases of cell lines developing a resistance to gemcitabine treatment. As gemcitabine is one of the most common chemotherapy drugs prescribed for pancreatic cancers, the potential for pancreatic cancer cells building up a resistance to the drug is highly concerning. In the interest of combatting this, the researchers in this study also examined the effects of CBD on activation pathways that are thought to be associated with gemcitabine resistance, such as increased ERK activity. The team found that CBD was able to decrease ERK activity, and as a result, could hinder at least one of the potential pathways to chemotherapy resistance.

As well as the increased life expectancy and decreased drug resistance, Professor Marco Falasca, the corresponding author on the research project, also emphasized additional benefits to using CBD in conjunction with traditional chemotherapy drugs.

Speaking to Analytical Cannabis, Professor Falasca explained, “Cannabidiol is also known to improve the side effects of chemotherapy, including nausea, diarrhea, and vomiting, meaning it could also improve the quality of life of patients undergoing chemotherapy.”

Professor Falasca also addressed the practicalities of using CBD together with chemotherapy treatments, stating “cannabidiol is also already approved for use in clinics, which means we can quickly go on to test this in human clinical trials. If we can reproduce these effects in humans, cannabidiol could be in use in cancer clinics almost immediately, compared to having to wait for authorities to approve a new drug.”​

https://www.analyticalcannabis.com/...romising-results-in-animal-model-study-307430

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CBD and cancer: other studies

Cannabidiol reaction to protein examined for possible tumor anti-metastasis [https://www.ncbi.nlm.nih.gov/pubmed/28888984]
Cannabinoids – a new weapon against cancer? [https://www.ncbi.nlm.nih.gov/pubmed/28100841]
In vitro and in vivo efficacy of CBD in neuroblastoma [https://www.ncbi.nlm.nih.gov/pubmed/27022310]
CBD as potential anticancer drug [https://www.ncbi.nlm.nih.gov/pubmed/22506672]
The inhibitory effects of CBD on systemic malignant tumors [https://www.ncbi.nlm.nih.gov/pubmed/23544909]
CBD inhibits angiogenesis by multiple mechanisms [https://www.ncbi.nlm.nih.gov/pubmed/22624859]
CBD may help relieve chemotherapy related neuropathy pain [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249239/]
Efficacy, safety, and tolerability of THC and CBD extract in patients with intractable cancer-related pain [https://www.ncbi.nlm.nih.gov/pubmed/19896326]
CBD inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1 [https://www.ncbi.nlm.nih.gov/pubmed/19914218]

 

[mr peabody]

University of Insubria

CBD as a potential anticancer drug

Paola Massi, Marta Solinas, Valentina Cinquina, Daniela Parolaro

In recent years, several lines of evidence support an antitumourigenic effect of cannabinoids including tetrahydrocannabinol, synthetic agonists, endocannabinoids and endocannabinoid transport or degradation inhibitors. Indeed, cannabinoids possess anti-proliferative and pro-apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization. However, the clinical use of THC and additional cannabinoid agonists is often limited by their unwanted psychoactive side effects, and for this reason interest in non-psychoactive cannabinoid compounds with structural affinity for THC, such as cannabidiol (CBD), has substantially increased in recent years. The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents. Collectively, the non-psychoactive plant-derived cannabinoid CBD exhibits pro-apoptotic and anti-proliferative actions in different types of tumours and may also exert anti-migratory, anti-invasive, anti-metastatic and perhaps anti-angiogenic properties. On the basis of these results, evidence is emerging to suggest that CBD is a potent inhibitor of both cancer growth and spread.

The anticancer effect of this compound seems to be selective for cancer cells, at least in vitro, since it does not affect normal cell lines. The efficacy of CBD is linked to its ability to target multiple cellular pathways that control tumourigenesis through the modulation of different intracellular signalling depending on the cancer type considered. The most common effect of CBD is the increase in ROS production that seems to be determinant for triggering its beneficial action in all the considered cancer cell types. The role of cannabinoid/vanilloid receptors in mediating CBD effects is more controversial. In some cases (lung, leukaemia, colon) a clear contribution of these receptors was demonstrated through the use of specific antagonists, but in other cancer types (glioma and breast) their relevance appears only marginal or absent. Besides the in vitro data, the efficacy of CBD in reducing tumour growth and, in some cases, metastasization was confirmed in experimental animal models. However, the potential clinical application of CBD for cancer therapy needs some consideration. Its low toxicity is certainly a good starting point. CBD behaves as a non toxic compound; indeed oral administration of CBD 700 mg day-1 for 6 weeks did not show any overt toxicity in humans suggesting its possible exploitation for prolonged treatment. The route of administration appears more problematic since CBD oral absorption is slow and unpredictable. However, 6 weeks of oral CBD treatment 10 mg kg-1 day-1 provoked a plasma concentration of CBD that did not differ significantly over the 6 weeks of administration.

This range of concentration was demonstrated to be active in inhibiting lung cancer cell invasion, thus suggesting that in some cases the oral route could be the appropriate choice. Additionally, experimental data showed that combined treatment with CBD and THC could be more effective in reducing cancer cell proliferation, suggesting that co-administration may represent a better choice for cancer therapy. Accordingly, oromucosal treatment with Sativex™ 10 mg (a formulation with a 1:1 ratio of CBD and THC, recently approved for multiple sclerosis) resulted in a CBD plasma concentration of effective in reducing lung cell invasion in vitro. Thus, the results obtained with Sativex™ suggest the use of different associations of phytocannabinoids in a variable proportion might lead to a better outcome without pharmacokinetic interaction. Moreover, oromucosal administration may represent a first choice in the presence of nausea and vomiting. Finally, the use of CBD/Sativex can be suggested in combination with classical chemotherapeutic agents to check for the presence of a synergistic effect that might potentially allow clinical chemotherapeutic dose reduction, thereby reducing toxicity while maintaining efficacy. In the light of its safety record and considering that CBD is already currently used in patients with multiple sclerosis, the findings here summarized suggest that CBD might be worthy of clinical consideration for cancer therapy.​

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579246/

 

[mr peabody]

Voacangine found to inhibit solid tumor growth and metastasis

Yonghyo Kim, Hye Jin Jung, Ho Jeong Kwon

Voacangine is an iboga alkaloid and tryptamine derivative found in the rootbark of the tree Voacanga africana and Tabernanthe iboga.

Voacangine exhibits potent anti-angiogenic activity both in vitro and in vivo. Voacangine inhibits tumor-induced angiogenesis by suppressing HIF-1a, and could be the basis for the development of novel anti-angiogenic agents.

Angiogenesis, the formation of new blood vessels from pre-existing ones, plays a critical role in normal and pathological phenotypes, including solid tumor growth and metastasis. Accordingly, development of new anti-angiogenic agents is considered an efficient strategy for the treatment of cancer and other human diseases linked with angiogenesis. We have identified voacangine, isolated from Voacanga africana, as a novel anti-angiogenic agent. Voacangine inhibits the proliferation of HUVECs at an IC50 of 18 uM with no cytotoxic effects. Voacangine significantly suppressed in vitro angiogenesis, such as VEGF-induced tube formation and chemoinvasion. Moreover, the compound inhibits in vivo angiogenesis in the chorioallantoic membrane at non-toxic doses. In addition, voacangine decreased the expression levels of hypoxia inducible factor-1a and its target gene, VEGF, in a dose-dependent manner. Taken together, these results suggest that the naturally occurring compound, voacangine, is a novel anti-angiogenic compound.​

https://www.ncbi.nlm.nih.gov/pubmed/22155252

 

[mr peabody]

Eduardo Schenberg, family and colleagues


Case studies suggest Ayahuasca may be successfully used in the Treatment of Cancer

by Eduardo Schenberg

Based on case evidence of the effectiveness in affecting a range of cancers, he proposes a theoretical model based on known cellular, molecular, and psychosocial effects of the active ingredients of ayahuasca. Schenberg proposes they may counteract some of the classic hallmarks of cancer such as angiogenesis, apoptosis, and cell metabolism through their combined actions, leading to a reduction of blood supply to the tumors, the activation of apoptotic pathways, a reduction of cell proliferation, and reducing the Warburg effect, the energetic metabolic imnalance found within cancer cells. Based on recent findings that DMT (N,N-dimethyltryptamine) has agonist properties at the sigma-1 receptors, Schenberg postulates that ayahuasca may exercise therapeutic effects through the action of DMT on intracelluler sigma-1 receptors.

Schenberg proposes two models of DMT effects on sigma-1 receptors, high and low concentration effects. Effects at low concentrations provide a regulation of calcium flow to the mitochondria, while high concentrations inhibit voltage-gated sodium channels and exert a range of effects in the plasma membrane region. He proposes that because chloride ion channels modulate the cell cycle and regulation, interactions of sigma-1 receptors with the volume-regulated chloride channel may have effects on cancer. Given the role of calcium influx into the mitochondria, he postulates that DMT regulates cancer in managing the energetic imbalance bewteen cystolic aerobic glycolysis and mitochondrial oxidative phosphorylation (the Warburg effect), considered a hallmark of cancer. The hyperpolarization of the mitochondrial membrane potential that is a metabolic profile of cancer cells could be counteracted by the calcium influx which is triggered by DMT binding to the sigma-1 receptor.

The effects of high concentrations of DMT produces an influx of calcium and a depolorization of the mitochondrial membrane that could enhance permeability transition pore which could cause the swelling and rupture of mitochondria and cell death. The beta-carbolines of ayahuasca brews may also have antineoplastic effects; Schenberg reviews research reporting their roles in the apoptosis (cell death) of melanoma through inhibition od neo-vessel formation by decreasing serum levels pf pro-angiogenic factors as well as through inhibitory effect on proliferation of carcinoma cells. Both harmine and harmaline reduce proliferation of leukemia cells in humans, while harmine produces apoptosis in hepatocellular carcinoma cells. Schenberg proposes that harmine may exert anticancer effects through inhibitory action on DYRK1A kinase, which has been implicated in the resistance of many cancerous tissues, as well as the proliferation and migration of cancer cells.​

https://books.google.ca/books?id=FK1mCgAAQBAJ&pg=PA106&lpg=PA106&dq=b+caapi+cancer&source=bl&ots=mtFkDwPoB6&sig=AF_t4_rdcE7wpYo5RMgZ0nP8-3Y&hl=en&sa=X&ved=0ahUKEwjK_YWay-XbAhWMjywKHSquDQY4ChDoAQhTMAg#v=onepage&q=b caapi cancer&f=false

 

[mr peabody]

Brazilian Scientist: Ayahuasca can effectively treat cancer

by Liam S. Whittaker | CS GLOBE

Eduardo Schenberg, of the University of Sao Paulo, Brazil, recently published a piece in Sage Journals, detailing his belief that Ayahuasca has cancer-fighting abilities, essentially encouraging the legalization of research in the field.

Similar to the way cancer has been successfully treated with cannabis oil, or vitamin B-17 from the apricot pit, it is emerging as a viable possibility that Ayahuasca is another herbal, ancient cure to disease found in abundance in the new world of synthetic consumption.

Ayahuasca, as many viewers of this article likely know, is a psychoactive, ancient, sacred ancient brew, with deep roots in South American shamanic practice. Since at least 500 BC, South American shamans have used Ayahuasca for ceremonial purposes, and as a medicine of many functions.

Many people believe that DMT is created in the pineal gland of human beings when we dream, when we are born, and when we die. Critics of this theory say there is no evidence to back up these claims, but as of 2013, studies from the University of Michigan have shown that indeed dimethyltryptamine is created in the pineal glands of rats, and with the biological similarities us mammals share, it is very likely that DMT is synthesized in our pineal glands as well. According to Dr. Rick Strassman, author of the critically acclaimed book DMT- The Spirit Molecule, the human body metabolizes DMT rapidly, almost eager to consume the substance. Seretonin, the primary source of pleasure for us human beings, created in our brains and bodies daily of course, is 5-hydroxytryptamine, almost chemically identical to dimethyltryptamine. Yet, the US government classifies this molecule that may be part of our very being, as a schedule I, highly illegal drug.

It should be noted that Ayahuasca/DMT has characteristics similar to almost no ‘drugs’ except perhaps psilocybin mushrooms. Psilocin (what psilocybin metabolizes into), is also almost identical to chemicals already in our brains, similarly metabolized quickly by the body, more characteristic of a vitamin than an intoxicant.

For the viewers of this piece who do not already know, Ayahuasca is a brew consisting of many different psychoactive plants, including dimethyltryptamine containing foliage, and MAOI inhibiting plants that make the DMT active when ingested orally, namely the root bark of the Caapi vine. Caapi root bark contains monoamine oxidase inhibitors, harmala alkaloids. The DMT in Ayahuasca is primarily found in the leaves of the Psychotria Viridis plant, or the seeds of Syrian Rue, or both. Similar to cannabis’ ancient, rich history as a medicine, Ayahuasca has been a fundamental part of indigenous cultures in South America, namely the Amazonian rainforest and Peru, for thousands of years.

Ayahuasca is not typically looked at as a tool to treat cancer.

More often, people decide to drink Ayahuasca or ingest DMT in pursuit of life-changing experiences, epiphanies, to visit unexplored corners of the mind, in hopes of easing a wide range of psychological ailments and problems.

More often than not, people who consume Ayahuasca/DMT report extreme mental clarity after the experience, a difficult-to-explain sense of well-being, as if the substances organized the user’s subconscious and rarely touched areas of the brain.

It seems that simultaneously with all the other ways we are seeing a global paradigm shift, there is a shift taking place in the realm of medicine. After about a century of criminalizing plants and mind-altering products of the earth, people globally seem to be taking great interest in the Earth’s treasure chest of medicine in botany and nature, no longer concealed from us or alleged to be dangerous by proponents of pharmaceutical monopolies. Scientists such as Eduardo Schenberg will surely press on in their work, as the massive surge in popularity for these things grows exponentially. If you skipped the part of this article in which I explained the basics of Ayahuasca/DMT because you are already familiar with it, you are likely part of this very paradigm shift.

As could go without saying, more research and uninhibited analysis of Ayahuasca’s effect on human beings is necessary to understand the effectiveness of it as a treatment for cancer and who knows what else. The World Wide Web increasingly seems to push truths to the surface of the minds of those who pay attention, while false info can quickly debunked with little effort. This is the paradigm of our world today.​

http://csglobe.com/ayahuasca-can-effectively-treat-cancer/

 

[mr peabody]

P. Harmala

Harmine against thyroid cancer

Ruan S, Jia F, Li J
Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Harmine is a fluorescent harmala alkaloid belonging to the beta-carboline family of compounds. P. harmala and B. caapi are both traditionally used for their psychoactive effects. Isolated from the plant Peganum harmala, harmine has already been shown to strongly inhibit the growth of cancer cells originating from breast, lung, bone and pancreas.

Thyroid cancer is one of the most common types of cancer in the endocrine system. In recent studies, Harmine inhibited the growth of several cancers in vitro and in vivo. In the current study, we evaluated the in vitro and in vivo anticancer efficiency of Harmine against thyroid cancer cell line TPC-1. The in vitro cytotoxicity of Harmine evaluated by XTT assay indicated that Harmine suppressed the proliferation of TPC-1 cells in a dose- and time-dependent manner. Moreover, Harmine induced apoptosis of TPC-1 cells by regulating the ratio of Bcl-2/Bax. The colony forming ability of TPC-1 cells was also time-dependently inhibited by Harmine. In vivo evaluation showed that Harmine effectively inhibited the growth of thyroid cancer in a dose-dependent manner. Harmine is a promising herbal medicine in the therapy of thyroid cancer, and further efforts are needed to explore this therapeutic strategy.

https://www.ncbi.nlm.nih.gov/pubmed/28270853​

 

[mr peabody]

Is (R)-DOI a super-potent anti-cancer medicine?*

(R)-DOI (2,5-Dimethoxy-4-iodoamphetamine) is a psychedelic first synthesized by Alexander Shulgin. It is a potent inhibitor of Tumor Necrosis Factor-a inflammation, which exerts strong anti-cancer and anti-inflammatory effects through the modulation of innate and adaptive immune processes. (R)-DOI seems to be a superpower in regulating the 5HT2a receptor to inhibit TNF-α-mediated inflammation in the body. Activation of the 5-HT2A receptor represents a novel and extraordinarily potent therapeutic avenue for treating chronic inflammatory conditions, infections and cancer.

(R)-DOI is a psychedelic and mixed 5-HT2A/5-HT2C receptor agonist which acts via 5-HT2A receptors to inhibit the inflammatory effects of tumor necrosis factor (TNF)-α. Tumor necrosis factor-alpha (TNF)-α plays a key role in inflammation, and its production and signaling contribute to many inflammatory related diseases. Recently, we discovered that selective activation of serotonin 5-HT2A receptors with the agonist (R)-DOI produces a super-potent blockade of pro-inflammatory markers. Here we demonstrate that systemic administration of (R)-DOI can block the systemic effects of (TNF)-α in whole animal. Importantly, the mechanism underlying the systemic anti-inflammatory effects of (R)-DOI is activation of serotonin 5-HT2A receptors. Our results highlight a powerful new role for the serotonin 5-HT2A receptor in inflammatory processes, and indicate that agonism of serotonin receptors may represent an effective and novel approach to develop powerful small molecule therapeutics for inflammatory diseases.​

*From the article here: http://pharmrev.aspetjournals.org/co...2/264.full.pdf

 

[mr peabody]

Anti-tumor activity of the skin of the toad Bufo bufo gargarizans Cantor

Qi F., Li A, Inagaki Y., Kokudo N., Tamura S., Nakata M., Tang W.
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan

Bufo toads contain bufotenine (5-HO-DMT) and the alkaloid tryptamine (5-MeO-DMT), a potent psychedelic. Compounds derived from their skin-secretions can be used as medicine against cardiac-problems, multi-drug resistant bacteria, HIV and cancer. The most interesting aspect in therapeutic use of components present in toad skin secretions other than their antimicrobial effect is their anti-cancerous activity.

The skin of the toad Bufo bufo gargarizans Cantor is known to be rich in bufadienolides, peptides and alkaloids. It has been found to be a source of some extracts and biologically active compounds with anti-tumor activity. Cinobufacini (HuaChanSu), a Chinese medicine prepared from the dried toad skin, has been widely used in clinical therapy for various cancers in China. Bufadienolides, such as bufalin, cinobufagin, resibufogenin, and telocinobufagin, are the major active compounds derived from the toad skin. They are the maker biologically active compounds of cinobufagin while the anti-tumor activity of cinobufagin may be due to this kind of components.

Research suggests that cinobufacini and its active compounds (bufalin and cinobufagin) exhibit significant anti-tumor activity, including inhibition of cell proliferation, induction of cell differentiation, induction of apoptosis, disruption of the cell cycle, inhibition of cancer angiogenesis, reversal of multi-drug resistance, and regulation of the immune response. Clinical data have indicated that cinobufacini may have effective anticancer activity with low toxicity and few side effects. Data to date suggest it may also enhance quality of life for patients with cancer. Thus, this review briefly summarizes recent studies on the anticancer activity of cinobufacini and some of its active compounds from the skin of the toad Bufo bufo gargarizans Cantor. This might provide additional evidence for further study of the extracts and active compounds from the toad skin in cancer treatment.​

https://www.ncbi.nlm.nih.gov/pubmed/21185919

 

[mr peabody]

Spectacular research results: Ayahuasca in the battle against cancer

A powerful psychedelic brew consumed by shamans deep in the Amazon could help in the fight against cancer and should be researched, according to a Brazilian scientist.

Ayahuasca, meaning the vine of the souls, is traditionally prepared using the Banisteriopsis caapi vine and Psychotria viridis leaves, though other combinations of plants are
sometimes used. Psychotria viridis contains N,N-dimethyltryptamine (DMT) in the leaves, while Banisteriopsis caapi contains beta-carbolines such as harmine and harmaline.

For centuries, the psychedelic brew has been used in shamanistic healing rituals. A Natural Geographic reporter who participated in an ayahuasca ritual described the experience as terrifying but enlightening.

Eduardo Schenberg of the Federal University of Sao Paulo thinks some of the healing powers attributed to ayahuasca deserve scientific attention, particularly when it comes to cancer.

There is enough available evidence that ayahuasca's active principles, especially DMT and harmine, have positive effects in some cell cultures used to study cancer, and in biochemical processes important in cancer treatment, both in vitro and in vivo, he wrote in an article published in SAGE Open Medicine. Therefore, the available reports of people benefiting from ayahuasca in their cancer treatment experiences should be taken seriously. The hypothesis is that the combination of (beta-carboline) alkaloids and dimethyltryptamine present in ayahuasca blocks the transportation of nutrients to tumors, lessens the dividing process of cancer cells, and changes the unbalanced mutation-causing metabolism in cancer cells.

Rumors of ayahuasca helping people with cancer are common, according to Schenberg, and there are at least nine case reports of cancer patients using ayahuasca during their treatment. Of these 9 reports, 3 showed improvements after consuming the psychedelic brew. The physiological effects of the drug suggest there might be some truth behind them, Schenberg said.

DMT produces a powerful psychedelic experience by binding to serotonin receptors in the brain. The drug also binds to the Sigma-1R receptor, which is found throughout the body and is involved in many cellular functions. The sigma 1 receptor appears to be implicated in the death signalling of cancer cells.

In addition, harmine has been shown to induce the death of some cancer cells, and inhibit the proliferation of human carcinoma cells.

Other physiological factors suggest the combination of DMT and harmine could have medically-important antitumor effects, though more research is need.

It is hypothesized that the combined actions of β-carbolines and DMT present in ayahuasca may diminish tumor blood supply, activate apoptotic pathways, diminish cell proliferation, and change the energetic metabolic imbalance of cancer cells, which is known as the Warburg effect*, Schenberg wrote. Therefore, ayahuasca may act on cancer hallmarks such as angiogenesis, apoptosis, and cell metabolism.

https://mysticablog.wordpress.com/20...gainst-cancer/

*Dr. Otto Warburg discovered in the early 1900’s that there are a few factors common amongst all types of cancer, the most important of which is that cancer ferments glucose (sugar) in the presence of oxygen to produce energy. This is known simply as the Warburg effect.​

 

[mr peabody]

First study to show that DMT protects the body's immune system from cancer

Beckley Foundation

New study led by Ede Frecska and Jordi Riba is the first to bring some clarity to the mystique surrounding this hotly-debated subject.

The team took 3 types of human cells – neurons derived from pluripotent stem cells (a cell that can develop into any other cell type), monocyte-derived macrophages and dendritic cells (these two are both key players in the body’s immune system, working to engulf and annihilate undesirable particles, such as harmful bacteria or cancer cells). The team then restricted the cells’ supply of oxygen (hypoxia). A few hours of severe hypoxia reliably kills the majority of neurons, and a significant proportion of the immune cells.

The scientists then tested whether DMT could protect the cells from this fate. And indeed, they found that DMT-treated cell cultures had a much higher survival rate! Moreover, the amount of DMT needed to protect the cells was relatively low.

Hypoxia usually causes dramatic alterations to unprotected cells. One of the most reliable markers of being oxygen-deprived –the hypoxic condition- is the presence of the so-called hypoxia-inducible factor (HIF)-1, which can be clearly visualised, but disappears when there is sufficient amount of oxygen. In the presence of DMT, there was significantly less HIF-1 detected in the cells, as well as the other oxygen-sensitive proteins. Therefore, DMT could be seen to actively reduce cellular stress in hypoxic environments.

So, the DMT-treated cells underwent – on a, literally, microcosmic level – a “near-death” experience, as opposed to a deadly one. The question is: How does DMT protect these cells?

Szabo et al. decided to investigate how important the action of the Sigma-1 receptors (Sig-1R) is in bringing about the protective effects of DMT. Located inside the immune and brain cells (and cells from other organs such as liver, kidney), these receptors have important functions in the synthesis of energy molecules, as well as facilitating stress signalling. On a molecular level, “stress,” does not correspond to the difficulties and hurdles of everyday life, but to all the nasty things that threaten a cell’s well-being, such as changes in oxygen level (used in this study), temperature, toxins and mechanical damage. DMT has been previously shown to bind to Sigma-1 receptors, and more DMT is detected in the central nervous system under stress.

Suspecting that the effects of DMT hinge on the action of these receptors, the team selectively silenced (i.e. switched off) the genes responsible for SIG-1R development. The results were drastic and immediately apparent: switching of the Sigma-1 receptors led to complete annihilation of the DMT-related effects on cell survival and HIF-1 markers! Therefore, the researchers concluded that Sig-1R receptors are absolutely instrumental in enabling the protective, anti-stress effects of DMT.

By finding out that these effects are mediated through the Sig-1 receptors, Szabo et al. have brought us one step closer to finding out mechanisms behind DMT’s neuroprotective effects. We can look more confidently to a future where the workings of DMT are better understood. Currently plausible hypotheses include the idea that DMT is fine tuning the regulation of oxygen metabolism, or relating to other molecules involved in cell survival.

Conclusion: “Our results suggest a novel and important role of DMT in human cellular physiology and point out to the relevance of DMT-mediated Sig-1R modulation in future therapies concerning hypoxia/ischemia-related pathologies.” If these results are applicable to other stressors and replicated in humans, the implications are huge. DMT could be administered to save neurones that would otherwise die from exposure to harmful events, such as to protect patients’ brains against damage caused by oxygen starvation – e.g. during heart attack or stroke. And the damage wrought by tragic neurodegenerative diseases, like Parkinson’s and Alzheimer’s – for which there are currently no cures – could potentially be redressed. On a biological level, DMT could be a life-saving agent, administered in order to give cells, and the bodies they belong to, a second chance at life.​

http://beckleyfoundation.org/2016/09...-under-stress/

 

[mr peabody]

The anti-cancer effects of Bufadienolides

Bufadienolide is a chemical compound with steroid structure. Its derivatives are collectively known as bufadienolides.

In China, the practice of using toad venom to treat cancer is known as HuaChanSu. Toad venom and toad skin are widely used for treating various cancers in China. Bufadienolides are regarded as the main anti-cancer components in toad venom and toad skin.

Recent studies have revealed the therapeutic potential of bufadienolides in immunomodulation, anti-inflammation, and antineoplastic activity. It has also been found that ancient people of Mesoamerica had used toads, B. marinus or B. alvarius, as a psychedelic. The indolealkylamines in toad skin, primarily bufotenine, are responsible for these psychedelic effects. IAAs are biogenic amines and derivatives of 5-hydroxytryptamine which produce their effects through the binding of serotonin receptors.

HuaChanSu is a traditional Chinese medicine extracted from the skin of the Bufo toad that is believed to slow the spread of cancerous cells. The skin of the Bufo toad secretes a venom which is dried and dissolved in water. The solution is injected into the cancerous area and targets specific cancer cells. Bufadienolides are responsible for the anti-cancer properties of HuaChanSu through disruption and consequent inhibition of cell proliferation.

Activation of cell apoptosis by Bufotalin

Dysregulation of cell apoptosis (programmed cell death) is associated with a number of human chronic diseases, including cancer, and induction of cancer cell apoptosis has been identified as an effective way to treat cancer. The growth inhibitory activities of anticancer drugs on cancer cells are achieved through the induction of apoptosis. The results from MTT assay in the present study demonstrated that bufotalin exhibited markedly increased anticancer efficacy as compared with bufalin.

To conclude, the in vitro and in vivo anticancer efficacies of two bufadienolides (bufotalin and bufalin) were examined, and the results demonstrated that bufotalin and bufalin effectively suppressed the viability of esophageal squamous-cell carcinoma (ESCC) cell lines by the induction of cell apoptosis occurring through activation of the p53 signaling pathway. Collectively, these results illustrate the therapeutic potential of bufadienolides against cancer by regulating the p53 signaling pathway.​

 

[mr peabody]

Dr. Harendra Parekh

Cane toad venom attacks prostate cancer cells, spares healthy cells

by Rosa Ellen and Xavier La Canna

Bufo is a group of over 150 species of toads. Nearly all of these contain a venom in their skin called bufotoxin, a mild psychedelic, and bufotenin, a tryptamine related to the neurotransmitter serotonin. The Cane toad is one of these. Researchers have found that cane toad secretion kills prostate cancer cells while sparing healthy cells.

Dr. Harendra Parekh from the University of Queensland said a student had discovered Australia's toad to be similar to the Asiatic toad which has been used in Chinese medicine for thousands of years.

"We have what we believe is a selectively toxic agent, which can kill tumor cells, but spare healthy cells. The poison from Cane toads is very effective at killing cancer cells, and in particular, prostate cancer cells," Dr. Parekh said.

But while the drug has been used for a long time in Asia it can be dangerous in its raw form, and Dr. Parekh and his team have been trying to make the drug more soluble.

"Once we determine that the toxicity has been sustained, even after increasing solubility, the next stage will involve innovative drug delivery systems, sent to cancer tissue," he said.

The team at the Queensland University has received a grant from the Hong Kong Polytechnic University and a Chinese research institute. Dr Jing Jing comes from a long line of Chinese medical practitioners and said she could foresee a market for Australian cane toads. In China the Asiatic toad is threatened by over demand and pollution making the animals harder to obtain. The researchers said Australia's cane toads could also be seen as more desirable because of their relatively clean habitat.​

The researchers hope to have the initial screenings and studies carried out on the venom within 12-18 months.

"It is about bringing Chinese medicine into the 21st century so that it can be more accepted and more marketable in the West," Dr. Parekh said.

http://www.abc.net.au/news/2014-09-1...-cells/5750114

 

[mr peabody]

Anti-tumor activity of CBD

Studies in mice and rats have shown that cannabinoids may inhibit tumor growth by causing cell death, blocking cell growth, and blocking the development of blood vessels needed by tumors to grow. Laboratory and animal studies have shown that cannabinoids may be able to kill cancer cells while protecting normal cells.

A study in mice showed that cannabinoids may protect against inflammation of the colon and may have potential in reducing the risk of colon cancer, and possibly in its treatment.

A laboratory study of delta-9-THC in hepatocellular carcinoma (liver cancer) cells showed that it damaged or killed the cancer cells. The same study of delta-9-THC in mouse models of liver cancer showed that it had antitumor effects. Delta-9-THC has been shown to cause these effects by acting on molecules that may also be found in non-small cell lung cancer cells and breast cancer cells.

A laboratory study of cannabidiol (CBD) in estrogen receptor positive and estrogen receptor negative breast cancer cells showed that it caused cancer cell death while having little effect on normal breast cells. Studies in mouse models of metastatic breast cancer showed that cannabinoids may lessen the growth, number, and spread of tumors.

A review of 34 studies of cannabinoids in glioma tumor models found that all but one study showed that cannabinoids can kill cancer cells without harming normal cells.

A laboratory study of cannabidiol (CBD) in human glioma cells showed that when given along with chemotherapy, CBD may make chemotherapy more effective and increase cancer cell death without harming normal cells. Studies in mouse models of cancer showed that CBD together with delta-9-THC may make chemotherapy such as temozolomide more effective.

A review of bladder cancer rates in Cannabis users and non-users was done in over 84,000 men who took part in the California Men's Health Study. Over 16 years of follow-up and adjusting for age, race/ethnic group and body mass index (BMI), rates of bladder cancer were found to be 45% lower in Cannabis users than in men who did not report Cannabis use.​

Cannabis and cannabinoids have been studied in clinical trials for ways to manage side effects of cancer and cancer therapies, including the following:

CBD has been given by mouth to treat solid tumors that have recurred.

An oral spray combining 2 cannabinoids (delta-9-THC and CBD) has been given with temozolomide to treat recurrent glioblastoma multiforme.

CBD has been used to treat acute graft-versus-host disease in patients who have undergone allogeneic hematopoietic stem cell transplantation.

https://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq#link/_13

 

[mr peabody]

Ayahuasca and cancer

Ayahuasca contains a mixture of plants that have other active compounds in addition to DMT, such as harmala alkaloids.

Ayahuasca also contains small compounds called β–carbolines. These compounds inhibit the enzyme MAO-A, which is responsible for breaking down DMT and the neurotransmitters dopamine, serotonin, and noradrenaline. MAO-A inhibition increases the levels of these neurotransmitters in addition to prolonging the effects of DMT.

Beta-carbolines may be responsible for the anti-cancer aspects of ayahuasca. They are also the reason why ayahuasca may interact negatively with different drugs such as modern antidepressants (MAO inhibitors), SSRI’s, and St. John’s Wort.

Indolethylamine N-methyltransferase (INMT) is the enzyme that synthesizes DMT. The activity of the INMT gene that makes this enzyme is greatly reduced in certain forms of cancer.

Lower INMT activity is linked to more aggressive forms of prostate cancer.

By activating serotonin receptors, DMT helps coordinate the immune system, which may increase detection of cancerous tissues.

DMT and Inflammation

Sigma receptors (including Sig-1R) are found on many immune cells, suggesting they may play a role in immune function.

DMT increases the production of the cytokines interferon-gamma and interferon beta in natural killer and dendritic cells. These cytokines help fight viral infections and improve immune function.

In immune cells that were exposed to toxins, DMT activated the Sig-1R, and reduced production of the inflammatory cytokines IL-1β, IL-6, and TNFα and increased production of the anti-inflammatory cytokine IL-10. This research suggests DMT may play a role in immune regulation and has the potential to treat autoimmune or chronic inflammatory diseases.​

Mechanisms of Action

- DMT binds to and activates the sigma-1 receptor (Sig-1R), which protects against inflammation and cell death.

- DMT binds to and activates receptors of the serotonin system (5-HT1A, 5-HT2A, and 5-HT2C).

- Activation of serotonin receptors causes the release of glutamate, which activates glutamate receptors.

- Additionally, the psychedelic effects of DMT are attributed to the activation of the trace amine associated receptor (TAAR6).

https://selfhacked.com/blog/dmt/

 

[mr peabody]

CBD as a potential anticancer drug

Paola Massi, Marta Solinas, Valentina Cinquina, Daniela Parolaro

In recent years, several lines of evidence support an antitumourigenic effect of cannabinoids including tetrahydrocannabinol, synthetic agonists, endocannabinoids and endocannabinoid transport or degradation inhibitors. Indeed, cannabinoids possess anti-proliferative and pro-apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization. However, the clinical use of THC and additional cannabinoid agonists is often limited by their unwanted psychoactive side effects, and for this reason interest in non-psychoactive cannabinoid compounds with structural affinity for THC, such as cannabidiol (CBD), has substantially increased in recent years. The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents. Collectively, the non-psychoactive plant-derived cannabinoid CBD exhibits pro-apoptotic and anti-proliferative actions in different types of tumours and may also exert anti-migratory, anti-invasive, anti-metastatic and perhaps anti-angiogenic properties. On the basis of these results, evidence is emerging to suggest that CBD is a potent inhibitor of both cancer growth and spread.

The anticancer effect of this compound seems to be selective for cancer cells, at least in vitro, since it does not affect normal cell lines. The efficacy of CBD is linked to its ability to target multiple cellular pathways that control tumourigenesis through the modulation of different intracellular signalling depending on the cancer type considered. The most common effect of CBD is the increase in ROS production that seems to be determinant for triggering its beneficial action in all the considered cancer cell types. The role of cannabinoid/vanilloid receptors in mediating CBD effects is more controversial. In some cases (lung, leukaemia, colon) a clear contribution of these receptors was demonstrated through the use of specific antagonists, but in other cancer types (glioma and breast) their relevance appears only marginal or absent. Besides the in vitro data, the efficacy of CBD in reducing tumour growth and, in some cases, metastasization was confirmed in experimental animal models. However, the potential clinical application of CBD for cancer therapy needs some consideration. Its low toxicity is certainly a good starting point. CBD behaves as a non toxic compound; indeed oral administration of CBD 700 mg day-1 for 6 weeks did not show any overt toxicity in humans suggesting its possible exploitation for prolonged treatment. The route of administration appears more problematic since CBD oral absorption is slow and unpredictable. However, 6 weeks of oral CBD treatment 10 mg kg-1 day-1 provoked a plasma concentration of CBD that did not differ significantly over the 6 weeks of administration.

This range of concentration was demonstrated to be active in inhibiting lung cancer cell invasion, thus suggesting that in some cases the oral route could be the appropriate choice. Additionally, experimental data showed that combined treatment with CBD and THC could be more effective in reducing cancer cell proliferation, suggesting that co-administration may represent a better choice for cancer therapy. Accordingly, oromucosal treatment with Sativex? 10 mg (a formulation with a 1:1 ratio of CBD and THC, recently approved for multiple sclerosis) resulted in a CBD plasma concentration of effective in reducing lung cell invasion in vitro. Thus, the results obtained with Sativex suggest the use of different associations of phytocannabinoids in a variable proportion might lead to a better outcome without pharmacokinetic interaction. Moreover, oromucosal administration may represent a first choice in the presence of nausea and vomiting. Finally, the use of CBD/Sativex can be suggested in combination with classical chemotherapeutic agents to check for the presence of a synergistic effect that might potentially allow clinical chemotherapeutic dose reduction, thereby reducing toxicity while maintaining efficacy. In the light of its safety record and considering that CBD is already currently used in patients with multiple sclerosis, the findings here summarized suggest that CBD might be worthy of clinical consideration for cancer therapy.​

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579246/

 

[mr peabody]

The anti-cancer properties of P. harmala*

by Giorgio Samorini | KAHPI | 1 Mar 2019

Peganum harmala is a psychedelic plant that has a lot in common with the psychoactive vine, ayahuasca. They share a similar molecule profile, and both have been associated with many types of healing in different cultures. Peganum harmala is the most powerful plant source of MAO-inhibitors and DMT, respectively, in the world.

Beta-carboline alkaloids, especially the harmala alkaloids, have been studied as promising anti-cancer agents. Harmine is one of the most interesting. Its properties of inducing apoptosis ("suicide") in malignant cells have been ascertained in laboratory studies and as such give credibility to the highly acclaimed anti-cancer properties of both ayahuasca and harmel.

Harmel is a real melting pot of active ingredients, in particular beta-carboline and quinazoline alkaloids. In large quantities in the roots, and even higher concentrations in the seeds, the main beta-carboline alkaloids, cumulatively referred to as the harmala alkaloids, are harmine and harmaline. These same compounds are among the ingredients of ayahuasca, where they play the role of MAO-inhibitors allowing the absorption of the second group of alkaloids present in the drink, specifically the dimethyltryptamine (DMT).

Two interesting case reports on the treatment of cancer with Peganum harmala seed extracts have recently been described by an Israeli research team directed by Ephraim Lansky. The first case involved a young 29-year-old man suffering from a highly malignant brain tumor (oligoastrocytome). After numerous surgical excisions without success, the young man decided to switch to alternative therapies with medicinal herbs (including cannabis oil), a ketogenic diet, and harmel seeds. After four years of these therapies and two years of continuous administration of harmel seeds, the patient achieved complete remission from the tumor.

In the second case, an ovarian carcinoma in a 53-year-old woman was treated in a very original way, that is, by spreading the harmel seed oil on the skin at the height of the tumor and where the transdermal migration of the active ingredient harmine toward the cancer had been facilitated by infrared light. Once the cancer was reached, harmine induced apoptosis of the malignant cells.​

*From the article here: https://kahpi.net/peganum-harmala-ayahuasca/

 

[mr peabody]

CBD + chemotherapy triples cancer survival rates in mice

by David DiSalvo | Forbes | 31 Jul 2018

Mice with pancreatic cancer treated with a combination of CBD and chemotherapy survived nearly three times longer than those treated with chemotherapy alone, according to a new study that spotlights the potential for human treatment.

CBD has already been shown to improve side effects of chemotherapy like nausea and vomiting. The latest results provide more justification for testing in humans, building on prior animal research that uncovered possible anti-cancer properties of the compound.

"CBD is already approved for use in clinics in the UK, which means we can quickly go on to test this in human clinical trials,” said lead researcher Marco Falasca from Queen Mary University of London.

While human trials involving CBD as a cancer treatment may move faster in the UK, similar efforts could face obstacles in the U.S., where CBD derived from marijuana is still considered an illegal (Schedule 1) substance under federal law. Progress is being made, however, with the US FDA approving the first drug comprised of CBD to treat severe forms of epilepsy in June of this year.

Pancreatic cancer is among the deadliest forms of cancer in the world in terms of overall survival rates. According to the American Cancer Society, for all stages of pancreatic cancer combined, the one-year relative survival rate is 20%, and the five-year rate is just under 7%. It’s the 12th most common cancer globally, with the highest incidence occuring in developed countries.

"The life expectancy for pancreatic cancer patients has barely changed in the last 40 years because there are very few, and mostly only palliative care, treatments available,” Dr. Falasca added in a press statement. “Given the five-year survival rate for people with pancreatic cancer is less than seven percent, the discovery of new treatments and therapeutic strategies is urgently needed."

While this study hasn't yet been replicated in humans, the results underscore the importance of continued research involving marijuana compounds. As we’ve seen since the legalization movement started its push forward, studies have linked the compounds to multiple promising results, from easing migraine symptoms to improving stroke recovery to decreasing seizure severity, among others.

The more we learn about the potential of these compounds, the more it seems clear that decades of research being blocked by federal law deprived us of medical advances that are only now starting to surface.​