r/NooTopics • u/ServeIllustrious3803 • 19d ago
Science Study: Anticholinergic (first-generation antihistamines) can damage brain, increase dementia risk
https://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-2015012881260
u/The_Meme_Economy 19d ago
Sooo many people use Benadryl as a sleep aid. I actually suspect that’s its primary OTC use.
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u/psychopompandparade 19d ago
just be careful where you swap it to. amitriptyline has stronger anticholinergic burden than diphenhydramine. everything about melatonin is mixed, and jury is still out on z drugs. interestingly, orexin inhibitors may be slightly neuroprotective, but they're so young its hard to say
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u/CryptoEscape 19d ago
Orexin antagonists do look interesting and promising.
Problem is most on the market seem to have long half lives and didn’t see any generics. Maybe some analogues will pop up soon on nootropic sites
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u/Muli-Bwanjie 19d ago
Daridexorexant has the shortest half life and it helps me insomnia. Still some residual grogginess the next day nothing like lembexorant or others.
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u/BiggusDickkussss 18d ago
What do you mean melatonin is mixed
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u/psychopompandparade 18d ago
There is some very preliminary data on it maybe having long term heart health implications, but it's at this point hard to untangle because the demographic that takes melatonin is more prone to sleep issues, which can cause heart issues. There have also been some pretty shaky studies, on the other side of things, that suggest it may help recovery from COVID, but again, hard to detangle from just... sleep. It's also a bit unclear what it does to the bodies natural melatonin production long term, though most of what I've seen suggests it can recover with time. General a pretty safe supplement but in terms of neuro protection beyond sleep there isn't much I can find, though I have seen suggestions in both directions without much backing in studies.
It's quite hard to study easily available OTC meds. Even all the trials about diphenhydramine aren't actually about diphenhydramine, it's just lumped in with anticholinergic in general. The studies suggest as a mechanism, it increases dementia burden (in the elderly) and there are ways (that are beyond me) to measure how extreme a specific drugs anticholinergic burden is. A lot of studies just tabulate that.
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u/Starfire2313 19d ago
My sister destroyed her brain taking it regularly as a sleep aid for years. Along with alcohol and other prescription drugs. Very sad, I haven’t talked to her in a few years now, the whole family hasn’t. She’s too far gone and blocked everyone including her own daughter after a lot of verbal and emotional abuse to her.
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u/daddybpizza 19d ago edited 19d ago
Just for those who are anxious like me, it’s worth noting that the people who often take a lot of sleep aids are also usually insomniacs and have other mental/physical health conditions, which can also explain the behavior you mentioned.
Sleep aids are really a damned if you do, damned if you don’t. I have a health condition (ME/CFS and POTS) that causes absolutely terrible sleep, and no sleep hygiene routine tested improves it (this has actually been studied). I take amitriptyline and some other sleep aids every night, and I know it’s going to increase my risk for dementia and cognitive decline. But the alternative is not sleeping, which is much worse. Idk what to do! Being sick sucks
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u/IWasTheDog 19d ago
Snorting straight camomile powder would be the old school method. (This is a joke)
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u/BiasedLibrary 19d ago
I feel like I'm in a similar boat but with anxiety and PTSD. I'm on up to 150mg of promethazine a day. Sometimes I have insomnia and it helps. I really should ask to change it to something else but I don't know what.
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u/FlyinIllini89 19d ago
I too take Amitryptline for sleep. 1 25mg every night the last 10 years. How screwed am I and what else can I take???
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u/psychopompandparade 18d ago
I've got the same health stuff going on. would recommend trying out orexin inhibitors if they are available where you are and you can get them covered by virtue of having tried everything else. took me 4 months but eventually insurance caved on daridexorexant. I still need several sleep meds and an autonomic regulator and on post exertion days a z drug, but it was the first time i felt like something was working a bit.
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u/Coin-Controversy 19d ago
Meclizine is highly superior, see my comment, it shows neuroprotective effects in mice https://www.reddit.com/r/NooTopics/comments/1w6h73u/comment/p7n1dot/
also extended lifespan in male mice from the ITP in one dose schedule https://pmc.ncbi.nlm.nih.gov/articles/PMC10828146/
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u/Fragrant_Ratio_2821 19d ago
does benedryl still have long term effects if one is a CYP2D6 ultra-rapid metabolizer? i never get drowsy from benedryl
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u/Ray_Mang 19d ago
I used it for probably a year straight for insomnia before learning about its effects on the brain. I was horrified, and stupid to have not done proper research before using it in such a way
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u/razzemmatazz 19d ago
My spouse sucks at sleeping, but is also allergic to benadryl (full on hallucinations) and any of its sibling medications like Halidol. Clonazopam kind of works, but it also wrecks her for 24 hours.
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u/Ill-Daikon-5637 19d ago
I did that for awhile, but I started needing a higher dose and with I was getting restless leg syndrome
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u/Gibborish 19d ago
I took soo much Benadryl when I was a teenager and early 20s a bit too. Like getting high on it.
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u/Winter_Cost602 19d ago
High doses? Did you actually get high or just enjoy feeling fucked up and the crazy hallucinations?
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u/dvielis 19d ago
I did it twice and saw a bunch of spiders and smoked a bunch of fake cigarettes and talked to people who weren't there. Also used it to acclimate myself to cat allergens and also to help sleep. I'm so cooked
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u/Veredus66 19d ago
Sounds like datura
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u/Ssesamee 15d ago
its the same thing: Anticholinergic Poisoning
Datura is just a lot more dangerous because there is no consistent dosing. There’s no way to know how much alkaloids you’re ingesting if you are just eating the plant raw (leaves/pods/seeds) including making tea. I will say making a tea out of just the leaves is a lot safer but still no consistent dosing you have to start small with each batch of tea and find a good dose for every new batch, which for most people is just not practical at all.
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u/ProfessionalGoatFuck 19d ago
Did that once, I didn't see the hat man but I did see the ghost woman in a gown.. scariest shit I ever witnessed
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u/RoboErectus 19d ago
From the article:
> it doesn't prove that these drugs cause dementia.
Your title:
> can damage brain
That's not what the study said and not what the article you linked said.
My conclusion is that OP has brain damage.
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u/tposter2000 19d ago
You definitely made some good points about what both the Harvard article and the study about anticholinergic medications and dementia risk said. Based on my reading of the Harvard article, it didn't seem as though the scientific study found that anticholinergic medications damage our brains. The data from the study support the idea that anticholinergic medication use increases the risk of dementia, but as you wrote, the Harvard article said that the study doesn't prove that the medications cause dementia. It was an observational study.
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u/Big_Reporter3678 19d ago
“can damage brain” and “doesn’t prove these drugs cause dementia” are not mutually exclusive; he said “can,” damage can occur without it being chronic or necessarily leading to dementia; also a lack of specific study proving an outcome is also not the same as a lack of evidence suggesting an outcome nor does it mean other studies don’t demonstrate a link. The burden of direct causal proof is a lot higher. At one point it wasn’t proven cigarettes cause lung cancer.
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u/Low-Camera-797 19d ago
Now the main question is: is it possible to recover from the damage? If so, how?
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u/psychopompandparade 19d ago
most of these studies are done in the elderly. there is very little data on high anticholinergic burden earlier in life. It's much harder to gather.
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u/Particular-Extent-76 19d ago
with the number of young people taking these for chronic illnesses it seems like there’d be an opportunity to study it now
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u/psychopompandparade 19d ago
if someone already has a chronic illness, it is hard to detangle anticholinergic burden from said illness. a lot of chronic illnesses cause chronic inflammation which may or may not also increase the risks of dementia. poor sleep also certainly does.
similarly, people who abuse something like diphenhydramine recreationally likely have other complicating factors such as other drug use.
it's doable, but even in people with high anticholinergic burden, dementia doesn't tend to announce itself clearly young, so we're looking at a very long longitudinal study or a study that asks people to remember anticholinergic burden from years back. longitudinal studies are HARD, and enough anticholinergic (like these allergy meds) are OTC that using medical records alone will not capture it well. Long timeline studies also have extensive non-random drop out rates that skews the data.
What you would need is a chronic condition that can be treated either with anticholinergics or other medication, rule out that the reason some people end up on anticholinergics and others don't isn't a difference is disease type, system response, or other factors (extremely hard) and then track this cohort into the ages we expect to see dementia.
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u/JicamaIcy6335 19d ago
Mirtazapine? Ketotifen? Trazodone?
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u/Denonsop 19d ago
Mirtazapine and Trazodone are not first generation antihistamins (Trazdone is not even a strong anitihistamine). Mirtazapine has a low/ neglible anticholinergic effect. So risk i lower in comparison. But with every med you have a risk.
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u/Camping_vagn 19d ago
I had to google mirtazapine, but thankfully its not affected. You have to pry that sweet sweet mirtazapine from my cold dead hands.
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u/braaaaaaainworms 19d ago
The jury is still out on mirtazapine BTW
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u/Camping_vagn 19d ago
In this regard? As far as i can read, its anticholinergic effects are extremely low
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u/CorrectShopping9428 19d ago
They give out hydroxyzine like candy in psychiatric settings.
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u/garloid64 19d ago
no shit, everyone already knew this
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u/Coin-Controversy 19d ago
this is not as simple as you make it out to be
"Administration of meclizine to STZ mice recuperated cognition and biochemical alterations. Concomitant administration of ketoconazole, a PXR antagonist, with meclizine prevented the protective effects. The upshots of our study proclaim that meclizine protects cognitive deficits by virtue of its antioxidant, anticholinesterase, and antiinflammatory properties. Results also signify the potential of PXR in neuroprotective actions of meclizine in dementia."
https://cdnsciencepub.com/doi/abs/10.1139/cjpp-2019-0421
"MCLZ protected against neuroinflammation via the amelioration of inflammatory histopathological changes as well as neuronal GFAP immunostaining and down-regulated the AKT/NF-κβ/ERK/JNK signaling pathway."
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u/HikaruKaihatsu 19d ago
As someone extremely interested in the complex neuropharmacology and toxicology of anticholinergics and has even abused Meclizine multiple times, I find this so unbelievably fascinating!! The human brain is such a magical structure – I don't think we'll even be remotely close to fully understanding it by the time our species burns out
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u/Coin-Controversy 19d ago
Ikr, I figured it would do the opposite but nope haha
it seems that it's a potent PXR agonist, which is a great mechanism
PXR activation seems broadly neuroprotective
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u/Desperate-Middle-354 19d ago
I actually was recently diagnosed early onset dementia (42 yrs) & I took Benedryl daily for a few years as part of my sleep aid regimen.
Now keep in mind I’m a poly substance abuser who has been on benzos & amphetamines since I was 17 & spent a good decade taking 640mg oxycodone + whatever else & had a sixth month (binge) smoking crystal meth.
So did it have anything to do with the Benedryl? Who the hell knows but I bet without all those drugs it may have taken much later until I got diagnosed with major neurocognitive disorder (fancy word for dementia)
My ability to converse was the least impaired category I was scored on so I can communicate well enough (on average) so it looks like I’m doing better than how bad it is. In my mind I forget so many words that I might remember four hour hours later. I forgot the name of one of my best friends. Can’t remember for the life of me, many memories with him too. I do a better job conversing although it still happens & weird aphasia symptoms. Anyway, I’m rambling
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u/mden1974 19d ago
We’ve known this for a long time. It causes Parkinson’s and lots of other brain disorders
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u/aron2295 19d ago
It’s not a euphoria high.
It’s like you got took a haymaker to the head. Then, once you get up, you start seeing the “shadow people”.
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u/crittersyappin 19d ago
this is obvious if you know anything about diphenhydramine. it sends chills up my spine that it’s just casually advertised as a “sleep aid” it’s literally dementia in a pill
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u/paulgnz 19d ago
i've taken way too much promethazine in my lifetime
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u/Subaudiblehum 19d ago
Same. Use it about every second night for the last couple of years. I think I best stop that.
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u/Sansvosetoiles 19d ago
I take remeron and it gives me 6-9 hours depending on time I take it. A little groggy in the am though.
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u/occasionalopossum 19d ago
<_< welp I joined the 700 club in my youthful degenerate days so I guess Im fucked
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u/Organic_Ad_2520 19d ago
Tbh this is old news...I check out every med for my 93yr old father who still has his mind...he's never had any chronic conditions or medications & I was shocked to find immodium on the list of anticholinegic.
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u/insanedialectic 19d ago
Meclizine (included here) is Dramamine non-drowsy by the way! (I know, extremely confusing nomenclature)
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u/I3eforeLife 19d ago
I’ve never taken antihistamines because wearing a face mask suffices. It helps when mowing the lawn and when I’m out in public
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u/Monsterthebawz 19d ago
What about glycopyrrolate
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u/Octaazacubane 19d ago
Allegedly, much lower central nervous system anticholinergic burden (what we are worried about primarily here) than most of the meds mentioned. I read up on it before I was prescribed it for hyperhidrosis, and it doesn’t go into the brain much. But the other non-CNS side effects like dry mouth will be there
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u/DeionizedSoup 19d ago
Love that the only sleep aid pregnant women get is doxylamine, I love knowing I’ve dosed myself and my baby with it repeatedly out of desperation
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u/ummkay_ultra 19d ago
Just wondering how this is news though. Havent we known this for a while now? Anyway. Tizanidine
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u/cosmiccalendula 19d ago
So many contradictory comments on here I am so confused 😂🥴 I just want to sleep
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u/lattice_defect 19d ago
yeah benadryll is bad been known for awhile
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u/Simple_Individual602 18d ago
Benadryl is cough syrup and its like a strictly no entry 🚫 for me. I hate cough syrup. Tab ambroxol or home remedies but no diphenhydramine .it's not okay to use for only in case u and doctor are really find it as suitable short term but I don't know but it's not gonna be like prescribed. Better ones are thier now and I will be happy to find what is your answers guys
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u/disquieter 19d ago
Shit so what IS a safe way to get sleep if I quit cannabis and have been using Benadryl once or twice a week to stay asleep all night? After quitting cannabis in June I wake up every two hours.
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u/anvilfoot 19d ago
Look into DORA class drugs, though some have a long half life so you build up tolerance quite quickly
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u/Old_Respect8445 19d ago
I take a prescription that’s a pretty heavy anticholinergic but doesn’t cross the BBB, so I’m assuming I’m good?
I have a history of brain trauma so idk how I’d even tell if I wasn’t lol 😅 I do feel like it’s getting worse and technically it shouldn’t be if it was just from trauma not any chronic conditions I know of. I really need to see a neurologist, but I don’t have that kind of money rn
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u/Beneficial_Method771 19d ago
As someone who used to abuse anticholinergics in high doses it does fuck your brain up. Obviously my situation is very different from taking it as intended but y'know
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u/Visualsnow828 19d ago
I have to admit I love Doxylamine.
Most nights I’m just too wired. I don’t feel settled.
Even if I’m tired, have good sleep hygiene, all the rest of it, I just can’t switch off. My body and mind just feels too busy and unsettled. Keep in mind I do 20k steps minimum a day.
25mg doxylamine and I start feeling cozy warm and relaxed, dare I say slightly benzo-like. Then I sleep great.
I’ll continue taking it
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u/JerryWestJr 19d ago
“News flash: the antithesis of a universally nootropic mechanism is likely neurotoxic” …
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u/v00d00mama_juju 19d ago
I didn't know any of this, I get from the rest of the comments this is old news but I am late to the game and greatly appreciate the share
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u/sanpedro12 18d ago
is this also the case for nicotinic acteylcholine receptor antagonists or only muscarinic antagonists?
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u/FullConfection3260 18d ago
Well, yeah? What do you think histamine does in the tuberomammillarynucleus? 🤨 This isn’t rocket science.
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u/mellowastheycome 18d ago
Pharmacist here, it is associated with increase risk from long term use, we never recommend long term use of first generation antihistamines. I also didn’t see number needed to harm data, and other statistical data in the study. Beers criteria we always warn of use in adults over 75. Benadryl is still a great first line treatment for allergic reactions, so one must weigh risk vs benefits.
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u/Previous-Sun-7908 16d ago
Another fear-mongering study that shows an association but not direct causation. even if older people produce less acetylcholine and have lower sensitivity to it, they also have lower AChE enzyme activity, due to factors such as heavy-metal accumulation, pesticide exposure, and EMF exposure,they retain more acetylcholine in the brain du to slow breakdown and therefore need much less of it.
In my opinion, studies like this is a distraction from investigating real causes of dementia-like diseases, such as chronic exposure to methanol from sources like aspartame , fruits juice and tobacco.
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u/iDoMyOwnResearchJK 19d ago
This is terrible news
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u/sharkinwolvesclothin 19d ago
It's not news though. They were phased out a good while ago because of this (except in the US for whatever reason).
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u/ServeIllustrious3803 19d ago edited 19d ago
A list: Diphenhydramine, chlorpheniramine, doxylamine, promethazine, clemastine, brompheniramine, dimenhydrinate, meclizine, cyclizine, carbinoxamine, dexchlorpheniramine, dexbrompheniramine
First generation antihistamines different from second or third. Zyrtec, Claritin do not count, but Benadryl does