Hacker News Re-Imagined

Long-term benzodiazepine use causes synapse loss and cognitive deficits in mice

  • 325 points
  • 10 days ago

  • @sternmere
  • Created a post

Long-term benzodiazepine use causes synapse loss and cognitive deficits in mice


@pizza 10 days

Replying to @sternmere 🎙

Much of the brain is about error correction of information transfer, bc two neurons have a typical *less than ten percent* chance of a message from A reaching B.

So if I were to put on my speculator’s hat for a second, having something that destroys neural connections at a local scale would probably be compensated with increased volume of noisy communication at a global scale.

And having heard ex-benzo addicts describe the withdrawal as like having your brain lit on fire, well, that tracks..

Reply


@ineedasername 10 days

Replying to @sternmere 🎙

>sleep-inducing dosage

I don't know why benzos are used for sleep anymore. It's generally a higher dose than what's needed to manage anxiety, so there's increased risk of dependency and you build up tolerance quickly.

In contrast, something like a low dose of Seroquel is at least as effective, has a much lower addictions & abuse profile, and tolerance doesn't build up very quickly at all.

On top of which there should very rarely be any need for regular sleep aids. Chronic idiopathic insomnia is relatively rare, and any other forms should have treatment protocols that don't involve heavy duty maintenance meds.

Reply


@mountainriver 9 days

Replying to @sternmere 🎙

Benzodiazepines are one of the worst drugs we have. We should be moving to outlaw them all together

Reply


@johntfella 10 days

Replying to @sternmere 🎙

be interesting to study someone, or a mouse I guess with said damages and doses of ambien for repair (https://jamanetwork.com/journals/jamaneurology/article-abstr...)

Reply


@foolfoolz 10 days

Replying to @sternmere 🎙

i think mental health medication has been borderline fraudulent for over 50 years. the drugs rarely beat placebos. when they work the methodologies of study are rarely replicated. this is just hanging some giant exit sign in front of desperate people saying we can get out out of this mess all the while knowing it’s a gamble. a gamble you’re paying with your health and someone else is winning by taking the money.

the “mental health movement” ignores this and is mostly lip service. clean your room. take a walk.

no one really cares about you but you and learning how to care for yourself is so hard. i hope we can train people in proper self care so we don’t need to prescribe their life away

Reply


@andrewinardeer 10 days

Replying to @sternmere 🎙

> Long-term use of benzodiazepines has been linked to cognitive

Like, no shit?

Reply


@ppg677 10 days

Replying to @sternmere 🎙

I take a half tablet (10mg) of Xanax every once in awhile. (Maybe once a month on average).

It makes me feel so relaxed.

I knew it was too good to be true.

Reply


@rootw0rm 10 days

Replying to @sternmere 🎙

Not too long ago I had an abundant supply of phenazepam from my days as a dealer in designer drugs. Being the raging addict that I was, I used it daily for insomnia. After wrecking my car while on a mix of MXE/phenazepam/alcohol I entered treatment and embraced sobriety. 6 months later I still feel like I'm recovering from the effects...

Reply


@randomopining 10 days

Replying to @sternmere 🎙

Was just in Mexico and took them 3-4 days in a row (0.5mg - 2mg) to sleep after drinking or the next morning. Slept amazing those few nights. Felt terrible 2 days after the last one, and even now close to a week later I don’t even feel that good. Pretty sure they are terrible for you.

Reply


@thepasswordis 10 days

Replying to @sternmere 🎙

In many people the alternative to benzodiazepine use is suicide.

Reply


@parentheses 10 days

Replying to @sternmere 🎙

Benzo use results in therapeutic benefits for many. The synaptic losses can pale in comparison to the anxiety it’s exchanged for. I know this to be true for at least one person close to me.

Reply


@jimmar 10 days

Replying to @sternmere 🎙

I took 1 benzodiazepine bill once about 15 years ago and I still remember the effect--instant total relaxation. I remember thinking that it felt too good and that it's something I shouldn't let myself have again. Hearing about its long term effects, I feel somewhat lucky.

Reply


@codeulike 10 days

Replying to @sternmere 🎙



@bjornsing 10 days

Replying to @sternmere 🎙

Benzodiazepines seem to have extremely different long term effects in humans depending on genetics and/or personality (or at least so it seems to me).

For example I’ve taken (prescribed) oxazepam and/or diazepam in significant doses every 6/12 hours for 3+ months, and then just suddenly stopped. Never felt the slightest urge to take the diazepam I had left in my bathroom cabinet.

But I’ve heard stories of people becoming severely addicted after consuming less than 10% of that total dosage.

So “your mileage may vary” as they say, and better safe than sorry.

Reply


@SemanticStrengh 10 days

Replying to @sternmere 🎙

anyone knows wether ghb is neurotoxic?

Reply


@arbuge 10 days

Replying to @sternmere 🎙

From the article: "When diazepam medication was stopped, the effects lingered for a while but were eventually reversed."

Reply


@bunnyfoofoo 10 days

Replying to @sternmere 🎙

Anyone have a mirror of the study [1]? It’s not available on scihub yet.

1: https://www.nature.com/articles/s41593-022-01013-9

Reply


@inmyunix 10 days

Replying to @sternmere 🎙

Does anyone have access to the article? I'm curious what the relative dose was.

Reply


@kbos87 10 days

Replying to @sternmere 🎙

I’ve been on Xanax on two occasions for very short periods of time to handle some acute anxiety issues and I can see why they are so addictive. At least at first, they are so clearly and massively effective.

My doctor very thankfully instilled a level of fear and skepticism in me from day one when he prescribed them, explaining that while they were a viable option for me in the moment, the effect begins permanently wearing off very quickly. They got me through some stuff but I was happy to stop taking them and hope I never am at the point where I need to consider them again having heard where it so often goes for people.

Reply


@narag 10 days

Replying to @sternmere 🎙

I know someone that has been abusing benzos for more than forty years. In hindsight, the weird thing is she's still somehow functional, at least in Twitter. But of course: needs four or five pills to sleep four hours a day, paranoia, migraines and dissociative behaviour.

Reply


@abstrct 10 days

Replying to @sternmere 🎙

I will always miss those I’ve lost to benzos. Some of my favourite people that I’ll never again share a new memory with.

Reply


@Commodore63 10 days

Replying to @sternmere 🎙

Jordan Peterson had a horrible time with these drugs and resorted to extreme measures to get off them (eight days in an induced coma!) Even today he might still be on them - he is pretty cagey about his present pharma situation when asked about it on podcasts.

https://nationalpost.com/health/jordan-peterson-benzodiazepi...

Horrible drug.

Reply


@SemanticStrengh 10 days

Replying to @sternmere 🎙

few people know it but you can fight a benzo addiction with flumazenil injections. You can even do it yourself if you have to avoid multiyear waiting lists.. (e.g. OTC on indiamart) however you must be extremely extremely careful to take the minimum needed dose, if you take too much you risk passing out/epilepsy. but at the medical dose, it is safe and will accelerate recovery time and quality dramatically.

Reply


@cosmiccatnap 10 days

Replying to @sternmere 🎙

I thought this was well known as Peterson effect.

Reply


@extant_lifeform 10 days

Replying to @sternmere 🎙

We now know what happened to jordan b peterson

Reply


@listless 10 days

Replying to @sternmere 🎙

I take .5 mg Klonopin for sleep every night.

Reply


@tinyhouse 10 days

Replying to @sternmere 🎙

Why there aren't more studies on humans? It's not difficult to find people who have been taking benzos or other related drugs for years.

Reply


@sedeki 10 days

Replying to @sternmere 🎙

Is it reasonable to assume that the same thing applies to the Z-drugs too, specifically Zolpidem?

I have a family member that I'm worried about, that has taken Zolpidem for several years straight (apart from minor breaks in between prescription refills because of overconsumption during the previous refill...).

Reply


@smithmayowa 10 days

Replying to @sternmere 🎙

Just came off benzos withdrawal those things are insanely horrible, delirium, depersonalization, derealization, muscle tremors, and persistent headaches were some of the symptoms I experienced. Thank God I did not have seizures.

Reply


@peri 10 days

Replying to @sternmere 🎙

I'm unsure why this took so long to be published here; the pre-print versions were also very clear about this with regards to other tranquilizers with similar methods of activity/chirality.

NB: I am a senior network security software engineer with a B.A. currently applying for Ph.D.s. I suggest that nobody believe anything online, regardless of provenance, until 10 years after publication.

Reply


@symlinkk 10 days

Replying to @sternmere 🎙

You know what else causes brain damage? Anxiety

Reply


@SemanticStrengh 10 days

Replying to @sternmere 🎙

The world of medecine is degenerate. Sustainable, non addictive and non neurotoxic anxiolytics exists: the #1 being opipramol the sigmaergic. emoxypine (which btw cure hangover) and guanfacine are worth mentioning. Maybe beta blockers to some extent. NMDA antagonists such as memantine have side effects but are not neurotoxic to my knowledge and there are milder ones such as mg-lthreonate. afobazole is interesting but its pharmacology is too weird to be sure. Etifoxine is revolutionnary, it double axon length growth rate so ironically a great cure to benzo neurodamage. its acts on the mitochondria benzodiazepine receptor. It's unclear to me wether it is subject to a tolerance effect and if so if it is lower. Also etifoxine can interact badly with other drugs on the liver. Note that there exists ultra-atypical mechanisms, such as inositol megadose or tofisopam but they are not firstline.

So yeah, basically opipramol and guanfacine should be what humans take as first line. Glycine is a nice obvious augmentation (kinda absurd that people forget about the second inhibitor neurotransmitter in the brain, especially since the effect feel nice and doesn't really lead to tolerance). if you have benzo neurodamage, take magnesium lthreonate which is a very potent synaptotrophic.

also fun fact: the benzo cartel was so strong it was the most prescribed drug in the world, all classes, in the 70s

Reply


@tunnuz 10 days

Replying to @sternmere 🎙

I was prescribed Diazepam some time ago (and loved it). But as far as I know you're not supposed to be on benzodiazepines for very long?

Reply


@meowface 10 days

Replying to @sternmere 🎙

>Experiments conducted by the researchers revealed that synapse loss in mice that were given a daily sleep-inducing dosage of the benzodiazepine diazepam for several weeks resulted in cognitive deficits.

I know it's only in mice, but it's pretty scary if it also has this effect in humans even when only taking it for a few weeks. Based on the title, I was initially kind of expecting something like daily use for years.

Reply


@SemanticStrengh 10 days

Replying to @sternmere 🎙

xan not workib

Reply


@sibeliuss 10 days

Replying to @sternmere 🎙

As someone with a few family members addicted to Xanax (long term) and have repeatedly bore witness to the destruction, I can say with certainty that it's an evil drug. It's like the person crawls inside a space where they can safely project all of their anxieties onto others. Their problems becomes your problems, a fully projected virtual experience. It's definitely psychosis-like, and I've always wondered if there was some brain damage involved. Well, here's the answer to that.

Reply


@robwwilliams 10 days

Replying to @sternmere 🎙

Caution: While this is a cool study in Nature Neuroscience, almost all facets of this work are based on a single fully inbred strain of mouse—-C57BL/6J. This strain also happens to have a major mutation in the GABRA2 gene that reduces expression about 2X relative to almost all other strains of mice. GABRA2 is one of the most important receptors involved in inhibitory responses in CNS and benzodiazepine responses.

This same strain also has a well known splice variant mutation in a key mitochondrial gene, NNT, that modulates both mitochondrial and macrophage function. The microglial mentioned in this paper are a special class of macrophages that reside in the CNS.

Given these comments, when the authors refer to “wild type” (WT) mice, remember these are anything but true wild type mice. Fully inbred strains always carry numerous homozygous recessive and dominant mutations (several hundred each) that often affect CNS, immune systems, and mitochondrial functions.

The results may well hold up in other strains, but I would not count on it. Do benzodiazepines affect all humans uniformly?

Would studies of other strains or types have been practical? Yes. The Thy1-GFP and Thy1-YFP lines can be crossed to make F1 hybrids. This particular transgene is also available on at least one other strain of mouse (DBA/2J).

Unfortunately, most reviewers at Nature Neuroscience are not geneticists ;-) They are typically strong molecular neurobiologists who are used to reductionist methods. They are perfectly content with submission to Nature journals that are based entirely on with N=1 mouse genome—almost always the mutant C57BL/6J inbred strain.

In my own work I try to avoid this N=1 trap. (But I have also failed ;-)

Generality and robustness of results (see quote below) should ideally be established across two or more diverse genomes before making broad claims of relevance to other species, including od course to humans.

The quote:

“We have demonstrated that microglia in WT mice alter their morphology and functions upon diazepam treatment and cease to do so in Tspo−/− mice.”

Reply


@jmcgough 10 days

Replying to @sternmere 🎙

Daily use of benzos is extremely bad in general - the physical addiction is not pleasant to withdraw from, and it significantly increases the risk of dementia in old age.

Reply


@doubtfuluser 9 days

Replying to @sternmere 🎙

While this doesn’t feel totally surprising - I have worked with people who were using benzos for many years, still this was: #in_mice

Reply


@samhw 10 days

Replying to @sternmere 🎙

On the bright side, has anyone else ever considered what an amazing amount of information there must be for mouse vets?

Reply


@kayodelycaon 10 days

Replying to @sternmere 🎙

This doesn’t surprise me. I have Klonopin for as needed use. (Since early 2019, I’ve used 106 0.5mg pills, so not a significant amount.)

Being bipolar, I find they are necessary for suitations my regular medication and coping mechanisms can’t handle. Without them, living a normal life would be difficult.

That said… benzos scare me. Taking one pill will calm me today, but at the expense for increased anxiety the next two.

If I go to a convention, I’ll have ramped up to my max dose around the second or third day. After that, it becomes less effective because I can’t (and won’t) increase it more. I’ve only gone five days at most and by the fifth day, my anxiety is the same it would be without medication. Coming off that afterwards is brutal.

If I had another effective option, I would use it. I’ve tried very hard to “power through” my symptoms or find alternatives during my first year being diagnosed. My psychiatrist, therapist, and friends had to just about physically slap me to use them.

Reply


@ineedasername 10 days

Replying to @sternmere 🎙

As a PSA, something to be aware of is the stimulant paradox for anxiety due to ADHD. Typically anxiety & stimulants would be a no-go combination, but for folks with ADHD-induced anxiety stimulants can actually help. I know someone whose child was (finally) properly diagnosed with ADHD only after they let their child try a tiny bit of their coffee and there was a significant change. It was the revelation needed to get to a good treatment path.

Reply


@AirStreamer27 10 days

Replying to @sternmere 🎙

This article makes me genuinely concerned for my own health and future. I was originally placed on clonazepam at 0.5mg/day back when I was a Freshman in High School and have definitely felt reduced levels of cognition whilst on it. I’ve only recently stopped taking it, around 10 years later.

Reply


@zosima 10 days

Replying to @sternmere 🎙

This is quite interesting as for a long time there has been some evidence that Benzodiazepine usage can increase the risk of Alzheimer's diseases and it has often shown up as a risk factor when doing large-scale database studies. Summary here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960222/

I won't jump to the conclusion that this is the mechanism, or be certain that the we are talking about causation rather than correlation, but evidence like this certainly tilts the weight towards causation.

Reply


@glerk 10 days

Replying to @sternmere 🎙

Benzos are pretty terrible drugs in general. The physical addiction potential and withdrawal people are going through are enough to dissuade me from touching them. For folks dealing with anxiety, I recommend trying propranolol. It is not as powerful, but sometimes it is enough to achieve the desired effect and the side effects are way less severe.

Reply


@ilikeitdark 10 days

Replying to @sternmere 🎙

Doctor gave me for anxiety in the day and sleeping at night. On it for way too long,and horrible. Definitely not worth it.

Reply


@colechristensen 10 days

Replying to @sternmere 🎙

Missing from the reactions here is the following line:

>When diazepam medication was stopped, the effects lingered for a while but were eventually reversed.

Also when making a conclusions from this mouse model to a human is how much were they actually giving the mice… a sleep inducing dose could be small or heroic.

Reply


@pyuser583 10 days

Replying to @sternmere 🎙

The effects it mentions in humans are not new.

Reply


@transfire 10 days

Replying to @sternmere 🎙

Benzos disrupt REM sleep. Eventually you will go mad.

Reply


@jquery 10 days

Replying to @sternmere 🎙

I wrote a long comment and then deleted it. I'm just here to say benzos are no joke. Do not take them unless you absolutely have to. Please, stop taking them if you suspect you are dependent, with a professional helping you taper and prescribing alternative non-benzo drugs as needed.

Benzos are a deal with Satan incarnate. They can be lifesaving but they extract a terrible cost.

Reply


@ldjkfkdsjnv 10 days

Replying to @sternmere 🎙

The reality is many drugs have long term effects, we just can't see them yet. But if you are close to someone who is a user, over the long run you will notice differences. Sometimes its just that they don't have the same spark. Regardless, 100 years down the line we will look back in horror at the state of pharmaceutical drugs. All it takes is going to a doctor, saying you have anxiety, and the doctor pops out a script. His "medical degree" and insurance demands that he "treats" his patient.

Reply


@twstdzppr 10 days

Replying to @sternmere 🎙

They are easily one of the most harmful classes of medications. Sure, they combat anxiety acutely, but wreck ones cognitive abilities in the process. This has been readily observable for a long time.

Plus, the anxiolytic effect quickly turns into a dependency, as when the withdrawal starts kicking in you're inclined to start having anxiety attacks.

Suppose you want to get off them. Now you have a significant problem. Can't quit cold turkey -- you're likely to have a seizure.

Reply


@shepardrtc 10 days

Replying to @sternmere 🎙

I was prescribed benzos because of sleeping issues, but I was also taking phenibut at the same time. After about 3 weeks of using large doses of the benzos every night, I stopped taking them, but a year later I still feel pangs of withdrawal sometimes when I get stressed. It took me another 4 months to get off the phenibut and a month or so after that before my sleep returned to normal. There were months where I maybe got an hour or two of sleep a night. If I got stressed, I simply wouldn't sleep at all. I once went three days without sleep. The torment of that combined with the withdrawal from the drugs showed me what hell was like. I tell everyone to never take benzos for any reasons. I don't care how safe the doctors say they are; they aren't. Period. There are repercussions - as this study shows - and they will not help the underlying cause of your issues. Treat the cause, not the symptoms.

Reply


@tinyhouse 10 days

Replying to @sternmere 🎙

Benzo got a terrible rep because of addicts. People who have addiction problems shouldn't be prescribed benzos. I can tell only my own experience working with a psychiatrist. I started on SSRI and the first month was horrible. They gave me benzo to help with anxiety and sleep. It really did the job, my sleep improved a lot. I used a low dose (1/2 of what I was prescribed) and had no symptoms besides being a bit more sleepy when walking up in the morning. I stopped taking it after two months of taking it daily, when things started to stabilize. I had no bad symptoms stopping it besides a hard time falling a sleep in the first few nights. About 4 days after I went back to normal and never had issues since.

I also know that in many countries benzos are the more common sleep drugs, unlike the US where z-drugs are more common. I know at least one person in my family that is now 90 who has been taking benzos for sleep for about 40 years. He is doing well cognitively. This is of course very anecdotal.

Reply


@nickstinemates 10 days

Replying to @sternmere 🎙

I read studied like this and just am thankful/grateful I don't need medication to function. People who live with having to be medicated sure have it rough.

Reply


About Us

site design / logo © 2022 Box Piper