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Psychedelics have a POTENT anti-inflammatory effects against TNF-alpha

By Adas, May 29, 2016 | Updated: May 29, 2016 | | |
  1. Adas
    Tumor necrosis factor alpha (TNF-α) plays a key role in inflammation, and its production and signaling contribute to many inflammatory related diseases. Recently, we discovered that selective activation of serotonin 5-HT2A receptors with the agonist (R)-DOI produces a super-potent blockade of proinflammatory markers in primary rat aortic smooth muscle cells. Here, we demonstrate that systemic administration of (R)-DOI can block the systemic effects of TNF-α in whole animal, with potent anti-inflammatory effects in the aortic arch and small intestine. This includes blockade of TNF-α-induced expression of pro-inflammatory cell adhesion (Icam-1, Vcam-1), cytokine (Il-6, IL-1b), and chemokine (Mcp-1, Cx3cl1) genes, and expression of VCAM-1 protein in the intestine. Further, systemic (R)-DOI also prevents the TNF-α-induced increase of circulating IL-6. Importantly, utilizing receptor selective antagonists, we have demonstrated that the mechanism underlying the systemic anti-inflammatory effects of (R)-DOI is activation of serotonin 5-HT2A receptors. Our results highlight a powerful new role for the serotonin 5-HT2A receptor in inflammatory processes, and indicate that agonism of serotonin receptors may represent an effective and novel approach to develop powerful small molecule therapeutics for inflammatory diseases and conditions such as atherosclerosis and inflammatory bowel disease.

    This is actually quite an awesome finding, I didn't know about it nor did I have any idea that such effect might be taking place. This might partly explain why some people believe that psychedelics like Ayahuasca also have physical healing properties. Cannabis is well-known for its anti-inflammatory properties, but it works through very different receptors. I think that this finding could have great implications. Will psychedelics become the new class of anti-inflammatory drugs? Do you or someone you know have any experience with such effects?



  1. best
    Maybe a 5-HT2A Agonist that is also a 5-HT1B &/or 5-HT1D Agonist (like Triptans) would be a dual action Migraine treatment.

    I feel like they would only give a 5-HT2A Agonist to patients that are in a hospital though, unless they figured a way to make it not too hallucinogenic at higher dosages.
  2. Adas
    If you're talking about cluster headaches, there is already 2-Br-LSD, a non-psychedelic analog that works against clusters just as well. So if they really wanted, we would already have an effective treatment. The problem is, big pharma makes a ton of money by selling ineffective drugs.

    To get back on topic, is there any link between migraines and TNF-alpha?
  3. LazyMonkey
    From "The Immune System and Headache", by Robbins and Maides

    The Rozen study (2007) is "Elevation of CSF tumor necrosis factor alpha levels in new daily persistent headache and treatment refractory chronic migraine".

    It seem there is a link but the role of TNF-a is just presumed.
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