Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities

[Hip]

With pentazocine I was hoping for the sigma1 agonist effects.

I happen to have a box of dextromethorphan cough tablets here. I might try taking several of these together, but well below the dose that creates psychedelic trips, and see if its sigma 1 agonism has any effect.

 

[Owl42]

I happen to have a box of dextromethorphan cough tablets here. I might try taking several of these together, but well below the dose that creates psychedelic trips, and see if its sigma 1 agonism has any effect.

I've read how dextromethorphan medicines use to add some laxative excipients to avoid the recreational use from any one who would look for it. There are some tutorials on the net teaching how to extract the active ingredient and which brands are best for it.

 

[Hip]

@Owl42
I did not realize that. I think my tablets are just pure dextromethorphan. Hard to tell though because the packet is printed in Polish.

 

[Owl42]

@Hip check internet resources to find how pure it is. There is a lot of people trying to get high from those kind of things so there's a lot of info about it.

 

[MeSci]

Not sure what you mean? If they were better when they were thin would that would mean it's a good sign of improvement by that reasoning?

Not really - the weight loss signalled the start of a chronic illness.

 

[Thomas]

Not really - the weight loss signalled the start of a chronic illness.

I agree! The weight loss thing is scary for me. Ive always been thin but since my ME onset and up until now it has been nothing but progressive weight loss, muscle wasting, all sorts of horrible things.

I had my annual physical last week and I weighed in at 124 lbs and I'm nearly 6 feet tall.

I don't buy this whole you need to hit rock bottom and waste away to near death before your body can rejuvenate. Weight loss is frightening when it's combined with illness. Especially a sedentary illness like ME. Yes I think stress doesn't help the situation but clearly something is wrong here.

I hope this can stabilize at some point soon. Sigh.

Hip let us know how the Dextromethorphan goes.

 

[Hip]

Hip let us know how the Dextromethorphan goes.

Will do. Feeling under par in the last few days, though, and only try new drug regimens when I am feeling relatively good (a precaution in case there are negative side effects).

 

[Owl42]

@Thomas in the wieght loss matter, I feel the same. I get scared often looking at my hands and the mirror has became an enemy of mine lately.

And I don't exercise at all. But I keep getting thinner and my bones are more and more noticeable... also my skin looks like my mother's now... It is really scary, for me and the people around me. It is what really kind of shows the others how sick I am... Even if that makes me get some response from the doctors, I really hate it.

 

[Thomas]

@Thomas in the wieght loss matter, I feel the same. I get scared often looking at my hands and the mirror has became an enemy of mine lately.

And I don't exercise at all. But I keep getting thinner and my bones are more and more noticeable... also my skin looks like my mother's now... It is really scary, for me and the people around me. It is what really kind of shows the others how sick I am... Even if that makes me get some response from the doctors, I really hate it.

I know right?! Worst. And I'm only 36. My friends and family say I look great but I know it's bullshit. I know me and my body and I know how dramatically it has changed. And I agree, my doctors believe my disease by my constant weight loss but it's not the worth it.

How old are you if you don't mind me asking?

 

[Owl42]

@Thomas I'm 23 I'm afraid I've lost my young body forever.

 

[Thomas]

@Thomas I'm 23 I'm afraid I've lost my young body forever.

Nothing's forever, there's still hope of rejuvenation! I think so and I'm 36, you're even younger so there's more time.
This is at least what I tell myself (I have to otherwise I'd get super depressed).

 

[GhostGum]

@Hip Meant to reply earlier, and could not be bothered at the moment to go back over everything but I believe you said earlier it would be nice to be able to replicate the actions of psychadelics without the trip, without the ego loss and potential to flare old symptoms like your psychosis. But people still do not seem to quite understand the difference between taking a dose to trip and therapeutic dose, I believe micro dosing LCD has become quite popular in different parts of the world, same with psilocybe. It would probably not be that hard to find the right dose to avoid ego loss, but would take some tinkering.

I have already said it before, people can keep looking at the chemistry all they want for answers, but the unique human element here, the depths of an individuals sub-conscious and the ability of psychedelics to highlight and shift brain states of an individual based on personal characteristics trumps the nuts and bolts IMO; the initial drug and chemistry is only a trigger. I realise this illness buries people to the point of complete loss of normalcy and basic sense of self, so it can be near impossible to add this element into the equation but ignore it completely for some rational approach at your peril. The depth and sensitivity of the experience on a psychedelic, coupled with many varying factors will lead to all kinds of shifts in consciousness, mood and essentially chemistry (have fun accounting for that over the course of a trip); the whole point being to find the ideal place to sit your brain and set the connections up to a more ideal position. The latter part is most difficult, people use psychedelics and it is generally just a passing experience, to not make it just a passing experience takes much personal work and dedication to be able to tinker and manipulate similar states within yourself.

Just because there is far too much going on and shifting within an individual with such an experience and which science has little hope of accounting for at this point of time, it does not make any of it wishy washy or new agey. People just give up their own ability to shift and manipulate within themselves, to recognise and trust in themselves over rational explanation.

And I have to state again I do not mean this in relation to ME, or that any of it is a solution for anyone, only that it very much applies to life across the board. But it is very much part of what I have had to do to get close to full recovery and rehab in the end, feel like I have had to scrape the bottom of my psyche, come to recognise every tiny little impulse, response, impression and come to terms with it all. I am not sure what it is about ME, at least for me but it had created such a hyper over sensitive state where many underlying aspects of life, which most normal people can ignore, or actually they ignore to their detriment also, become far too apparent during the course of the illness.

 

[Hip]

@GhostGum
We have covered most of this ground already on the thread.

If you think psychedelics improve ME/CFS by altering the mind, then you have very similar views to Simon Wessely, who sees ME/CFS as an "all in the mind" psychologically caused condition.

I don't think ME/CFS is caused by the mind; I think it is generally caused by neurological and immunological dysfunction.

I believe micro dosing LCD has become quite popular in different parts of the world, same with psilocybe. It would probably not be that hard to find the right dose to avoid ego loss, but would take some tinkering.

Yes I have read that microdosing psychedelics has become quite popular.

In my case, what seemed to screw the stability of my brain and mind quite severely was an episode of viral meningitis a had 10 years ago. Prior to that episode, I was capable of smoking Cannabis without any problem whatsoever (not that I smoked much, probably just once every 3 to 6 months; although in my early 20s it was much more frequent).

But ever since I had the meningitis, even one toke of a joint now throws my mind into a strange, uneasy, agitated, mild psychosis-like state. I used to enjoy the occasional Cannabis smoke, and I always felt it did me a lot of good. Now I can't touch it. So goodness knows what would happen to my mind if I took a microdose of a psychedelic drug.

 

[Thomas]

In my case, what seemed to screw the stability of my brain and mind quite severely was an episode of viral meningitis a had 10 years ago. Prior to that episode, I was capable of smoking Cannabis without any problem whatsoever (not that I smoked much, probably just once every 3 to 6 months; although in my early 20s it was much more frequent).

But ever since I had the meningitis, even one toke of a joint now throws my mind into a strange, uneasy, agitated, mild psychosis-like state. I used to enjoy the occasional Cannabis smoke, and I always felt it did me a lot of good. Now I can't touch it.

Interesting. When I was in high school I smoked a lot of weed and could handle it just fine and be around people etc. Then I guess at around age 17 when my brain began to develop just a tad of anxiety and introversion I haven't been able to tolerate it at all. I've tried many times even before getting ME and after.

Each time it's the same thing. It turns me into a person living in his head in bad paranoia and circular thoughts, bad anxiety, brain inflammation and other unwanted cognitive and neurological symptoms. Even too much of a 1% THC medicinal strain can be too much for me. Microdosing is fine but far from therapeutic.

Which is a real bummer and shame for me as I quite like "smoking" and "smoke" and this new marijuana culture. It's a fun hobby if one can tolerate it and remain functional on it. But not so with me.

I have friends who are healthy who cannot live without weed and they're still very functional business owners, fathers, friends etc. Yet some of my healthy friends are like me in the sense that they lost their tolerance for weed as they got older and now it turns them into introverted and stupid messes.

 

[GhostGum]

@GhostGum
We have covered most of this ground already on the thread.

If you think psychedelics improve ME/CFS by altering the mind, then you have very similar views to Simon Wessely, who sees ME/CFS as an "all in the mind" psychologically caused condition.

I don't think ME/CFS is caused by the mind; I think it is generally caused by neurological and immunological dysfunction.

How does what I have said end up in this? It really is unbelievable, to dumb it down to such a generalisation, and bringing Wessely up? It is complicated, life is complicated and there is overlap between hard science, biological mechanisms then human behaviour and conditioning. Sometimes there is clear cut biological explanations, sometimes impressions, events, behaviours have been impressed into the hard wiring, or built up over a period of time due to circumstance that are the problem. And I tried to clearly state already that it does not necessarily have much at all to do with any given persons circumstances with ME, but it makes up life and it is hugely influential on what takes place with the use of psychadelics because of the shift in conditioned responses that takes place.

All in the mind is some general term that seems to have little meaning honestly, it is all there is the brain and what is in the brain is an endless amount of neural connections which contain cellular and sensory data making up memories, impressions and conditioned responses that are all connected to the CNS and biology. It all makes up who people are, what drives them and their sense of self; a genetic blank slate means nothing without the sensory input that exists all around us.

Being able to hold and maintain the brain state that happens under psychadelics is probably the holy grail, but it has already been shown in studies on terminally ill cancer patients that it can be hugely successful in clearing their fear and trauma of their situations and giving them back perspective on their life. You can think that temporary full remission from a psychadelic is just a chemical response if you like, but it is clearly much more than that, neural connections and the hard wiring releasing. It is why they are so successful for a whole host of psychological disorders, but of course under the right circumstances with the right assistance, to help ride all the latent unhelpful connections, remove or replace them with other responses. The nature of psychadelics and the experience have been written about for over a century, that is all just fluff right and its just biology?

I believe ME is mostly caused by biological factors and triggers, I still need regular methylation supplements and likely will for life; but after 10+ years of absolutely devastating circumstances I have also needed to re-gig the sails using certain methods to overcome such deep suffering.

Maybe one day we will all be able to reset the circuit board permanently with a simple device and no need for drugs, or years of cold exposure and meditation. I would not think for a second this would cure ME, it might help some over the line, and very likely help symptom management; but for now it will just continue to be complicated.

 

[Hip]

it has already been shown in studies on terminally ill cancer patients that it can be hugely successful in clearing their fear and trauma of their situations and giving them back perspective on their life.

And similarly, I posted links earlier to studies which showed psychedelics were helpful to PTSD. But both the fear and anxiety in cancer, and the extreme stress and fear that triggers of PTSD, are psychological factors. That is to say, they are factors more at the level of mind than the level of brain. So it is not so surprising that psychedelics help.


But symptoms like brain fog, although they manifest in the mind, are mostly likely caused by neurological and immunological dysfunction of the brain. The fact that ME/CFS patients report DMT can clear the brain fog, suggests DMT may be temporarily addressing this neurological or immunological dysfunction. At least there is a reasonable possibility that this is the case.

In fact, one ME/CFS patient who took three ayahuasca trips reported that on each occasion, all of his ME/CFS symptoms disappeared, including brain fog, muscle weakness, fatigue, sinusitis and general malaise.

So that is why some speculative ideas about the biochemistry behind DMT's ability to temporarily put ME/CFS in into remission are being sought on this thread. Note that the subject of this thread is the possible immunomodulatory effects of DMT on ME/CFS patients.

 

[GhostGum]

And similarly, I posted links earlier to studies which showed psychedelics were helpful to PTSD. But both the fear and anxiety in cancer, and the extreme stress and fear that triggers of PTSD, are psychological factors. That is to say, they are factors more at the level of mind than the level of brain. So it is not so surprising that psychedelics help.


But symptoms like brain fog, although they manifest in the mind, are mostly likely caused by neurological and immunological dysfunction of the brain. The fact that ME/CFS patients report DMT can clear the brain fog, suggests DMT may be temporarily addressing this neurological or immunological dysfunction. At least there is a reasonable possibility that this is the case.

In fact, one ME/CFS patient who took three ayahuasca trips reported that on each occasion, all of his ME/CFS symptoms disappeared, including brain fog, muscle weakness, fatigue, sinusitis and general malaise.

So that is why some speculative ideas about the biochemistry behind DMT's ability to temporarily put ME/CFS in into remission are being sought on this thread. Note that the subject of this thread is the possible immunomodulatory effects of DMT on ME/CFS patients.

I am probably generalising quite a bit, and there could be specific mechanism at play from a specific psychedelics, but it must be terrible hard to assess given the nature of psychedelics. To me they clearly temporarily release inhibiting neural connections, which will have biological and physiological links (muscle memory) giving temporary release and relief from many possible ailments, and peoples revelations on psychedelics or even hitting nirvana or satori we could say is finding an ideal brain and biological state due to complete release of unhelpful brain states/connections. Of course if there is a very serious and specific underlying issue it is probably not going to miraculously change this.

Can not help but to point out, your mention of psychosis and worry of inducing this with psychedelics, is exactly what I am talking about, triggering an old mechanism/connection and my opinion is that with the right assistance, as with the cancer patients, actually using a psychedelic to bring this out and having the tools there to manage it would likely be very beneficial in the long run. I say this as someone who has also had it, and I have been re-inducing the symptoms ever since starting cannabis again 6+ months ago, all that fear, anxiety and tension was there, even trepidation before use but with the right tools I have been able to grab it by the scruff and take control of it, see it for the false anxiety, useless mechanism and memory that it is. I will even admit that I believe my methylation treatment has helped with this, but on the other hand extensive use of professional hypnosis, self hypnosis, cold shock conditioning and different brain training tricks has also clearly helped. I will never know the complete picture, but I stopped thinking about it a while ago.

I guess my view is things are simply not mechanical and independent of the self (I know that is loaded), as with what I said about people using psychedelics but just being bystanders rather than having awareness of how to control elements of what is happening and carrying the experience over into life afterwards.

Sorry if it seems off topic but I just do not think you can talk about psychedelics without some recognition of where the potential therapeutic aspects are coming from due to the massive brain and conscious/sub-conscious changes. Maybe that person using ayahuasca has relief due to a certain biological mechanism, or maybe they got relief due to the massive neurological shift, which is recognised throughout psychedelics; all my point is really and I would probably lean towards the latter.

 

[MeSci]

I think that using psychedelic drugs is very different from the Wesselyite approach. In the first, you are allowing things to happen in your brain. In the second, you are trying to force things to happen.

 

[Hip]

Sorry if it seems off topic but I just do not think you can talk about psychedelics without some recognition of where the potential therapeutic aspects are coming from due to the massive brain and conscious/sub-conscious changes.

I am not denying the mental effects and the often profoundly beneficial changes to personality and spiritual outlook that taking psychedelics can have.

In fact, personally, my main interest in reading about psychedelics has always been centered around their psychological, cultural and spiritual effects. Although I was born a decade too late, I have always been enthralled by the cultural movement of the 1960s: its exploration and expansion of consciousness through psychedelic drugs, and the effect these drugs had on the cultural and artistic expression of the time, and indeed their effect on the whole zeitgeist of the 1960s era. The cultural and social changes that were embryonic in the 1960s ended up profoundly transforming society and human culture, like for example the general shift to more liberal, tolerant and enlightened values we have witnessed.

I am not of course suggesting that psychedelics like LSD were entirely responsible for the 1960s and its cultural movements, but I think psychedelics played an important role.

In particular, I really loved the 1960s psychedelic and Eastern mysticism-fueled exploration of the outer reaches of the psyche, of consciousness and the human soul. That has always been my interest in psychedelics, for their exploratory potential (although as I mentioned, I was unfortunately generally too cowardly to take psychedelics myself).

The Greek-derived word psychedelic means "mind manifesting", and I feel so much of the ethos of the 1960s revolves around a manifestation of mind, consciousness, and soul.


By contrast, I find the inclinations and aspirations of society at present are a bit lacking in terms of its philosophical, ideological and spiritual dimensions. Society currently has become more machine-like, with less manifestation of mind and soul. At present, human activities and ambitions seem material, commercial and formulaic, like the commercial and formulaic musical dross pumped out by entertainment impresarios like Simon Cowell, or the bland commercial profit-driven films pumped out Hollywood over the last say 15 years.

At the moment it is hard to find any intuition-derived artistic expression that carries a perceptive message or ideology. It is mostly formulaic entertainment, carrying little cultural meaning, and not offering much exploration of the mind, human character, or the human condition.

In the 1960s and 70s, the activities of university students were often driven by all sorts of ideologies; nowadays students are mostly focused on personal financial reward (in part though out of necessity, since insidious factors such as high house prices make it hard to dedicate time and energy to anything else but material gain).

There has also been a shift in human character and personality away from subjectivity: in the 1960s and 70s people were characters, each person an expression their individual mind — the subject himself was the center of his universe. In recent times, there has been a shift towards objectivity of character: these days mindset is much more determined by external objective fact and external requirement; political correctness is one of these modern objective requirements imposed on human character; not suggesting this is a bad thing, but it definitely thwarts subjectivity).

Though with the current focus on materialism and factual objectivity, the world is doing well in terms of scientific and technological progress, including in medicine and the explosion of understanding of the human body and its metabolic pathways. I guess materialism is the zeitgeist of this age.



Anyway, enough of this rambling. Going back to using DMT to treat ME/CFS: I am not disputing the profound effects the psychedelics can have on the psyche; it's just my hunch that in the case of ME/CFS, this effect on mind is not the basis for DMT's temporary amelioration of ME/CFS symptoms; my hunch is that the basis is immunological.

One bit of suggestive evidence to support this hunch is the fact that these improvements in ME/CFS symptoms are temporary; since we agree that psychedelics can produce significant long-lasting shifts in the mind, if the benefits for ME/CFS came from these mental shifts, then you would expect these ME/CFS benefits would to also be long-lasting, not the temporary benefits that are reported.

The trick is to get your hunches right about whether the cause of an illness like ME/CFS that has mental symptoms is psychological or physiological. A lot hangs on this.

Wessely almost certainly got it wrong in suggesting that ME/CFS is due to psychological rather than physiological factors, with tragic and catastrophic consequences for the whole of ME/CFS research.

Although I am prepared to accept it is possible that in a very small minority of ME/CFS cases, there could be some stress-related psychological factors playing a role; and in fact in these cases, the psychological effects of DMT, not just its physiological effects, could conceivably lead to permanent improvements in ME/CFS.

 

[GhostGum]

@Hip I will try to keep this simple and short (epic fail), and much of what I have been doing is thinking out loud myself and theorising on the go, but when we are talking about the psyche, psychology and the personality I still see it as connections in the brain, functioning off different brain states which is all connected to different mechanism, neural transmitters, hormones/chemical functions; when you have a dramatic change on a psychedelic all that is shifting as well, inhibiting connections and biological functions can be released.

Of course the magical question is to what extend can psychedelics open up a whole host of different biological responses and release inhibiting ones? And medically what this could benefit by such dramatic brain change. I doubt we will have the answer to this any time soon. The irony in all this of course is the opposite can happen where a negative response, like a grain of sand finds its way in and perpetuates into a total panic and leaves its mark in the longer term as well; again I still see this as biological and connections being made. I also see all the cultural changes you talk about, as shifts in literal conditioned behaviours and physiology, changes in brain states (perception) and thinking. The objectivity you talk about is people being able to find the comfort and space away from survival mode, and lower primal states to higher thinking ones.

The bottom line is DMT might have these specific mechanisms but it also opens up a whole host of other mechanisms and responses based on complicated circumstance; it is not just psychology or personality, it is a whole host of complicated coming and going connections, responses and potential triggers. I don't doubt the positive response from it could be immunological but its just a bet either way.

I do believe ME has clear biological triggers, which can be very persistent and present in some, but on the other hand I think aspects of it can linger due to the severe nature of the condition and the devastating effect it has on the brain which becomes embedded. Most good feeling and sense of normalcy becomes deeply buried and lost in this condition, and even if found on occasion is a shadow of itself and I believe at some point needs to be rediscovered again. It has nothing to do with beliefs or mentality, it has to do with trying to re-trigger the brain and certain functions again; basic pleasures, comfort, connection. And I do not think it is easy at all, and will likely not work at all for many but as I have said before it has been my necessary end game, to have any hope of full recovery at all after making slow gains over a decade. The extent I have had to go to as well seems extreme, induction work on myself basically every day, cold exposure, meditation, stretching and physical therapies to challenge poor muscle memory and conditioning, eye training/brain spotting tricks (I have been surprised by how good this is), cannabis as a mild psychedelic. It is still a battle, but I just do not look back any more and do everything in my power, every hour of every day to harness any benefit I can. This has also meant quite distinct changes in my 'personality' or self, but again what is that? An endless array of connections and responses in my brain. Maybe under it all somewhere and beyond hindering physical limitations is my actual true self, but that is a whole other can of worms

I always thought stress was a fairly common factor in the development of ME? Not the direct cause of course but at least combined with other contributing biological or genetic factors. Stress is still a biological function anyway, and there is certainly much of it during the process of years of suffering and limitations involved; it may be a secondary factor but it is impossible to get away from.