4 ms·

As far as I understand the science, that clarity is in part the perceived experience of reduced inflammation in the central nervous system. Psychedelics are ant

As far as I understand the science, that clarity is in part the perceived experience of reduced inflammation in the central nervous system. Psychedelics are anti-inflammatory. (Profoundly so. The anti-inflammatory effect is orders of magnitude stronger than the effects on the mind, i.e. a dose orders of magnitude smaller than we can directly perceive has a strong anti-inflammatory effect. Which is fascinating as these substances are well known for their unusual potency at changing perception and cognition.) As one start onto the trail of established science on the phenomenon, here’s a review paper from 2015: Psychedelics and immunomodulation: novel approaches and therapeutic opportunities – https://www.frontiersin.org/articles/10.3389/fimmu.2015.00358/full https://www.frontiersin.org/articles/10.3389/fimmu.2015.0035...

radicaldreamer 4y ago
This is interesting when combined with this study which showed that ketamine therapy with rapamycin was more effective (both are very strong anti-inflammatory drugs), despite the hypothesis being that rapamycin would inhibit the effects of ketamine due to MTORC suppression. https://www.nature.com/articles/s41386-020-0644-9 https://www.nature.com/articles/s41386-020-0644-9
- mod 4y ago
  If anyone is interested in some listening on this topic, Tim Ferris interviewed a guy recently who talked a lot about rapamycin on his podcast. https://tim.blog/2022/07/27/matt-kaeberlein-life-extension/ https://tim.blog/2022/07/27/matt-kaeberlein-life-extension/ There's a transcript linked if you'd rather read/skim it.
xhrpost 4y ago
Is it possible then to perhaps experience some of the effects via other anti-inflammatory supplements that are both legal and maybe carry fewer risks?
- AnthonBerg 4y ago
  Yes :) Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor (2006) — https://doi.org/10.1073/pnas.0603119103 https://doi.org/10.1073/pnas.0603119103 It’s super interesting to just stuff the names of the cytokines into Google Scholar and see what pops out. IL-6, IL-10, and TNF-alpha are some of the ones with a lot of papers out. There’s so much more knowledge out there than I could have imagined. It’s like almost nobody reads these papers. It’s wild.
echelon_musk 4y ago
I wonder if the anti inflammatory effects explain the mechanism of why Ergotamine is prescribed for migraines and cluster headaches! [0]. [0] https://en.wikipedia.org/wiki/Ergotamine#Medical_uses https://en.wikipedia.org/wiki/Ergotamine#Medical_uses (Many years ago I remember a reddit post of a college student who used his school's lab to convert Ergotamine tablets into LSD and lay blotter. The comments were mostly of people congratulating him for his skill and then telling him to remove his post before he was discovered.)
- AnthonBerg 4y ago
  I think it might be part of it! I also think it might be due to an effect on the Sigma-1 receptor. I can’t elucidate it further, I can only recall glimpses of insight from papers I was reading a while back. I only remember one title at the moment. Warning: EXTREMELY handwavy and speculative! Chronic activation of sigma-1 receptor evokes nociceptive activation of trigeminal nucleus caudalis in rats – https://doi.org/10.1016/j.pbb.2014.06.023 https://doi.org/10.1016/j.pbb.2014.06.023 My extremely speculative guess wrapped in hunch clad in doubt is that, well, as a premise, 5-HT2A activation due to psychedelics causes downregulation of that same receptor (5-HT2A). This is known and accepted afaik. And: The 5-HT2A receptor seems to be intimately related to the Sigma-1 receptor – and the Sigma-1 receptor is inside cells – so potentially it is the downregulation of the “outside” 5-HT2A receptor that then allows the Sigma-1 receptor set to get a bit of a break? Edit: Thing is, word on the street for literally decades has been that LSD and psilocybin help with migraine and cluster headaches. Finally there has been a study on it, which confirms the effect (to a certain degree; it’s a small preliminary study): Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin (2020) – https://doi.org/10.1007/s13311-020-00962-y https://doi.org/10.1007/s13311-020-00962-y
drcongo 4y ago
That's very interesting. As someone who has to take a fair amount of ibuprofen etc. for inflammatory arthritis, is it worth just tripping out from time to time?
- AnthonBerg 4y ago
  Well, the reason I was pointed to that Psychedelics and Immunomodulation paper is that an acquaintance ingested some of these substances in a very very responsible and safe way and had a significant, sudden, and obvious remission of a chronic autoimmune condition. Completely unexpected. There was NO expectation of this as far as I know. They started trying to dig up any info on what they might have done to cause it and this paper quickly cropped up. Edit: Please note that “immunomodulation” can mean immunosuppression! Take care! There’s lots of science on this stuff. Surprising amounts. I strongly advocate for reading it. It’s surprisingly readable once some key elements of the jargon are picked up!
  - copperx 4y ago
    What was this chronic condition? MS?
    - AnthonBerg 4y ago
      Nothing that serious! Just one of the annoying ones (and visible). If it were anything as serious as MS I’d be much more sceptical, and not so flippantly confident either. The papers do outline some mechanisms that at least don’t exclude the possibility •shrug• MS is in my family so, yeah. It’s no small thing.

radicaldreamer 4y ago

This is interesting when combined with this study which showed that ketamine therapy with rapamycin was more effective (both are very strong anti-inflammatory drugs), despite the hypothesis being that rapamycin would inhibit the effects of ketamine due to MTORC suppression. https://www.nature.com/articles/s41386-020-0644-9 https://www.nature.com/articles/s41386-020-0644-9

mod 4y ago
If anyone is interested in some listening on this topic, Tim Ferris interviewed a guy recently who talked a lot about rapamycin on his podcast. https://tim.blog/2022/07/27/matt-kaeberlein-life-extension/ https://tim.blog/2022/07/27/matt-kaeberlein-life-extension/ There's a transcript linked if you'd rather read/skim it.

xhrpost 4y ago

Is it possible then to perhaps experience some of the effects via other anti-inflammatory supplements that are both legal and maybe carry fewer risks?

AnthonBerg 4y ago
Yes :) Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor (2006) — https://doi.org/10.1073/pnas.0603119103 https://doi.org/10.1073/pnas.0603119103 It’s super interesting to just stuff the names of the cytokines into Google Scholar and see what pops out. IL-6, IL-10, and TNF-alpha are some of the ones with a lot of papers out. There’s so much more knowledge out there than I could have imagined. It’s like almost nobody reads these papers. It’s wild.

echelon_musk 4y ago

I wonder if the anti inflammatory effects explain the mechanism of why Ergotamine is prescribed for migraines and cluster headaches! [0]. [0] https://en.wikipedia.org/wiki/Ergotamine#Medical_uses https://en.wikipedia.org/wiki/Ergotamine#Medical_uses (Many years ago I remember a reddit post of a college student who used his school's lab to convert Ergotamine tablets into LSD and lay blotter. The comments were mostly of people congratulating him for his skill and then telling him to remove his post before he was discovered.)

AnthonBerg 4y ago
I think it might be part of it! I also think it might be due to an effect on the Sigma-1 receptor. I can’t elucidate it further, I can only recall glimpses of insight from papers I was reading a while back. I only remember one title at the moment. Warning: EXTREMELY handwavy and speculative! Chronic activation of sigma-1 receptor evokes nociceptive activation of trigeminal nucleus caudalis in rats – https://doi.org/10.1016/j.pbb.2014.06.023 https://doi.org/10.1016/j.pbb.2014.06.023 My extremely speculative guess wrapped in hunch clad in doubt is that, well, as a premise, 5-HT2A activation due to psychedelics causes downregulation of that same receptor (5-HT2A). This is known and accepted afaik. And: The 5-HT2A receptor seems to be intimately related to the Sigma-1 receptor – and the Sigma-1 receptor is inside cells – so potentially it is the downregulation of the “outside” 5-HT2A receptor that then allows the Sigma-1 receptor set to get a bit of a break? Edit: Thing is, word on the street for literally decades has been that LSD and psilocybin help with migraine and cluster headaches. Finally there has been a study on it, which confirms the effect (to a certain degree; it’s a small preliminary study): Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin (2020) – https://doi.org/10.1007/s13311-020-00962-y https://doi.org/10.1007/s13311-020-00962-y

drcongo 4y ago

That's very interesting. As someone who has to take a fair amount of ibuprofen etc. for inflammatory arthritis, is it worth just tripping out from time to time?

AnthonBerg 4y ago
Well, the reason I was pointed to that Psychedelics and Immunomodulation paper is that an acquaintance ingested some of these substances in a very very responsible and safe way and had a significant, sudden, and obvious remission of a chronic autoimmune condition. Completely unexpected. There was NO expectation of this as far as I know. They started trying to dig up any info on what they might have done to cause it and this paper quickly cropped up. Edit: Please note that “immunomodulation” can mean immunosuppression! Take care! There’s lots of science on this stuff. Surprising amounts. I strongly advocate for reading it. It’s surprisingly readable once some key elements of the jargon are picked up!
- copperx 4y ago
  What was this chronic condition? MS?
  - AnthonBerg 4y ago
    Nothing that serious! Just one of the annoying ones (and visible). If it were anything as serious as MS I’d be much more sceptical, and not so flippantly confident either. The papers do outline some mechanisms that at least don’t exclude the possibility •shrug• MS is in my family so, yeah. It’s no small thing.