Review: 'Through the Shadowlands’ describes Julie Rehmeyer's ME/CFS Odyssey
I should note at the outset that this review is based on an audio version of the galleys and the epilogue from the finished work. Julie Rehmeyer sent me the final version as a PDF, but for some reason my text to voice software (Kurzweil) had issues with it. I understand that it is...
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Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities

Discussion in 'Other Health News and Research' started by Owl42, Jan 24, 2016.

  1. Owl42

    Owl42 Psychedelic bird

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    I wanted to read your opinions on this matter. This is a recent study explaining the effect of psychedelics in the immune system mostly through their effect on the sigma1 receptor.

    I've seen some of you have already discussed cases of short term healing of most symptoms in some people after the use of classic psychedelics like ayahuasca. I, after testing those myself from the effects of vaped N,N-DMT (I wanted to avoid the iMAOs that is used in ayahuasca to make DMT active in oral form) looked for some other testimonials of those effects. I found some people with CFS/ME reporting the same (being cured from CFS) in some forums about the substance and also around some sites about CFS.

    Then I was pointed to this research that I think touches a lot of subjects we PWC are concerned about.

    It talks about the effect of some psychedelics on cytokines, ion channels balance, and many other things related to NF-κB, celullar activation, and lots of factor implied in NO/ONOO cycle.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500993/

    What do you guys think?
     
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  2. Hip

    Hip Senior Member

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    Would you have any links to these stories?

    I came across one account of an ME/CFS patient having the disease for 6 years who reported being cured after just one dose of pure smoked dimethyltryptamine (DMT); but he only posted follow up comments for around a month.

    And then I read this account of an ME/CFS patient who took 3 ayahuasca trips on different occasions, and each time he said he had 100% remission from ME/CFS and all its symptoms, but only for the duration of the ayahuasca trips, which last for several hours. The main active psychedelic in ayahuasca is of course DMT.



    Looks like an interesting paper, although I just briefly glanced through it. I will have a better look tomorrow.

    This I found significant though:
    The RIG-I-like receptors (there are three of them: RIG-I, MDA5 and LGP2) are involved in sensing viral dsRNA inside human cells, and then instigating an immune response on this viral dsRNA. The work of Dr John Chia and others has indicated that enteroviral dsRNA living and replicating inside cells may be a major causal factor of ME/CFS (enteroviral dsRNA is also known as a non-cytolytic enterovirus, and you will find lots of info about this on this forum).

    Enterovirus tries to destroy the RIG-I receptor, in order to prevent the immune system from detecting and responding to enteroviral dsRNA in human cells (ref: 1). So this may be one of the reasons it is hard to clear intracellular enterovirus dsRNA infections.

    So if DMT is modulating the RIG-I-like receptors, that might have some antiviral effects on the intracellular enteroviral dsRNA infections many ME/CFS patients appear to have.

    Conversely, if DMT is temporarily reducing inflammation and the immune response, that could help explain the report of ayahuasca putting ME/CFS into remission for a few hours.


    @halcyon is also interested in the RIG-I-like receptors in enterovirus infections.
     
    Last edited: Jan 25, 2016
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  3. GhostGum

    GhostGum Senior Member

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    Some people might not like this opinion, no doubt, but with the use of psychadelics for many psychological applications these days, terminally ill cancer patients, PTSD, depression, especially in the most serious sessions, psilocybe (cancer patients), ibogaine (heroin addicts), ayahuasca sessions you are creating ego death and a space to reset the neural connections. When people are guided by professionals under these circumstances they are obviously intending to guide and condition in more healthy connections while the window is open, if in the least by helping the patient/tripper regain perspective over their whole life and the myriad of experiences they have had, in contrast to the persistent trauma/rut that someone has been permanently dealing with and which has been over-riding everything else.

    Simply psychadelics have helped and cured people of different health issues for exactly the same reason, you reset the switch board/brain, you clear out restricting connections, muscle memory, behavioural patterns and it also results in changes in biological behaviour.

    Of course when you are dealing with probable complicated biological issues in some, it is likely not going to do much; but when you are dealing with something that relates more to a bunch of undesired trauma/patterns in the brain it has great potential. Because when you say someone has temporary remission under the influence it is clear, at least IMO, that they are glimpsing the open window, full open neural pathways but just can not hold it afterwards and sit back into the old state (harder for some to benefit from the open window than others, depending on the conditioning I guess).

    I think if you are going to dabble into psychedelics some experience with brain training, conditioning and manipulation is essential; or best yet under the supervision of a professional who can guide you therapeutically.

    If you want to look at it from a purely chemical point of view and no real appreciation for the psychadelic experience and your own inner mind, I would not bother.
     
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  4. Hip

    Hip Senior Member

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    Maps.org have conducted quite a bit of research into the psychedelic + psychotherapy combination for conditions like PTSD and anxiety.


    However, DMT appears to have some immunomodulatory properties, which could explain on a biological rather than psychological basis why DMT / ayahuasca has been reported to temporarily eliminate ME/CFS symptoms:

    Some other interesting excerpts from the paper:
    Note that one study found 1.7% of ME/CFS patients have autoantibodies to the serotonin 5-HT1A receptor.
     
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  5. Hip

    Hip Senior Member

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    Some more excerpts from the review paper about the sigma-1 receptor:
    In the context of ME/CFS, note that high intracellular calcium (Ca2+) levels activate calpain, and calpain cleaves the RNase L which would normally destroy non-cytolytic enterovirus infections, and in this way, high intracellular calcium may prevent viral clearance of these intracellular infections.


    Note that as well as DMT, dextromethorphan (found in cough mixture), amitriptyline, and the SSRI drugs sertraline (Zoloft) and fluvoxamine (Faverin) are all agonists of the sigma-1 receptor (ref: here).
     
  6. Owl42

    Owl42 Psychedelic bird

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    @Hip You can find some of the experiences in this thread.

    I love to see you've made some sense out of it, I've been fighting with it for some days since I got better from taking DMT but it's already remitting (effects lasted for about a week) and even if I don't have that heavy mental fog my concentration is not so good. Also I have no skills on medicine, so I just tend to read lots about everything and can get all my info messed up easily.
     
  7. Hip

    Hip Senior Member

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    Don't worry, I think most people (myself included) on this forum had no medical knowledge before they were hit with ME/CFS, and picked up some bits of biochemistry along the way over the years.



    Can you provide a few more details on the remission of ME/CFS symptoms you experienced after taking DMT please?

    • What would say your level of ME/CFS is: mild, moderate or severe? For a description of these three levels, see this post; basically, mild is when you just about can do a full time or part time job; whereas at the other end of the spectrum, severe is where you are usually bedbound much of the day.

    • After smoking (vaping) DMT, how quickly did your ME/CFS symptoms improve, and how much did they improve by (did your symptoms completely disappear, was there a major improvement, or just a minor improvement)?

    • And you say the improvement lasted for around a week before it wore off? Just to be clear, was 1 week the time when the benefits just started to wear off? Or was 1 week the time when the benefits had worn off completely, and you were back to your normal ME/CFS state of illhealth?



    Very courageous of you to take DMT, by the way!

    I myself unfortunately have had very little past experience with taking psychedelics (only experience with softer drugs like Cannabis); although I have friends who did plenty of psychedelic experimentation. Nevertheless, I have always been fascinated with reading and learning about psychedelic drugs from the spiritual or philosophical perspective, especially reading about DMT and Salvia divinorum.

    Correct me if I am wrong, but I understand that when you smoke DMT, the trip lasts around 5 or 10 minutes (compared to taking DMT in ayahuasca form, when the trips lasts 5 to 10 hours). But I have heard people saying that subjectively, those five minutes of DMT psychedelic reality can, from the tripper's perspective, feel like they last for much, much longer, and when you come back to normal reality, it can feel like you had been away somewhere for weeks or months.

    Many consider DMT to be a much stronger psychedelic than LSD, so I guess your DMT trip was pretty intense. Was it an OK experience, or were there some scary moments? I am not sure I'd have the courage to take DMT — unless of course a permanent cure from ME/CFS was a guaranteed outcome.

    Though one thing I was considering was daily DMT microdosing, which would avoid going on a full-scale DMT trip, yet might provide the same medical benefits as the full DMT dose.
     
    Last edited: Jan 26, 2016
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  8. GhostGum

    GhostGum Senior Member

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    Just to expand on what I wrote above,

    http://www.scientificamerican.com/article/do-psychedelics-expand-mind-reducing-brain-activity/

    Because I do not want to make psychological generalizations, it is just hard to be pragmatic about something that is not well understood. When we are talking about 'opening windows' with psychadelics and resetting connections I see this as a very literal process, causing change in brain states, which will inevitably cause change in personality and biology. It is all made tricky because of the combination of the drug and the 'self', it is impossible to remove the characteristics of any given person from the equation and how things transpire in their own brain/psyche.

    It is just currently things are still looked at far too autonomously and fixed when it comes to the human mind/brain, when in fact it is so much more open to tinkering, manipulation, re-conditioning.

    @Owl42 Are you aware of Wim Hof? I believe what he has done and is showing people is pretty much the same thing as psychadelics, just using cold shock to open up the brain instead of a chemical. I have been doing it myself for over 6 months now, along with cannabis as a psychadelic to help reset everything and it is the best combined treatments I have ever tried by far.

    I think for me this is all an end game, last quarter strategy though, to really fully recover, reset and get back to what total normalcy was like, as subjective as that maybe. In the depths of the ME it would just not have been possible and can not imagine it as an option for those at the serious end of the scale, might even be quite dangerous given the level of suffering some are in.
     
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  9. Dufresne

    Dufresne almost there...

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    Daniel Pinchbeck wrote in his novel, 2012, that he believed there's a risk in DMT use, if not all psychedelics. He mentioned seeing spiders and such for some time after a particular DMT trip and I got the impression he felt as if he'd bitten off a bit too much.

    Terence McKenna makes the point that you're still "you" after smoking DMT, that there's no head buzz to it. So the typical psychedelic "ego death" doesn't take place. And you don't tend to hear users claiming any kind of enlightenment was experienced, rather it was just a really strange, mind-blowing trip. But, hey, maybe that's just what the ME/CFS brain needs.

    If anyone is thinking of venturing down the rabbit hole I'd recommend starting with THC and psilocybin, and even starting with micro-doses. I'm considering modest doses of shrooms just because they used to make me feel really on top of things mentally and spiritually. The best part always came in the hours after peeking when I felt so clear and like everything made sense. I can't recall another time I was even close to being that satisfied with my brain/existence. I'm thinking It would be nice to go back there a few times a year: a sort of vacation from ME consciousness.

    Incidentally I find just listening to McKenna's lectures, or even the McKenna soundbites played over trippy visuals on YouTube always puts things back into perspective. It's a little taste of the antidote.

     
  10. Owl42

    Owl42 Psychedelic bird

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    @Hip I've tried microdosing with great results, mostly using it before going to bed and feeling quite well waking up the next morning (Something I have only achieved since I started suffering CFS after getting to know DMT)

    About my state: I fluctuate a lot, 2 months ago I could get out and assist to rehabilitation for my neck daily. Now I'm back at home and not being able to do much, with hardcore sleep dissorders again... I've been suffering for 5 years now and haven't been able to keep up with college at all.

    About the intensity of the trip, which effects started to fade away after the first week, I only took about a 20mg dose and it's like the minimun for a psychedelic experience, you don't really "break through" from that dose, so there were no signifficant temporal perception changes (there were but I didn't feel like I spent years, not even days, in the minutes I was under the influence of it) mostly touch perception was altered, I felt like some kind of light and music was calling me from above and I could see lots of beautiful geometry and patterns with closed eyes.

    It was a very positive experience for me and I've already took high doses of psilocybic mushrooms feeling the "vacation from ME perception" @Dufresne was talking about and also feeling a little relieved from the condition (it wasn't as severe as it's now, tho) the days after.
     
    Last edited: Jan 27, 2016
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  11. cigana

    cigana Senior Member

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  12. cigana

    cigana Senior Member

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    From the anecdotal reports I've seen, use of psychedelics has brought rapid improvement/recovery, so that suggests to me there is not enough time for viral clearance...I think it's more likely the effect is from immunomodulation.
     
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  13. cigana

    cigana Senior Member

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    I think you're right, we have to approach this carefully - it may not simply be a "chemical" effect, but rather resetting the fight-or-flight/stress pathways.
    It could be a rapid form of neural feedback, that seems to help some people.
     
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  14. Owl42

    Owl42 Psychedelic bird

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    Well, I've experienced almost instant recovery myself from low doses (and a big helping in information processing and concentration on microdosing) but I felt like the most recovery when I took an actual dose happened around the second and third day of it... I think I'm taking another dose tonight, I will tell you more about it tomorrow (or if I don't break trhough maybe I'll come here to explain in vivo so memory don't betray me later).
     
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  15. Owl42

    Owl42 Psychedelic bird

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    I don't know Wim Hof, I'll research it but can you explain it briefly so I can approach it without having to do a hard mental exercise in understanding it? :)

    Thanks for your interest in this thread guys, it's being a great help and hope for me to see you as optimistic as I am.
     
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  16. Hip

    Hip Senior Member

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    That is intriguing. If DMT were improving ME/CFS symptom by a straightforward anti-inflammatory effect, you might expect the highest level of benefit to appear when you take DMT and in the hours that follow. But you are finding that the peak benefits from DMT appear two or three days after you take a single DMT dose.

    It suggests that there may be more going on than just an anti-inflammatory action.



    Regarding the fact that DMT agonizes the sigma 1 receptor, and its benefits may come from this: note that other sigma 1 receptor agonists are listed here: Sigma-1 receptor - Wikipedia

    Probably the most easy-to-obtain sigma 1 receptor agonist from this list is dextromethorphan, which is found in some cough mixtures, and can also be bought in pill form.

    I found this article by a fibromyalgia patient who also has POTS: he observed that a singe dose of 150 mg of dextromethorphan has antidepressant and anti-pain effect that kicks in within 2 hours, and lasts several days.

    Dextromethorphan, incidentally, is also used in higher doses (240 mg to 1500 mg) as a sort of poor man's psychedelic drug (though dextromethorphan seems to have a relatively high incidence of triggering psychosis, compared to other psychedelics).



    Although there may be more going on that just agonizing the sigma 1 receptor: this study says that DMT's binding to the 5-HT2A and 5-HT1A serotonin receptors may also have immunological effects:


    That study also notes that DMT's effect on the sigma 1 receptor could also help autoimmune diseases (and of course, ME/CFS could well be an autoimmune disease), and help chronic inflammatory conditions in the central nervous system:
     
    Last edited: Jan 27, 2016
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  17. Hip

    Hip Senior Member

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    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.
     
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  18. Owl42

    Owl42 Psychedelic bird

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    Thanks for your great researching work, @Hip. It makes me get a little confy on my experiment on myself, tho I'm getting worried about the smoking thing. My throat hurts.

    Well I took a bigger dose yesterday, I've spent most of the day sleeping (12 hours or maybe more) and I think It's been a very recovering sleep. I feel with more concentration and energy. My pulse is more stable too, It's been quite low the last days.

    I've been feeling really bad lately and today it's been more bearable. I cannot talk about total recovery but I feel quite better, I've done more things and with less effort. I still feel sleepy and I feel like sleeping will help me get better.

    I will report again tomorrow.
     
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  19. Owl42

    Owl42 Psychedelic bird

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    Sleepy day again. I don't know if it's the weather (rainy and cloudy) or the effects from DMT, I think both.

    When I get to wake up (12 hours of sleep again) I feel "normal", no nausea, not feeling as rigid as I use to and able to eat soon. I've been woken up just for a few hours today and I've done more than I've been able to in the last weeks, walked out my dog, took care of my plants, went upstairs easily, also I've been able to read a lot around the forum and check the enterovirus theory @Hip was talking about.

    On this matter I'd want to know if there's enough evidence of those and if I should talk about it with my inmunology doctor who I'm visiting tomorrow... I'll be interrupting the DMT experimentation to get her testing done. I don't think I'll mention DMT, for I've had really awful reactions from my doctors when talking about cannabis.
     
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  20. Hip

    Hip Senior Member

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    No, this is not the sort of thing you want to mention to your doctor.



    In terms of treatments that are generally helpful for ME/CFS, and that people on the forum have found helpful, you may want to look at vitamin B12 injections (or high dose B12 sublingual tablets), the methylation protocol, low-dose naltrexone (LDN), or immunomodulators like oxymatrine (especially for enterovirus infections). Note that LDN may not work unless you also take vitamin D3.

    This document may be helpful: Chronic Fatigue Syndrome — A Roadmap For Testing And Treatment
     
    Last edited: Jul 20, 2017
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