Psychedelic immunosupressant?

[RhythmSpring]

I have heard that some psychedelics temporarily lower immune system activity. Does that classify them as immunosuppressants?

I have an autoimmune condition (most likely triggered by lyme's disease): a LOT of joint/synovium inflammation aka rheumatoid arthritis, resulting from the immune system attacking the joints.

I've been noticing drastic improvements for days after using a psychedelic. Peyote cut the inflammation down to like 15 percent for a day or so, and smoking DMT relieved the symptoms almost completely for a week.

 

[Quanta]

Cool that DMT gave you a week of relief! It has been reported that the common psychedelics strognly inhibit TNF-alpha production which is a validated target for many autoimmune conditions. If I recall the paper cited below looked mainly at DOI, LSD and DMT. The term "immunosupressant" is probably too strong but perhaps they are immunomodulators through this mechanism. Not my area of specialty so others may be able to offer more detailed explanation.

Journal of Pharmacology and Experimental Therapeutics 2008, 327, 316-323.

 

[Hammilton]

I have lymes disease too, but I never had joint pain. Well, I do, but that is due to nerve damage according to the doc, though the nerve conduction study (the most painful experience in my life, I had tears in my eyes) found only mild slowing.

Mushrooms and 4-ho-DIPT are the few I've used. I felt better for a few days after using both, but I assumed that was psychic. Very interesting.

 

[indelibleface]

I've heard that the purported immune system weakening effects caused by drugs like MDMA is basically just stress related and not actually a significant immunosuppressive action, meaning that when you take MDMA, you are simply in a state of increased stress (not emotional--physical stress!) which has been shown to temporarily and slightly weaken the immune system. I assume that related drugs to MDMA probably have similar action.

Bottom line: I don't think any commonly used psychedelic drug could be considered an immunosuppressant. In fact, my belief is that the effect isn't anything to worry about--one should take the usual precautions to avoid contracting illness when tripping.

*shrug* I haven't kept up with the latest medical journals or anything, though.

 

[Hammilton]

well if they're strongly inhibiting TNF-alpha production, that suggests that it's much more than physical stress, which psychedelics don't produce that much of.

 

[Quanta]

^Precisely. These are systemic effects. The 5-HT2 receptor is not only expressed in the brain.

 

[hamhurricane]

if stress weakens the immune system, why is it that autoimmune disorders like psoriasis are exacerbated by stress?

 

[RhythmSpring]

I'm gonna bump this. I don't feel that the anti-inflammatory effects and other medicinal qualities of psychedelics get enough attention. This is big.

 

[RhythmSpring]

So here's the link to the abstract that says activation of the 5HT2A receptors strongly inhibits TNF-induced inflammation: http://jpet.aspetjournals.org/cgi/content/abstract/327/2/316?ck=nck

Now, it appears that they only used R-DOI. What are the implications for more available psychedelics such as LSD, psilocybin, mescaline, DMT, etc? Would they work as well? Why did they only use DOI? (law?) Would it work with regular DOI as opposed to the r-isomer? Would it work with other DOx?

 

[MurphyClox]

I guess they used the R-isomer because it is reportedly the more active isomer. Practically, it served as a prototype for the whole class of 5HT2A-mediated psychedelics ("hallucinogenics"; call 'em as you like).

In theory LSD, psilocybine and alike should act similarly, as long as the reported effect* is indeed caused via 5HT2A-receptors, because these compounds are thought to act via the same second messenger pathway like DOI:

*

We have now discovered that activation of 5-HT2A receptors in primary aortic smooth muscle cells provides a previously unknown and extremely potent inhibition of tumor necrosis factor (TNF)-α-mediated inflammation. 5-HT2A receptor stimulation with the agonist (R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(R)-DOI] rapidly inhibits a variety of TNF-α-mediated proinflammatory markers, including intracellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), and interleukin (IL)-6 gene expression, nitric-oxide synthase activity, and nuclear translocation of nuclear factor κB, with IC50 values of only 10 to 20 pM.

I think that psychedelic doses are out of question for the diseases mentioned before, like psoriasis or lyme disease, as the psychological effects outweigh clearly the benefit. But IF those 5HT2A-agonists are indeed as potent as suspected, I'd think that prolonged, sub-psychedelic dosing could be helpful with regard to maladies that are caused by pathologically increased TNF-α-levels.

Very low prolonged dosing with psychedelics was already mentioned by a Bluelighter in a different context, but this article sheds a completely new light on the whole discussion.

Peace! Murphy

 

[Quanta]

I would agree that since they all share the same receptor it is a reasonable assumption that they will have similiar activities on TNF-alpha expression, albeit with different potencies. The work in the article was done in vitro but 10-20 pM is outstanding potency for R-DOI and I think that chronic sub-psychedelic doses could be acheived as Murphy mentioned with some of the drugs. Interesting.

 

[grue]

>if stress weakens the immune system, why is it that autoimmune disorders like psoriasis are exacerbated by stress?

very complex topic, and a lot is still not known, although understanding & research of autoimmune conditions has picked up in the last decade.

as you say, stress - chronic, harmful stress that for (multiple) whatever reasons is poorly adapted to - raises inflammation but also leads to higher rates of illness. this chronic stress as opposed to normal/controlled/healthy stresses, such as the correct amount of exercise.

unfortunately in autoimmune conditions it's not necessarily a question of "too much immune system activity" so much as an imbalance or "too much in certain systems" (e.g. tumor necrosis factor alpha, or as another example some research has talked about a ratio between IL-1 and IL-2) and maybe "not enough in others".

One mechanism I can throw out: the taxing of endogenous protective systems, such as glutathione, associated with chronic elevated stress markers. This definitely happens, and not only is low glutathione heavily associated with any autoimmune condition, but also the agent is a general detoxifier, and for example protects the liver, and if the liver becomes worse at removing toxins then plenty of problems will worsen ... etc.

endless loops within loops! almost as bad as neurochemistry when you look a little closely