Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities

Owl42

Psychedelic bird
Messages
53
Location
Mexico
Hi guys, I'm back. I'm not taking DMT anymore for I have a new immunological treatment, but I think it helped me get in the state of recovery I'm right now. (I haven't been so good last week tho) I wanted to talk with you about the antiviral, antimicrobial and antifungical role of MAOis used in ayahuasca allonside DMT. They cross the BB barrier and I think it can be interesting for us and also explain why ayahuasca has been the ultimate medicine for some cultures.

https://www.researchgate.net/profil..._harmala_L/links/02bfe5127249b122ea000000.pdf

http://www.sid.ir/en/VEWSSID/J_pdf/119220080402.pdf

http://bmcresnotes.biomedcentral.com/articles/10.1186/1756-0500-6-193

This is the most interesting finding I've got to, reviewing the action of Harmaline on the lysine-specific demethylase-1 (LSD1), suppresing viral gene expression. http://www.sciencedirect.com/science/article/pii/S0166354214000503 I've found other interesting articles on LSD1 and herpevirus after this.
 

Hip

Senior Member
Messages
18,148
@Owl42
Thanks for those links.

Interesting though they are, often there may 5 or 10 or more different herbal or natural supplements that have antiviral effects against a specific virus.

For example, you can see here the list of herbal (and pharmaceutical) antivirals I compiled that have antiviral efficacy against coxsackievirus B and echovirus (two viruses strongly linked to ME/CFS).

And here you can see various other herbs that have antiviral effects against herpes simplex virus 1.

But generally, herbal antivirals are not strong (in fact even most pharmaceutical antivirals are not very strong).
 

Owl42

Psychedelic bird
Messages
53
Location
Mexico
I've been reading this article and thougt you guys would like it. Maybe @Hip can get more out of it. I think it is related to the things you were mentioning some time ago!

"The data presented suggest that DMT may regulate intracellular calcium overload and pro- apoptotic gene expression via activation of Sig-1R recep- tors. This mechanism can result in a DMT-mediated neu- roprotection during and after ischemia and acidosis. The pathological consequences of hypoxic–anoxic damages can be further mitigated by DMT-facilitated Sig-1R dependent plasticity changes"

A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity https://www.researchgate.net/public...n_tissue_protection_regeneration_and_immunity
 

Hip

Senior Member
Messages
18,148
Thanks for the link, @Owl42.

Just recently I found something interesting about the sigma-1 receptors: it seems that dextromethorphan, which like DMT agonizes the sigma-1 receptors, is a treatment for emotional lability (pseudobulbar affect), which is one of the emotional symptoms of ME/CFS:
What is emotional lability?

Emotional lability refers to rapid, often exaggerated changes in mood, where strong emotions or feelings (uncontrollable laughing or crying, or heightened irritability or temper) occur. These very strong emotions are sometimes expressed in a way that is not related to the person’s emotional state.

Source: Understanding Emotional Lability
Emotional lability is a symptom of ME/CFS listed in the CCC definition of ME/CFS.



It seems that dextromethorphan's ability to treat emotional lability may be connected to its agonism of the sigma-1 receptors:

This study said that sigma-1 receptors
are widely distributed in the brain, but probably most heavily in the limbic system, suggesting that dextromethorphan may exert its emotion-controlling effects via these receptors.


Not that many ME/CFS patients seem to suffer from emotional lability, though; but most patients do suffer from emotional hypersensitivity (eg: witnessing even minor social discord can feel very unpleasant when you have ME/CFS). And some ME/CFS patients like myself experience flat emotions, which is also an ME/CFS symptom listed in the CCC.

So I wonder if sigma-1 agonism might be generally helpful for all the emotional symptoms of ME/CFS?

I have not yet tried high dose dextromethorphan, but when I do, I will be on the lookout to see if it can rectify ME/CFS emotional symptoms.
 

actup

Senior Member
Messages
162
Location
Pacific NW
I plan to plow through this wonderful research material. I have tried shrooms once ( fairly obtainable in my state- my nephew knows where to pick them and my 60 yr old brother is not big on alcohol but loves his shrooms). My lovely brother set up the experience for me on a deserted beach in Puget Sound on a beautiful day. Gave me what he judged to be a 1/2 dose and my experience was subtle and allowed me to enjoy the beautiful details of nature without distraction. I spent hours looking at shell fish in tide pools and reminiscing with my brother. I would be happy to use shrooms every day but for the cost. A second experience has just gone to the top of my to do list.
 

Dufresne

almost there...
Messages
1,039
Location
Laurentians, Quebec
I would be happy to use shrooms every day but for the cost. A second experience has just gone to the top of my to do list.

Tolerance to psychedelics develops quickly. By the third or fourth day of dosing you'd get next to nothing from them. However normal sensitivity returns within 7 days.
 

actup

Senior Member
Messages
162
Location
Pacific NW
Thanks @Dufresne for this info. I wonder if tolerance can be controlled with weekly or monthly use. Dosage is of course difficult to control when you are eating dried mushrooms grown in the wild. We have a tolerant view of shrooms for personal use(still illegal in Wa) and pot( legal in state of WA) in the Pacific NW. When I moved here 29 yrs ago guests brought pot rather than wine. We need a break from the anhedonia.
 

Owl42

Psychedelic bird
Messages
53
Location
Mexico
@actup when I was using shrooms I got very good results from dosing once a month, or once every three weeks. Shrooms doesn't seem to interact with sigma receptors tho, just serotonine receptors, so they won't modulate immune system, at least not so directly as DMT, for serotonin does affect immunity but in a total different level and scale.
 

actup

Senior Member
Messages
162
Location
Pacific NW
@actup when I was using shrooms I got very good results from dosing once a month, or once every three weeks. Shrooms doesn't seem to interact with sigma receptors tho, just serotonine receptors, so they won't modulate immune system, at least not so directly as DMT, for serotonin does affect immunity but in a total different level and scale.

@Owl42 I've been reading through this thread from the beginning so your advice is much appreciated. I am evaluating the low dose DMT regimen. Thanks!
 

knackers323

Senior Member
Messages
1,625
In terms of the anti-inflammatory effects of DMT, the study I cited above found that, via its action on the sigma 1 receptor, DMT:

• Inhibited the secretion of pro-inflammatory cytokines IL-1β, TNF-α and IL-6
• Inhibited the secretion the chemokine IL-8
• Increased the secretion of the anti-inflammatory cytokine IL-10


The first thing to note is that IL-1β, TNF-α and IL-6 are sickness behavior cytokines.

Michael VanElzakker's theory is that ME/CFS is due to the chronic activation of sickness behavior. Sickness behavior is an automatic bodily response to infection; it creates the symptoms (such as fatigue, brain fog, depression) you feel when you get the flu or a fever. VanElzakker's idea is that the chronic infections found in ME/CFS may be constantly triggering sickness behavior, thus leading to the symptoms of ME/CFS.

So, if DMT is inhibiting the production of these sickness behavior cytokines IL-1β, TNF-α and IL-6, this may in part explain why DMT appears to eliminate or greatly reduce ME/CFS symptoms on a temporary basis.



The other interesting thing is that a study found that high levels of IL-8 is related to the fatigue experienced in ME/CFS. So again, the fact that DMT reduces IL-8 secretion may in part explain why DMT can have benefits in ME/CFS.

Aware of any other things aside from bmt that can lower these cytokines?
 
Messages
76
Found this on the web.

"
Interesting, I think neuroinflammation could explain a huge part of what is going on. I’ve taken LSD 3 times since being ill with CFS/ME (been ill for 2 and a half years now, I am virtually housebound) and each time my symptoms have gone away COMPLETELY for 3 days afterwards. LSD is a powerful anti-inflammatory and I did feel very much like i had received a deep massage from the inside of my body out-wards, like cooling balm being rubbed on a hyperactive frazzled nervous system. I was able to walk a few miles and play the guitar and sing for hours with strong fingers and a strong voice (can’t usually do that at all!) as well as read much more during the 3 days post-tripping. My symptoms returned quickly however and a week later (on all 3 occasions) I was just as ill as before I took it, so it’s positive effects are short.

This has led me to the theory that neuroinflammation is causing a lot of my CFS symptoms. Sadly one cannot take LSD regularly as the profound spiritual and emotional experience it induced need integrating in to daily life and it’s just not convenient. But I am curious about BROMO-LSD, a non-hallicinogenic form of LSD being developed for cluster headaches. Perhaps that would have the same effect and could be taken regularly enough to be beneficial long term for CFS/ME sufferers? I wonder if you have come across anyone else with similar experience, as I seem to be one of the only CFS sufferers to have tried LSD while ill…"
 

Tunguska

Senior Member
Messages
516
I only see detailed posts about DMT... what mechanism is supposed behind LSD specifically helping? Sorry if it's been mentioned. (The closest I've tried were DXM and lisuride (both legally available), hard to gauge, though DXM is closer to ketamine anyhow)

You mentioned sigma-1, it's modulated by steroids also (DHEA) and those are already altered in CFS/ME I believe.
 

frozenborderline

Senior Member
Messages
4,405
@manna
The aspects of DMT trips you are bring up do interest me a lot, but ideally they should be in a thread of their own, as this thread is supposed to be on the immunomodulatory properties of psychedelics, which is biochemistry.

But with the risk of going even further of topic, I will answer your points:



Nowadays there is a scientific understanding of how inflammation in the gut can affect the brain: a major gut-to-brain route is the vagus nerve, which runs from gut to brain, and has detectors for inflammation. This nerve will signal to the brain when it senses inflammation in the gut. When the brain receives this signal from the vagus nerve, the brain turns on sickness behavior, which interestingly has symptoms very similar to those of ME/CFS.





I agree that first hand descriptions of DMT experiences are valid and worthy of study, and I have read many such accounts. However, when those DMT trippers start creating theoretical frameworks or ornate theologies as an attempt to explain or embellish what they experienced on DMT, then I reserve the right to be skeptical, especially when those people don't have a scientific stance, and so often tend to create their belief system based on what they would like to be true, or based on what beliefs may support the social cohesion of the tribe.

To give you an example: I have read many accounts of people taking DMT encountering what Terence McKenna called "self-transforming machine elves," otherwise known as fractal elves, or just machine elves. Most DMT trippers tend to assume these machine elves are beings distinct from their own self; ie, they assume these machine elves have their own separate existence, mainly because they seem to behave autonomously.

However, in one of the rare DMT trip accounts I read from a scientist, he wanted to put this idea of the autonomous existence of machine elves to the test. So during his DMT trip, he made mental efforts to control appearance and behavior of these machine elves, and after a while, succeeded in doing so. This experiment indicates that machine elves are likely just manifestations of your own mind, rather than autonomous beings or autonomous consciousnesses.

If I remember rightly, I think I came across a study many years ago suggesting that the fractal imagery seen during DMT and LSD trips may be generated in the optic nerve, as a result of the action of these drugs on this nerve.





One thing that does interest me about DMT is the reporting of certain recurrent themes that different trippers independently observe. For example, snakes seem to be seen a great deal. Perhaps taking ayahuasca in the Amazon rainforest might explain that in terms of cultural conditioning, as perhaps indigenous peoples in the Amazon may for good reason be fearful of snakes. However, when taking DMT in an urban environment, it is hard to explain why snakes are seen. Though I understand it make take many trips of DMT before you first see a snake, so they are not that common.

The appearance of gnomes or alien creatures with large eyes and smooth faces also seems to be a commonly reported experience of DMT. DMT or psilocybin in naturally growing plants may explain why there are so many "gnome sitings" reported in Iceland. My theory to explain the numerous Icelandic gnome sitings is that these naturally growing plants or mushrooms may be used in food, perhaps then leading to gnome hallucinations.

Iceland takes gnome sitings so seriously, that a couple of years ago, a highway project was canceled because it was thought that the new road might disturb the elf environment!





I personally think that consciousness may well have transcendental qualities (as in transcending space and time), and that one day these might be better understood when the theories of quantum consciousness that are currently in their infancy are better developed.

Love, like any other emotion, can be become the content of consciousness, as can the sensations of an itch on your ankle; but whether love is anything more than one of the sensations or feeling that consciousness can contain — a color of consciousness if you like — that's another question.





The art of science is being able to work out what factors are causally relevant in a given situation, are what are not. I think what makes a good scientific mind is the uncanny ability to sift the relevant from the non-relevant.

Conversely, those without this scientific ability are often caught up and confused by all the myriad minutiae of any situation; they cannot filter out the causally relevant from the causally non-relevant. And these are usually the same people who have an anti-science stance.





You would have to study science to understand that fully.

But even ignoring way the utility of science, there is a great pleasure involved in performing this reductionism. When you take any given situation or system, there is almost an infinite number of ways that you could dissect that system into component parts, or conceptual elements. You can consider these parts or elements of the system as perhaps the invention of human mind, divisions we impose on the system, or lines of demarkation we ourselves draw up, dividing the system into parts.

But the uncanny ability to perform reductionist analysis on a system involves seeing (or is it creating) the parts or elements that have causal relationships to each other.

Anyone can come along and mentally divide the world into arbitrary parts. That's easy. But to divide the world into the right parts that then have a causal and mathematical relationship to each other, that usually takes genius.

The recurrence of elves in DMT trips makes me think of this obscure physiology stuff on ontogeny, phylogeny, neoteny, etc... and how the ideal human form is elven. It was on a deleted blog that referenced szentgyorgyi among others. weird stuff but he did cite some studies so it was not as far off as some of the very speculative psychedelics stuff.
 

frozenborderline

Senior Member
Messages
4,405
The recurrence of elves in DMT trips makes me think of this obscure physiology stuff on ontogeny, phylogeny, neoteny, etc... and how the ideal human form is elven. It was on a deleted blog that referenced szentgyorgyi among others. weird stuff but he did cite some studies so it was not as far off as some of the very speculative psychedelics stuff.
https://drive.google.com/file/d/0B4_grloGUraLZ2hvU3BZVkpqNG8/view?usp=sharing

https://web.archive.org/web/20160314035459/https://pranarupa.wordpress.com/
 

Hip

Senior Member
Messages
18,148
The recurrence of elves in DMT trips makes me think of this obscure physiology stuff on ontogeny, phylogeny, neoteny, etc... and how the ideal human form is elven.

From what I have read about DMT trips, these elves appear like mathematical fractals, which might be produced from the brain's intrinsic mathematical capabilities (ie, neurons can compute).
 

Marylib

Senior Member
Messages
1,168
Psylocibin gave me the most lovely, "normal" sleep I had had in years. I will do almost anything for sleep, except for addictive drugs, like opiates or benzodiazepines. Am really glad no one ever prescribed the dreaded clonazepam (klonopin) for sleep. So not worth the addiction. Have known too many people with ME who are desperately trying to come off it. I would only use benzo's on a very occasional basis. I do with psylocibin could get the research it deserves - not that it is in any way a cure for what ails us.
 

frozenborderline

Senior Member
Messages
4,405
Psylocibin gave me the most lovely, "normal" sleep I had had in years. I will do almost anything for sleep, except for addictive drugs, like opiates or benzodiazepines. Am really glad no one ever prescribed the dreaded clonazepam (klonopin) for sleep. So not worth the addiction. Have known too many people with ME who are desperately trying to come off it. I would only use benzo's on a very occasional basis. I do with psylocibin could get the research it deserves - not that it is in any way a cure for what ails us.
this is interesting. I loved psilocybin and LSD pre-illness but I think that full-on trips tend to be physically stressful and use up the body's reserves and we have none, but I wonder about small doses. Psilocybin can also be more physically relaxing than LSD so..
I remember making tea with it gets around the nausea problem totally too.
 
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