Ranked Serotonin Antagonists And Anti-Inflammatories

Tenglish

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I would like help ranking the various metabolism friendly substances by anti-seratonin activity and by anti-inflammatory activity, and any help connecting the two mechanistically would also be appreciated. I have been following the work on Psychadelics for depression and reduced inflammation and while promising, it is missing the metabolic perspective of this community as well as the more readily available substances such as lisuride, cyprheptadine etc. Curiously, DOI, a little know psychedelic, has been shown to be hugely anti-inflammatory which might also be related to its seratonin receptor half life being quite long. All of these are also related to immuno-modulation and potential suppression in which we might also include substances like vitamin-d, vitamin-k, melatonin (another tryptamine) etc. Relatedly, I would like to know if higher metabolisms across populations induce more melatonin - thus more endogenous DMT synthesis during REM sleep. This seems the case across the life span...REM sleep decreases with age (as does melatonin). Here are some studies in this genre:
Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities
Psychedelics As A New Anti-Inflammatory Therapeutic For Atherosclerosis
Genetic and biochemical changes of the serotonergic system in migraine pathobiology
Melatonin has also been found to be altered in other central nervous system (CNS) disorders, such as stroke, obsessive-compulsive disorder, mood and schizophrenia [114, 115]. Melatonin has regulatory effects on gastrointestinal tract motility and sensation, has sleep promoting effects and mood regulation and anti-stress effects [116]. Consequently, it is not surprising that melatonin supplements have shown potential in diminishing pain intensity in migraine co-morbid conditions such as fibromyalgia and irritable bowel syndrome [116, 117].
Melatonin and N-acetylserotonin inhibit leukocyte rolling and adhesion to rat microcirculation. - PubMed - NCBI
REM Sleep Percentage in Children with Autism Compared to Children with Developmental Delay and Typical Development
Selective modulation of autophagy, innate immunity and adaptive immunity by small molecules
Increased IL-1β signaling also underlies a group of autoinflammatory syndromes, many of which respond clinically to IL-1β blockade.(37, 38) These include monogenic conditions such as cryopyrin associated periodic syndrome, as well as genetically complex diseases such as systemic juvenile idiopathic rheumatoid arthritis and Still's disease.
Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z
Individuals suffering from a substance use disorder, are consequently affected by Reward Deficiency Syndrome (RDS), which is characterized by a hypodopaminergic state or trait. A hypodopaminergic state may result from the toxic effects of binge drug intake, or chronic uncontrollable stress and predisposes individuals to self-medicate to elevate or stimulate dopamine release (sup patent: https://www.google.com/patents/US20130195827)
https://www.ncbi.nlm.nih.gov/pubmed/26132915
 
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Tenglish

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Just found this: https with serotonin receptor binding profiles://books.google.at/books?id=7v0kBQAAQBAJ&pg=PA22&lpg=PA22&dq=metergoline+binding+profile&source=bl&ots=_WQMr-se8M&sig=ay9Wj2-IUq7miLBlbrkSTYcDUcU&hl=de&sa=X&ved=0ahUKEwjt8Zf20vDOAhVISZoKHVfgA98Q6AEIWDAG#v=onepage&q=metergoline%20binding%20profile&f=false
 
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Tenglish

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if you give me a list, I'll rank them
By receptor activation strength and anti-inflammatory activity? A first good list would be everything at Idea Labs then we can go from there to include common RP friendly supplements.
 

meatbag

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By receptor activation strength and anti-inflammatory activity? A first good list would be everything at Idea Labs then we can go from there to include common RP friendly supplements.
What are you gonna do with this list? :emoji_thinking:
 
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Tenglish

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I'm thinking we would all just see it and use it to choose our approached to better health. Personally, I'm working in a place where I might be able to move public health expenses from expensive pharma immune modulators to some RP friendly options....in due time. I am very interested in DOI, but it would be nice to see a non-psychadelic alternative. I suppose rapamycin or metformin might be in this category, but they do not seem very RP friendly. Maybe metergoline is of similar strength? I'd also like to see if the inflammation dampening is linked to the serotonin receptor activation and which specific ones. Ideally, people could use non-scheduled options to get many of the same benefits of psychadelics etc. without the legal risk. In my case I have cyproheptadine, aspirin, MB, and various other substances without a good idea of the relative strengths (of course, dose will also play a critical role), but the doses are often standardized.
 

meatbag

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I'm thinking we would all just see it and use it to choose our approached to better health. Personally, I'm working in a place where I might be able to move public health expenses from expensive pharma immune modulators to some RP friendly options....in due time. I am very interested in DOI, but it would be nice to see a non-psychadelic alternative. I suppose rapamycin or metformin might be in this category, but they do not seem very RP friendly. Maybe metergoline is of similar strength? I'd also like to see if the inflammation dampening is linked to the serotonin receptor activation and which specific ones. Ideally, people could use non-scheduled options to get many of the same benefits of psychadelics etc. without the legal risk. In my case I have cyproheptadine, aspirin, MB, and various other substances without a good idea of the relative strengths (of course, dose will also play a critical role), but the doses are often standardized.

if you google a compound and include something like '5ht affinity' or serotonin antagonist you should be able to find the affinities for that receptor, the lower the value the more it binds to that receptor. Another good way is to search the compound and include 'serotonin syndrome' , usually if its anti-serotonin there will be something about it improving that condition.

Have you read any of the articles on Peat's site? Such as these;
Serotonin: Effects in disease, aging and inflammation

Regeneration and degeneration:Types of inflammation change with aging

Serotonin, depression, and aggression: The problem of brain energy

Tryptophan, serotonin, and aging

There's also a ridiculous amount of info on the forum about those two topics, serotonin and inflammation;
serotonin | Ray Peat Forum

inflammation | Ray Peat Forum
https://raypeatforum.com/community/tags/inflammation/
 
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Tenglish

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Thanks I'll revisit those... I've tried to read everything on his site, but not memorize. So again thanks for the reference to the most relevant writings...I'll work on the affinity table on my own spare time. The specifics I can see from Ray are: "Several cytokines (proteins that regulate cell functions) appear at much higher concentrations in adult tissues than in fetal tissues (PDGF A, three forms of TGF, IGF 1, and bFGF; Wagner, et al., 2007)" & "In adults, prostaglandins are known to be involved in many of the harmful effects of inflammation." & " The embryo or fetus is enclosed in a germ-free environment, so it doesn’t need an “immune system” in the ordinary sense, but it does contain phagocytes". I take the seratonin and estrogen as stress response hormones as very accurate. Ok, so I am all for Niacinamide, sugar, CO2, Thyroid, progesterone, etc. etc. but I'm curious to link more a bit mechanistically. So I found this: (Serotonin 5-HT2A Receptor Activation Blocks TNF-α Mediated Inflammation In Vivo) which is talking about TNF-a blockage by DOI (a cousin of LSD) based on "selective activation of serotonin 5-HT2A", so that receptor activation is where I'd want to map out optimal inflammatory substances first I suppose.
Here is one colorful legal TNF-a inhibitor (Curcumin Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers)
 

TreasureVibe

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What does this mean/come down to?

Increased IL-1β signaling also underlies a group of autoinflammatory syndromes, many of which respond clinically to IL-1β blockade.(37, 38) These include monogenic conditions such as cryopyrin associated periodic syndrome, as well as genetically complex diseases such as systemic juvenile idiopathic rheumatoid arthritis and Still's disease.

I have Still's disease.
 

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