Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities.

[cave paintings]

A very cool review paper by Szabo I just noticed this morning. Gonna start chugging through it now. Nice to have a comprehensive look at all the different info on the topic.

Full text

Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities

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 ...

www.ncbi.nlm.nih.gov

 

[null24]

Thanks for the link, this is really interesting to me. I came across this about the same time that i was experimenting with lower doses of DMT, and seemed to recognize a feeling that was more than similar to the way i feel upon being woken from a deep sleep, and making the connection between how the body goes through maintenance work during that time made me wonder if there is some relation between these things. If this leads to specific treatment modalities for various ailments, seriously, think of what could be done. Would symptomatic treatment be a thing of the past in favor of true health? With something as monetarily inexpensive as DMT? Pardon me while i dream of a different world...

I just skipped through a few pages of the article, not being able to dedicate full attention to it a.t.m., but what I've seen has fascinating implications. This stuff is here for a reason, folks. This is all such important work, the research into the various benefits of our chemical friends. Gives me hope in a world that i don't recognize sometimes.

 

[Swarupa]

Thanks for bringing this to our attention, great work :thumb_up:

 

[obliguhl]

The classical psychedelics discussed in this paper have been shown to exert strong anti-cancer and anti-inflammatory effects through the modulation of innate and adaptive immune processes.

Wow, that is quite an intense statement.

 

[steppa]

The classical psychedelics discussed in this paper have been shown to exert strong anti-cancer and anti-inflammatory effects through the modulation of innate and adaptive immune processes.

Hm...looking at the causes of death of some of the psychedelic advocates leads me into thinking that the anti-cancer effect may not be THAT strong.

 

[Global]

The classical psychedelics discussed in this paper have been shown to exert strong anti-cancer and anti-inflammatory effects through the modulation of innate and adaptive immune processes.

Hm...looking at the causes of death of some of the psychedelic advocates leads me into thinking that the anti-cancer effect may not be THAT strong.

That seems like cherry picking.

 

[steppa]

I don't know Global. What do you think is wrong with I said?

My logic is -> If psychedelics would cure cancer, people who use psychedelics frequently wouldn't die from cancer.

Yeah...of course, they may have anti-cancer properties. But so does basil.

What I want to say...I think... is, that those "anti-cancer properties", at the given moment, seem pretty meaningless to me.

 

[Heyt]

I don't know Global. What do you think is wrong with I said?

My logic is -> If psychedelics would cure cancer, people who use psychedelics frequently wouldn't die from cancer.

Yeah...of course, they may have anti-cancer properties. But so does basil.

What I want to say...I think... is, that those "anti-cancer properties", at the given moment, seem pretty meaningless to me.

Yeah, but you're using anecdotes. Plenty of people smoke cannabis and die from cancer, and plenty of people die from cancer despite chemo treatment. There are always outliers and always exceptions to every rule. Right now, we don't really know too much about the anti-cancer properties of psychedelics, so your point is speculation without any real evidence. Even if the top 100 psychedelic pioneers died from cancer, that's 100 cases out of millions of people with cancer who also use(d) psychedelics. I think perhaps it's more fruitful to base a hypothesis on the mechanism(s) which we do understand and what little statistical information we have. I'm not saying I think psychedelics cure cancer, but now we have some hard evidence as to how they might do that, so shrugging it off and saying "yeah but all the most famous psychedelic users had cancer" is kind of counter-productive. I mean, even Bob Marley died of cancer and we know for a fact that certain cannabinoids induce apoptosis in certain types of tumors.

I hope you don't read a tone from my post, I intend none whatsoever. Peace and love :thumb_up:

Recently, we and others demonstrated that DMT has the capability to modulate immune responses in in vitro human primary cell cultures (88, 104). In these studies, DMT was shown to act as a non-competitive inhibitor of indoleamine 2,3-dioxygenase (IDO) and as a strong inducer of anti-tumor cytotoxic activity in the co-cultures of human PBMCs and a glioma cell line ( 88 ). Furthermore, DMT and its analog 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) were found to exert potent anti-inflammatory activity through the sigmar-1 in human monocyte-derived dendritic cell (moDC) cultures. MoDCs are key cell types of the mammalian immune system connecting and orchestrating innate and adaptive immune responses as professional antigen-presenting cells (APCs) (20).

I think that's exciting, even if its implications in treating cancer aren't certain.

 

[steppa]

"yeah but all the most famous psychedelic users had cancer" is kind of counter-productive.

I do not think that this is counter productive. It's just what we know. A sad truth if you will.

And I still stand with this:

If psychedelics would cure cancer, people who use psychedelics frequently wouldn't die from cancer.

I don't know man...I'm just thinking that we shouldn't be over-enthusiastic because of some "anti-cancer-effects".

Many spices and vegetables have those scientifically proven "anti-cancer effects", still I don't see people raving about carrots.

 

[Heyt]

Nobody is saying that smoking DMT will make your tumor disappear. But, we now have a paper with hard evidence of an anti-cancer mechanism of action for DMT and other tryptamines. How is that not a big deal? And scientists are currently using some of the plants you've mentioned to work on new cancer treatments. Why do you only wish to see the negative?

Unlike your anecdotal accounts of famous people dying of cancer, this paper poses actual data about tryptamines and tumor growth - something that can actually be used to help someone someday. What do you expect to accomplish by cherry picking cases where people died of cancer despite psychedelic use? How about the millions of people who use psychedelics and don't die of cancer? Until we have actual data on those numbers, you're just speculating with no more certainty than flipping a coin.

 

[steppa]

Nobody is saying that smoking DMT will make your tumor disappear.

Good. So we agree on this.

How is that not a big deal?

To me it isn't a big deal because anti cancer effects are found in many things. Still...next to nothing really helps.

Would it be a great thing if dmt would help battling cancer? Yes.
Do I think that this will happen? Not really.

 

[cave paintings]

Steppa,
Wouldn't it be more interesting if we could discuss the mechanisms and science of this paper rather than say "lots of things have anticancer properties, those don't work cause people still die of cancer, we should probably add DMT to the list"

There are lots of ways different compounds that exert anticancer activity, and there are lots of different cancers stemming from different mutations in different tissues that respond differently to treatments. So yes, cancer is hard to treat. This is coming from someone who has personally worked in developing anti-cancer therapeutics, specifically against gliomas.

Frankly, we all likely have had small tumors occur inside us that have been killed by our immune system, and re-activation of the immune system against tumors is proving to be one of the most promising avenues of anti-cancer research at the moment. I personally trust an endogenous modulator of immune activity against something like cancer anyway, where the blunt knives of chemotherapy have often failed in the past due to the mutable and adaptive nature of cancer.

The authors propose relevant mechanisms by which DMT might act to modulate the immune system toward tumoricidal responses (inhibition of indole 2,3 dioxygenase) and other mechanisms involving the Sigma receptor and alteration of mitochondrial balance. It just seems pretty unfair to me to brush off these results as "pretty meaningless".
Do I think DMT is a magic bullet for cancer? No probably not, but it certainly might have positive effects, as suggested by this paper and other past studies. And I'm sure many people who have cancer would appreciate any sort of life extension.

 

[Cognitive Heart]

One difference between non-psychedelic substances that have anti-cancer effects and psychedelic substances that have anti-cancer effects, is that psychedelics shift consciousness. For example, polysaccharides from mushrooms have known, powerful anti-cancer effects within the body, but these compounds are not known to shift consciousness.

Anyways, I think we can safely say that we now hold strategies for enhancing medicine, spirituality(such as end of life care), and recovery within various stages of cancer, and helping others to prevent disease and enhance lives.

 

[steppa]

Steppa,
Wouldn't it be more interesting if we could discuss the mechanisms and science of this paper

I'm certainly not holding you back. I just expessed my opinion on that matter and why I'm not as stoked as some (to me) seem to be.

So please feel free to discuss the mechanisms and science of this paper.

 

[Adhara]

I've experienced great results in my condition (CFS/ME) after vaping little doses of N,N-DMT.

After that I contacted the NGO ICEERS that told me about this paper. I've started a thread on the matter cause I've read similar experiences on this forum so if you'd like to join the discussion on the contrasted (subjetively by patients) benefits of DMT in this common but unsolved condition you can do it here:

CFS/ME patients and DMT immune regulation - Collaborative Research Project - Welcome to the DMT-Nexus

:thumb_up: hope you find it interesting.

 

[Psilociraptor]

Glad i stumbled on this thread. Pulled this paper back up yesterday with intent to read it after my physics test and totally forgot

Steppa,
Wouldn't it be more interesting if we could discuss the mechanisms and science of this paper rather than say "lots of things have anticancer properties, those don't work cause people still die of cancer, we should probably add DMT to the list"

There are lots of ways different compounds that exert anticancer activity, and there are lots of different cancers stemming from different mutations in different tissues that respond differently to treatments. So yes, cancer is hard to treat. This is coming from someone who has personally worked in developing anti-cancer therapeutics, specifically against gliomas.

Frankly, we all likely have had small tumors occur inside us that have been killed by our immune system, and re-activation of the immune system against tumors is proving to be one of the most promising avenues of anti-cancer research at the moment. I personally trust an endogenous modulator of immune activity against something like cancer anyway, where the blunt knives of chemotherapy have often failed in the past due to the mutable and adaptive nature of cancer.

The authors propose relevant mechanisms by which DMT might act to modulate the immune system toward tumoricidal responses (inhibition of indole 2,3 dioxygenase) and other mechanisms involving the Sigma receptor and alteration of mitochondrial balance. It just seems pretty unfair to me to brush off these results as "pretty meaningless".
Do I think DMT is a magic bullet for cancer? No probably not, but it certainly might have positive effects, as suggested by this paper and other past studies. And I'm sure many people who have cancer would appreciate any sort of life extension.

Yeah the immune system really should be looked at as the most viable interface for which to deal with cancer. In many ways cancer is better thought of as "tissue healing gone wrong" than the classical view that it is a rogue evolutionary process driven by the accumulation of random mutations. The problem this brings however, is that reductionist approaches will likely fall short as the immune system is both responsible for killing cancer and creating it. It is not like some binary switch we can just push one direction. In some cases we may be able to nudge it just right, but optimal functioning requires a far more pristine balance based on a normalization of the microenvironment. Don't get me wrong. If i had cancer i would go out with a headfull of ayahuasca both for my minds sake and for any possibility it would help. But when it comes to optimizing treatment and prevention, removing noxious immune stimuli from the source is probably going to be the best course of action. In this day and age we should really be exploring the therapeutic role of fecal microbial transplants on inflammatory and neoplastic diseases. As well as protecting those tribal populations who are our last window into the evolutionary relationship between man and microbe...

As for my own experience... I have chronic inflammatory demyelinating polyneuropathy (CIDP) and some other vague and ill-defined immune pathologies causing chest pain, palpitations, dyslipidemia, lymphadenopathy and random aches. I am almost positive these are microbially induced as the CIDP is triggered by environmental conditions like swimming in still-water, and the others respond heavily to antibiotics. Beyond that I've had a stool test showing E. coli populations six times the high end of the reference range with massive amounts of beta-glucoronidase activity. Psychedelics pretty much kill my symptoms. The neuropathy can still be noticeable at times (wouldn't expect that to heal in mere hours), but i feel about as healthy as I have been since incurring this mess while on psychedelics. That said it's entirely temporary and it is my belief that such substances are of little use from the physical aspects of the illness (they can be therapeutic for the mental aspects of dealing with illness). If you really want to tackle inflammatory disorders though... go to the source. Look into the roles of the microbiome and intestinal permeability in metabolic endotoxemia. I got about 80% remission from eating a diet called AIP that focuses on this and I'm seriously considering a DIY FMT to push for that last 20%. This paper so far is incredibly interesting from an intellectual standpoint, but the proposal to use these substances in the treatment of immune/autoimmune disorders is unrealistic imo. In the little time i spent in a formal laboratory studying C. elegans, it was a frequent tactic to write in about cancer and other diseases in the grant proposal. Ask for money to study psychedelics effects on the immune system, forget about it. Say they can be novel tools in the treatment of various diseases, now you've got people listening. The truth is though you can tack that shit on any paper because every aspect of your physiology contributes to your overall health. But as we can see with the lack of viable cancer treatments, that doesn't mean every connection is exploitable for therapeutic purposes.