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Endocannabinoid system role in ME/CFS

Discussion in 'General ME/CFS Discussion' started by Owl42, Dec 19, 2016.

  1. Owl42

    Owl42 Psychedelic bird

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    Hi again, it's been a while since I've been around here. Not a good year, a lot of new conditions affected me after I started a therapy with who I now know were a pretty irresponsible medical practitioner.

    So now I've dropped these therapies, I'm back into my research of the things that have helped me for the last years (and after starting these new treatments seemed to stop helping :grumpy:)

    I was pretty excited to see cannabinoids show up in the Naviaux paper and I've been looking into it, but the paper itself doesn't give much info, at least not that I know how to interprete. Any of you can provide some more about it?

    I'm pretty bad at this momment, really dense brainfog and not much mental energy, so this is intended to be a colaborative investigation thread in hope we can figure out what the true role of endocannabonoids is in ME/CFS.

    In case you don't know about endocannabinoids or endocannabinoid system here you've got some explanatory resources about it:

    https://www.leafly.com/news/science-tech/what-is-the-endocannabinoid-system

    https://en.wikipedia.org/wiki/Endocannabinoid_system

    There are plenty of exciting articles about endocannabinoids' role and pharmacological potential in pubmed, I'm sure a lot of the more ilustrated PR users will be able to find the most related to the ME/CFS pathology.

    This is an unexplored therapeutic path that we cannot leave behind, lots of Fibromyalgia sufferers already bennefit from the endocannabinoid regulation through cannabis, maybe cannabis is not the solution for ME/CFS but there are other ways to interact with the endocannabinoid system.
     
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  2. IThinkImTurningJapanese

    IThinkImTurningJapanese Senior Member

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  3. Owl42

    Owl42 Psychedelic bird

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    This is a pretty interesting research, I didn't know CB1 agonist had an effect on mast cells increasing cAMP.

    cAMP is also related to epinephrine.

    Really revealing, I have to investigate this further.

    Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430692/#R146


    Anti-inflammatory potential of CB1-mediated cAMP elevation in mast cells
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1138953/
     
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  4. Owl42

    Owl42 Psychedelic bird

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    I'm already experimenting with endocannabinoids and endocannabinoid system related enzymes with great results.

    I'll try to update you with my progress.

    My concern now is getting to the bottom of the 2-AG role, I suspect it is either too increased or decreased in CFS/ME, or at least in my body. I'm composing some graphics that help me think this all over and maybe it could help you, I will upload a picture of them once they are finished.

    The data I'm using right now (increasing with my investigation)that relates endocannabinoids and CFS/ME is this:

    Anandamide (AEA):
    -Inhibits mast cell activation by action in CB1 repector through cAMP
    -Absorbs NO, PGE2, Arachidonic Acid and PEA (In presence of hidroxocobalamine the absortion is reduced)

    2-AG:
    -Augments free intracelluar calcium
    -Is hydrolized by MAGL at an 85% in the brain, MALG hydrolizes Glutation too without distinction.
    -Is related to Omega-6 content.


    This is the next thing I'll read:

    The Endocannabinoid System in Energy Homeostasis and the Etiopathology of Metabolic Disorders


    http://www.sciencedirect.com/science/article/pii/S1550413113001034
     
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  5. Owl42

    Owl42 Psychedelic bird

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    New updates and theorisation.

    If my theory of 2-AG being the principal target (at least the most difficult to reach) is correct, I suspect increasing it would be the best way to see if I'm in a good direction.

    There's not many ways of doing so.

    One would be using the analogue CBD cannabinoid in order not just to reproduce its effects and see if it helps but also to let the endogenous levels raise by cummulation.

    Another would be increasing the substances used in the synthezisation of 2-AG, there are two pathways for this, and I'll better quote wikipedia for a better explanation that I'd give:

    And the last one and the most interesting in my opinion would be inhibiting the enzymes responsible of its degradation, and I'm specially interested in the ones working in the brain, after all I think we can say now there's a neurological inflammatory factor in CFS/ME without making a fool of ourselves.

    So I'm concerned about MAGL inhibition, and I've seen I'm not the only one. It seems promising for a bunch of conditions related to ours but there aren't many good inhibitors for it out there.

    http://science.sciencemag.org/content/334/6057/809

    Also, if you've seen the last studies on pyruvate dehydrogenase you could be interested in this. PPAR-y seems to be activated and it is related to the endocannabinoid system.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2220031/
     
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  6. erin

    erin Senior Member

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    Thanks for this. I searched the products. I have severe proctitis and LS, my GP is running a test for IBD too. I decided to try the suppositories, ordered them and used last night for the first time. The result was good. No pain, good quality sleep, feel really relieved. I hope the effect will last.
     
  7. perrier

    perrier Senior Member

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    Hi Erin

    Where did you obtain the suppositories. I tried the link and it says the page doesn't exist.

    Where can one obtain suppositories that are not psychoactive.
    Thanks
     
    erin likes this.
  8. IThinkImTurningJapanese

    IThinkImTurningJapanese Senior Member

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    I posted the link in Spanish, sorry it's quit working.

    All of their products are non-psychoactive, here is a working link in English.

    https://www.endoca.com/en/products
     
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  9. IThinkImTurningJapanese

    IThinkImTurningJapanese Senior Member

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    You are quite welcome.

    I'm glad this is helping you, I have been using considerably smaller doses of CBD oil for about two years now and haven't experienced any reduction in benefit.

    I hope this continues to work well for you.:)
     
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  10. erin

    erin Senior Member

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    @perrier, ThinkImTurningJapanese given the link above, good luck and let us know if you benefit from it.
     
  11. perrier

    perrier Senior Member

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    So which exact
    Which is the suppository product? They have capsules but not suppositories. Please let me know which exact product you purchased. Thanks both of you.
     
  12. perrier

    perrier Senior Member

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    Ok I found suppositories. But please indicate if this is the product,or if capsules were used.
     
  13. erin

    erin Senior Member

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  14. carer51

    carer51 carer/partner of moderate/severe sufferer

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    I did initially buy a bottle of the Endoca (oral) capsules but realised on receipt that the listed 300mg dosage actually related to the dosage of the entire bottle, rather than an individual capsule.

    We currently buy 100mg capsules from cbd brothers. James takes 2 a day as this is what we can afford, we also have a bottle of the 250mg capsules as an extra for bad days. It seems to help somewhat with the pain, but we are currently tapering off his gabapentin, so that will be when we are in a better position to know if the CBD oil is helping. He is very sensitive to pain medication, gets nauseous very easily and this is an issue with the gabapentin along with other side effects.

    We also tried the sublingual oil but James found that quite unpleasant and I think it was difficult to modulate the dosage/amount and work out a budget etc.
     
    Last edited: Feb 1, 2017
  15. erin

    erin Senior Member

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    @carer51, if he is sensitive and nauseous maybe best to use the suppository as well. Apparently they absorbed much quicker than orally. They are also absorbed better in the intestines, CBD reaches to the brain first and then the liver. No nausea, no unpleasant taste. Oral use the CBD passes the stomach and then liver where its filtered and the effect is reduced and it is a longer process.
     
  16. carer51

    carer51 carer/partner of moderate/severe sufferer

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    Thank you Erin, I will look into that!
     
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  17. carer51

    carer51 carer/partner of moderate/severe sufferer

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    I am now actually considering making suppositories by emptying the capsules we have and using coconut oil and a mould...ha....
     
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  18. erin

    erin Senior Member

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    That's a great idea, why pay for the suppositories while you have the ingredients? CBD products are so expensive unfortunately.
     
  19. carer51

    carer51 carer/partner of moderate/severe sufferer

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    A nice little DIY craft project :p
     
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  20. carer51

    carer51 carer/partner of moderate/severe sufferer

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    Craft project is go, made a suppository, james tried it before bed last night so he'd be lying down. And didn't take one of the capsules he normally takes orally in the day.

    I came back from a meeting an hour ago and asked how he was and he said 'not too bad' in a relatively upbeat tone. Can't remember the last time I heard him say that! And we went out on Saturday night.

    Could be an anomaly, will see what happens. I read that CBD is actually a bit activating so I was a bit concerned it might interfere with his sleep rather than help but it seems he got a better night's sleep than me last night.
     
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