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mr peabody

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How I beat cancer with cannabis oil

by Kelly Hauf

My name is Kelly, I’m 52 years old, and I would like to share my amazing story with you.

In January 2000, after a severe headache prompted a CAT scan, a 3cm tumor was discovered in the left frontal lobe of my brain. I was 38 years old. My two daughters were ages 15
and 12. Immediate brain surgery was recommended by my surgeon. However, after further discussion, due to slow growth and no adjacent edema, he felt it would not be negligent to postpone surgery and monitor the tumor every 3 months with an MRI. The tumor remained stable for a little over three years then suddenly grew 25%.

On September 4, 2003, when I was 41, on my husband’s 42nd birthday, I had surgery at Cedars Sinai in Los Angeles. I spent the next day, our 19th wedding anniversary in ICU. The pathology report came back an Oligodendroglioma grade 2. The surgery was an apparent success and neither radiation nor chemotherapy were recommended. However, since it’s unlikely every cancer cell can be detected and removed, and the nature of gliomas are to grow back over time, it was necessary to continue MRI monitoring every 3 months. Living from MRI to MRI had become our “normal”.

All MRI reports remained stable until November 2013 when my quarterly MRI came back showing regrowth of the tumor. My brain surgeon in Los Angeles recommended 4-6 months of chemotherapy, and if that didn't work, another brain surgery to go in and clean up the regrowth would be considered. He also gave me anti-seizure medication for auras that had started to manifest as strong unexplainable odors. My doctor described this experience as an olfactory seizure. While researching Charlotte’s Web cannabis oil as an alternative to the prescribed seizure medicine I also found out that cannabis oil was also showing promise as a cancer treatment and could be an alternative to chemotherapy. I was living in a state that did not have legal access to cannabis but my youngest daughter, Jillian, was living in San Francisco where medical marijuana was legal.

When Jillian came home for Christmas she and my husband, Rick, decided it was time for me to make a decision to do something. I wasn't ready to decide anything just yet. I wanted to have Christmas with my family. The day after Christmas I made up my mind to drive out to California to investigate cannabis oil as a treatment. My husband took an emergency leave of absence from his job. We then put away the Christmas tree ornaments, cleaned the house, loaded up the car, and headed to California. We talked with doctors, met with support groups taking the oil, read articles about successful brain tumor results in Spain and Amsterdam and gathered information wherever we could. We decided to give the cannabis oil a try, especially after we read a paper on a study about the chemotherapy my doctor had recommended. That study suggested patients with tumors like mine appeared to get better at first with the chemo but then the left over tumor cells would mutate and turn aggressive over time.

After many conversations with my husband we decided to commit to a 90-day cannabis treatment protocol. My San Francisco neuro oncologist felt like my situation was not a dire emergency and felt like I could be allowed the 90 days to try this unorthodox treatment, however if that didn't work, another surgery would be likely. After we had chosen this path incredible healers came forward to help support me through this unknown territory. These healers included one of the best neurological teams in the world. I know I have been incredibly fortunate. I am so very grateful to each person who came forward with his or her special expertise and other gifts to make this treatment possible for me.

After establishing residency in San Francisco, I was able to get a medical marijuana card. The card was for cancer treatment but, amazingly, the cannabis oil has helped me with my fibromyalgia pain, joint pain, and chronic headaches. I had this pain for many years and it was getting worse. I literally have no pain now. My blood pressure had been creeping up over the years and was consistently pre-hypertensive, now it’s consistently on the low side of normal. I have not taken any other medication except the cannabis oil, supplements, and good clean healthy food over the last 8 months.

When we arrived in San Francisco, my husband, Rick, became my Angel from Heaven. He took on my full time care, and I made him my legal caregiver so he could pick up my medicine at the dispensary if I was not able. He bought a good juicer and began juicing all organic non-GMO veggies every day. He prepared almost all of my organic gluten free meals and took me out for a walk and fresh air daily. Our temporary home was across the street from the Golden Gate Park so we walked through the park down to the beach daily during my treatment. I began calling the park Grandmother GG, because I felt so nurtured in her abundance, and this daily ritual in the beauty of nature was, I believe, a major contributor to my healing. We got a machine to create pure alkaline drinking water. I had an arsenal of cancer fighting supplements, foods, and daily practices to work on my physical, spiritual and emotional health.

The plan was to do the Rick Simpson cancer treatment protocol of 60 grams of highly concentrated cannabis oil over a 90 day period, the higher the THC the better for killing tumors. My 90 day MRI was scheduled for April. I had not reached a gram a day by that time and was concerned that the MRI results wouldn't be what we were hoping for. Indeed the report showed no change in the main tumor’s regrowth; however, there was a smaller inoperable tumor, in the cingular gyrus that we had been monitoring since my first tumor surgery ten years prior that was completely gone. We were amazed and it gave us the encouragement we needed to continue the cannabis protocol. To get to the amount of a gram of oil a day took months of building up my tolerance. I had very physical challenges and setbacks during this process such as seizures, middle of the night walks, tremors, convulsions, nausea, frustration, lack of appetite, and many tears. I finally reached a gram a day and eventually up to two grams a day on the final two weeks before my second MRI at the end of August.

In August, eight months after beginning the cannabis treatment, my MRI was reviewed by a leading Radiologist, my Neuro Oncologist, and my world renowned Brain Surgeon, and it was concluded that all that was remaining of the tumor regrowth was scar tissue. I will have another MRI in December. Because these tumors are chronic and tend to grow back, I will always be living MRI to MRI, but the key word here is that I am living …and in great health with a great immune system. I was not left with my immune system compromised by chemo and radiation, which is the standard protocol for these types of tumors as well as other cancers.
 
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mr peabody

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My beloved wife was suffering from breast cancer and the doctor told me that there was nothing he could do to save her. Then a friend told me that hemp oil can cure cancer. I told him that my wife’s breast cancer was in the last stage and I didn't think the hemp oil would cure it, but he persuaded me to try it. So I did some research and I found a doctor who helped me with the cannabis oil, and he assured me that after 4 months the cancer would be gone. I bought it, she used it, and it worked exactly as he said it would. Thanks to the doctor for taking away the sorrow in my life. Can you imagine, that I and my wife have a 6 year-old daughter and a 3 year-old son? What would I have done?

-anon

---

The real answer is whole plant medicine. Just CBD is good, don't get me wrong. But the best way to get pain relief is the mix the whole plant brings. When I was diagnosed with cancer I started a CBD regimen. But I didn't notice anything till I went to RSO (Rick Simpson oil). I was able to get away with no opiate-based meds for pain. And my recovery was impressive - I have zero cancer now. So far so good. Whole plant medicine - that's the key.

-Nathaniel Smith

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As for the actual efficacy of CBD in the treatment of advanced cancer...this is groundbreaking. I know of anecdotal reports of patients so weakened from cancer that they had stopped eating and taking fluids and have had 100% so-called miracle shrinkage and complete remission of Stage 4b tumors. Supplemental antioxidants and other nutrients are probably critical to full effectiveness. Cannabinoids are a radically new approach to cancer treatment---they don't seem to kill or destroy the cells directly--BUT CANNABIS SEEMS TO HAVE THE ABILITY TO INDUCE APOPTOSIS (normal, programmed cell death and replacement) in cancer cells in the body.

Almost all the evidence for anti-cancer effectiveness has been with High THC/Full Spectrum concentrates. CBD by itself seems to be effective for certain symptoms (anxiety, depression, chronic pain) but not very effective for others (acute pain, nausea, lack of appetite). As for TREATMENT of cancer, high THC Rick Simpson Oil COMBINED WITH live resin or extract seems to be the most effective, but the quantities necessary will KNOCK THE SOCKS OFF anyone who does not already have an incredibly high tolerance to cannabis. Most need to literally start with a dose no larger than a single standard grain of rice. Then, over a period of a few weeks, you can slowly work your tolerance up to full dosage.

Rick Simpson recommends 60 grams in as short a time period as practical (generally 60 grams over about 90 days since the first month or so is spent in slowly building up tolerance). I am beginning to hear anecdotal reports of folks getting their dose up to 3 or 4 grams a day to "cure" cancer or AIDS. I personally can attest to taking about 80 grams over 45 days to treat my HIV and Chronic Hep B with excellent results. Again, cannabis seems to work best as an "ensemble" or "entourage" therapy, meaning, the synergistic effects of the combined cannabinoids and terpenoids in the plant are much greater than the effect of any single component including THC or CBD.

-Louis Byron
 
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mr peabody

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

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/
 
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mr peabody

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Cannabinoids as a potential cancer treatment

In collaboration with Profs Manuel Guzman and Guillermo Velasco at Madrid Complutense University, we plan to investigate the anti-cancer properties of cannabis and its individual cannabinoids, with the aim of establishing the most effective combination of cannabinoids. Together with the Spanish Group of Neurooncology (GEINO), Profs Guzman and Velasco will conduct a clinical trial in 4 centres in Spain. In this study, patients with newly diagnosed glioblastoma (brain tumour) will receive cannabinoids in combination with traditional anticancer drugs and radiation therapy. Results will help clarify the question of whether cannabinoids can be used to fight cancer.

This programme is investigating the anti-cancer properties of cannabis and individual cannabinoids, such as THC and CBD, that have been found to exhibit anti-tumour effects in a wide array of animal models and in vitro studies of cancer. Together with the Spanish Neurooncology Group GEINO, we are now preparing to conduct a clinical trial to test whether cannabinoids can help fight tumour growth in cancer patients.

How cannabinoids may help cure cancer

1. They are Anti-proliferative, meaning they prevent cancer cells from reproducing. Cannabinoids have been shown to possess anti-proliferative effects in vitro as well as in vivo in different cancer models. - Chakravarti B., et al. (2014)

2. They are Anti-angiogenic, meaning they prevent formation of new blood vessels needed by tumors to grow. Cannabinoids inhibit tumor growth in laboratory animals by inducing apoptosis (programmed cell death) of tumor cells and impairing tumor angiogenesis. - Blazquez C., et al. (2009)

3. They are Anti-metastatic, meaning they prevent cancer from spreading to other organs. Cannabinoids decrease cancer cell migration. Cannabinoids decrease matastasis in various tumor types in laboratory animals. - Velasco G., et al. (2015)

4. They are Apoptotic, meaning they induce cancer cells to seek their own death. Treatment with a cannabis compound reduced the viability and invasiveness of treated tumor cells in vitro and induced apoptosis. - Fisher T., et al. (2016)

http://beckleyfoundation.org/science...ctions/cancer/
 
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mr peabody

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Rick Simpson and the cure for cancer

In 2003 Rick Simpson was diagnosed with basal cell carcinoma skin cancer. He had 3 spots of cancer, two on his face and one on his neck. Rick's decision on how to handle this diagnosis would be world changing.

After not having much luck with surgery Rick decided to try something different. Rick had been extracting cannabis oil and ingesting it orally. He had been taking the oil for other health reasons but the cancer diagnosis reminded him of something and gave him an idea. He remembered a radio headline he heard almost 30 years earlier, that the University of Virginia had found the cannabinoid in cannabis THC could kill cancer in mice. He figured that if it kills cancer in mice it would kill his cancer too.

Rick's decision was to apply cannabis oil to his skin cancer. He applied his cannabis oil to some bandages and put them on the skin cancer. After 4 days of waiting he decided it was time to see if anything had happened under the bandages. To Ricks surprise the cancer was gone. His cannabis oil had cured his cancer.

Rick tried to tell his doctor, but they wouldn't listen. He even went to the cancer organizations and tried to get their help, but nobody wanted anything to do with his discovery. At that point Rick took matters into his own hands. He started growing cannabis on his own land and producing his own cannabis oil. He gave the oil away for free to anyone who needed it. Even after having his home raided multiple times and having over 2600 cannabis plants cut down and taken by the RCMP he still continued to produce the oil and help others.

In 2008 Rick put out a free documentary on YouTube called "Run From the Cure". If you haven't watched it you should. This documentary has been viewed millions of times worldwide and has helped millions of people. If not for Rick and "Run From the Cure" who knows where cannabis medicine would be today.

Its now been over 10 years since Rick began his journey to tell others that cannabis oil can cure cancer. Rick has healed over 5000 people personally with this amazing oil not to mention the countless others all over the world who have heard his story and have been healed. Rick was the inspiration for me to start CureYourOwnCancer and start helping others. The world owes this great man a thank you for his bravery and persistence in making sure that everyone everywhere knows about cannabis oil and what it can do.

https://www.cureyourowncancer.org/testimonials.html
 
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mr peabody

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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. 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.
 
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mr peabody

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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/
 
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mr peabody

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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 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
 
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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
 
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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 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/
 
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Bufadienolides induce apoptosis in Esophageal Squamous Cell Carcinoma cells

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

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 skin and glands of the toad Bufo bufo gargarizans Cantor exhibit wide-spectrum anti-cancer activities. However, the effects and mechanisms of bufadienolides on esophageal squamous cell carcinoma cells (ESCC) 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 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.
 
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Beating prostate cancer with cannabis oil

by Dennis Hill, Biochemist

3 years ago, after a prostate biopsy, I received the diagnosis of aggressive Stage III adenocarcinoma. I didn?t know what to do. The urologist made appointments for me to start radiation, and maybe chemo. Then a friend told me cannabis cures cancer. It just so happened that the first human trials of cannabis treatment of astrocytomas (inoperable brain cancer), were published with encouraging results. So I decided; rather than die from the medical treatment, I would do the cannabis cure. Now, where to get some. There was no dispensary in the area, but a friend made me cannabis butter, so I took that, up to tolerance. In 3 months the primary cancer was gone, only minor metastatic lesions were left. After that I found a supplier for Rick Simpson oil and killed off the metastases in the next 3 months. Now I just take a maintenance dose of locally produced hash oil that is 1:1 THC:CBD with about a 30% potency. This will certainly keep me clear of cancer, anywhere, forever.

My point in telling this story is that in the face of advanced aggressive cancer, all I had was very weak cannabutter, but it was enough to eliminate the primary tumor. Now there are strains of 95% THC. But is this necessary? If you have cancer and want to pursue the cannabis treatment, any at all will be good. More important than extreme potency, is balance between THC and CBD. If you can get high potency, great. If not, common potencies will work perfectly.

Finally, if you choose cannabinoid treatment, start small, then increase dosage as rapidly as tolerable. To kill cancer you have to hit it hard, be conscientious about your treatment. Cannabis does no harm to the body, it is a metabolic support for the immune system.

The alternative

As the body, its organs and tissues, fall out of balance or become diseased, cannabinoids have a restorative effect wherever the tissues are damaged, bringing optimal health in all structures and functions. To illustrate this, one particular cannabinoid detects proliferation of tumor cells, binds to the appropriate receptor site (CB2), and causes cancer cell death, leaving normal cells untouched. This effect is shown easily in the lab, but is this scalable to the human condition? We shall see.

In my high school physiology course, the first important concept I learned was homeostasis, the persistent tendency of the body to maintain metabolic balance. It does this through several related systems; so we see that the body likes to be healthy and happy. That is its nature.

Why does the body allow these foreign cannabinoids to come in and take control of such essential physiological processes, without some kind of reaction? It is simply because this modulation system is already set up, and has been functional for millions of years; it's in the DNA of all living creatures. Only it's called the endocannabinoid system. Let's look and see what this system is all about. In the Journal of Neuroimmunology we find a succinct summary:

The endocannabinoid system consists of cannabinoid receptors, their endogenous ligands and enzymes for synthesis and degradation of endocannabinoids and represents a local messenger system within and between the nervous and immune system. Apparently, the endocannabinoid system is involved in immune control and neuroprotection.

This is amazing. Our own endocannabinoid system covers all cells and nerves; it is the messenger of information flowing between our immune system and the central nervous system (CNS). It is responsible for neuroprotection, and micro-manages the immune system. This is the primary control system that maintains homeostasis; our well being.

Just out of curiosity, how does the work get done at the cellular level, and where does the body make the endocannabinoids? Here is a quick look:

In standard neurotransmission, the pre-synaptic neuron releases neurotransmitter into the synaptic cleft which binds to cognate receptors expressed on the post-synaptic neuron. Upon binding, the neuron depolarizes. This depolarization facilitates the influx of calcium into the neuron; this increase in calcium activates an enzyme called transacylase which catalyzes the first step of endocannabinoid biosynthesis.

Here we see that endocannabinoids have their origin in nerve cells right at the synapse. When the body is compromised through illness or injury it calls insistently to the endocannabinoid system to direct the immune system to bring healing. If these homeostatic systems are weakened, it should be no surprise that hemp cannabinoids are therapeutic. It helps the body in the most natural way possible.

The endocannabinoid system

To see how this works we visualize the cannabinoid as a 3-dimensional molecule, where one part of the molecule is configured to fit the nerve or immune cell receptor site just like a key in a lock. There are at least two types of cannabinoid receptor sites, CB1 (CNS) and CB2 (immune). In general CB1 gives us the buzz, and CB2 activates the immune system, but it's much more complex than this. Both THC and anandamide activate both receptor sites. Other cannabinoids activate one or the other receptor sites. Among the strains of Cannabis, C. sativa tends toward the CB1 receptor, and C. indica tends toward CB2. So sativa is better for buzz, and indica is better for healing. Another factor here is that sativa is dominated by THC cannabinoids, and indica is predominately CBD (cannabidiol).

It is known that THC and CBD are biomimetic to anandamide, that is, the body can use both interchangeably. Thus, when stress, injury, or illness demand more from endogenous anandamide than can be produced by the body, its mimetic exocannabinoids can be administered. If the stress is transitory, then the treatment can be transitory. If the demand is sustained, such as in cancer, then treatment needs to provide sustained pressure of the modulating agent on the homeostatic systems. This is why Rick Simpson recommends twice daily doses of hemp oil extract (C. indica), for three months, in the case of cancer.

Typically CBD gravitates to the densely packed CB2 receptors in the spleen, home to the body's immune system. From there, immune cells seek out and destroy cancer cells. Interestingly, it has been shown that CBD cannabinoids have the ability to kill cancer cells directly without going through immune intermediaries. CBD hijacks the lipoxygenase pathway to directly inhibit tumor growth. As a side note, it has been discovered that CBD inhibits anandamide reuptake. This means that cannabidiol helps the body preserve its own natural endocannabinoid by inhibiting the enzyme that breaks down anandamide.

Coincidentally, it is not only CBD that is specifically cytotoxic to cancer cells, THC takes a different approach the task:

THC achieves this wizardry by binding to protein receptors on a cancerous cell?s surface. Once attached, the THC induces the cell to make a fatty substance called ceramide, which prompts the cell to start devouring itself. We see programmed cell death. What's more, noncancerous cells don't make ceramide when they come into contact with THC. The healthy cells don't die.

Just for clarity, endogenous ceramide (a signaling sphingolipid) disrupts the mitochondrial function of making ATP (adenosine triphosphate), thus the cancer cell becomes energy starved. ATP is the energy donor for all essential cell functions. Once the mitochondria shut down, the cell dies.

Endogenous ceramide's day job is to speed destruction of already stressed or senescent cells. We seen now that in the presence of THC, ceramide senses cancer cells as stressed or senescent, thus speeding their death.

Before leaving this topic it is important that we differentiate between plant based ceramide (phytosphingosine) and mammalian ceramide (endogenous sphignosine). Plant ceramide has a slightly different molecular structure but very different bioactivity. Ingested, it is a moisturizing lipid that supports the skin (stratum corneum) enhancing the moisture barrier that keeps epidermis from drying out. This is good, you should get some. I tried it and liked it.

How cannabis oil works

First let's look at what keeps cancer cells alive, then we will come back and examine how the cannabinoids CBD (cannabidiol) and THC (tetrahydrocannabinol) unravels cancer?s aliveness.

In every cell there is a family of interconvertible sphingolipids that specifically manage the life and death of that cell. This profile of factors is called the "Sphingolipid Rheostat." If endogenous ceramide (a signaling metabolite of sphingosine-1-phosphate) is high, then cell death (apoptosis) is imminent. If ceramide is low, the cell is strong in its vitality.

Very simply, when THC connects to the CB1 or CB2 cannabinoid receptor site on the cancer cell, it causes an increase in ceramide synthesis which drives cell death. A normal healthy cell does not produce ceramide in the presence of THC, thus is not affected by the cannabinoid.

The cancer cell dies, not because of cytotoxic chemicals, but because of a tiny little shift in the mitochondria. Within most cells there is a cell nucleus, numerous mitochondria (hundreds to thousands), and various other organelles in the cytoplasm. The purpose of the mitochondria is to produce energy (ATP) for cell use. As ceramide starts to accumulate, turning up the Sphingolipid Rheostat, it increases the mitochondrial membrane pore permeability to cytochrome c, a critical protein in energy synthesis. Cytochrome c is pushed out of the mitochondria, killing the source of energy for the cell.

Ceramide also causes genotoxic stress in the cancer cell nucleus generating a protein called p53, whose job it is to disrupt calcium metabolism in the mitochondria. If this weren't enough, ceramide disrupts the cellular lysosome, the cell's digestive system that provides nutrients for all cell functions. Ceramide, and other sphingolipids, actively inhibit pro-survival pathways in the cell leaving no possibility at all of cancer cell survival.

The key to this process is the accumulation of ceramide in the system. This means taking therapeutic amounts of CBD and THC, steadily, over a period of time, keeping metabolic pressure on this cancer cell death pathway.

How did this pathway come to be? Why is it that the body can take a simple plant enzyme and use it for profound healing in many different physiological systems? This endocannabinoid system exists in all animal life, just waiting for its matched exocannabinoid activator.

This is interesting. Our own endocannabinoid system covers all cells and nerves; it is the messenger of information flowing between our immune system and the central nervous system (CNS). It is responsible for neuroprotection, and micro-manages the immune system. This is the primary control system that maintains homeostasis; our well being.

How does the work get done at the cellular level, and where does the body make the endocannabinoids? Here we see that endocannabinoids have their origin in nerve cells right at the synapse. When the body is compromised through illness or injury it calls insistently to the endocannabinoid system and directs the immune system to bring healing. If these homeostatic systems are weakened, it should be no surprise that exocannabinoids are therapeutic. It helps the body in the most natural way possible.

To see how this works we visualize the cannabinoid as a three dimensional molecule, where one part of the molecule is configured to fit the nerve or immune cell receptor site just like a key in a lock. There are at least two types of cannabinoid receptor sites, CB1 (CNS) and CB2 (immune). In general CB1 activates the CNS messaging system, and CB2 activates the immune system, but it's much more complex than this. Both THC and anandamide activate both receptor sites. Other cannabinoids activate one or the other receptor sites. Among the strains of Cannabis, C. sativa tends toward the CB1 receptor, and C. indica tends toward CB2. So sativa is more neuroactive, and indica is more immunoactive. Another factor here is that sativa is dominated by THC cannabinoids, and indica is predominately CBD (cannabidiol).

It is known that THC and CBD are biomimetic to anandamide, that is, the body can use both interchangeably. Thus, when stress, injury, or illness demand more from endogenous anandamide than can be produced by the body, its mimetic exocannabinoids are activated. If the stress is transitory, then the treatment can be transitory. If the demand is sustained, such as in cancer, then treatment needs to provide sustained pressure of the modulating agent on the homeostatic systems.

Typically, CBD gravitates to the densely packed CB2 receptors in the spleen, home to the body's immune system. From there, immune cells seek out and destroy cancer cells. Interestingly, it has been shown that THC and CBD cannabinoids have the ability to kill cancer cells directly without going through immune intermediaries. THC and CBD hijack the lipoxygenase pathway to directly inhibit tumor growth. As a side note, it has been discovered that CBD inhibits anandamide reuptake. Here we see that cannabidiol helps the body preserve its own natural endocannabinoid by inhibiting the enzyme that breaks down anandamide.

This brief survey touches lightly on a few essential concepts. Mostly I would like to leave you with an appreciation that nature has designed the perfect medicine that fits exactly with our own immune system of receptors and signaling metabolites to provide rapid and complete immune response for systemic integrity and metabolic homeostasis.

ttps://www.cureyourowncancer.org/de...nabis-oil.html
 
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D’Or Institute


Inflammation, neurodegeneration and 5-MeO-DMT

D’Or Institute for Research and Education | Neuroscience News | 9 Oct 2017

A new study reveals psychedelic substances may have a neuroprotective role when it comes to inflammation. Researchers also report psychedelics can alter signaling pathways associated with neuroplasticity. .

A new study has identified changes in signaling pathways associated with neural plasticity, inflammation and neurodegeneration triggered by a compound from 5-MeO-DMT.

"For the first time we could describe psychedelic related changes in the molecular functioning of human neural tissue," said Stevens Rehen, study leader, Professor of Federal University
of Rio de Janeiro (UFRJ) and Head of Research at D'Or Institute for Research and Education (IDOR).

Though recent studies have demonstrated that psychedelic substances, such as LSD, MDMA and ayahuasca, hold therapeutic potential with possible anti-inflammatory and antidepressant effects, the lack of appropriate biological tools has been shown as a critical limitation for the identification of molecular pathways targeted by psychedelics in the brain.

In order to unveil the effects of 5-MeO-DMT, Vanja Dakic (IDOR) and Juliana Minardi Nascimento (IDOR) have exposed cerebral organoids, which are 3D cultures of neural cells that mimic a developing human brain, to a single dose of the psychedelic.

By employing mass spectrometry-based proteomics to analyze cerebral organoids, they found that 5-MeO-DMT altered the expression of nearly one thousand proteins. Then, they mapped which proteins were impacted by the psychedelic substance and their role in the human brain.

Researchers found that proteins important for synaptic formation and maintenance were upregulated, among them, proteins related to cellular mechanisms of learning and memory, key components of brain functioning.

On the other hand, proteins involved in inflammation, degeneration and brain lesion were downregulated, suggesting a potential neuroprotective role for the psychedelic substance.

"Results suggest that classic psychedelics are powerful inducers of neuroplasticity, a tool of psychobiological transformation that we know very little about," said Sidarta Ribeiro, Director of the Brain Institute of Federal University of Rio Grande do Norte (UFRN) and coauthor of the study.

http://neurosciencenews.com/psychede...inibrain-7690/
 
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Psychedelics’ anti-inflammatory effects


Scientists have discovered that a number of psychedelics can reduce inflammation throughout the body. Animal studies with one of these drugs, DOI, which is an especially potent anti-inflammatory compound, are starting to reveal the mechanism behind these effects. According to one hypothesis, DOI binds to and activates the serotonin 2A (5-HT2A) receptor to recruit protein kinase C (PKC). This is thought to block the downstream effects of the binding of tumor necrosis factor-alpha (TNF-α) to its receptor (TNFR), which is known to initiate a signaling cascade that promotes the transcription of proinflammatory genes.

All the classic psychedelic drugs—psilocybin, LSD, and N,N-dimethyltryptamine (DMT), the active component in ayahuasca—activate serotonin 2A (5-HT2A) receptors, which are distributed throughout the brain. In all likelihood, this receptor plays a key role in the drugs’ effects. Krahenmann and his colleagues in Zurich have discovered that ketanserin, a 5-HT2A receptor antagonist, blocks LSD’s hallucinogenic properties and prevents individuals from entering a dreamlike state or attributing personal relevance to the experience.

Other research groups have found that, in rodent brains, 2,5-dimethoxy-4-iodoamphetamine (DOI), a highly potent and selective 5-HT2A receptor agonist, can modify the expression of brain-derived neurotrophic factor (BDNF)—a protein that, among other things, regulates neuronal survival, differentiation, and synaptic plasticity. This has led some scientists to hypothesize that, through this pathway, psychedelics may enhance neuroplasticity, the ability to form new neuronal connections in the brain. “We’re still working on that and trying to figure out what is so special about the receptor and where it is involved,” says Katrin Preller, a postdoc studying psychedelics at the University of Zurich. “But it seems like this combination of serotonin 2A receptors and BDNF leads to a kind of different organizational state in the brain that leads to what people experience under the influence of psychedelics.”

This serotonin receptor isn’t limited to the central nervous system. Work by Charles Nichols, a pharmacology professor at Louisiana State University, has revealed that 5-HT2A receptor agonists can reduce inflammation throughout the body. Nichols and his former postdoc Bangning Yu stumbled upon this discovery by accident, while testing the effects of DOI on smooth muscle cells from rat aortas. When they added this drug to the rodent cells in culture, it blocked the effects of tumor necrosis factor-alpha (TNF-α), a key inflammatory cytokine.

“It was completely unexpected,” Nichols recalls. "The effects were so bewildering," he says, "that they repeated the experiment twice to convince themselves that the results were correct." Before publishing the findings in 2008, they tested a few other 5-HT2A receptor agonists, including LSD, and found consistent anti-inflammatory effects, though none of the drugs’ effects were as strong as DOI’s. “Most of the psychedelics I have tested are about as potent as a corticosteroid at their target, but there’s something very unique about DOI that makes it much more potent,” Nichols says.

After seeing the effect these drugs could have in cells, Nichols and his team moved on to whole animals. When they treated mouse models of system-wide inflammation with DOI, they found potent anti-inflammatory effects throughout the rodents’ bodies, with the strongest effects in the small intestine and a section of the main cardiac artery known as the aortic arch. “I think that’s really when it felt that we were onto something big, when we saw it in the whole animal,” Nichols says.

The group is now focused on testing DOI as a potential therapeutic for inflammatory diseases. In a 2015 study, they reported that DOI could block the development of asthma in a mouse model of the condition, and last December, the team received a patent to use DOI for four indications: asthma, Crohn’s disease, rheumatoid arthritis, and irritable bowel syndrome. They are now working to move the treatment into clinical trials. "The benefit of using DOI for these conditions," Nichols says, "is that because of its potency, only small amounts will be required—far below the amounts required to produce psychedelic effects."

"In addition to opening the door to a new class of diseases that could benefit from psychedelics-inspired therapy, Nichols’s work suggests that there may be some enduring changes that are mediated through anti-inflammatory effects,”
Griffiths says. Recent studies suggest that inflammation may play a role in a number of psychological disorders, including depression and addiction.

“If somebody has neuroinflammation and that’s causing depression, and something like psilocybin makes it better through the subjective experience but the brain is still inflamed, it’s going to fall back into the depressed rut,” Nichols says. "But if psilocybin is also treating the inflammation," he adds, “it won’t have that rut to fall back into.”




Scientists have discovered that a number of psychedelics can reduce inflammation throughout the body. Animal studies with one of these drugs, DOI, which is an especially potent anti-inflammatory compound, are starting to reveal the mechanism behind these effects. According to one hypothesis, DOI binds to and activates the serotonin 2A (5-HT2A) receptor to recruit protein kinase C (PKC). This is thought to block the downstream effects of the binding of tumor necrosis factor-alpha (TNF-α) to its receptor (TNFR), which is known to initiate a signaling cascade that promotes the transcription of proinflammatory genes.

If psychedelics do have anti-inflammatory effects in the brain, the drugs’ therapeutic uses could be even broader than scientists now envision. “In terms of neurodegenerative disease, every one of these disorders is mediated by inflammatory cytokines,” says Juan Sanchez-Ramos, a neuroscientist at the University of South Florida who in 2013 reported that small doses of psilocybin could promote neurogenesis in the mouse hippocampus. “That’s why I think, with Alzheimer’s, for example, if you attenuate the inflammation, it could help slow the progression of the disease.”

https://www.the-scientist.com/features/decoding-the-tripping-brain-30240
 
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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/
 
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The anti-cancer properties of P. harmala*

by Giorgio Samorini - March 1, 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/
 
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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.
 
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Peganum harmala and cancer*

Lamchouri, Zemzami, Jossang, Settaf, Israili, Lyoussi

P. harmala is a dense, bright green blooming succulent that grows from a perennial woody root in semi-arid environments. It is a psychedelic with origins dating back to Central Asia, where it frequently grows among the ruins of ancient cities in the Middle East. B-carbolines, harmaline and harmine, are the major alkaloids present in P. harmala. These alkaloids are known as herbal active principals with potential use in pharmaceutical and medicine.

P. harmala has been used in traditional medicine to treat various diseases including cancer. Our preliminary studies show that the alkaloidal extract of PH seed is cytotoxic to several tumor cell lines in vitro and has antitumor effect in a tumor model in vivo. The present investigation was aimed at extending our previous studies in identifying the components in P. harmala seed-extract responsible for the cytotoxic effects, and study the cytotoxic and antiproliferative activity of isolated alkaloids and total alkaloidal fraction (TAF) in several tumor cell lines.

The present study of the cytotoxic and antiproliferative effects in experimental models of cancer show that the TAF and three of the four alkaloids (harmine, harmalacidine and vasicinone) isolated from the seed extract of P. harmala have significant in vitro cytotoxic activity in tumor cell lines, and antiproliferative activity on Jurkat line, E6-1 clone. The results of the present investigation and previous studies suggest that P. harmala seed alkaloids have significant antitumor activity, and the B-carboline structure could be an important basis for the design and synthesis of new antitumor drugs.

*From the study here: https://pdfs.semanticscholar.org/d10c/fcde0104d3ee49488356addab38788a83959.pdf
 
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Some cancers become contagious

by Katarina Zimmer | Apr 1, 2019

So far, six animal species are known to carry transmissible, “parasitic” forms of cancer, but researchers are still mystified as to how cancer can become infectious.

The untrained eye likely wouldn’t have noticed, but doctoral student Ruth Pye immediately spotted something unusual about the way the cells were arranged in a tissue sample from a facial tumor of a Tasmanian devil. Tumor cells plucked from the marsupials normally grew and divided more slowly, but these established themselves much faster in culture, and had longer projections extending from their spindle-shaped cell bodies, she recalls.

It was early 2014, and Pye was examining a biopsy taken from a diseased devil on a remote peninsula on the southeast side of Tasmania. Her lab at the Menzies Institute for Medical Research at the University of Tasmania received such samples as part of a government-sponsored monitoring program to study the notorious cancer that had been decimating populations of the island’s namesake marsupial. Known as devil facial tumor disease (DFTD), the cancer differs from most in that it exists as a single transformed cell line, thought to have originated in a devil that lived more than 20 years ago, that is capable of moving between individuals. Each cell genetically resembles the founder devil, and is distinct from the cells of healthy devils.

Such contagious cancers are exceedingly rare: at the time Pye noticed the strange-looking samples, the only other transmissible cancer known was a sexually transmitted oncogenic cell line in dogs, which was by and large harmless to the animals. In Tasmanian devils, DFTD is thought to be transmitted when the animals bite one another, whether it be during battles for mates, during mating itself, or when scrapping over meals of dead animals. Cancerous cells that become lodged in the open wounds of the mouth or face quickly colonize the host tissue, triggering the growth of disfiguring tumors that impair the animals’ ability to feed. Since the first reported case of DFTD in 1996, devil numbers have plummeted by nearly 80 percent in areas affected by the disease.

Pye made a note of her observation regarding the unusual sheets of cancer cells and put it aside. But when a similar sample came in from a different devil that lived in the same area as the first, she decided to investigate. Neither tumor stained positive for the protein periaxin, a diagnostic marker for DFTD. Karyotyping revealed hallmarks of a transmissible cancer: the tumor cells were different from host cells, but were identical to one another, sharing the same chromosomal aberrations even across devils. This suggested that the cells came from a transmissible cancer that originated, not in the individual carrying the tumor, but from another devil who had passed along its disease, according to Pye, now a research veterinarian at the Menzies Institute.

After puzzling over the findings with her supervisors at the time, Greg Woods and Bruce Lyons, Pye sent some samples to the University of Cambridge in the UK, where Elizabeth Murchison and her team conducted a microsatellite analysis. Sure enough, the results revealed that the fast-growing cells in the two samples represented a distinct transmissible cancer that appeared to have arisen completely independently. “I remember when we got the results off the machine, and it was immediately clear that it wasn’t DFTD,” Murchison says. “We just couldn’t believe it.”

The finding challenged the idea that DFTD, now named DFT1, was a one-off. If a second contagious cancer, since named DFT2, could emerge within a few decades of the first, perhaps the phenomenon of cancerous cell lines spreading between individuals was a lot more common than researchers realized, Murchison says. It’s possible, she muses, that researchers only identified DFT2 because the devils were already under such close surveillance due to the original cancer, and that other examples of animals spreading tumors to one another have flown under the radar. “The discovery really changed everything we thought we knew” about transmissible cancers, she says.

At the time Pye identified the first unusual samples of Tasmanian devils’ tumors, researchers in the United States were already investigating a leukemia that had been decimating populations of a soft-shelled clam (Mya arenaria) off the coast of New England. In 2015, virologist Stephen Goff and his team at Columbia University reported that leukemia cells across individuals were genetically identical to one another, but genetically different from their host’s healthy cells. “We were forced to the realization at the time that this was a third example of a transmissible tumor happening,” Goff recalls, after the cancers known in devils and dogs. A year later, he and his team found three other species of bivalve that carry their own contagious cancers, raising the number of species affected by naturally occurring transmissible cancers to six.

The realization that such contagious cancers may be more widespread than previously thought has intensified efforts to understand their biology—not just for the sake of the species they affect, but also to understand how cancer can become an infectious disease. Many questions remain unanswered, including how these diseases emerge and in what populations. But in the last few years, genetic and immunological studies have provided some insight into these cancers’ interactions with their hosts. The findings have led researchers to view them as independent parasites, with the survival of their host species depending on a delicate interplay between the animals’ immune systems and the cancers’ ability to evade them.

So far, only dogs, Tasmanian devils, and four bivalve species are known to carry transmissible cancers, which have varying effects on their hosts.





The birth of a cancer parasite

When North American settlers wandered across the Bering Strait while it was frozen during the last ice age, they brought their dogs with them. Sometime later—some 8,000 years ago—a tumor emerged in one of the canines’ descendants. But something unusual happened. Rather than dying with its canine victim, the cancer began to jump from one pup to another.

That’s according to a 2016 Science study of canine evolution in the Americas. In that paper, Murchison and her collaborators traced back the origins of the oldest known contagious cancer—canine transmissible venereal tumor (CTVT)—through estimations of its mutation rate. Currently, the cancer lives on as a cauliflower-like tumor on the genitals of dogs around the world. But because CTVT has accumulated so many mutations over the course of its long history, it’s difficult to identify which ones contributed to its emergence, explains University College London (UCL) immunologist Ariberto Fassati, who together with UCL virologist Robin Weiss conclusively established CTVT’s transmissibility in 2006.

Murchison and colleagues’ analysis of the more recently arisen DFT1 and DFT2 lines was more successful at uncovering clues to the cancers’ origins.6 Based on the proteins these cancer cells produce, the researchers surmised that both cancer types appear to have emerged in a type of cell associated with the nervous system. DFT1 was already known to produce periaxin and other proteins associated with Schwann cells, which wrap around nerves and rapidly proliferate after nerve injury. DFT2 doesn’t produce periaxin. But like DFT1 it has a mutation in the Hippo pathway, a signaling cascade altered in certain Schwann cell cancers in humans. “Our theory is that they both come from a Schwann cell which has become stuck in this repair mode,” Murchison says.

Still, it’s not clear what made the cancer cells first able to jump hosts. Biologists have proposed that transmissibility results from a perfect storm of four key factors. First, tumor cells need a route of transmission to a new host, and second, they must be able to maintain survival during that transition. Third, the species must have an immune environment that facilitates invasion by foreign cells. And finally, the tumors must have mechanisms to evade immune attacks by their new host.

The sustained physical contact during canine intercourse and the devils’ habit of biting other individuals during the mating season set the stage for transmission to occur. Then, low genetic diversity in both species might have allowed the cancers to flourish in new but similar environments.

Under normal circumstances, foreign cells are rejected through a vertebrate’s self/nonself recognition immune system. Individual-specific cell surface antigens known as the major histocompatibility complex (MHC) classes I and II alert the animal’s T cells to the presence of foreign material, the former triggering killer T cells to attack. In Tasmanian devils, however, MHC diversity is very low, as a result of major population bottlenecks caused by extreme climatic events throughout the species’ history. And the CTVT founder dog is believed to have been a member of a population with low genetic diversity: “It looks like it came from quite an isolated population,” says Máire Ní Leathlobhair, a doctoral student in Murchison’s lab. The role of low host genetic diversity in the emergence of transmissible cancers is also supported by experiments from the 1960s showing that a sarcoma could be transmitted between individuals of an inbred laboratory population of Syrian hamsters by the injection of tumor cells. Despite the fact that the cells were of nonself origin, the hamsters’ immune systems did not reject them.

In bivalves, cancerous cells are released from infected animals and drift through the water to other individuals, which are thought to pick them up during filter feeding, explains Michael Metzger, a former postdoc in Goff’s lab, who now heads a lab at the Pacific Northwest Research Institute. And the mollusks lack the adaptive immune system that includes the self/nonself recognition system in vertebrates, he adds. “That seems to lower the bar for transmissible cancers.”

Once these initial hurdles are cleared, the tumors can adapt to their new environment to evade immune attacks by their hosts, says Frédéric Thomas, an evolutionary biologist at the French National Center for Scientific Research who with colleagues formalized the “perfect storm” hypothesis in 2016. “Once the process is started, it’s equivalent to the creation of a novel parasitic species, with its own dynamic and its own evolution.”

Immune hide and seek

For a while, researchers believed that the devils’ precariously low MHC diversity was enough to explain why DFT1 could thrive in different individuals. But an experiment in 2011 turned that idea on its head. When researchers at the University of Tasmania cut small skin slices from five healthy devils and transplanted them to other individuals, all of the allografts were rejected within 14 days. This suggested that MHC diversity in devils is sufficient for them to reject tissue from other individuals, puzzling immunologists as to how a cancer could be so easily transmitted. “Why would this transmissible cancer not be rejected like any regular tissue transplant would be?” asks the University of Tasmania’s Lyons.

A clue surfaced in 2013, when British researchers demonstrated that DFT1 cells don’t express any MHC antigens.10 It turns out that the tumor cells epigenetically downregulate several genes that encode proteins required for building MHC antigens. Murchison’s group reported last year that DFT1 lacks a copy of β2 microglobulin (B2M), which encodes a component of MHC class I molecules. “That’s probably at least part of the reason why the immune system isn’t able to detect [the cancer cells] as being foreign,” Murchison says. Researchers have similarly shown that CTVT cells downregulate MHC class I expression in dogs.

The devil is in the details
In one of the most extensive studies of devil facial tumor disease (DFT1) to date, an international team of researchers has uncovered a mechanism that drives the cancer’s metastasis and helps it to evade the Tasmanian devils’ immune system.

Interference with the MHC system is a mechanism also exploited by human cancers to hide from the immune system. Several large-scale studies have established a frequent occurrence of downregulation among genes encoding human leukocyte antigens (HLA)—the human variant of MHC—in head, neck, lung, and other tumors. And in a rare case of transmission of cancer cells from a pregnant mother to her developing fetus in 2009, genetic analysis indicated that the fetus’s maternally derived leukemic cells carried a deletion of a particular HLA allele.

Earlier this year, an international group of researchers uncovered a mechanism that explains how the devils’ tumors manipulate the production of MHC proteins. The team found that two proteins, ERBB and Stat3, known to boost the expression of metastasis-driving genes in human cancers, are overactive in DFT1 cells. These proteins are part of “a very well-described signaling cascade in human cancer,” explains senior author and immunologist Andreas Bergthaler of the Research Center for Molecular Medicine of the Austrian Academy of Sciences. But in devils, the pathway has an additional effect: it also regulates MHC class I production by stifling the expression of genes required for the creation of MHC proteins, such as B2M. Blocking the pathway in immunodeficient mice not only stunted the growth of DFT1 cells by crippling the expression of genes that drive metastasis, it also revived MHC class I expression on the surface of DFT1 cells. In mice with functioning immune systems, this could further slow tumor growth by triggering T cells to attack the cancer cells, explains Bergthaler.

But stunted MHC production alone doesn’t explain why DFT1 is not rejected by new hosts. Vertebrate immune systems have other mechanisms to ward off pathogens. For instance, natural killer (NK) cells that fight infections would normally detect and attack cells that don’t produce MHC proteins. NK cells function in devils, yet for reasons that are unclear, they don’t seem to attack DFT1, suggesting that the cancers exploit additional mechanisms to evade them, such as by secreting immunosuppressive cytokines, says Pye.

DFT2 cells, however, do present MHC class I molecules—at least in cell culture, Murchison’s group established last year. This finding indicates that the loss of these MHC antigens may not be necessary for the emergence of a contagious cancer. Perhaps for now, DFT2 can spread thanks to extremely low genetic diversity of the southeastern devil population, the researchers speculate. Indeed, Murchison and colleagues found that the MHC class I molecules of DFT2 are very similar to those of devils infected by the cancer. DFT2 may also eventually begin to mimic DFT1 and lose its MHC expression if it spreads to less closely related individuals.

“It’s quite possible that DFT2 is just a precursor, so to speak, to DFT1,” notes Fassati.




Prayer for the devil

The devil as a species is safe for now. Years ago, biologists gathered a number of uninfected animals and shuttled them to an uninhabited island off the coast of Tasmania for safekeeping, and numerous breeding populations live in zoos around the world. But the race is still on to protect the 25,000 or fewer wild animals that remain in Tasmania. For them, DFT2 is not yet a threat, as the disease hasn’t spread beyond a small area in southern Tasmania. But DFT1 is still killing off devils at an alarming rate, worrying researchers about the fate of the charismatic marsupials. Many fear that the demise of the island’s only remaining native carnivore will bring major disruption to the Tasmanian ecosystem.

One approach to protecting the devils is to vaccinate uninfected animals kept in captivity or on the uninhabited island against the contagious cancers before returning them to the wild. Vaccines produced from heat-treated or otherwise damaged DFT1 cells, for example, were used on devils released in groups of 19 or more in different parts of Tasmania between 2015 and 2018. But trapping the animals again to see whether the vaccine had any protective effect has proven difficult, as devils disperse widely across the island and often become victims of vehicular collisions, explains Carolyn Hogg, a conservation biologist at the University of Sydney who is working with the Tasmanian government–sponsored Save the Tasmanian Devil Program.

Another tack is to treat infected individuals. A combined vaccine and immunotherapy trial with six devils in 2017 proved promising, with half of the animals’ tumors vanishing entirely. “It was essentially a cure,” for those devils, says Lyons, who led the study. For him, the trial is a proof of principle that the devils’ immune system is capable of fighting off the cancer, and it could help the team build better vaccines in the future. But capturing wild devils and treating them with immunotherapy isn’t logistically feasible on a large scale, he notes.

Fortunately, devils seem to be getting better at battling the disease without medical intervention. “We’re getting an increasing number of animals that are actually surviving, [in which] the tumors regress and in some cases disappear,” says Menna Jones, a zoologist at the University of Tasmania. “And some of those individuals will live to quite a ripe old age.” Such resilient devils appear to be genetically different from devils that succumb to the tumor, she and others found last year. For example, alleles thought to underlie cancer risk and immune responses to tumors in humans were overrepresented among the survivors. This suggests that some populations are adapting to the disease, Jones says.

On the flip side, the cancer itself also appears to be evolving. In a 2013 study, researchers found that large areas of the DFT1 genome have become demethylated over time, possibly resulting in a change in gene expression. “We think that the tumors are adapting to the immune response and tumor suppressor response from the host via epigenetic modification,” explains lead author Beata Ujvari, an evolutionary biologist then at the University of Sydney.

Contagious cancer cases in humans

The “elephant in the room” of transmissible cancer research is the question of whether one could arise in humans, says immunologist Andreas Bergthaler of Vienna’s Research Center for Molecular Medicine of the Austrian Academy of Sciences. But so far, there have only been “freak cases” of cancers jumping from one person to another, he says. In some two dozen cases over the past several decades, for instance, doctors have reported mother-to-child transfer of cancer cells during pregnancy. It is unclear how most of these occurred, but genetic analyses suggest that, in some cases, mutations arise in the cancer cells that allow them to escape immune detection by their new host.

One of the first well-documented examples of cancer transmission between two adults came in 1996, when a surgeon was reported to have developed a tumor-like swelling after he injured his palm during an operation on a cancer patient. The tumor was excised, and didn’t grow back. Clinicians aren’t sure why the malignant cells weren’t initially rejected by the surgeon’s immune system, but suggest they could have escaped immune detection by tinkering with their expression of MHC molecules that help the body discern self from foreign cells—the same mechanisms employed by transmissible cancers in Tasmanian devils.

In other cases, cancer appears to have made the leap between humans when a person’s immune system is not functioning properly. Organ transplant recipients, for instance, can be vulnerable to contracting cancer from organ donors, as they are administered immunosuppressive drugs to prevent rejection of foreign tissue. Just last year, for example, clinicians documented four patients who developed breast cancer after receiving kidneys, lungs, heart, and liver from a 53-year-old donor who had died due to stroke. The cancer cells did not match the patients’ own cells, but those of the donor, who at the time of the transplant was not known to have the disease. In an exceptionally unusual case that also involved an immunocompromised individual, a 41-year-old HIV patient was reported to have died of cancer contracted from a tapeworm living inside his gut.

Unless the immune system is compromised, there’s very little chance a contagious cancer could arise in humans, Bergthaler says, and “there’s no hard evidence” that anything akin to the devils’ or dogs’ cancer is making the rounds in human populations. Then again, he adds, there was a time when scientists only knew of retroviruses that could infect animals other than humans. While it’s highly unlikely the story could turn the same way for transmissible cancers, “it goes to show we might still be unaware of certain diseases in humans. . . . We just don’t know.”





Ujvari, now at Deakin University near Melbourne, thinks there’s also a possibility that DFT1 cells are facing a selective pressure to become less virulent. From a parasite’s perspective, it might be advantageous to allow its devil host to survive as long as possible, in order to increase its chances of transmission. This could explain why dogs rarely die from CTVT, which could have been a much more aggressive cancer in the past, she speculates. “The host and the cancer cell line have achieved an evolutionary equilibrium where the cancer cells don’t kill the dogs anymore.” This is the trend that has been documented in some clam populations, which have rebounded after being ravaged by a transmissible leukemia. However, Metzger notes, “this could be due to the cancer evolving to be less pathogenic, but it could also be a case of the clams evolving resistance to the disease.”

Andrew Storfer, an evolutionary geneticist at Washington State University, argues that, with regard to the Tasmanian devil, which normally lives five to seven years in the wild, the latter hypothesis is more likely. Because devils tend to survive for several months with the cancer before they die, they have plenty of time to transmit the disease, he says. “Given the slow-burning nature of the disease, there doesn’t seem to be a strong selection to evolve to lower virulence.” Ujvari and her colleagues are currently working to develop mathematical models to predict the evolutionary trajectory of DFT1 and DFT2 to better understand the disease in the context of host-parasite co-evolution.

Like other scientists, Ujvari wonders whether transmissible cancers may be more common than realized. Perhaps they drove their hosts to extinction, she suggests, or they have reached such a stable equilibrium they are no longer detectable. To get to the root of this question, some researchers have begun to actively search for more such transmissible cancers in nature. If more examples can be identified, it could point to common factors that allow the oncogenic cell lines to jump from one individual to another.

To more directly investigate how contagious cancers arise, Fassati plans to recreate a transmissible tumor in mice. He hopes that learning how contagious cancers outsmart their hosts’ immune systems will lead to insights into how non-transmissible cancers do the same, and perhaps pave the way for more-effective immunotherapies that coax human immune cells into recognizing and attacking hard-to-treat tumor cells.

“I first got into studying transmissible cancers because I wanted to help the devil,” says Murchison, who is originally from Tasmania. “Now, I still want to help the devils, but it’s also just a fascinating area of research where we can learn so much about cancer in general.”

 
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