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    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. Studies have shown that indolealkylamines (IAAs) 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. Due to this, bufotenine has drawn the attention of scientists interested in studying its potential for treating neuropsychiatric disorders.

    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 - HuaChanSu - 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) has been shown to be associated with a number of human chronic diseases, including cancer. 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.
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    Psychedelics as anti-inflammatory agents


    Thomas Flanagan, Charles Nichols

    Serotonin, 5-hydroxytryptamine, 5-HT2A receptor agonists have recently emerged as promising new treatment options for a variety of disorders. The recent success of these agonists, also known as psychedelics, like psilocybin for the treatment of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has ushered in a renaissance in the way these compounds are perceived in the medical community and populace at large. One emerging therapeutic area that holds significant promise is their use as anti-inflammatory agents. Activation of 5-HT2A receptors produces potent anti-inflammatory effects in animal models of human inflammatory disorders at sub-behavioural levels.

    This review discusses the role of the 5-HT2A receptor in the inflammatory response, and highlights studies using the 5-HT2A agonist (R)-DOI to treat inflammation in cellular and animal models. It also examines potential mechanisms by which 5-HT2A agonists produce their therapeutic effects. Overall, psychedelics regulate inflammatory pathways via novel mechanisms, and may represent a new and exciting treatment strategy for several inflammatory disorders.

    https://www.medscape.com/medline/abstract/30102081
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    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

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    Curing cancer with cannabis oil


    Here is an interesting interview with Rick Simpson where he claims using high quality cannabis oil with THC, Not CBD, is the key to cancer treatment.

    Alright. Rick, it’s a pleasure to meet you, I’m Curt at Cannabis.net, and you’re kinda one of my Michael Jordan heroes. So, thanks for taking the time with us today.

    Well, the real hero in all of this is actually the extracts, I’m just the messenger.

    So, just to update people, there’s a lot of things on the internet about your oil, I don’t wanna go too far in the beginning of the story, but… How about you tell us… A lot of people think you live in the US or Canada, can you explain where you’re at right now in life and why, living?

    I’m living in Croatia, I’m in Europe. I gave up on Canada a couple of years ago. Actually, for the last… Well, since 2009 I’ve been spending most of my time in Europe, but I don’t… People are under the misconception that I live in the US and all of this, and I can’t even travel into the US. The Canadian government gave me a criminal record for saving people’s lives and that prohibits me from even traveling into the United States. So, I haven’t been in the US since… What was that?

    Do you feel if you entered the US you would be arrested? Say if you flew into New York or LA?

    Oh, they would probably… They’d likely toss me in Guantanamo Bay for God’s sakes, I’m a medical terrorist.

    [laughter]

    Honestly, I don’t know what’s wrong with the the American people, or for that matter people everywhere. Why do they take this nonsense from their governments? It’s a God given plant that we all have the right to use, and yet people cower and are afraid of their stupid governments and their police forces. And I have to laugh at these people in a way because these police officers themselves, they have family members that these extracts would be a great benefit for. But I treated many police officers myself and their families, and believe me, when one of them are dying, well then they started singing a whole different tune in regards to this medication. It’s just sickening, the simple truth is the American government.. nobody anywhere ever had the right to outlaw this plant’s use in the first place. We used it for thousands of years all through history. It was basically man’s best fiend. But the big money didn’t want it that way, the same big money that controls our governments in the shadows, they wanted sell their own… Do the things their own way so they could make big profits, so the first thing you do, prohibit cannabis. Cannabis doesn’t present a danger to the public, but it does present a great danger to these big money types.

    Gotcha. Well, they say that people have changed due to inspiration or desperation and it feels like we’re at desperate times now for some of these medical researchers and people who are dying in-sick. Could you just tell our viewers a little bit what’s the difference who people that are neophytes and just beginning between Rick Simpson Oil and say temp oil or CBD type oil? Give us a background.

    Well, the oils that I produced were all from the indica strains, they heavy sedative indica strains, and the more powerful the better. And that really, that’s the real what they call now, the Rick Simpson Oil, that’s the real oil, but thanks to Sanjay Gupta and fools like that, they get on CNN and they start spurting off about about CBD. Now, my oils or the extracts that I produced did contain a certain amount of CBD, there’s no question, maybe 2%, maybe even up to 6%, but the THC levels in the oils that I produced were very very high. So, and if you look at things, like the American Cancer Institute itself openly admits that THC is very effective in the treatment of several different forms of cancer. I’ll tell you one thing brother, if you’ve got cancer, you better be looking for THC. Having a small CBD content could be beneficial, no question, but it’s the THC that to me it’s the main cancer killer.

    And I would also like to tell people out there that I do not sell this oil, I’m not in the position to supply the extract even to myself, but there’s all kinds of people out there making claims that they’re selling the real Rick Simpson Oil, and they’re… They’re using my name to sell their products. And in many cases people order these extracts and what they get has little or no healing value at all. So, it really is one big scam and I’m disgusted about it all.

    I mean, it really disgusts me that this type of thing is going on. And of course the governments, they’re happy to see this taking place, because they wanna see these extracts discredited, and what better way to do that than to let all these criminals scam the public with these extracts that have, like I said, no healing values. It discredits the use of this medication. But the real extracts themselves, if they’re properly made, they really do have the healing powers that I’ve always told the public, so this is what people have to understand. I’m not in this for the money, I simply… We put up the phoenixtears.ca website back in 2004, and we told the whole world how to heal themselves, for nothing. The information’s all there. I sold… I have two books on this subject which are available on my website too, and we brought up the… And actually the first book, Phoenix Tears: The Rick Simpson Story, that’s available in print.

    And if we… We just started a publishing firm here in Europe called simpsonramadur.com and you can order the Spanish translations and the English books through that website as well. But the idea was is to give people the knowledge so they could make their own extracts and become self-sufficient. But so many people they just, “No, where do I buy it?” I get these emails all the time, “Where can I go to get the extracts?” Well, how would I know? I have no idea about the medical qualities of extracts produced by others. So, it’s impossible for me to answer such questions and like I said, my goal was to have people produce their own. And they always come back, “Well, it’s against the law where I live.” Damn, it was against the law practically everywhere until just recently, but if you have a sick or dying loved one, damn the laws. Roll the cannabis you need and produce the extract to heal them. These governments, and the whole thing is nothing but a fraud, and I think it’s just about time for the human race to grow up.

    That sounds like it’s happening worldwide. You’re actually right at the beginning of the legal tipping point and tidal wave for this subject. In our lifetime, in 2016. Look what’s going on in the US and Europe, and what’s gonna happen when the US goes federally. You’ll be one of the guys on the Mount Rushmore of this movement.

    Well, I don’t really care about that, it’s like I said, the oil is really the hero in all of this… It’s just that I got put in the circumstances where I had to use the oil to deal with my own medical problems. And believe me, when I started discovering the real healing powers of this substance, I was just blown away.

    I had cancer patients coming to me, people dying with terminal cancer, they were also diabetics, they had arthritis, and all kinds of problems. They would get on these extracts and everything that was wrong with them would just disappear over a short period of time. I had arthritis and things myself, it all disappeared. The oil brought me back to a healthy weight, and then it cured my cancer. People get up there and they say, “Oh, how dare you say that cannabis cures cancer.” Well, I have the pathology reports and everything to prove that it had. And I had a huge amount of evidence to back me up.

    I went through the corrupted legal system in Canada. And these judges and the rest of them, they’re all involved in this right up to their necks. Because again, like I said, no one ever had the right to outlaw this plant in the first place. And really, what’s been going on in Canada, 1923, they outlawed it in Canada. 1937 they used the tax act in the US to basically outlaw it. And since that time, both the Canadian government and the American government have been committing genocide against their own people. Harry Anslinger went to United Nations, I think it was in 1954, and he had cannabis declared to be a non medicinal plant. Look at this plant’s history. It’s used in medicine.

    How dare anybody say that cannabis is non medicinal. And then the single convention tree in 1961 and then some treaties afterwards… Basically if you wanted to be a member of the esteemed United Nations, which is also controlled by the rich elite, then you had to make sure that your public did not have access to cannabis. The whole thing is a fraud and it disturbs me that so many people worldwide are suffering and dying, for no other reason than greed. And this is what this is all about because in reality our world is being run by… You can only call them what they are, they’re a pack of psychopaths. And all they want is money and power, and they don’t care who they have to hurt or harm to get what they want. And that’s whats going on.

    Let me ask you... as far as having as much history and knowledge about the oil, if I had a time machine and could look three years in the future, when there’s a lot of research on this and you’ll be vindicated or validated; what are the three things that the oil you’re recommending are gonna show us. What are the three that I don’t know right now. Is it gonna cure x cancer… What do you know that that we’re all gonna find out say, three years from now?

    Well, see, the problem is the proper research has always been held back.

    Yep.

    This has been my goal, to get a big facility, a big firm, grow the proper strains, produce the extracts, and then evolve them to even higher healing levels, which would be quite easy to do. But when people caught on to all this and they all started running off in different directions. To me, what I see happening in the US makes absolutely no sense. Even the cannabis movement itself, you look at organizations like NORML, and they’re going along with the government. Please tax and regulate it. We don’t need… We grew this plant for thousands of years with no regulations at all, so why do we need to regulate it? Nobody dies from cannabis. This is ridiculous. But, what I see happening right now, the governments are all trying to keep a lid on this because they want their friends in the pharmaceutical industry to control this. But the simple truth is, most of us really don’t have much money. And are we gonna go out, and are we going to pay the pharmaceutical industry tens of thousands of dollars for a treatment that we can grow right in our own backyards and produce ourselves? By now people should realize the pharmaceutical industry, they’re nothing but a pack of gangsters. And if they supplied extracts, they would never supply you with the real thing, because they don’t want you to heal.

    They want you to keep coming back and buying more. So this is what I see happening. The governments are playing this control game right now, but I think in a short time within the next couple years, that people will just say, “Get lost.” They’ll go out and grow their own cannabis. They can’t put everybody in jail. And I really think that what’s happening now is going to allow the cannabis plant to set itself free. And when we set the cannabis plant free, we also set ourselves free from all this domination from these mega rich individuals.

    And here’s what people have to understand. These big-money types they control our governments, our governments in turn control the medical system, the legal system and practically everything else in our lives. And they’re all bought and paid for. They’re not working for the people, and I don’t think they ever have.

    https://www.sociedelic.com/cure-cancer-with-cannabis-thc-not-cbd-says-rick-simpson/
    Last edited by mr peabody; 25-12-2018 at 22:41.
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    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 (Bufo marinus) is one of these species.

    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 packaging it in 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

    -----

    Cannabis improves symptoms of Crohn's disease

    In the first study of its kind, cannabis oil has been shown to significantly improve the symptoms of Crohn's disease and the quality of life of sufferers but, contrary to previous medical thinking, has no effect on gut inflammation.

    In a randomised, placebo-controlled study, researchers from Israel have shown that cannabis can produce clinical remission in up to 65% of individuals after 8 weeks of treatment, but that this improvement does not appear to result from a dampening down of the underlying inflammatory process.

    Speaking at UEG Week 2018 in Vienna, lead researcher, Dr. Timna Naftali explained, "Cannabis has been used for centuries to treat a wide range of medical conditions, and studies have shown that many people with Crohn's disease use cannabis regularly to relieve their symptoms. It has always been thought that this improvement was related to a reduction in inflammation in the gut and the aim of this study was to investigate this."

    The Israeli team recruited 46 people with moderately severe Crohn's disease, and randomized them to receive 8 weeks of treatment with either cannabis oil containing 15% cannabidiol and 4% tetrahydrocannabinol or placebo. Symptom severity and quality of life were measured before, during, and after treatment using validated research instruments. Inflammation in the gut was assessed endoscopically and by measuring inflammatory markers in blood and stool samples.

    After 8 weeks of treatment, the group receiving the cannabis oil had a significant reduction in their Crohn's disease symptoms compared with the placebo group, and 65%met strict criteria for clinical remission (versus 35% of the placebo recipients). The cannabis group also had significant improvements in their quality of life compared with the placebo group.

    "We have previously demonstrated that cannabis can produce measurable improvements in Crohn's disease symptoms but, to our surprise, we saw no statistically significant improvements in endoscopic scores or in the inflammatory markers we measured in the cannabis oil group compared with the placebo group," said Dr. Naftali. "We know that cannabinoids can have profound anti-inflammatory effects but this study indicates that the improvement in symptoms may not be related to these anti-inflammatory properties."

    Looking ahead, the research group plans to explore further the potential anti-inflammatory properties of cannabis in the treatment of inflammatory bowel disease. "There are very good grounds to believe that the endocannabinoid system is a potential therapeutic target in Crohn's disease and other gastrointestinal diseases," said Dr. Naftali. "For now, however, we can only consider medicinal cannabis as an alternative or additional intervention that provides temporary symptom relief for some people with Crohn's disease.'

    https://medicalxpress.com/news/2018-...se-effect.html

    -----

    CBD + chemotherapy triples cancer survival rates in mice

    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.

    https://www.forbes.com/sites/daviddi.../#3c78958c4630
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    Antitumor activity of cannabinoids


    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/...s-pdq#link/_13
    Last edited by mr peabody; 09-01-2019 at 20:14.
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    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 (dendritic 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/
    Last edited by mr peabody; 09-01-2019 at 20:28.
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    Bufadienolides induce p53-mediated apoptosis in Esophageal Squamous Cell Carcinoma cells in vitro and in vivo

    Shaohuan Lin, Junhong LV, Panli Peng, Changqing Cai, Jianming Deng, Haihong Deng, Xuejun Li, Xinyue Tang

    Bufadienolides are cardiotonic steroids isolated from the skin and parotid venom glands of the toad Bufo bufo gargarizans Cantor, and exhibit wide-spectrum anti-cancer activities. However, the effects and mechanisms of bufadienolides on esophageal squamous cell carcinoma (ESCC) cells remain unknown. In the present study, the anti-cancer 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.

    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. Collectively, the results suggest that bufadienolides exert anti-cancer effects against ESCC by regulating the p53 signaling pathway.

    In conclusion, in the present study, the in vitro and in vivo anti-cancer 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 the induction of cell apoptosis occurring through activation of the p53 signaling pathway. In addition, bufotalin demonstrated in vivo anticancer efficacy, where bufotalin markedly suppressed tumor growth through activation of the p53 signaling pathway.
    Last edited by mr peabody; 14-01-2019 at 02:51.
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