• Psychedelic Medicine
  • Psychedelic Medicine Moderator: mr peabody
  • Bluelight HOT THREADS
  • Let's Welcome Our NEW MEMBERS!

Science Cancer

Status
Not open for further replies.

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



Can 5-MeO help cure cancer?*

Research on the therapeutic potential of 5-MeO for cancer is still in the early stages, but the few studies that have been done are very promising. For example, it has been shown to exert strong anti-cancer and anti-inflammatory effects through the modulation of innate and adaptive immune processes. Its regulatory effect on the sigma-1 receptor, which plays a significant role in cancer, is especially interesting.

Classical psychedelics are psychoactive substances, which, besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation, and cell survival via activating NF-kB and mitogen-activated protein kinases. Recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have also been shown to play crucial roles in numerous immunological processes. This emerging field also offers promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer.

In this paper, the immunomodulatory potential of the classical serotonergic psychedelics DMT, 5-MeO-DMT and LSD are discussed from a perspective of molecular immunology and pharmacology. Special attention is given to the functional interaction of serotonin and sigma-1 receptors and their cross-talk with toll-like and RIG-I-like pattern-recognition receptor-mediated signaling. Since both NF-kB and type I IFN signaling contribute to the transcriptional regulation of genes that are involved in cellular proliferation and survival, and many psychedelics exhibit in vitro anti-cancer potential through 5-HTRs, these compounds could be promising candidates in novel therapies of cancer.

Thus, as a target for future pharmacological investigations, DMT emerges as a potent and promising candidate in novel therapies of peripheral and CNS autoimmune diseases and cancer.

Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the treatment of autoimmune diseases and chronic inflammatory conditions of the CNS and/or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor.

*From the articles here:
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500993/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149582/
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN
Cannflavin B found to kill cancer cells*

by Randy Robinson | Aug 16 2019

Until recently, research on medical cannabis has focused almost entirely on the plant’s major cannabinoids, THC and CBD. But a new study revealed that the plant's flavonoids offer health benefits, as well.

THC is the world’s most well-known cannabinoid. It’s the part of weed that gets people intoxicated, and it possesses medical properties, too. And, as far as we know, only cannabis produces THC; no other plant on the planet makes this wondrous compound.

Yet there’s another compound found exclusively in cannabis, but it’s not nearly as famous as THC. That compound is cannflavin B – which is a flavonoid, not a cannabinoid. And even though cannflavin B doesn’t get people lit, a new study suggests that this flavonoid can also help kill cancer cells, just like THC.

The study, published recently in the journal Frontiers in Oncology, found that cannflavin B worked especially well against pancreatic cancer. Pancreatic cancer is one of the deadliest cancers known: A diagnosis is essentially a death sentence, with a dismal 8 percent survival rate, even with the latest developments in chemotherapy, radiation therapies, and surgeries.

Pancreatic cancer is especially lethal since the pancreas’s functions are essential to human health, and the human body contains only one pancreas. The pancreas releases hormones that raise and lower blood sugar levels. Without it, the body cannot balance how much sugar is being processed, eventually leading to nerve death and permanent organ failure.

“The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer,” the study’s authors wrote. “The results justify further studies to optimize therapy outcomes toward clinical translation.”

How does cannflavin B fight pancreatic cancer? According to the study, the molecule not only causes some of the cancer cells to “commit suicide” through a process called apoptosis, it also enhances the effectiveness of common chemo- and radiation therapies, as well. So, basically, cannflavin B could synergistically improve both medical marijuana and conventional cancer treatments simultaneously.

But, there are a couple of catches here. First, this study didn’t look at pancreatic cancer in humans. Like most lab-run weed studies, it only assessed pancreatic cancer in mice.

Second, although the researchers did study cannflavin B in rodent pancreatic cancers, their true aim wasn’t to bolster cannabis’s reputation as a cancer treatment. Rather, they primarily looked at a synthetic, lab-made version of cannflavin B, which they called FBL-03G.

Of course, since FBL-03G doesn’t naturally occur in nature, it’s patented. And the drug company that created this synthetic flavonoid, Flavocure Biotech Inc., funded this study. Although the scientists stated in their “Conflict of Interest” section that “the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest,” keep in mind that the data was collected to ultimately determine the cancer-fighting efficacy of FBL-03G, not cannflavin B.

A separate study published earlier this month indicated that the weed flavonoids cannflavin A and cannflavin B could combat pain better than THC or CBD, again raising even more questions about how cannabis truly works as a medicine.

Regardless, both the pancreatic cancer study and the flavonoid pain study may finally trigger new academic (and commercial) interests to further explore cannabis’s potential as a medicine. There’s a lot more in our favorite plant besides THC and CBD.

*From the article here:

 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



DMT and cancer


We have recently stumbled down the rabbit hole of monoamine oxidase (MAO) activity, and the potential correlation with endogenous DMT synthesis. As MAO is responsible for the rapid breakdown of DMT, it seems logical that fluctuations in MAO activity might provide a potential bio-marker for DMT formation within the body. There are two forms of MAO within the body, MAO-A and MAO-B. Both are found throughout the nervous system, MAO-A in the liver, lungs, gastrointestinal tract and placenta, and MAO-B in the blood platelets.

The plant that acts as the MAO inhibitor in the psychedelic brew Ayahuasca is Banisteriopsis caapi (B. Caapi). The active compounds in this plant responsible for the MAO inhibitions are harmine, harmaline, and tetrahydroharmine. A 2009 study published in the Journal of Ethnopharmacology found that B. Caapi suppressed MAO-A activity 2,500 times more potently than it suppressed MAO-B activity.

Another well-known plant that often accompanies DMT ingestion as a MAOI is Peganum Harmala (Syrian Rue). In a 2010 study published in the journal Food & Chemical Toxicology it was revealed that Peganum Harmala was a potent inhibitor of MAO-A activity while being a poor inhibitor of MAO-B.

This leads us to believe that one of the main indicators of DMT upregulation in the body might be MAO-A activity suppression. This is why we find it intriguing that a 2008 study in BMC Genomics revealed the following regarding MAO-A activity and cancer:

Our analysis found that significant downregulation of MAO-A, the enzyme that metabolizes serotonin, occurred in multiple tissues from humans, rodents, and fish. MAO-A expression was decreased in 95.4% of human cancer patients and 94.2% of animal cancer cases compared to the non-cancerous controls. The study proposes that low levels of MAO-A can act as a bio-marker for cancer. It was also noted that this was a significant finding based on the fact that it was a reliable change found in many different types of cancer.

Switching gears for a moment:

While it is clear that the body has the ability to heal itself after suffering lacerations to the skin and even broken bones if aligned properly. When it comes to disease, the prevailing medical/scientific narrative is that the body is a mistake maker. This is especially prominent when discussing any disease labeled as an autoimmune disorder, or cancer. For many decades the prevailing wisdom was that due to random, faulty genetic expression a person was susceptible to whatever debilitating conditions their fate had in store. However, in more recent times the epigenetic discussion has surged making it clear that the composition of the interior terrain of ones body such as hormone levels, autonomic signaling, ionic balance, and dominant brainwaves all contribute to genetic upregulation or downregulation.

*An excellent review of the vast number of organs/systems that can regenerate themselves was summarized in 2012 in the Journal Birth Defects Research. It almost appears as though the majority of organs in the human body can regenerate themselves to varying degrees.



An example of an epigenetic factor influencing genetic expression would be the recent 2017 study in Scientific Reports regarding the effects of 5-MeO-DMT on human mini-brains. It was observed that out of the 6,728 identified proteins, 934 were found differentially expressed in 5-MeO-DMT-treated cerebral organoids. This signifies that biochemical exposure can change genetic signaling.

A 2011 write-up in The Journal of Physiology documents the various manners in which elevated carbon dioxide levels lead to the suppression of genes involved in the regulation of innate immunity and inflammation. A 2016 study in Pharmacogenetics and Genomics observed numerous genetic expression changes in human colon tissue associated with dietary influence. The meat-related genetic upregulation was associated with cancer, organismal injury/abnormalities, and tumor morphology.

In a 2009 study in the Journal of Biological Chemistry it was observed that over 2,600 different genes exhibited differences in expression in the pineal gland of rats based on the time of day (mid-day or midnight). That seems like a significant number of genetic expression changes in one small, single organ imagine the amount of changes found throughout the entire system!?!?

These are clear examples that genetic expression is unequivocally influenced by changes in biochemistry, diet, respiratory/metabolic fluctuations, and circadian rhythm/changes in states of consciousness. This insinuates that the random, faulty genetic expression perspective is rather incomplete and lacking. We believe the body is constantly in a state of repair. It is an infinitely complex symphony of chemicals, ions, and autonomic signaling that lead to these mechanisms transpiring. There have been many a person now and throughout history that has alleviated their incurable disease via drastic changes in lifestyle. This is not mythical or far-fetched when integrating the latest findings regarding basic biological and metabolic principles.

(When I refer to a drastic change in lifestyle I am referring to something akin to a hamburger eating, french fry loving, soda/beer swilling, shallow breathing, sunlight shunning, stressed out insomnia transforming into a person that consumes a predominantly plant-based diet, only drinks high-quality water, receives regular daily sun exposure, practices respiratory exercises daily, and prioritizes getting 8 hours of high quality sleep every night. It would be silly for any person with a science or even non-scientific background to shun the notion that these types of radical changes would quantitatively change ones own inner terrain and subsequently their genetic expression throughout the system.)

In a chapter from the book Recent Advances in the Biology, Therapy and Management of Melanoma, the effects of oxidative stress on melanoma development and progression were outlined. "Oxidative stress" is used to describe the harmful effects of reactive oxygen species (ROS) and free radicals including: superoxide anion radical, hydroxyl radical, and the alkoxyl radical. It was outlined in the chapter that an accumulation of ROS influenced tumor development of many different types of cancers including melanoma, leukemia, gastric, prostate, breast, and colon cancer.

As cited in the past, a 2001 study published in the journal Life Sciences observed the effects of increased hydroxyl radical generation and the effects on MAO-A and MAO-B activity. It was discovered that the generation of hydroxyl radical significantly reduced both MAO-A and MAO-B activities, exhibiting a linear correlation between both MAO-A and MAO-B activities.

This suppression of MAO activity via surges in hydroxyl radical levels points us back to the 2008 BMC Genomics study in which significant downregulation of MAO-A activity occurred in multiple tissues in various organisms that expressed different types of cancer. This would point to the potentiality for measurable DMT levels to appear in the vicinity of the greatest concentration of ROS in or around the cancer cells themselves.

In 2014, a study published in Biochemical Pharmacology observed the biosynthesis of DMT in a melanoma (skin cancer) cell line. The researchers reported a never before seen metabolic pathway for DMT synthesis within human cells. A 2016 write-up in the journal Neura Regeneration Research cited the role of the sigma-1 receptor in terms of cellular survival in hypoxia (increased levels of ROS) and resistance against oxidative stress. The write-up also emphasized the affinity that DMT has for the sigma-1 receptor and the potential role of DMT as an anti-inflammatory agent.

What role does this compound play in terms of cancer? Does it make the disease worse or better? Perhaps DMT is much more than just a psychedelic molecule?

Earlier in this piece we cited that there are differing perspectives on the regenerative capabilities of the body. When it comes to disease, such as cancer, there are also differing perspectives. One viewpoint is that cancer occurs due to random DNA damage/mutations leading to tumor growth and eventual death. Also, the internal terrain of the body dictates biological reactions and in the case of cancer the body is attempting to sequester an overflux of detrimental components leading to tumor formation. We find it increasingly interesting that melatonin is one of the body's most powerful free radical scavengers/DNA regulators and that low levels of melatonin production has been linked to a large number of different types of cancer.

To put more succinctly, we believe that a disease such as cancer is the result of a lack of garbage men (ex. melatonin, glutathione), a chronic overflux of garbage (ex. ROS, toxic compounds) and blocked elimination pathways (ex. digestive, lympathic) that induce adaptive mechanisms. We wildly speculate that these adaptive mechanisms are our body's attempt to avoid mass cellular death and possibly poisoning of the bloodstream leading to a more accelerated death process. This might not be the popular perspective amongst mainstream, medical academics but we believe there is more than enough supportive data to warrant this viewpoint.

We believe that one of DMT's role in cancer is to provide a protective mechanism to the body by attempting to neutralize the elevated levels of ROS within cancer cells in order to slow down proliferation. Future studies are necessary in order to verify the role of DMT in cancer.

There are numerous abnormal ionic/electrical based qualities associated with cancer cells such as a more depolarized cell membrane potential, a hyperpolarized mitochondria, elevated intracellular sodium concentrations, and suppressed intracellular chloride concentrations.

In 2013, a case study report published in SAGE Open Medicine would review 9 separate cases of people reporting the effects of Ayahuasca ingestion on different types of cancer (prostate, brain, ovarian, uterine, stomach, breast, and colon cancers). Seven cases were reported as improvements, one was considered a regression, and one was too difficult to evaluate. The author would propose a theoretical model regarding the mechanisms of how the effects transpired as follows:

DMT binds sigma-1 receptors with moderate affinity and, at high concentrations, is also capable of inhibiting voltage-gated sodium channels. Thus, DMT may exert two types of effects through sigma-1 receptors: at low concentrations, it regulates calcium flow from the endoplasmic reticulum to the mitochondria, whereas at higher concentrations, it exerts diverse effects at the plasma membrane region. The effect on calcium influx into the mitochondria may be extremely important for cancer treatment given that an energetic imbalance between excessive cytosolic aerobic glycolysis and reduced mitochondrial oxidative phosphorylation (the Warburg effect) was recently suggested as the seventh hallmark of cancer. This metabolic profile of cancer cells is accompanied by a hyperpolarization of the mitochondrial membrane potential that may be reduced by the calcium influx triggered by DMT binding to the sigma-1 receptor at the mitochondria-associated endoplasmic reticulum membrane. This effect may facilitate the electrochemical processes at the electron transport chain inside the mitochondria, thus increasing the production of reactive oxygen species (ROS) and leading these cells to apoptotic pathways. When high DMT concentrations induce sigma-1 receptor translocation to the plasma membrane, many cellular effects would occur due to the receptor's interaction with different ion channels. At high concentrations of DMT, a calcium influx and mitochondrial membrane depolarization might be enough to also activate the permeability transition pore (PTP), inducing mitochondria swelling, rupture, and apoptosis.

It is important to note that in the write-up many of the 7 subjects who recovered from cancer were also noted to integrate a plant-based diet into their habits. Obviously this could play an additional factor in their systemic recovery process.

The discussion of Ayahuasca and it's therapeutic efficacy regarding cancer is an interesting one as there have been many anecdotal cases of remission of disease following ingestion of the psychedelic brew. Some are reported to be more spontaneous in nature while others have been cited to take months of consistent ingestion. There are numerous studies showcasing various cancers coinciding with dysfunction of autonomic nervous system signaling (1, 2, 3, 4, 5). While the cellular mechanisms correlating with remission will be difficult to verify, we do believe that the neuroplasticity inducing properties of Ayahuasca correlate with alterations (a fix of sorts) in the signaling between the brain and the autonomic nervous system. A recent 2017 write-up in New Scientist addresses nervous system signal dysfunction and the potential therapeutic effects of blocking nerve signaling to cancer cells in an attempt to thwart disease progression. It is interesting to note the effects of synthetic analgesics cited in the write-up being that the endogenous molecule 5-MEO-DMT has been shown to have analgesic properties as well.

In regards to our own perspective of the mechanisms for the effectiveness of Ayahuasca, there lies the potentiality that the reversal of faulty signaling coincides with region specific release of DMT (amongst other biochemicals) in the cancer site that induces cancer remission via a rebalancing of the ionic composition of the cell via sigma-1 receptor activation. While this is highly speculative if this were to be the case, it might insinuate that DMT has the potential to be synthesized in glial cells found abundantly throughout the central nervous system (we suspect DMT is synthesized in the same places that melatonin is synthesized glial cells included). We don't believe that it's a case of DMT release from the pineal finding its way to the tumor site.

While the cancer-DMT discussion is ultimately very complex and involves many layers of the body, it seems important to discuss when speculating on the mechanisms for healing. Spontaneous remission is a scientifically and medically accepted term for unexplainable disappearance of disease within the body. It's a basic concession that something occurs without understanding the mechanisms for its occurrence. In many cases of spontaneous remission, the subjects claim a spiritual phenomena that occurs alongside the healing mechanism. We've come across many anecdotal claims of this type of healing from Ayahuasca, yoga/meditation, Wim Hof Method, hypnosis, Ajna Light exposure, deep visualization exercises, and even placebo. Interestingly enough these are all altered states of consciousness that we have speculated to correlate with increased DMT levels. We've also touched upon the measurably altered electrical activity in the brain and body during these states as well.

Hopefully more studies can be developed going forward to better understand our endogenous healing mechanisms and DMT's role within it. However, an acceptance of a distinct change in perspective of physiology might be necessary to better understand what is actually taking place. We believe that DMT has a much more common and functional role in the body other than solely mystical experiences.

PS. In some small percentage of cases, a person is born with a congenital disease that manifests due to numerous factors. We need to remain cognizant that even a fetus can be exposed to detrimental environmental factors via the placenta that will ultimately effect their gene expression and formation of disease. However, there are cases of people (a small percentage) suffering from a rare disease for unknown reasons which can be traced back to a gene but that doesn't necessarily equate to blaming genetics for all disease formation.

http://q4lt.com/cancer-and-dmt
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



New blood test for prostate cancer is highly-accurate and avoids invasive biopsies

Queen Mary, University of London | Medical Xpress | 10 Sep 2019

A new and simple blood test has been found to efficiently and accurately detect the presence of aggressive prostate cancer, according to research by Queen Mary University of London.

In combination with the current prostate specific antigen (PSA) test, the new test could help men avoid unnecessary and invasive biopsies, over-diagnosis and over-treatment.

Prostate cancer is the most common cancer in Western men, with 1.3 million new cases being diagnosed each year worldwide. It is currently detected using a blood test that measures PSA levels. Although it provides early diagnosis, the PSA blood test has a low specificity (high false positives) with about 75 percent of all PSA positive results ending up with negative biopsies that do not find cancer.

When a high PSA level in the blood is detected, the patient undergoes a tissue biopsy of the prostate gland, which is invasive and carries a significant risk of bleeding and infection. On biopsy, the majority of patients with elevated PSA levels are found not to have cancer.

Additionally, most diagnosed early-stage prostate cancers are not fatal if left untreated. The current practice of the combined PSA test and biopsy for prostate cancer therefore results in unnecessary biopsies and over-diagnosis and overtreatment of many men.

The new prostate cancer test (the Parsortix system from ANGLE plc) detects early cancer cells, or circulating tumor cells (CTCs), that have left the original tumour and entered the bloodstream prior to spreading around the body. By measuring intact living cancer cells in the patient's blood, rather than the PSA protein which may be present in the blood for reasons other than cancer, it potentially provides a more accurate test for prostate cancer.

The study, published in the Journal of Urology, looked at the use of the CTC test in 98 pre-biopsy patients and 155 newly diagnosed prostate cancer patients enrolled at St Bartholomew's Hospital in London.

The research team found that the presence of CTCs in pre-biopsy blood samples were indicative of the presence of aggressive prostate cancer, and efficiently and non-invasively predicted the later outcome of biopsy results.

When the CTC tests were used in combination with the current PSA test, it was able to predict the presence of aggressive prostate cancer in subsequent biopsies with over 90 percent accuracy, better than any previously reported biomarkers.

Additionally, the number and type of CTCs present in the blood was also indicative of the aggressiveness of the cancer. Focusing on more aggressive prostate cancer may reduce over-treatment and unnecessary biopsies for benign and non-aggressive conditions.

Lead researcher Professor Yong-Jie Lu from Queen Mary University of London said: "The current prostate cancer test often leads to unnecessary invasive biopsies and over-diagnosis and overtreatment of many men, causing significant harm to patients and a waste of valuable healthcare resources. There is clearly a need for better selection of patients to undergo the biopsy procedure."

"Testing for circulating tumour cells is efficient, non-invasive and potentially accurate, and we've now demonstrated its potential to improve the current standard of care. By combining the new CTC analysis with the current PSA test, we were able to detect prostate cancer with the highest level of accuracy ever seen in any biomarker test, which could spare many patients unnecessary biopsies. This could lead to a paradigm shift in the way we diagnose prostate cancer."


As this is a single centre study, the results need to be further validated in other independent research centres before the CTC test is available either privately or on the NHS in the UK, which could take a further 3-5 years. Clearance by the US Food and Drug Administration could also take 3-5 years.

 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN

National Institute of Genetic Engineering and Biotechnology, Tehran


Growth inhibitory impact of P. Harmala on breast cancer cell lines

Sahar Seyed Hassan Tehrani, Somayeh Hashemi Sheikh Shabani, Sattar Tahmasebi Enferadi, Zohreh Rabieiorcid

P. harmala is a dense, bright green 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.

The growth inhibitory effect of phyto-alkaloids, harmaline and harmine were assessed on two breast cancer cell lines. P. harmala extracts significantly decreased growth rate and cell survival of the cancer cell lines. The extract induced cell death regarding natural cell growth rate.

The results of the research address the anti-cancer effect of the P. harmala alkaloid components hamine and harmaline. The P. harmala extract exposure against two cancer cell lines, MDA-MB-231 and Mcf-7, showed cell growth inhibition, and in higher concentration, complete cell death occurred. Cell mortality rate and IC50 data confirmed the inhibition effect of P. harmala on this cancer cell line.

http://www.ijbiotech.com/article_7245_12.html
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



Evaluating the anti-cancer effect of P. Harmala on cervical cancer cell lines

Forouzandeh F., Salimi S., Naghsh N., Zamani N., Jahani S.

Cervical cancer is the second most common cancer in women. P. Harmala is an herb used in traditional medicine as an anticancer agent in Iran. In this study, cultured HeLa (human cervical epithelial-derived) cells were used to determine the anticancer effect of harmala seed extract on cervical cancer. The cells exposed to different doses of P. harmala seed extract were incubated for 24, 48 and 72 hours. The results showed that the effects of P. Harmala are dose and time dependent for preventing the growth of cervical cancer cell lines.

http://www.sid.ir/En/Journal/ViewPaper.aspx?ID=420873
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



HuaChanSu found to suppress bladder cancer cell growth

Tao Yang, Runlin Shi, Lei Chang, Kun Tang, Ke Chen, Gan Yu, Yuanfeng Tian, Yonglian Guo, Wei He, Xiaodong Song, Hua Xu, Zhangqun Ye

Bufo is a group of over 150 species of toads. Nearly all of these species contain a venom in their skin called bufotoxin - a mild psychedelic - and bufotenin - a tryptamine related to the neurotransmitter serotonin. Similar in chemical structure to the psychedelics psilocin (4-HO-DMT), 5-MeO-DMT, and DMT, bufotenin is also known as 5-HO-DMT.

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

HuaChanSu (HCS) is a class of toxic steroids extracted from toad venom which has been shown to be a valuable anticancer drug in many kinds of cancers. In this study, we focused on the antitumor activities and related mechanisms of HCS on bladder cancer in vitro and in vivo. Early apoptosis (programmed cell death) induced by HCS was evaluated by flow cytometry, and the expression level of apoptosis-related molecules was detected using Western blot. Our results showed that HCS could efficiently inhibit proliferation and induce apoptosis in human bladder cancer cell lines. In vivo, HCS treatment significantly suppressed tumor growth and induced apoptosis (programmed cell death) in human bladder cancer cells in vitro and in vivo.

https://jeccr.biomedcentral.com/arti...046-015-0134-9
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



Spinal-Z

Iranian researchers have succeeded in developing a new herbal medication effective in treating gastrointestinal tumors. Spinal-Z, a methanolic mixture of dried powdered seeds of the psychedelic plant Peganum harmala L. and the leaf of D. kotschyii, is "the first drug which can impede the progress of stomach cancer."

D. kotschyii has been shown to inhibit tumor proliferation in mice. The active ingredient is a flavone identified as xanthomicrol. Xanthomicrol was able to inhibit proliferation of various malignant cells.

http://www.iranreview.org/content/Do...ncer_Pills.htm

-----

Cancer and P. Harmala L.

Since ancient times, P. Harmala L. has been used by traditional healers to make various preparations for the treatment of cancer. It has been commonly used in the traditional medicine of Morocco for treating skin and subcutaneous tumors. The powdered seeds of P. Harmala L. is the main component of a common ethnobotanical preparation used against different cancers and neoplasms in Iran, namely Spinal-Z.

The antitumor activity of P. Harmala L. has attracted the attention of researchers, which has led to various pharmacological studies regarding this important effect of P. Harmala L. Various authors have reported cytotoxicity of P. Harmala L. on tumor cell lines in vitro and in vivo. In one study, the methanolic extract of P. Harmala L. significantly reduced the proliferation of the tumor cell lines tested.

P. Harmala L. has shown a higher selectivity towards malignant cells than common anti-cancer drugs like Doxorubicin. These data suggest that P. Harmala L. has the potential to be used as a novel antioxidant and anti-tumor agent in anti-cancer therapy.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841998/
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN
Cytotoxicity of alkaloids isolated from peganum harmala seeds

Fatima Lamchouri, Mustapha Zemzami, Akino Jossang, Abdellatif Settaf, Zafar H Israili, Badiaa Lyoussi

Peganum harmala (Syrian rue) has been used in traditional medicine to treat a number of diseases including cancer. Studies have shown 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 3 of the 4 alkaloids (harmine, harmalacidine and vasicinone) isolated from the seed extract of P. harmala have significant in vitro cytotoxic activity in tumor cell lines. 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.

https://pdfs.semanticscholar.org/d10...8788a83959.pdf
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



Psychedelics modulate innate and adaptive inflammatory responses through the Sigma-1R receptor

Attila Szabo, Attila Kovacs, Ede Frecska, Eva Rajnavolgyi

The orphan receptor Sigma-1R is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal
differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models.

Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via Sigmar-1R that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the Sigma-1R receptor.

http://publichealthwell.ie/journal/p..._complete=true

• • •

Sigma-1 and Sigma-2 receptors expressed in a wide variety of tumor cell lines

In the last two decades there has been a surge of scientific and lay interest in Ayahuasca. Here I briefly highlight the salient points of a recent review entitled “The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization,” which was published in Frontiers in Pharmacology and aimed to summarize what is currently known about ayahuasca.

Ayahuasca is comprised of two primary ingredients: dimethyltryptamine (DMT), from chacruna leaves, and the beta-carboline alkaloids, harmine, tetrahydroharmine and harmaline arising from the ayahuasca vine. DMT is the psychedelic component of the brew. The alkaloids found in the ayahuasca vine prevent a key enzyme found in our bodies known as monoamine oxidase (MAO) from normally breaking down orally ingested DMT, thus allowing DMT to cross the blood-brain barrier and exert its psychoactive effects.

Though DMT has been studied primarily in terms of its psychedelic effects, it may play an even wider biological role. The latest molecular target that binds to DMT, known as the Sigma-1R receptor, may be a critical nexus point in DMT’s therapeutic effects relative to many common disease states.

The Sigma-1R receptor is essential for managing intracellular stress and can be found in various tissues such as the brain, retina, liver, lung, heart, and immune system. Sigma-1R is a special kind of protein receptor known as a molecular chaperone—a protein with the function of helping other proteins fold correctly into their 3-dimensional conformations, especially under stressful situations. Many diseases are associated with dysfunctional chaperones, and the Sigma-1R receptor/chaperone has been linked to cancer.

The function of dimethyltryptamines may extend the central nervous system activity and play a more universal role in immune regulation. NN-DMT and 5-MeO-DMT have potent immunomodulatory effects on the functional activities of human dendritic cells operating through the Sigma-1R receptor. DMT-mediated sigmar-1 activation can interfere with both
innate and adaptive immune responses. On the one hand, it strongly decreases the levels of pro-inflammatory cytokines and chemokines, while upregulating the production of the anti-inflammatory cytokine IL-10. These findings greatly expand the biological role of dimethyltryptamines, which may act not only as neuromodulators or psychedelics, but also as important regulators of both innate and adaptive immunity. Thus, the DMT-sigmar-1 axis emerges as a promising candidate for novel pharmacotherapies of chronic inflammatory and autoimmune diseases.

As DMT naturally binds to the Sigma-1R receptor, the authors suggest that DMT may have a physiological role beyond its psychoactivity, and posit that DMT may elicit cell protective effects by acting on Sigma-1R. Some of these protective effects include restoration of neurons and modulation of immunity.

Sigma-1R is a central component involved in regulating various causes of cellular stress that can be traced to ailments such as cancer. Sigma-1R is an ideal molecular candidate for interfering with the conversion of environmental and psychological stress into cellular stress.

http://reset.me/study/scientists-explore-the-therapeutic-benefits-of-ayahuasca/

• • •

The Sigma-1R ER chaperone function is essential for the metabotropic receptor signaling and for the survival against cellular, particularly ER stress. Dysfunctional chaperones are responsible for numerous diseases. Altogether, no other receptor has ever been associated with so many different diseases as the Sig-1R. It has so far been implicated in illnesses like Alzheimer’s disease, Parkinson’s disease, cancer, cardiomyopathy, retinal dysfunction, perinatal and traumatic brain injury, frontal motor neuron degeneration, Amyotrophic Lateral Sclerosis, HIV-related dementia, major depression, and psychostimulant addiction. How those two modes of actions of the Sig-1R may relate to this plethora of diseases remain to be clarified but its protective influence has been verified on various aspects of cellular processes, such as calcium signaling, mitochondrial functions, ER stress, survival and apoptotic pathways, and tumor cell proliferation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773875/

• • •

The Sigma-2R receptor is a sigma receptor subtype that has been found highly expressed in malignant cancer cells, and is currently under investigation for its potential diagnostic and therapeutic uses. Sigma-2R receptors are highly expressed in breast, ovarian, lung, brain, bladder, colon cancers, and melanoma. This novelty makes them a valuable biomarker for identifying cancerous tissues. Furthermore, studies have shown that they are more highly expressed in malignant tumors than dormant tumors. Because Sigma-2R receptors are highly expressed in tumor cells and are part of the cell proliferation mechanism, PET scans using sigma-2 targeted tracers can reveal if a tumor is proliferating and what its growth rate is.

Sigma receptor ligands can act as agonists or antagonists, generating different cellular responses. Agonists inhibit tumor cell proliferation and induce apoptosis. Antagonists promote tumor cell proliferation, but this mechanism is less understood. Sigma-2R receptor ligands have been conjugated to nanoparticles and peptides to deliver cancer treatment to tumor cells without targeting other tissues. The success with these methods have been limited to in vitro trials. Additionally, using Sigma-2R receptors to target tumor cells allows for synergizing anti-cancer drug therapies. Some studies have shown that certain Sigma-2R receptor inhibitors increase cancer cells' susceptibility to chemotherapy. Other types of binding to Sigma receptors increase the cytotoxicity of doxorubicin, antinomyocin, and other cancer cell-killing drugs.

https://ipfs.io/ipfs/QmXoypizjW3WknF..._receptor.html
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



Scientists unlock the potential of Kambo to treat cancer

Scientists at Queen's University Belfast have discovered the potential of proteins found in the secretion of the skins of the Waxy Monkey Frog and Giant Firebellied Toad to treat cancer by regulating blood vessel growth. The secretion, Kambo, a psychedelic long used by indigenous tribes for traditional rituals, is administered directly into the body through application onto freshly inflicted burn wounds, and is said to generate an altered state of reality, clear inner sight and a resurgence of long forgotten memories.

The research, led by Professor Chris Shaw, has identified two proteins, or 'peptides', which can be used in a controlled and targeted way to regulate 'angiogenesis' - the process by which blood vessels grow in the body. The discovery holds the potential to develop new treatments for cancer.

The proteins are found in secretions on the skin of the frogs. Scientists capture the frogs and gently extract the secretions, before releasing them back in to the wild. The animals are not harmed in any way during this process.

"These proteins have the ability to either stimulate or inhibit the growth of blood vessels. By 'switching off' angiogenesis and inhibiting blood vessel growth, a protein from the Waxy Monkey Frog has the potential to kill cancer tumors. Most cancer tumors can only grow to a certain size before they need blood vessels to grow into the tumor to supply it with vital oxygen and nutrients. Stopping the blood vessels from growing will make the tumor less likely to spread and may eventually kill it. This has the potential to transform cancer from a terminal illness into a chronic condition," Shaw said.

"A protein from the Giant Firebellied Toad has been found to 'switch on' angiogenesis and stimulate blood vessel growth. This has the potential to treat an array of diseases and conditions that require blood vessels to repair quickly, such as wound healing, organ transplants, diabetic ulcers, and damage caused by strokes or heart conditions."

"Because of its huge potential, angiogenesis has been a prime target for drugs development research over the past 40 years. But despite an investment of around $4-5 billion by scientists and drugs companies around the world, they have yet to develop a drug that can effectively target, control and regulate the growth of blood vessels,"
Shaw said.

"The aim of our work at Queen's is to unlock the potential of the natural world -- in this case the secretions found on frog and toad skins -- to alleviate human suffering. We are absolutely convinced that the natural world holds the solutions to many of our problems, we just need to pose the right questions to find them.

"It would be a great shame to have something in nature that is potentially the wonder drug to treat cancer and not aim to do everything in our power to harness that."


https://www.sciencedaily.com/release...0606181137.htm
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN

University of Birmingham


Modified MDMA compounds have powerful anti-cancer properties

by Christian Nordqvist | Medical News Today

Altered forms of MDMA (Ecstasy) which are 100 times better at destroying cancer cells could be used to effectively treat patients with leukemia, lymphoma, and myeloma, according to an article in Investigational New Drugs. The authors, from the University of Birmingham, UK, explained that while Ecstasy is already known to have anti-cancer qualities, these modified forms of the drug are 100 times more powerful.

Ecstasy is the colloquial term for MDMA (3,4-Methylenedioxymethamphetamine), a drug that produces distinctive emotional and social effects (an entactogenic drug). It is a drug of the phenethylamine and amphetamine class. Ecstasy can reduce anxiety and induce euphoria and a sense of intimacy with others. In the majority of countries, the possession, manufacture and sale of MDMA is criminalized, except for some limited scientific or medical research purposes.

Scientists at the same research department at the University of Birmingham had already discovered that certain psychotropic drugs, such as Ecstasy, some antidepressants and weight-loss pills were effective in suppressing the development of white blood cancer cells.

The problem was that in order for those drugs to have any significant effect on cancer patients, the dosage would have to be so high that it would kill them. Hence, the researchers have spent the last six years trying to separate and isolate their cancer-busting properties so that patients could be spared being given the toxic ingredients. They worked with scientists from the University of Western Australia.

The Australian scientists created the new, modified compounds.

The British researchers found that these modified compounds were 100 times more powerful at combating cancer cells than Ecstasy. They say they also now understand the mechanism behind them.



Professor John Gordon, lead author, said:

“Together, we were looking at structures of compounds that were more effective. They started to look more lipophilic, that is, they were attracted to the lipids that make up cell walls. This would make them more ‘soapy’ so they would end up getting into the cancer cells more easily and possibly even start dissolving them.

By knowing this we can theoretically make even more potent analogues of MDMA and eventually reach a point where we will have in our drug cabinet the most potent form we could.”


This is an enormous step forward in their quest for an effective treatment for those with some forms of blood cancer, Professor Gordon added.

The modified forms of MDMA have not been tested on animals yet, because of the toxic effects they have on the brain and nervous system. In this study, the scientists added various molecular groups to the drug and then tested the MDMA analogues against B cell lymphoma cells (Burkitt’s lymphoma), and then against other B-cell lymphomas. They were able to observe how the compounds destroyed the cancer cells. Initially, their compounds were found to be 10 times as effective as MDMA. After adding other related compounds the effectiveness rose to 100 times more powerful than Ecstasy.

Gordon added:

“While we would not wish to give people false hope, the results of this research hold the potential for improvement in treatments in years to come.”

The scientists plan to progress to pre-clinical studies soon.

Dr. David Grant, Scientific Director of Leukaemia & Lymphoma Research, a UK charity that helped fund this study, said:

“The prospect of being able to target blood cancer with a drug derived from Ecstasy is a genuinely exciting proposition. Many types of lymphoma remain hard to treat and non-toxic drugs which are both effective and have few side effects are desperately needed. Further work is required but this research is a significant step forward in developing a potential new cancer drug.”

https://www.medicalnewstoday.com/articles/233121.php
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



Sweet, sweet cancers

by Pasquale Pellegrini

So many times, I order my coffee while hesitantly eyeing the seductive pastries. This time I’ll resist these sweet beauties.

Last night I came across a lecture from Einstein’s friend, Otto Heinrich Warburg (Nobel Prize in Medicine, 1931). It was 1966 and he was at the meeting of Nobel Laureates in Lindau, Germany:

“Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.”

To put it simply, Warburg believed cancer cells use an alternative way to extract energy from glucose, which is called fermentation.

A half-century after that lecture we still know very little about what’s going on inside cancer cells. Warburg was not entirely correct about fermentation being the only mechanism that cancer cells use to extract energy, but he did discover something crucial: glucose powers cancerous cells.

In the late 70s a new diagnostic test for cancer was discovered, called FDG-PET. This test is still widely used in clinics, and allows doctors to detect cancers and metastases simply by looking at tissues that absorb high levels of glucose. Scary huh?

We still don’t know if high levels of glucose uptake actually cause cancer or if cancer cells strive for more glucose intake.

What came first? The chicken or the egg? The sugar absorption or the cancer cell?

Dr. Mina Bissell (Berkeley University), demonstrated that a healthy cell can become a cancer cell by simply increasing its glucose uptake. The study shows that when cells absorb a high amount of glucose, a molecular storm can be triggered inside leading to uncontrolled cell growth.

High levels of glucose in the bloodstream (hyperglycemia) is a risk factor for cancer in several organs including pancreas, esophagus, liver, colon, rectum, stomach and prostate. Cancer cells burn more sugar than normal cells. This phenomenon contributes to disrupting the metabolism of people with cancer in a very complex and obscure way that the doctors call metabolic syndrome. The weight loss (cachexia) observed in cancer patients is most likely a result of this syndrome.

So, is it conceivable that glucose by itself can initiate cancer as Dr. Warburg was claiming 50 years ago?

If this theory is true, it could explain why 90% of people with cancer don’t have any inherited genetic mutation. In other words, this idea could explain why many cancer patients don’t have a family history of the disease.

Put cancer on a diet!

Cancers can double their size within a few days. Such fast and aggressive growth can only be sustained with a steady supply of energy, so cancer becomes more and more ‘addicted’ to glucose as it grows.

Calorie restriction in animal models of cancer have been demonstrated to be effective in slowing the progression of the disease. So why don’t we put cancer on a strict glucose-free diet? This is something that scientists are actually trying to do although the metabolism of cancer cells is very complex and difficult to target with drugs. Scientists continue to make discoveries on how glucose is used by cancer cells, which provides the basis of knowledge needed to develop drugs that specifically block glucose breakdown.

Although the research on cancer metabolism continues to progress, discoveries so far haven’t resulted in an effective therapy against cancer, although they have led to improvements in the detection of cancers.

Would this have disappointed Dr. Warburg? Who knows. He was certainly upset about the “continual discovery of cancer agents…” which apparently could “hinder necessary preventive measures and thereby become responsible for cancer cases.”.

So here I am at my favorite café, unconcerned about Warburg’s “preventive measures”, with my disarming need to choose between the banana split and a double fudge cake. A man in a bowler hat is sitting next to me. He reminds me of post-war Germany. The same Germany where Dr. Warburg was compulsively looking for fresh and low-sugar food, unaware of the organic diet trend of our times.

Dr. Warburg was a hard worker. He pursued his research until the age of 87. He loved riding horses, he never dated and never showed any particular interest in social life. During his late life, he became particularly obsessed with his healthy habits (by most accounts he used to bring his own food to restaurants). He died in 1970.

 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



Harmine found to suppress proliferation of ovarian cancer cells

Jun Gao, Hong Zhu, Hong Wan, Xia Zou, Xiaoxin Ma, Guolan Gao

Harmine is a fluorescent harmala alkaloid belonging to the beta-carboline family of compounds. It occurs in a number of different plants, most notably the Middle Eastern plant Syrian rue (Peganum harmala), and the South American vine Banisteriopsis caapi (Ayuhuasca). P. harmala and B. caapi are both traditionally used for their psychoactive effects. Isolated from the plant Peganum harmala, harmine has already been shown to strongly inhibit the growth of cancer cells originating from breast, lung, bone and pancreas.

Ovarian cancer is the most lethal gynaecological cancer among Western women. In recent studies Harmine displayed obvious anticancer effects in several cancer cell types. In the present study, the effect of harmine on the cell proliferation and migration of ovarian cancer SKOV-3 cells and the underlying mechanism were investigated. Results indicate that Harmine significantly suppressed the proliferation of SKOV-3 cells in a dose-dependent manner. Interestingly, it also inhibited the epidermal growth factor (EGF)-induced proliferation of SKOV-3 cells. Moreover, the migration of SKOV-3 cells was markedly inhibited by Harmine treatment. Finally, Harmine significantly suppressed the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) family MMP-2, and MMP-9. In conclusion, our data revealed that Harmine inhibited the proliferation and migration of SKOV-3 cells, which might be mediated by ERK/CREB pathway. These findings elucidate that Harmine may act as a potential therapeutic drug for ovarian cancer treatment.

https://www.ncbi.nlm.nih.gov/pubmed/28901502
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN

University of São Paulo


Tryptamine and dimethyltryptamine found to increase the tumor-reactivity of peripheral blood cells

Tourino, de Oliveira, Belle, Campa, Knebel, Albuquerque, Dorr, Okada

Indoleamine 2,3-dioxygenase (IDO) is an interferon-γ (IFN-γ)-induced tryptophan-degrading enzyme, producing kynurenine (KYN) that participates in the mechanism of tumor immune tolerance. Thus, IDO inhibition has been considered a strategy for anticancer therapy. The aim of this study was to identify whether the metabolites originating from the competitive routes of tryptophan metabolism, such as the serotonergic or N, N-dimethyltryptamine (DMT) pathways, have inhibitory effects on recombinant human IDO (rhIDO) activity. Serotonin and melatonin had no effect; on the other hand, tryptamine (TRY) and DMT modulated the activity of rhIDO as classical non-competitive inhibitors. TRY and DMT increased the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays. We therefore conclude that the IDO inhibition by TRY and DMT contributed to a more effective tumor-reactive response by the PBMCs.

Tryptophan (TRP) metabolism has been studied for many years. Thereafter, this issue has become increasingly attractive for immunologists, primarily concerning investigations of the role of TRP depletion and KYN formation in the immune system and cancer progression. The key component in cancer-associated immunosuppression by TRP degradation and KYN formation is the enzymatic activity of indoleamine 2,3 dioxygenase (IDO). Because KYN has tolerogenic effects on dendritic cells and suppresses T cell proliferation, the up-regulation of IDO has been strongly associated with the way malignant cells escape immune surveillance, and the inhibition of IDO activity has been regarded as a main target in pharmacological interventions related to immunoescape.

The objective of this study was to identify whether these compounds have inhibitory effects on the activity of recombinant human IDO (rhIDO) and increase the tumor-reactive effect of peripheral blood mononuclear cells (PBMC).

At first, the idea that TRY and DMT could be natural endogenous inhibitors of IDO sounds improbable because they are present at very low concentrations in mammalian cells. However, in some circumstances, the concentration of these compounds could be enough to provide IDO inhibition. This assumption is supported by the following findings: (i) the transcriptional expression of the enzymes responsible for the synthesis of TRY and DMT has been described in diverse mammalian tissues; (ii) DMT is actively transported and accumulated in the brain and storage vesicles; and (iii) DMT injected in rabbits persists in the brain at micromolar concentrations.

In conclusion, we have identified a previously unknown inhibitory activity of TRY and DMT on IDO activity that contributed to a more effective tumor-reactive response by immune cells.

https://www.researchgate.net/publica...onuclear_cells
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN
Biosynthesis of DMT in a melanoma cell line

Gomesa, Coimbra, Claraa, Dorr, Carolina, Chagas, Tufik, Pinto, Catalanic, Campa

Tryptophan (TRP) is essential for many physiological processes, and its metabolism changes in some diseases such as infection and cancer. The most studied aspects of TRP metabolism are the kynurenine and serotonin pathways. A minor metabolic route, tryptamine and N,N-dimethyltryptamine (DMT) biosynthesis, has received far less attention, probably because of the very low amounts of these compounds detected only in some tissues, leading them to be considered as trace amines. In a previous study, we showed a metabolic interrelationship for TRP in melanoma cell lines.



This study describes a possible alternative metabolic pathway for DMT involving peroxidases not previously described in humans and identifies DMT and metabolites in a melanoma cell line. The extension of these findings to other cell types and the biological effects of DMT and its metabolites on cell proliferation and function are key questions for future studies.

Biochemical and toxicological studies involving trace amines have attracted attention because of their numerous effects on cognition, perception, satiety and their possible participation in psychiatric and neurodegenerative disorders, and even in the social/religious framework utilizing psychedelic drinks prepared from plants rich in these compounds, such as Ayahuasca tea. In this study, we describe an alternative metabolic pathway for DMT that has not been previously identified in human cells.

https://www.sciencedirect.com/scienc...06295214000744
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN
Ayahuasca's effects on cancer, and the role of endogenous DMT

B. caapi, locally called ayahuasca, added to Psychotria viridis, locally called chakruna, together make up "ayahuasca," a brew thought to have been used for over 5,400 years in the Amazon river basin. The caapi vine contains a monoamine oxidase inhibitor (MAOI) which allows the dimethyltriptamine (DMT) containing chakruna to be released into the blood stream, and cross the blood-brain barrier. Without the MAOI, the affects of the DMT would not be felt. The alkaloids found in the vine are both neurogenic and anti-carcinogenic. The following is a detailed functional scientific analysis of ayahuasca's anti-carcinogenic activity: “DMT binds to the sigma-1 receptor, which provides new opportunities for understanding how ayahuasca may produce its marked effects on the body and mind and what might be the role of endogenous DMT and how ayahuasca may have effects on cancer. The human sigma-1 receptor has been cloned and shows no homology with other mammalian proteins.

Single-photon emission tomography (SPET) analysis in humans revealed that these receptors are present in organs such as the lung and liver, and most concentrated in the brain. Sigma-1 receptor activity has been implicated in a variety of diseases, including cancer. Sigma-1 receptors are found in high densities in many human cancer cell lines, including lung, prostate, colon, ovaries, breast, and brain; thus, sigma ligands are regarded as potential novel anti-neoplastic tools. For these effects to help explain the available case reports of ayahuasca on cancer treatment, DMT’s physiological degradation by enteric monoamine oxidase (primarily MAO-A) after oral consumption should be inhibited, thus allowing the DMT to pass into circulation. The pharmacological activity of β-carbolines (primarily harmine) in ayahuasca inhibits MAO, with a high affinity for MAO-A. Therefore, the specific effects of ayahuasca on the different types of cancer could also vary depending on the predominant MAO subtype, given that the ratio of MAO-A to MAO-B varies, for example, from 1:3 in the brain to 4:1 in the intestine, and the placenta has only MAO-A and blood platelets have only MAO-B. Another consequence of inhibiting MAO in different tissues is interference with apoptotic pathways, thus strengthening the synergistic action of β-carbolines and DMT.

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

https://www.munaymedicine.com/pages/the-science.aspx
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



Bufo toad skin-secretion a potent anti-cancer agent

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

Bufadienolides are the most effective components in Cinobufacini injection (HuaChanSu) for the treatment of liver and gastric cancers. One such component, Bufalin, was found to induce apoptosis in leukemia cells by altering expression of apoptotic genes c-myc and bcl-2. Another component, Cinobufagin, has been shown to treat infection during combined chemotherapy. It reduced the risk of infection as well as duration of granulocytopenia associated with malignant blood diseases. Certain other toad skin-secretion components have also been recently found to exert inhibitory effects on cancer cell lines.

https://www.researchgate.net/publica...cant_compounds
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



Psychedelics and cancer

I've been interested in the question of what effect psychedelics have on cancer ever since I read about Terence McKenna's tragic fate. My suspicion is that Terence's cancer wasn't caused by his use of DMT and psilocybe mushrooms, based on the evidence I've seen. In fact, I believe psychedelics deserve serious consideration as a potential treatment for cancer.

Let us start with the history we have of documented cases of spontaneous late stage cancer regression apparently induced by Ayahuasca ceremonies. The question we are left with is what the underlying mechanism could be by which this regression may have happened. Practically all cancer cell lines tend to express sigma-1 and sigma-2 receptors in high amounts, this has been known for quite some time now. Research has also found that sigma receptor agonists can induce apoptosis in cancer cells. It's possible that DMT as a sigma receptor agonist may rely on this pathway to induce apoptosis.

I suspect however, that if these cases of spontaneous cancer regression are genuinely caused by Ayahuasca, that another mechanism is more likely. Psychedelics are thought to cause their effects through the 5-HT2A receptors, but it has long been a mystery that some 5-HT2A agonists cause hallucinations, while others like Lisuride seem to agonize the receptor without causing hallucinations. The answer to this mystery I believe is functional selectivity, the observation that different ligands can activate different pathways upon agonizing a receptor.

In the case of LSD and other classical psychedelics, we now know that binding to the 5-HT2A receptor activates two genes that non-hallucinogenic ligands don't activate: EGR1 and EGR2. It is suspected, however, that other receptors, including the 5-HT2C receptor, also play a role, as selectively blocking this receptor reduces a lot of the effect of psychedelics. The 5-HT2A receptor is not just expressed in the nervous system, but in many different cell types, ranging from breast tissue, to bone tissue, to the cardiovascular system. Fascinatingly enough, ovarian cancer cell lines also express the 5-HT2A receptor, at densities up to 1600 times higher than normal ovarian cells.

So, we know that EGR1 and EGR2 are genes that are expressed in our tissues in response to psychedelics. What are the potential implications of that? It is well documented that these genes are involved in inducing apoptosis and thereby serve to prevent the development of cancer. The majority of cancer cell lines have much lower levels of endogenous EGR2 than regular healthy cells. As a result, they don't listen to the signals telling them to shut down.

Oddly enough, there has been surprisingly little research into any potential link between different classes of recreational drug use and cancer. There has been one study on a potential link between testicular germ cell tumors and different forms of cancer. What it found was that long-term duration of use of mushrooms was linked to a barely statistically significant reduction in cancer risk, by 68%. It's not much, but it's a start.

It will take a while before we start to see serious studies on this topic, but I'm looking forward to seeing what they say. I suspect that Ayahuasca makes use of the same pathways that other classes of psychedelics use and as a result, the same regression of cancer observed with Ayahuasca ceremonies (assuming these were not flukes) may be possible with other hallucinogenic 5-HT2A agonists, the main difference being that people tend to take Ayahuasca in high doses, resulting in much stronger effects than people have with psilocybin, mescaline and LSD.

-triggerexpert (reddit)
 
Last edited:

mr peabody

Moderator: PM
Staff member
Joined
Aug 31, 2016
Messages
3,016
Location
Frostbite Falls, MN



Psychedelics and immunomodulation

by Dr. Attila Szabo

Classical psychedelics are psychoactive substances that have been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation and cell survival by activating NF-κB and mitogen-activated protein kinases. Recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have been shown to play crucial roles in numerous immunological processes. This emerging field offers promising treatment modalities for various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer.

Scientific investigations concerning the possible immunological effects of psychedelics date back to the 1970s, but the biomedical Renaissance of psychedelic research began only a decade ago. An important antecedent was the identification of neuro-immune communication in mammals that has greatly expanded the domain of physiological activity of psychoactive substances. Since immune cells were found to also express many types of neurotransmitter receptors, an entirely new aspect was added to the biomedical paradigm. Early neuroimmunologists considered the immune and nervous systems as separate parts, but a crucial conceptual leap led to the emergence of the modern approach. This new concept represents neuroimmune communication as an integrated physiological entity, with the immune and nervous systems being its two aspects.

In the last two decades, several neurotransmitter receptors involved in the pharmacology of psychedelics have been identified as being crucial in many immunological processes pointing to novel therapeutic avenues. Classical psychedelics have been shown to exert strong anti-cancer and anti-inflammatory effects through the modulation of innate and adaptive immune processes. Two models have been proposed to address the possible biochemical dynamics of these interactions. On the one hand, (i) regulation may occur through the alteration of the cytokine-pattern of activated cells. The anti-inflammatory cytokines, IL-10 and TGFβ, and pro-inflammatory cytokines, TNFα and IFNγ, seem to be key players in this regulation. On the other hand, (ii) a complex intracellular cross-talk of pattern-recognition receptors (PRRs), serotonin, and sigma-1 receptors might be involved in the immunomodulatory process. While PRRs were shown to be crucial for innate and adaptive host defense, their inappropriate activation has been associated with autoimmunity and inflammatory diseases. Psychedelics, by modulating the activity of 5-HT1, 5-HT2, and sigmar-1 receptors, are potent anti-inflammatory agents.

https://pdfs.semanticscholar.org/0967/3ff5caa5ddaa6f2abcbabc161f8ea779ba61.pdf
 
Last edited:
Status
Not open for further replies.
Top