Caffeine Cessation And Receptor Changes

[MB50]

Although I love coffee/caffeine, I notice that I am much more capable of handling stress without daily consumption above 50mg. I don't think the changes in baseline cortisol are necessarily bad once tolerance is developed with chronic caffeine consumption, but what does bother me is studies showing amplified ACTH and cortisol responses to mental stress with caffeine. Of course, the problem would be the underlying stress, but this is almost unavoidable in real life and I am more focused on becoming more capable of handling this stress. Therefore, I am thinking of keeping caffeine consumption under 40mg/day for a while. I am wondering if anybody has any insight into how long receptor changes will take place following caffeine cessation?

I have seen the general consensus is most withdrawal symptoms are over after a maximum of 9 days, but because anecdotal reports suggest that people experience changes further than 9 days, it seems like there is still some change in adenosine, dopamine, serotonin, and acetylcholine receptors. I have seen no direct evidence saying this is the case, but does anybody have any idea how long receptor changes would occur for following such a change in caffeine consumption? Would it be at most weeks, or months?

Thanks for your input as always.

 

[dbh25]

Thanks for your post. @40mg/day, are you having 1 cup of green tea?
If I drink the equivalent caffeine in tea as coffee, I seem to have less of the bad effects.
I just went a week w/o coffee, but had a cup this morning. 8 oz. drip has 150mg caffeine, from what I found. I think I'll restart the no coffee experiment for longer. I definitely felt less stressed after not having it every day.

 

[MB50]

Yea I'm going to stick to a cup of white tea. I think caffeine can be good, but so much of it's psychological effects are dependent on many different variables. Iv seen evidence showing ADORA polymorphisms can affect individual tolerance and Im sure baseline stress or acute stressors can affect a persons response. For me I know I am heterozygous for the ADORA polymorphism and I also don't really feel the need for a lot of external stimulation. For other people, this could be completely different. Iv also supplemented with molybdenum and manganese prior to caffeine intake, which seems to help. But really the biggest thing Iv noticed is that I don't do well with caffeine when I have a mentally stressful event coming up.

 

[dbh25]

What are ADORA polymorphisms? Is this the slow or fast metabolizer gene associated with caffeine? I assume I am a slow metabolizer. I know some people feel no effects from coffee, I can't imagine. I definitely feel less stress tolerance and less patience overall.

 

[MB50]

What are ADORA polymorphisms? Is this the slow or fast metabolizer gene associated with caffeine? I assume I am a slow metabolizer. I know some people feel no effects from coffee, I can't imagine. I definitely feel less stress tolerance and less patience overall.

The ADORA2A gene is associated with adenosine receptors and some research suggests that certain polymorphisms (which I found out through using 23andme and then inputting the data to Prometheus) are associated with negative psychological reactions to caffeine. This isn't something that is set in stone and genes are certainly not deterministic, but it is a possible factor contributing to an individuals reaction to caffeine.

That polymorphism has nothing to do with being a fast or slow metabolizer AFAIK. Wondering if @Travis might have any thoughts on the length of changes that occur after stopping caffeine?

 

[Travis]

I don't know much about not drinking coffee. I have been drinking coffee every day (with very few exceptions) for over a decade.

But I did stumble across this neat quote just now in an unrelated article:

A modern approach to the mode of action of methylxanthines on the CNS is their blockade of adenosine receptors in concentrations (50-100 ~M) which are too low to really inhibit phosphodiesterase, but increase exploratory behaviour in animals. Since adenosine inhibits the firing of most central neurons and the release of several neurotransmitters, the blockade of adenosine receptors leads to central stimulation {for review see Daly et al., 1981). This action of methylxanthines in combination with their effects on Ca²⁺ disposition renders them interesting as potential amethystic agents.

Caffeine is a methylxanthine. It's nice to know that it "increase(s) exploratory behaviour in animals."

Linnoila, M., and M. J. Mattila. "How to antagonize ethanol-induced inebriation." Pharmacology & therapeutics 15.1 (1981): 99-109.

This was a fun article, but off-topic. The authors concluded that ethanol worked on so many different functions that just one antidote is unlikely to be found. But there are a few that work:

An effective ethanol antagonist is unlikely to be found. For particular circumstances, such as diving (hyperbaric oxygen), driving under the influence (behavioral means, nonspecific stimulants, prostaglandin synthetase antagonists), and arousing inebriated patients in emergency rooms (naloxone, physostigmine), partial solutions are available. Acceleration of the metabolism of ethanol by fructose might lead to BACs which are below the "legal" limit the next morning. If these partial solutions are even slightly successful they can make significant savings both in human suffering and material resources.

The hyperbaric oxygen reverses the membrane fluidity, the naloxone is actually kinda worthless, the physostigmine is an acetylcholine esterase inhibitor which prevents the breakdown of this important neurotransmitter and is probably the most effective antidote (nicotine works in a similar fashion and is mentioned in the article), indomethacin inhibits prostaglandin synthesis, and fructose increases the rate of ethanol metabolism by 30%.

For me I know I am heterozygous for the ADORA polymorphism and I also don't really feel the need for a lot of external stimulation.

I was just looking at the X-ray crystallographic models of the acetylcholine receptor. It's shaped like a hollow tube, and they think it works through a "conformation change" opening the pore to allow ion flow upon ligand binding. This is interesting. There has to be more to the story than just ion flow. I'll need to look at the other receptors someday. I need to know more about adenosine and caffeine.

But the differential effects of caffeine on certain genotypes seems convincing. There are three studies by different groups showing this effect. I noticed the anxiety scores were measured by tests, but it a polygraph tracing would be more convincing yet. Perhaps there are even newer studies on this?

Alsene, Karen, et al. "Association between A2a receptor gene polymorphisms and caffeine-induced anxiety." Neuropsychopharmacology28.9 (2003): 1694.
Rogers, Peter J., et al. "Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption." Neuropsychopharmacology 35.9 (2010): 1973.
Childs, Emma, et al. "Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety." Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology33.12 (2008): 2791.

 

[Travis]

Here's what the acetylcholine receptor looks like in case anyone's interested, as determined by X-ray crystallography. Acetylcholine binds to the α subunits, and the small acetylcholine molecule itself is roughly about the size and shape of the Greek lowercase gamma (γ) seen in the graphic representation. From reading what these scientists have to say about it, the entire function of acetylcholine seems to be reduced to the simple opening of a pore—or "ion gate."
Click to embiggen
There are some toxins which antagonize and inhibit this receptor—like mecamylamine and
α-bungarotoxin (from snake venom)—and lead to memory loss and/or paralysis. I think the strong-binding α-bungarotoxin cannot cross the BBB but mecamylamine can and leads to slower learning and short-term memory loss every single time that it's tested on people or animals.

 

[Such_Saturation]

amplified ACTH and cortisol responses to mental stress with caffeine

The point of being an adaptogen is doing the opposite.

 

[dbh25]

Is there a difference between caffeine found in tea or coffee? Something in coffee hits my system differently.

 

[Constatine]

Is there a difference between caffeine found in tea or coffee? Something in coffee hits my system differently.

Coffee has more bioactive compounds than just caffeine. As does tea.

 

[MB50]

Is there a difference between caffeine found in tea or coffee? Something in coffee hits my system differently.

Yea, definitely a bunch of different compounds than just caffeine. For me tea is much more subtle simply because the amount of caffeine is lower.

 

[MB50]

The point of being an adaptogen is doing the opposite.

Not sure what you mean by that. Are you saying you view caffeine as an adaptogen that doesn't result in an increase in these hormones?

 

[Travis]

You might want to look into theanine. Tea is full of it, in milligram amounts:

. Contrary to previous research, a standard (200 ml) cup of black tea was found to contain the most L-theanine (24.2 ± 5.7 mg) while a cup of green tea contained the least (7.9 ± 3.8 mg).

It crosses the blood brain barrier. I think these amounts can be psychoactive.

This difference has led to an interest in the effects of L-theanine on psychological measures, such as stress and anxiety. L-Theanine has been found to have a relaxing effect (Juneja, Chu, Okubo, Nagato, & Yokogoshi, 1999) and to increase alpha brain waves, synonymous with a relaxed yet alert state (Nobre, Rao & Owen, 2008). Recent research has found that L-theanine reduced both subjective and physiological stress responses during a stressful task situation (Kimura, Ozeki, Juneja, & Ohira, 2007), and that it may be useful for reducing raised blood pressure (Rogers et al., 2008). This relaxation effect of L-theanine may also explain the improvements seen in subjective sleep quality and mood upon awakening after L-theanine (Ozeki, Juneja, & Shirakawa, 2003). This interest in beneficial effects of L-theanine has raised the question of what quantities of L-theanine are contained in various commercially-available teas. Such data are essential for calculation of average daily consumption of L-theanine by tea consumers, similar to the reports for caffeine consumption (Rogers et al., 2008).

The serotonin data seems to be ambiguous, with both increases and decreases reported. This is not unusual, and many things have been shown to do this. It probably depends on the brain region measured. I once saw a study where melatonin significantly decreased serotonin in the cortex, but raised it in the hippocampus.

Besides theanine, fluoride is also a notorious component in tea. This can be counteracted with boron. The journal Flouride has dozens of studies showing that boron forms strong covalent bonds with the fluoride ion (F⁻) and removes it from the body (kidneys). It's a partial antidote. This been been scientifically-confirmed.

Keenan, Emma K., et al. "How much theanine in a cup of tea? Effects of tea type and method of preparation." Food chemistry 125.2 (2011): 588-594.

 

[dbh25]

Yea, definitely a bunch of different compounds than just caffeine. For me tea is much more subtle simply because the amount of caffeine is lower.

If I drink 5 cups of green tea, which has similar caffeine to a cup of coffee, I react differently. More of a head rush with the coffee

 

[MB50]

You might want to look into theanine. Tea is full of it, in milligram amounts:

It crosses the blood brain barrier. I think these amounts can be psychoactive.

The serotonin data seems to be ambiguous, with both increases and decreases reported. This is not unusual, and many things have been shown to do this. It probably depends on the brain region measured. I once saw a study where melatonin significantly decreased serotonin in the cortex, but raised it in the hippocampus.

Besides theanine, fluoride is also a notorious component in tea. This can be counteracted with boron. The journal Flouride has dozens of studies showing that boron forms strong covalent bonds with the fluoride ion (F⁻) and removes it from the body (kidneys). It's a partial antidote. This been been scientifically-confirmed.

Keenan, Emma K., et al. "How much theanine in a cup of tea? Effects of tea type and method of preparation." Food chemistry 125.2 (2011): 588-594.

Thanks for all of your detailed posts. Theanine with caffeine is definitely a great combination for me. The fluoride is definitely a concern. I drink white tea as it has the least amount of fluoride. Fluoride is taken up as the plant ages so the younger the leaf the less fluoride it has. I don't think that any amount of fluoride is good in addition to what we get from foods, but by being cognizant of avoiding tap water and restaurant water, my concerns are alleviated regarding tea consumption.

 

[InChristAlone]

I used caffeine for yrs to get me through parenting. Then during a strong coffee I had a sense of doom and terror. One of the worst panic attacks that just lasted for like 2 days straight. I quit all caffeine after that day. I went through up and down panic and anxiety for a month. Some times I thought I'd never feel good again. But then I did! And I have never wanted to go back to it. I could list all the ways I handle stress better now. But I was definitely one to get strung out and hypomanic on coffee. With periods of anxiety attacks. Some claim those mental side effects go away with better liver function and all that, but I felt like mine couldn't get any better while on it. Like there was no room for improvement while going through the ups and downs.

 

[MB50]

I used caffeine for yrs to get me through parenting. Then during a strong coffee I had a sense of doom and terror. One of the worst panic attacks that just lasted for like 2 days straight. I quit all caffeine after that day. I went through up and down panic and anxiety for a month. Some times I thought I'd never feel good again. But then I did! And I have never wanted to go back to it. I could list all the ways I handle stress better now. But I was definitely one to get strung out and hypomanic on coffee. With periods of anxiety attacks. Some claim those mental side effects go away with better liver function and all that, but I felt like mine couldn't get any better while on it. Like there was no room for improvement while going through the ups and downs.

That's why I am asking this question- reports just like yours. According to the pharmokinetics of caffeine, it shouldn't have been affecting you longer than a few days at most, but you didn't feel significant improvement for a month. Iv read many similar stories. I have also heard just as many great reports with caffeine. But it seems like there is some sort of recalibration that goes on with stopping caffeine. Most places I have read say adenosine receptors should be back to baseline around 9 days after stopping, which is when withdrawal symptoms should be over. However, i am convinced that a lot of things could go on longer.

For example, if somebody is using high dose caffeine while mentally stressed for a period of months, it is likely baseline cortisol will be pushed higher, which will take longer to get cortisol back to lower levels. I haven't seen many people interested in such work, but it's definitely interesting. Thanks for your story and other people's comments in this thread.

 

[BibleBeliever]

If I drink 5 cups of green tea, which has similar caffeine to a cup of coffee, I react differently. More of a head rush with the coffee

I've always been hesitant of green tea because of research that it can lower testosterone:
https://www.anabolicmen.com/green-tea-testosterone/

Have read it elsewhere too. Do you notice any negatives from 5 cups?

 

[InChristAlone]

That's why I am asking this question- reports just like yours. According to the pharmokinetics of caffeine, it shouldn't have been affecting you longer than a few days at most, but you didn't feel significant improvement for a month. Iv read many similar stories. I have also heard just as many great reports with caffeine. But it seems like there is some sort of recalibration that goes on with stopping caffeine. Most places I have read say adenosine receptors should be back to baseline around 9 days after stopping, which is when withdrawal symptoms should be over. However, i am convinced that a lot of things could go on longer.

For example, if somebody is using high dose caffeine while mentally stressed for a period of months, it is likely baseline cortisol will be pushed higher, which will take longer to get cortisol back to lower levels. I haven't seen many people interested in such work, but it's definitely interesting. Thanks for your story and other people's comments in this thread.

Yeah many accounts of complete recovery taking months. I was very interested in all of this when I was going through it. I definitely used it while under loads of stress and I think it altered my brain.

 

[dbh25]

I've always been hesitant of green tea because of research that it can lower testosterone:
https://www.anabolicmen.com/green-tea-testosterone/

Have read it elsewhere too. Do you notice any negatives from 5 cups?

Hi Jack, I haven't noticed any negatives from 5 cups green tea. Other than more urination. But I haven't drank that much for many days in a row, it's been an occasional substitute habit for coffee.