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Ketamine as an anti-inflammatory

RhythmSpring

RhythmSpring

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There are several studies out there that point to Ketamine's effectiveness in attenuating TNF-mediated inflammation, which is what happens in rheumatoid arthritis, which I have, which is why I'm interested in this, which is a run on sentence which uses "which" way too many times.

http://www.ncbi.nlm.nih.gov/pubmed/15228231

http://www.ncbi.nlm.nih.gov/pubmed/20006700

http://www.annclinlabsci.org/cgi/content/full/32/3/292

http://www.tumorres.com/wilms-tumor/34221.htm

http://www.ncbi.nlm.nih.gov/pubmed/18191973

http://www.google.com/url?sa=t&rct=...pL3yAw&usg=AFQjCNGh7i729lpKk6SE7ZtHkbJh08svpA

I did a bump last Wednesday night, and for the following 3-4 days I experienced an abatement of joint inflammation (along with a superb afterglow). I did a bump or two last night too, but didn't receive as much benefit. I'm trying to figure out the best way to use the ketamine for inflammation--frequent low doses? infrequent high doses?

There is a ketamine treatment for people with with the rare autoimmune nerve condition reflex sympathetic dystrophy, where the doctors essentially put them in a K-hole for about 10 days, and it has something around a 70% success rate for putting people in remission. Perhaps a similar attack dose is necessary for treating RA?

I'm convinced I am on to something here. Help me out?
 
Well there are NMDA channels everywhere in the body, but inhibiting them and activating mTOR scares the living piss out of me due to its possible effects on longevity. It has a complex effect on the cell cycle, and a reduction of inflammation via a Ca2+ dependent mechanism but the whole immune angle is new to me.

Good find though man, I'll add it to the stack I've got for further reading.
 
Don't ampakines also activate mTOR? This would mean racetams would decrease life span?
 
Amu said:
Don't ampakines also activate mTOR? This would mean racetams would decrease life span?
Click to expand...

Dude, I don't even know anymore. Might be a case of how much, where, and when more than a simple on/off switch. I can see mTOR inhibition being bad for say... stomach lining but even then its a complex picture.
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009979 inhibition good for Alzheimer's?
http://www.nature.com/nrm/journal/v12/n1/abs/nrm3025.html mTOR is pretty much a signal for how nutrient rich and environment is, with downstream effects on cell signalling. Maybe in non-dividing cells its good?

Its starting to look like mTOR is just being referred to in place of the giant ass mTOR complex, which might explain its difficult as fuck to interpret actions.
But damn, that is a complex system...
 
Epsilon Alpha said:
Dude, I don't even know anymore. Might be a case of how much, where, and when more than a simple on/off switch. I can see mTOR inhibition being bad for say... stomach lining but even then its a complex picture.
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009979 inhibition good for Alzheimer's?
http://www.nature.com/nrm/journal/v12/n1/abs/nrm3025.html mTOR is pretty much a signal for how nutrient rich and environment is, with downstream effects on cell signalling. Maybe in non-dividing cells its good?

Its starting to look like mTOR is just being referred to in place of the giant ass mTOR complex, which might explain its difficult as fuck to interpret actions.
But damn, that is a complex system...
Click to expand...

I have a PhD in Immunology and still have trouble with mTOR. It's a master switch for everything in the cell, from metabolism to division to inflammatory responses to death. Modulating mTOR pharmacologically has different effects in almost every cell type I've worked with. I wouldn't be too worried about the ketamine studies though.

mTOR inhibitors and mTOR activators are approved for human use. Rapamycin aka Sirolimus is a potent inhibitor of mTOR and used for organ rejection as it is an immunosupressant. The side effects/toxicity are not much different from those of other immunosuppressants. Many innocent compounds (caffeine and curcumin to name a couple) have been found to inhibit mTOR in cells, but don't do a thing in the human body.

Interestingly, mTOR activators are used in combination with toxic chemotherapy drugs, as they have been shown to prevent the development of certain toxic pathologies. There is one (can't remember the name off hand) that prevents the cardiac toxicity caused by the cancer drug doxorubicin.
 
^ So, Mr. Ph. D in Immunology, do you think ketamine has potential for dealing with chronic inflammation? I know other psychedelics work for that, albeit temporarily...
 
I was put on meloxicam for a long time, 15mg
Then i started getting nasty cramps, and pooing up liquidy black watery sludge. So i stopped taking them.

Ive been doing up to 300mg ketamine weekly, and i am always suffering with my joint pain. So it gets a no from me, however cannabis seems to help it a hell of a lot. In fact i would say the pain goes away as much as 95% id say, sometimes completely gone.
 
^ ^ Wow, thanks. Maybe I should try some weed. I avoid it because it makes me anxious, self-conscious, panic-attacky. But if it helps with my RA maybe I could get over that.

Is your arthritis auto-immune, or purely osteo? Does the cannabis just kill the pain, or does it decrease any inflammation as well?
 
RhythmSpring said:
^ So, Mr. Ph. D in Immunology, do you think ketamine has potential for dealing with chronic inflammation? I know other psychedelics work for that, albeit temporarily...
Click to expand...

It's almost impossible to say without good quality randomized controlled trials in humans. That one study you linked looking at TNF levels in bloods of patients post-surgery who received ketamine as an anaesthetic isn't really convincing. This is because pain itself causes release of inflammatory cytokines, so the more analgesics (which ketamine is) that you add into the mix, the less pain, and therefore the less inflammatory cytokines.

If I had to speculate based on the results from different cell models in the other studies you linked, I would say that ketamine wouldn't be successful at limiting active inflammation in RA or other autoimmune diseases. The reason I say this is because active joint inflammation in RA is mediated by the adaptive immune system (antigen dependent) and the studies have been using innate immune cells (antigen independent). Going back to the mTOR story, mTOR inhibitors shut down the adaptive system, but you report ketamine to be an mTOR activator.

As a further speculation I would say it might be useful in sustaining remission between RA flareups because initial flareups are triggered by cytokine release from innate immune cells.

Sorry to put a damper on this for you, I know how crappy the side effects are from long term use of corticosteroids and biologics.
 
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