Wednesday, 17 February 2016

Bright Idea or Dud

Katchan V, David P, Shoenfeld Y. Cannabinoids and autoimmune diseases: A systematic review. Autoimmun Rev. 2016 Feb 11. pii: S1568-9972(16)30034-9. 

Cannabinoids have shown to have a variety effects on body systems. Through CB1 and CB2 receptors, amongst other, they exert an effect by modulating neurotransmitter and cytokine release. Current research in the role of cannabinoids in the immune system shows that they possess immunosuppressive properties. They can inhibit proliferation of leucocytes, induce apoptosis of T cells and macrophages and reduce secretion of pro-inflammatory cytokines. In mice models, they are effective in reducing inflammation in arthritis, multiple sclerosis, have a positive effect on neuropathic pain and in type 1 diabetes mellitus. They are effective as treatment for fibromyalgia and have shown to have anti-fibrotic effect in scleroderma. Studies in human models are scarce and not conclusive and more research is required in this field. Cannabinoids can be therefore promising immunosuppressive and anti-fibrotic agents in the therapy of autoimmune disorders.

Sorry to say I fundementally disagree with this view. Cannabinoids are effective in reducing inflammation...maybe but they are not overtly immunosuppressive in our hands. If they were why would people with AIDS take cannabinoids which they do. 

If you increase the dose of cannabinoids until mice are zonked out .they are immunosuppressive but if they used tooth paste at high doses they would be immunosuppressive. 

However this view is sadly winnning and is being written into into history. There are more reviews on this subject than original work, If one reads the literature of  reviews, cannabinoids are immunosuppressive if you the read the papers they aren't:-(

Is this is me being arrogant...so be it

Croxford JL, Pryce G, Jackson SJ, Ledent C, Giovannoni G, Pertwee RG, Yamamura T, Baker D.Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis. J Neuroimmunol. 2008;193:120-9.
Cannabinoids may exhibit symptom control in multiple sclerosis (MS). We show here that cannabinoid receptor (CBR) agonists can also be immunosuppressive and neuroprotective in models of MS. Immunosuppression was associated with reduced: myelin-specific T cell responses; central nervous system infiltration and reduced clinical disease. This was found to be largely CB(1)R-dependent and only occurred at doses that induced significant cannabimimetic effects that would not be achieved clinically. Lower, non-immunosuppressive doses of cannabinoids however, slowed the accumulation of nerve loss and disability, despite failing to inhibit relapses. This further highlights the neuroprotective potential of cannabinoids to slow the progression of MS.

Don't believe me  what happens in humans


Katona S, Kaminski E, Sanders H, Zajicek J.Cannabinoid influence on cytokine profile in multiple sclerosis. Clin Exp Immunol. 2005;140:580-5.


Cannabinoids have been suggested as possessing immunomodulatory properties, and cannabinoid receptors are present on leucocytes. Clinically, there is some evidence that cannabinoids may be therapeutically useful in treating multiple sclerosis, which is generally believed to be an autoimmune condition. This paper reports data derived from the Cannabinoids in MS (CAMS) study, which was the largest randomized controlled trial yet conducted to evaluate the therapeutic efficacy of cannabinoids. We found no evidence for cannabinoid influence on serum levels of interferon (IFN)-gamma, interleukin (IL)-10, IL-12 or C-reactive protein as measured using enzyme-linked immunosorbent assay (ELISA), in comparison to control values. Mitogenic stimulation experiments also failed to demonstrate any significant reduction in percentage of CD3+, IFN-gamma producing cells after exposure to cannabinoids in vivo. Further work is needed to establish the functional significance of cannabinoid receptors on immune cells.


Sadly with the seeming failure of CUPID, no one is going to go near neuroprotectionagain I suspect. So again ineffective trial design sends years of science down the toilet 

5 comments:

  1. Actually I think your comments on this are not arrogant at all, you are giving your view and that's fine.

    But if you contrast this with some of your previous rants, there seems to be a huge change. Here is an example:

    http://multiple-sclerosis-research.blogspot.com/2013/08/burning-down-housetry-burning-idea.html

    The new Mouse Doctor seems more professional.

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    Replies
    1. Absolutely nothing wrong with the previous "rant" you mention.

      Delete
  2. After the failure of the CUPID trials, you guys should just leave this theory alone. Millions of dollars were squandered on a lame hypothesis, thus setting the MS cause back by decades.

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    Replies
    1. regarding the CUPID trial the results were more nuanced than you suggest. In a subset of pwMS at lower EDSS scores on entry there was a neuroprotective effect of THC treatment but the numbers of these subjects were too low to make a defintive conclusion. The CUPID trial actually performed a valuable service in showing how such trials should be performed.
      The hypothesis was anything but lame, as the abundant experimental evidence has demonstrated. It has certainly not set back the MS cause by decades and to suggest it has is pure hyperbole with no basis in fact.
      Sadly, its unlikely this sort of study with cannabinoids will ever be repeated but the search for other neuroprotectants that may have less side effects continues apace.

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    2. Millions of Dollars Squandered....yes the trial cost over £1 million but I didn't get to see any of that:-(

      It is not a lame hypothesis, it is biology my friend

      Why do you think Ocrelizumab showed some positive effect in PPMS..Because of its action is different from rituximab?....No....because they learned from the rituximab trial and loaded the trial up with people who could respond because it blocks active disease.

      The CUPID trial was loaded with peope who did not progress so if they do not progress it is hard to find something to stop it progressing.

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