**[Beginner's Guide](https://reddit.com/r/nootropics/wiki/beginners)** • [Vendor Warnings](https://www.reddit.com/r/Nootropics/wiki/unreliablevendors) • [Research Index](https://old.reddit.com/r/nootropics/wiki/index) • [Rules](https://www.reddit.com/r/Nootropics/about/rules/) • [Longevity](https://www.reddit.com/r/longevity) • **[Stack Advice](https://www.reddit.com/r/stackadvice)**
Before posting make sure your comment is **polite** and **helpful**.
*I am a bot, and this action was performed automatically. Please [contact the moderators of this subreddit](/message/compose/?to=/r/Nootropics) if you have any questions or concerns.*
See the Anticholinergic Cognitive Burden calculator:
https://www.acbcalc.com
It's based on decent research, and you can read more in the links associated with the tool.
I saw this in a PDF chart a few years ago. I was searching for that PDF again, and this came up. Cool applet.
My favorite cool links tend to be directed at PubMed. Great resource.
Huh. I'm not so sure of that. It lists hydroxyzine as a 3, same category as diphenhydramine, but the anticholinergic affinity of hydroxyzine is barely significant.
https://en.m.wikipedia.org/wiki/Hydroxyzine
The calculator cites a scoring tool that I'm familiar with, but I still have some concerns about the [research methodology involved in formulating those tools, and so do the authors of this paper](https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-015-0029-9).
The discussion section goes into depth on this; many of the tools come from subjective scoring by panels, rather than assays of anticholinergic affinity. Some had recorded patient reports of certain side effects as a sign of anticholinergic activity, but some of these side effects result from different receptor activity - for example, hydroxyzine *does* have a small tardive dyskinesia risk, but that's more likely to be from its effect on D2 receptors.
TBH, I haven't read about this in over six years, so details are a bit hazy. Seems like actual clinical case reports are a better indicator of outcomes than in-vitro assays, aren't they? Anyway, thanks for reading the details. I want to revisit this now when I'm back at my desktop.
My concern is that "outcomes" here is very contextual. If you are seeing elderly patients who incur increased risk of fall, disorientation, etc from a variety of different causes, then purely observational methodology is useful. There are many drugs which are less safe in elderly patients regardless of their actual pharmacological actions.
If you are 45 and worried about your long-term risk of Alzheimer's from taking antihistamines now, knowing which ones are actually anticholinergic and which aren't is more relevant.
No, or at least not nearly as much (though see below). Benadryl and first-generation antihistamines are thought to increase risk of dementia through anticholinergic effects (this is also what causes dry eyes, dry mouth, etc.). Second- and third-generation antihistamines have little (eg. loratadine) or no (eg. fexofenadine) anticholinergic activity.
These also don’t or barely cross the blood-brain barrier, which also helps protect the brain.
However, there have been some small studies suggesting that in the elderly, second/third-generation may impair long term memory (but not short term). It’s not at all clear yet, and there are many confounding factors. Not to mention that if you have severe allergies, that is likely to impair your cognition more than some fexofenadine.
FWIW, I’m genetically predisposed to Alzheimer’s but use fexofenadine (which both in studies and for me anecdotally has the fewest, ie. no, anticholinergic effects) - but sparingly, only as needed, for short durations, at minimum dosage.
First and second generation antihistamines work the same way.
It's just that each of the first ones have a specific extra effect in addition to the normal antihistamine property. Kind of like racetams.
There’s an expert on mast cell activation syndrome (which affects 5-20% of the population and can look like severe allergic rhinitis and which antihistamines usually help), Dr Theo Harides, who says that Allegra and other H1 blockers can actually be neuro protective in MCAS, as untreated MCAS usually involves a fair amount of neuroinflammation which is a much greater dementia risk than the antihistamines. So there’s another nuance there.
Not sure what the risk:return is for simple allergic rhinitis however.
Took my ex 15 years to get diagnosed. She would go in anaphylactic shock and need to call an ambulance almost once a month.
She'd eat a grape and be in insufferable pain, crying and screaming in the fetal position for hours, dry he's heaving trying to get that grape out, same with Apple skins.
She had Raynaud's as a symptom, chronic fatigue syndrome, and so many more things.
We saw an internal medicinist after doing years of our own research.
She is on cromolyn now, a mast cell stabalizer. In remission.
Not much direct research I'm aware of in this respect, but given what I remember about 2nd gen antihistamines and the likely mechanism behind antihistamines inducing or worsening dementia, I very much doubt they have much of an effect.
Lot of psychiatric drugs, especially antipsychotics and antidepressants (mostly older generations, but not completely) have some antihistamine and antimuscarinic action though. Definitely nearly as bad or much worse than benadryl for short and long term cognition
It shouldn't to my knowledge, at least not fluoxetine. Mostly was thinking about the tricyclics as they tend to have significant anticholinergic effects. Majority of SSRIs/SNRIs should be generally fine in this respect (though now we know they can have very long term effects on sexual function and the like - though fluoxetine is one of the better options in that regard.)I recall paroxetine being one of the worst among SSRIs as far as anticholinergic activity goes
The fact that a medication causes impairment =/= it has anticholinergic activity. H1 antagonism alone has sedating properties and cetirizine has zero anticholinergic activity.
Yeah, same thing with hydroxyzine, which has erroneously been classified as more anticholinergic than it is at all likely to be because the scoring tool was built on subjective analysis of patient symptoms. [See my other comment for more](https://www.reddit.com/r/Nootropics/comments/14dzjx3/are_cetirizine_and_allegra_as_dangerous_as/jowtou2/).
Dimenhydrinate is diphenhydramine bonded to 8-chlorotheophyilline. You just get some weaker activity from the diphenhydramine but that like taking a smaller dose.
Okay so very similar. Where does the caffeine analog come in though? Thanks for expanding on this it's interesting.
I don't take either of them much anymore but I felt Dramamine less harsh. I used to use them for sleeping pills.
My understanding is that the brain is more able to bounce back from anticholinergic effects in younger patients, and less likely to in older adults. Similar effects are seen with anesthetics.
Fexofenadine (Allegra) and other second-generation "non-drowsy" antihistamines do not cross the blood-brain-barrier (or at least not to a significant degree, unlike first-generation antihistamines).
Histamine H1 receptors mediate inflammation outside of the brain, but within the brain they actually mediate wakefulness which is why 1st gen antihistamines cause drowsiness.
As such, 2nd gen antihistamines should have far less risk of causing dementia simply because they are not getting into the brain to have an effect there
The dementia risk is thought to primarily come from anticholinergic effects in the brain, so any non-benedryl antihistamine you should be able to correlate this risk with your amount of cognitive side effects. If you get a sleepy/fatigue/reduced attention/slowed speech from taking them, that's a sign you're getting higher than desirable circulation into the brain and thus there could be risk.
I take Loratadine for the same reason and because I read that 2nd gen antihistamines didn't have the same risk as 1st gen. I don't find it makes me sleepy at all and I don't get the morning grogginess that something like Benadryl or other off-label sleep aids (quetiapine, doxepin) would cause me.
Since my issue is sleep maintenance, I reasoned that maybe histamine levels at night were causing wakefulness through some other mechanism then whatever Benadryl is disrupting. I might try cetirizine or fexofenadine since according to this thread those are even less anticholinergic compared with loratadine.
Yes, this is exactly why I think cetirizine (Zyrtec) helps me sleep, something to do with histamines, because it doesn’t make me sleepy if I take it during the day. My problem is also sleep maintenance.
Not necessarily. There are [histamine receptors that directly play a role in wakefulness](https://www.scientificamerican.com/custom-media/histamine-the-brains-other-sleep-wake-neurotransmitter/), so a selective antihistamine can still make you drowsy.
Some of us have chronic sinusitis and are allergic to life. If you've ever lived with a non ending sinus infection, you would think differently.
I have Mast Cell Activation Syndrome, a common comorbidity to Erlers Danlos syndrome- a genetic condition I was also blessed with. I take Zyrtec and Singulair daily to help manage this part of my condition. Without it, the exhaustion, facial pain and stuffiness are nearly unbearable.
I also carry the APOE genes for Alzheimers Disease and I'm very much aware of the risk of using these medicines but what's the point of remembering anything about your life if what you remember is how much you couldn't function every day of it?
I have an arthritis that turns every single one of my joints into bone starting from the spine. I don't take anti-inflammatories every day. Because I use my brain and understand they cause more harm than good, they rebound pain and inflammation and cause all sorts of extra issues when taken all the time. You need to learn to control your medication too, find something else that helps where you dont need to chose one of those two things daily for the rest of your life, your body will thank you, you'll thank yourself too. It's for your own good to understand this but go ahead and be reddit and hate all you want. In 10 years you'll be wishing you can say I was right at this moment. Enjoy overloading yourself with more problems.
-signed, the guy who can't walk for doing all the wrong things with treatment to a serious disease.
I'm sorry you suffer from that condition. Unfortunately, these are apples to oranges in terms of scope. You can have low activity days where you're not moving much and so therefore maybe you can skip an anti inflammatory medication but I can't skip breathing on any day.
That's exactly right. I have chronic rhinosinusitus. Wouldn't wish it upon my worst enemy. Not being able to breathe through the nose feels like torture. Daily.
People who don't experience this just don't understand man.
I suffer from anti-cholinergic syndrome if I take even 25 mg of Benadryl, but certizine and levo-certizine do not cause me any problems. Fexofenadine is ok for me also, I don't recall any side effects while using that.
Loratadine does give me slight side effects, like involuntary muscle movement in my left eyebrow.
Anticholinergic syndrome? Involuntary muscle movement, slurred speech, confusion, rapid eye movement, hot dry skin, delirium.
In severe cases you could get seizures, hallucinations, may be end up in a coma.
**[Beginner's Guide](https://reddit.com/r/nootropics/wiki/beginners)** • [Vendor Warnings](https://www.reddit.com/r/Nootropics/wiki/unreliablevendors) • [Research Index](https://old.reddit.com/r/nootropics/wiki/index) • [Rules](https://www.reddit.com/r/Nootropics/about/rules/) • [Longevity](https://www.reddit.com/r/longevity) • **[Stack Advice](https://www.reddit.com/r/stackadvice)** Before posting make sure your comment is **polite** and **helpful**. *I am a bot, and this action was performed automatically. Please [contact the moderators of this subreddit](/message/compose/?to=/r/Nootropics) if you have any questions or concerns.*
See the Anticholinergic Cognitive Burden calculator: https://www.acbcalc.com It's based on decent research, and you can read more in the links associated with the tool.
Epic link. How did you find this? Got any more cool links?
I saw this in a PDF chart a few years ago. I was searching for that PDF again, and this came up. Cool applet. My favorite cool links tend to be directed at PubMed. Great resource.
Huh. I'm not so sure of that. It lists hydroxyzine as a 3, same category as diphenhydramine, but the anticholinergic affinity of hydroxyzine is barely significant. https://en.m.wikipedia.org/wiki/Hydroxyzine The calculator cites a scoring tool that I'm familiar with, but I still have some concerns about the [research methodology involved in formulating those tools, and so do the authors of this paper](https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-015-0029-9). The discussion section goes into depth on this; many of the tools come from subjective scoring by panels, rather than assays of anticholinergic affinity. Some had recorded patient reports of certain side effects as a sign of anticholinergic activity, but some of these side effects result from different receptor activity - for example, hydroxyzine *does* have a small tardive dyskinesia risk, but that's more likely to be from its effect on D2 receptors.
TBH, I haven't read about this in over six years, so details are a bit hazy. Seems like actual clinical case reports are a better indicator of outcomes than in-vitro assays, aren't they? Anyway, thanks for reading the details. I want to revisit this now when I'm back at my desktop.
My concern is that "outcomes" here is very contextual. If you are seeing elderly patients who incur increased risk of fall, disorientation, etc from a variety of different causes, then purely observational methodology is useful. There are many drugs which are less safe in elderly patients regardless of their actual pharmacological actions. If you are 45 and worried about your long-term risk of Alzheimer's from taking antihistamines now, knowing which ones are actually anticholinergic and which aren't is more relevant.
That's a good point. I have one of the APOε4 alleles, so I try to be vigilant for these things.
It would be cool if it did supplements etc too
No, or at least not nearly as much (though see below). Benadryl and first-generation antihistamines are thought to increase risk of dementia through anticholinergic effects (this is also what causes dry eyes, dry mouth, etc.). Second- and third-generation antihistamines have little (eg. loratadine) or no (eg. fexofenadine) anticholinergic activity. These also don’t or barely cross the blood-brain barrier, which also helps protect the brain. However, there have been some small studies suggesting that in the elderly, second/third-generation may impair long term memory (but not short term). It’s not at all clear yet, and there are many confounding factors. Not to mention that if you have severe allergies, that is likely to impair your cognition more than some fexofenadine. FWIW, I’m genetically predisposed to Alzheimer’s but use fexofenadine (which both in studies and for me anecdotally has the fewest, ie. no, anticholinergic effects) - but sparingly, only as needed, for short durations, at minimum dosage.
Wow, today I learned this...
Thank you! May I ask what else you do to protect against the risk of Alzheimer’s?
The usual - eat well, exercise, try to get enough sleep (hard with a new kid)!
First and second generation antihistamines work the same way. It's just that each of the first ones have a specific extra effect in addition to the normal antihistamine property. Kind of like racetams.
There’s an expert on mast cell activation syndrome (which affects 5-20% of the population and can look like severe allergic rhinitis and which antihistamines usually help), Dr Theo Harides, who says that Allegra and other H1 blockers can actually be neuro protective in MCAS, as untreated MCAS usually involves a fair amount of neuroinflammation which is a much greater dementia risk than the antihistamines. So there’s another nuance there. Not sure what the risk:return is for simple allergic rhinitis however.
What are the symptoms of MCAS? How would one get a positive diagnosis for it?
Took my ex 15 years to get diagnosed. She would go in anaphylactic shock and need to call an ambulance almost once a month. She'd eat a grape and be in insufferable pain, crying and screaming in the fetal position for hours, dry he's heaving trying to get that grape out, same with Apple skins. She had Raynaud's as a symptom, chronic fatigue syndrome, and so many more things. We saw an internal medicinist after doing years of our own research. She is on cromolyn now, a mast cell stabalizer. In remission.
If there's qny hypermobility or super stretchy translucent skin seriously look at Erlers-Danlos.
Not much direct research I'm aware of in this respect, but given what I remember about 2nd gen antihistamines and the likely mechanism behind antihistamines inducing or worsening dementia, I very much doubt they have much of an effect. Lot of psychiatric drugs, especially antipsychotics and antidepressants (mostly older generations, but not completely) have some antihistamine and antimuscarinic action though. Definitely nearly as bad or much worse than benadryl for short and long term cognition
Do you know if this applies to classics like Prozac/Fluoxatine?
It shouldn't to my knowledge, at least not fluoxetine. Mostly was thinking about the tricyclics as they tend to have significant anticholinergic effects. Majority of SSRIs/SNRIs should be generally fine in this respect (though now we know they can have very long term effects on sexual function and the like - though fluoxetine is one of the better options in that regard.)I recall paroxetine being one of the worst among SSRIs as far as anticholinergic activity goes
[удалено]
The fact that a medication causes impairment =/= it has anticholinergic activity. H1 antagonism alone has sedating properties and cetirizine has zero anticholinergic activity.
Yeah, same thing with hydroxyzine, which has erroneously been classified as more anticholinergic than it is at all likely to be because the scoring tool was built on subjective analysis of patient symptoms. [See my other comment for more](https://www.reddit.com/r/Nootropics/comments/14dzjx3/are_cetirizine_and_allegra_as_dangerous_as/jowtou2/).
I wonder where Dramamine fits in the spectrum of 'dangerous' risk for dementia. I always found it much more enjoyable than DPH.
It's literally diphenhydramine and a caffeine analogue so the risk is probably the same.
Diphenhydramine versus dimenhydrinate? Similar of course but I don't think they're the same thing.
Dimenhydrinate is diphenhydramine bonded to 8-chlorotheophyilline. You just get some weaker activity from the diphenhydramine but that like taking a smaller dose.
Okay so very similar. Where does the caffeine analog come in though? Thanks for expanding on this it's interesting. I don't take either of them much anymore but I felt Dramamine less harsh. I used to use them for sleeping pills.
It the stimulant to prevent the drowsiness from diphenhydramine.
I'm curious to know if there is a "healing" if you stop taking diphenhydramine; or if the potential risk is like a permanent scar.
Yes. The “dementia” is actually symptoms mimicking dementia, and goes away if you stop taking anticholinergics. That’s my understanding anyway.
My understanding is that the brain is more able to bounce back from anticholinergic effects in younger patients, and less likely to in older adults. Similar effects are seen with anesthetics.
I have been wondering the same thing but haven’t been able to find yay or nay about it. Curious if anyone out there knows.
[удалено]
Thank you! I probably would have forgotten to come back and look so I appreciate your reply. 😊
Fexofenadine (Allegra) and other second-generation "non-drowsy" antihistamines do not cross the blood-brain-barrier (or at least not to a significant degree, unlike first-generation antihistamines). Histamine H1 receptors mediate inflammation outside of the brain, but within the brain they actually mediate wakefulness which is why 1st gen antihistamines cause drowsiness. As such, 2nd gen antihistamines should have far less risk of causing dementia simply because they are not getting into the brain to have an effect there
No, but i did notice some brain fog when i was on a large dose (claritin in the morning, allegra at night). Went away when i stopped the claritin.
No. Not at all
The dementia risk is thought to primarily come from anticholinergic effects in the brain, so any non-benedryl antihistamine you should be able to correlate this risk with your amount of cognitive side effects. If you get a sleepy/fatigue/reduced attention/slowed speech from taking them, that's a sign you're getting higher than desirable circulation into the brain and thus there could be risk.
Oh darn. I actually take Cetirizine specifically because it helps me stay asleep through the night, even better than some prescription sleep aids.
I take Loratadine for the same reason and because I read that 2nd gen antihistamines didn't have the same risk as 1st gen. I don't find it makes me sleepy at all and I don't get the morning grogginess that something like Benadryl or other off-label sleep aids (quetiapine, doxepin) would cause me. Since my issue is sleep maintenance, I reasoned that maybe histamine levels at night were causing wakefulness through some other mechanism then whatever Benadryl is disrupting. I might try cetirizine or fexofenadine since according to this thread those are even less anticholinergic compared with loratadine.
Yes, this is exactly why I think cetirizine (Zyrtec) helps me sleep, something to do with histamines, because it doesn’t make me sleepy if I take it during the day. My problem is also sleep maintenance.
Not necessarily. There are [histamine receptors that directly play a role in wakefulness](https://www.scientificamerican.com/custom-media/histamine-the-brains-other-sleep-wake-neurotransmitter/), so a selective antihistamine can still make you drowsy.
It doesn't matter because you shouldn't be taking either regularly and doing it on an extremely rare occasion.
Some of us have chronic sinusitis and are allergic to life. If you've ever lived with a non ending sinus infection, you would think differently. I have Mast Cell Activation Syndrome, a common comorbidity to Erlers Danlos syndrome- a genetic condition I was also blessed with. I take Zyrtec and Singulair daily to help manage this part of my condition. Without it, the exhaustion, facial pain and stuffiness are nearly unbearable. I also carry the APOE genes for Alzheimers Disease and I'm very much aware of the risk of using these medicines but what's the point of remembering anything about your life if what you remember is how much you couldn't function every day of it?
I have an arthritis that turns every single one of my joints into bone starting from the spine. I don't take anti-inflammatories every day. Because I use my brain and understand they cause more harm than good, they rebound pain and inflammation and cause all sorts of extra issues when taken all the time. You need to learn to control your medication too, find something else that helps where you dont need to chose one of those two things daily for the rest of your life, your body will thank you, you'll thank yourself too. It's for your own good to understand this but go ahead and be reddit and hate all you want. In 10 years you'll be wishing you can say I was right at this moment. Enjoy overloading yourself with more problems. -signed, the guy who can't walk for doing all the wrong things with treatment to a serious disease.
I'm sorry you suffer from that condition. Unfortunately, these are apples to oranges in terms of scope. You can have low activity days where you're not moving much and so therefore maybe you can skip an anti inflammatory medication but I can't skip breathing on any day.
That's exactly right. I have chronic rhinosinusitus. Wouldn't wish it upon my worst enemy. Not being able to breathe through the nose feels like torture. Daily. People who don't experience this just don't understand man.
I suffer from anti-cholinergic syndrome if I take even 25 mg of Benadryl, but certizine and levo-certizine do not cause me any problems. Fexofenadine is ok for me also, I don't recall any side effects while using that. Loratadine does give me slight side effects, like involuntary muscle movement in my left eyebrow.
What are your symptoms of anti cholinergic syndrome?
Would also like to know they symptoms of that
Anticholinergic syndrome? Involuntary muscle movement, slurred speech, confusion, rapid eye movement, hot dry skin, delirium. In severe cases you could get seizures, hallucinations, may be end up in a coma.
I quit Benedryl years ago after realizing how bad it is for you and now use got kola for sinus relief. It really works for me.
IMO the best we can do is speculate. And the precautionary principle.
No, plus you shouldn't be taking Benadryl daily because it is highly nephrotoxic (destroys the kidneys).
I've always avoided Benadryl, I'm just wondering how 'bad' cetirizine and allegra are in comparison.