Caffeine Is A Serotonin Receptor Antagonist

haidut

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I was thinking about this recently in light of the strong evidence that caffeine is effective in preventing and even reversing liver fibrosis.
It's Official - Caffeine Prevents And Slow Liver Fibrosis / Cirrhosis, Cancers

I have posted a number of studies showing that serotonin and especially activation of the 5-HT2B receptor is crucial for the development of fibrosis of organs like liver, heart and lungs. So, if caffeine is so effective at preventing and even treating said fibrosis then it follows that caffeine would be an antagonist of the 5-HT2B receptor. And indeed, it looks like caffeine does behave as 5-HT2 antagonist according to this study. Human dose equivalent to achieve these effects would be about 7mg/kg daily for 7 days. What is also of note is that caffeine seems to be a stronger serotonin antagonist than adenosine antagonist, and adenosine antagonism was thought to be caffeine's primary role.


Chronic Caffeine Alters the Density of Adenosine, Adrenergic, Cholinergic, GABA, and Serotonin Receptors and Calcium Channels in Mouse Brain

"...
1. Chronic ingestion of caffeine by male NIH strain mice alters the density of a variety of central receptors.

2. The density of cortical A1 adenosine receptors is increased by 20%, while the density of striatal A2Aadenosine receptors is unaltered.

3. The densities of cortical β1 and cerebellar β2 adrenergic receptors are reduced by ca. 25%, while the densities of cortical α1 and α2 adrenergic receptors are not significantly altered. Densities of striatal D1 and D2 dopaminergic receptors are unaltered. The densities of cortical 5 HT1 and 5 HT2 serotonergic receptors are increased by 26–30%. Densities of cortical muscarinic and nicotinic receptors are increased by 40–50%. The density of cortical benzodiazepine-binding sites associated with GABAA receptors is increased by 65%, and the affinity appears slightly decreased. The density of cortical MK-801 sites associated with NMDA-glutaminergic receptors appear unaltered.

4. The density of cortical nitrendipine-binding sites associated with calcium channels is increased by 18%.

5. The results indicate that chronic ingestion of caffeine equivalent to about 100 mg/kg/day in mice causes a wide range of biochemical alterations in the central nervous system."

This is the table summarizing the effects of caffeine on various receptors and ion channels.
Chronic Caffeine Alters the Density of Adenosine, Adrenergic, Cholinergic, GABA, and Serotonin Receptors and Calcium Channels in Mouse Brain
Increase in "receptor" density implies caffeine is an antagonist at that "receptor". Hence, the increase in densities of adenosine, serotonin, GABA, nicotine, etc "receptors".
 
Last edited:

ddjd

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I was thinking about this recently in light of the strong evidence that caffeine is effective in preventing and even reversing liver fibrosis.
It's Official - Caffeine Prevents And Slow Liver Fibrosis / Cirrhosis, Cancers

I have posted a number of studies showing that serotonin and especially activation of the 5-HT2B receptor is crucial for the development of fibrosis of organs like liver, heart and lungs. So, if caffeine is so effective at preventing and even treating said fibrosis then it follows that caffeine would be an antagonist of the 5-HT2B receptor. And indeed, it looks like caffeine does behave as 5-HT2 antagonist according to this study. Human dose equivalent to achieve these effects would be about 7mg/kg daily for 7 days. What is also of note is that caffeine seems to be a stronger serotonin antagonist than adenosine antagonist, and adenosine antagonism was thought to be caffeine's primary role.


Chronic Caffeine Alters the Density of Adenosine, Adrenergic, Cholinergic, GABA, and Serotonin Receptors and Calcium Channels in Mouse Brain

"...
1. Chronic ingestion of caffeine by male NIH strain mice alters the density of a variety of central receptors.

2. The density of cortical A1 adenosine receptors is increased by 20%, while the density of striatal A2Aadenosine receptors is unaltered.

3. The densities of cortical β1 and cerebellar β2 adrenergic receptors are reduced by ca. 25%, while the densities of cortical α1 and α2 adrenergic receptors are not significantly altered. Densities of striatal D1 and D2 dopaminergic receptors are unaltered. The densities of cortical 5 HT1 and 5 HT2 serotonergic receptors are increased by 26–30%. Densities of cortical muscarinic and nicotinic receptors are increased by 40–50%. The density of cortical benzodiazepine-binding sites associated with GABAA receptors is increased by 65%, and the affinity appears slightly decreased. The density of cortical MK-801 sites associated with NMDA-glutaminergic receptors appear unaltered.

4. The density of cortical nitrendipine-binding sites associated with calcium channels is increased by 18%.

5. The results indicate that chronic ingestion of caffeine equivalent to about 100 mg/kg/day in mice causes a wide range of biochemical alterations in the central nervous system."

This is the table summarizing the effects of caffeine on various receptors and ion channels.
Chronic Caffeine Alters the Density of Adenosine, Adrenergic, Cholinergic, GABA, and Serotonin Receptors and Calcium Channels in Mouse Brain
Increase in "receptor" density implies caffeine is an antagonist at that "receptor". Hence, the increase in densities of adenosine, serotonin, GABA, nicotine, etc "receptors".
i notice a strong serotonin increase when i consume coffee/ caffeine. the one thing i can compare it to is the same effect when i take methylene blue. MB is known for raising serotonin in many people also.
 

haidut

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i notice a strong serotonin increase when i consume coffee/ caffeine. the one thing i can compare it to is the same effect when i take methylene blue. MB is known for raising serotonin in many people also.

How do you know it is a serotonin increase? Caffeine is known to increase dopamine release more than anything else. I have not seen anything yet showing caffeine is serotonergic.
 

Vinero

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i notice a strong serotonin increase when i consume coffee/ caffeine. the one thing i can compare it to is the same effect when i take methylene blue. MB is known for raising serotonin in many people also.
Explain why you think it increases serotonin? Any uncomfortable bowel reactions after drinking coffee? If I feel tired or bored drinking some coffee gets me going again which points to a dopaminergic effect.
 

ddjd

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Explain why you think it increases serotonin? Any uncomfortable bowel reactions after drinking coffee? If I feel tired or bored drinking some coffee gets me going again which points to a dopaminergic effect.
Yes the straight to the toilet effect... I'm pretty sure that happens for most people no?
 

Frankdee20

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Yes the straight to the toilet effect... I'm pretty sure that happens for most people no?

It doesn’t effect me like that, even at 5-6 cups. I believe the oils in coffee are responsible. I doubt isolated caffeine would do this.
 

Frankdee20

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i notice a strong serotonin increase when i consume coffee/ caffeine. the one thing i can compare it to is the same effect when i take methylene blue. MB is known for raising serotonin in many people also.

Damn, it increases 5ht2 densities ? Not good, increases acetylcholine demsity too.
 

X3CyO

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Yes the straight to the toilet effect... I'm pretty sure that happens for most people no?

Cascara and emodin are digestive stimulants that are also serotonin antagonists.
I think the effect you're talking about is relaxation of the digestive system versus an agonist which would be more along the lines of causing brain fog, and possible stomach pain coupled with diarrhea and/or constipation within the intestine itself.
 

X3CyO

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Damn, it increases 5ht2 densities ? Not good, increases acetylcholine demsity too.

That's the natural response if the hormone isn't binding to the receptor.

Ironically that's how I found peat; tianeptine, and trying to increase my serotonin receptor density (Because I thought it would increase serotonins effect which I thought at the time was a good thing.) Technically it worked. Albeit for the wrong reasons, which I now know are the right reasons. Funny how thinking backwards can still be in a way thinking forwards.
 

Frankdee20

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That's the natural response if the hormone isn't binding to the receptor.

Ironically that's how I found peat; tianeptine, and trying to increase my serotonin receptor density (Because I thought it would increase serotonins effect which I thought at the time was a good thing.) Technically it worked. Albeit for the wrong reasons, which I now know are the right reasons. Funny how thinking backwards can still be in a way thinking forwards.

Life’s a paradox lol
 

Frankdee20

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How do you know it is a serotonin increase? Caffeine is known to increase dopamine release more than anything else. I have not seen anything yet showing caffeine is serotonergic.

I don’t know about Serotonin, coffee primarily blocks Adenosine from its receptor. This can indirectly help Dopamine release. It also blocks the GABA receptor.
 

ddjd

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Cascara and emodin are digestive stimulants that are also serotonin antagonists.
I think the effect you're talking about is relaxation of the digestive system versus an agonist which would be more along the lines of causing brain fog, and possible stomach pain coupled with diarrhea and/or constipation within the intestine itself.
I think it's something related to nitric oxide. Everything that reduces Nitric oxide seems to make me need the toilet! Methylene blue, caffeine, Cascara all lower NO
 

rei

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How about nicotine? Tobacco and coffee are commonly known as the dump initiators in this part of the world.
 

Frankdee20

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How about nicotine? Tobacco and coffee are commonly known as the dump initiators in this part of the world.

Nicotine stimulates gastric secretions, and norepinephrine.
 

ddjd

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How do you know it is a serotonin increase? Caffeine is known to increase dopamine release more than anything else. I have not seen anything yet showing caffeine is serotonergic.
could an increase in cortisol from coffee raise serotonin then?
 
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