Long-term benzodiazepine use causes synapse loss and cognitive deficits in mice | Hacker News Reader

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

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325 pointssternmere385 comments

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.

> I tell everyone to never take benzos for any reasons

You can't generalise your experience. Everybody is different and that's the doctor's job to assess whether the benefits outweigh the cost, considering the patient and their problems.

Personally, I've been taking benzos very occasionally for 20 years (never more than a few days at a time) and they helped me overcome difficult times. Never had the slightest addiction or side effects.

> Treat the cause, not the symptoms.

Easier said than done

Same here. Occasional clonazepam use for panic attacks which are secondary to post-traumatic stress disorder.

Never even the tiniest sign of dependence. Sometimes I go months between uses.

I am also a chronic pain patient and I worry that benzos are going to get the opioid treatment.

There was a period in the mid to late 2010s where patients who depended on opioids for any sort of quality of life were taken off of their medication without any sort of alternative. It’s something that people love to gloss over when they talk about the opioid crisis, but if you knew someone personally who went through that, you know that we collectively subjected those people to torture.

long term constant exposure to opioids will literally begin cause the pain they purport to solve. If you give a perfectly healthy person with no pain at all opioids for long enough they will be indistinguishable from a person who has an actual chronic pain issue.

people should only ever take opioids VERY TEMPORARILY to get through surgeries or other such things. Opioids are not for long term pain management.

Same thing with benzos and anxiety.

Not correct, at least for some opioids.

Nearly all opioids present the hazard of dose escalation over time to maintain their efficacy. Hence the dose escalation commonly seen with morphine, oxycontin, etc.

Most opioids, in addition to interacting with mu-opioid receptors (the mechanism of pain relief), also activate NMDA receptors, which enhance pain sensitivity. So for most opioids, there's an adverse dynamic in which analgesic activity competes with nociceptive activity, leading to dose escalation.

Methadone is one of two opioids that don't activate the NMDA receptor system. (The other is dextromethorphan, the OTC cough suppressant.) Methadone has been used very successfully to treat chronic pain, and does not exhibit dose escalation issues. Methadone has slow kinetics and does depress respiration, so when putting patients on it, dosages should be titrated slowly to avoid hazardous or fatal events. This is easily managed in ordinary clinical practice.

A close family member has been treated with methadone for chronic refractory migraines for >20 years. She transitioned to methadone from morphine SR after experiencing the classic need for increased dose. With methadone, she's had no dose escalation, no impairment due to psychotropic effects...it's simply given her a life to live.

Are you being treated with chronic pain by any pain killers? I've heard this before, but it's not exactly as you put it. Chronic opioid use leads to sensitization to pain. This doesn't mean it is equivalent to the pain being treated. In my experiencing minor sensitization to pain in exchange for treating debilitating, disabling, and depression-inducing pain is an amazing trade. I'd do it again without a second thought. It gave me the ability to go to school and start a career, as opposed to being permanently disabled

"long term constant exposure to opioids will literally begin cause the pain they purport to solve."

From peronal albeit limited experience, I don't doubt that opioids can cause pain they purport to relieve.

I used to take an OTC painkiller for headaches that was a combination of 500mg acetaminophen (aka paracetamol) and 10mg codeine and whilst it was somewhat effective the frequency of my headaches actually increased.

It eventually dawned on me that the painkiller and or the frequency of taking it was causing some rebound effect and that the likely culprit was the codeine - given that it was an opiate and thus potentially addictive.

I then switched to acetaminophen-only tablets and although less effective as a painkiller than the combination, the frequency of my headaches decreased quite dramatically.

I never exceeded the recommended daily dose nor did I take the tablets every day (as I've always been aware of acetaminophen's potential to cause life threatening liver damage on overdose), so my codeine intake would have been within acceptable limits (especially given the painkiller's OTC status).

That said, I abruptly switched to the non-codeine formulation without any noticeable withdrawal symptoms.

The fact that codeine could cause headache pain when taken at dose levels below that which would be considered potentially addictive has never been lost on me. I'm very surprised that the public hasn't been warned more widely about this issue.

"people should only ever take opioids VERY TEMPORARILY to get through surgeries or other such things. Opioids are not for long term pain management."

Or realize that people should follow their doctor's advice and realize that opioids definitely can be a part of long-term pain management. Not all long-term use is equal. You can have long-term pain and long-term use of opioids without needing to take them daily just like you can use benzos for years without needing to take them daily for that entire time.

You are vastly incorrect.

My family was addicted to benzos by a quack doctor who hands them out like candy. He has many seniors on it long term for "anxiety" and though seniors are at particular risk and are not supposed to use more than 6 months.

I got to see this side of American medicine while in high school. My great aunt unofficially overdosed on a cocktail of drugs prescribed by a group of loosely coordinating doctors.

When she passed, her cocktail included 12 prescriptions. One of her doctors had prescribed her medication to lower her blood pressure while another had her on medication to raise it.

Ouch. People are really bad at handling their own medical care. I’m legitimately on 8 different medications and 3 supplements (not including vitamins), per doctor’s instructions.

There is no way I’m going to any appointment (including my dentist) without a printed list of everything, including the dosages, instructions, and reason for being on it.

Edit: I apologize for the poor phrasing. It comes off being flippant. The reality is the American system is often broken, and it’s up to the patient to manage their own care. And for many reasons, people don’t or can’t.

What I was trying to say is, I have to do this and be diligent about it because no one else will. :(

Here in the Basque Country we have a public health system, named Osakidetza. Such system implemented, like five years ago, a centralized electronic prescription system. Now doctors in the public system have to use that to make prescriptions which solved all problems caused by bad doctors handwriting, and also solved problems like you mentioned, because the system detects and warns against conflicting medications.

Yes, I have seen something similar happen too - a temporary illnes that most likely didn't need any drugs, prescription for drugs that caused side effects, but then another drug for those side effects and the situation repeated 5 times in total, passing 3 different doctors. The real solution that worked was to stop taking everything.

Unfortunately listening to average doctor is a recipe for illness. Doctors belong to a medieval-style guild that managed to make it illegal to heal other people if you aren't its member, and extremely hard to buy needed drugs for yourself because of prescription (fortunately it's possible now because of internet pharmacies) - the latter of which is borderline slavery.

Against all 'expert' opinion, I'm pretty on average everyone would be better off trying to cure themselves using information from the internet - or at the very least everyone on hn.

My mother had hypothyroidism and got prescribed levothyroxine. She didn't like the idea of taking it forever, and after researching the internet found out selenium deficiency can cause it too. Directed blood test found a severe deficiency. After a month of taking selenium supplements thyroid hormones normalized. Internet self-diagnosis > average doctor.

Did she go to different pharmacies? I'd think within a pharmacy system the system would flag drugs that contradict each other.

I have friend who was at nursing school, and she'd get them prescribed for the few occasions where she had to do a presentation, as she would get extremely nervous. She never took them after. Maybe she could've addressed the issue differently, but it worked for her, and she never got hooked. But milage varies, and so on. She also told me that at the hospital, benzos are readily available and they kinda hand then out like candy to manage patients (there doesn't seem to be any rigorous bookkeeping about them).

I also tried a few many years ago, but they didn't really do anything for me. I think they only work if you got anxiety or something, so some underlying issue which -if chronic- is probably not a good fit. Never had any cravings since.

> I think they only work if you got anxiety or something

Probably something to that. I didn't feel much at the prescribed dose. Being curious and foolish, I took 3x. Did feel that. Socially effusive. Good sleep. There was a physical aspect. A warm glow, muscles that felt relaxed rather than stiff. Like waking up in warm sun after a particularly good night's sleep.

People without anxiety, who aren't literally and metaphorically tense, probably get far less of that. But that's what it does for a really anxious person like me, especially with a bit too much. So of course I did it again the next day.

You quickly come to long for, or believe that you're just better off, in that state all the time. But there is tolerance. It stops working like that at the same dose after a few days in my experience. So, take more. I was in big trouble within a month. That's the psychological addiction in my experience, the strong desire or preference for being in that state, emotionally.

I couldn't stop. No physical consequences but intolerable withdrawal mostly of rebound anxiety and insomnia. I eventually got off them with a very long taper. ~5 months with the dose adjusted weekly. No significant physical withdrawal. At the right dose of a long-lasting benzodiazepine, I felt like before I had started taking them, more or less. I did have to learn to deal with the psychological need to be more disinhibited than normal. If I could do that, and not escalate doses, getting off would be possible. It was, and I haven't taken any since the last dose of the taper. I think about that state and sometimes I do long for aspects of it, but they're not really cravings anymore. Only get those for nicotine.

Were you receiving any other kind of therapy for your anxiety during this time?

I tend to see it a bit like “medication stabilizes; therapy heals”.

I tend to see the opioid epidemic (which is comparable to the current benzo problem) as a systemic failure. You were handed a loaded gun and no one taught you how to use it.

Our medical system is designed to be transactional, but the experience of a chronic condition is a narrative.

I’ve reacted differently to different benzos. One did nothing. Another triggered one hell of a mood swing (I’m bipolar). Finally settled on Klonopin, which has a long half-life. It seems to be less.. harsh?

Psychoactive medications are fun…

I really only ever tried the ones with a short halflife personally.

Now that I think of it, a benzo actually did help me once, when I got my wisdom teeth removed. Made me a bit more calm about it. But it was fairly tolerable overall anyways.

I've been told that benzos are a good option for someone anxious about flying. They make the flight tolerable and help the person feel comfortable flying in the future. They may only need to learn that there's nothing to fear in flying, and benzos can help them learn that.

I trust the person who told me that, but have heard a lot of benzo horror stories.

(I'm not afraid of flying)

Unfortunately, I’m one of those individuals illogically terrified of flying. A small dose of a benzo (in my case, Ativan), makes the flight bearable.

Agreed, I have pretty bad social anxiety with hypervigilance. Taking on average 3 5mg (occasionally a 10mg dose) tablets a week when needed for presentations or meetings with more weight allows me to keep my job.

Even such a small dose I feel restores a sense of normality that I haven't experienced in over 10 years without them, I'm able to rationalise what I want to say, conversation flows, I feel in control. With all that said, I've been doing this for a while and have never come close to addiction and no noticeable side effects. I continue to work on the underlying causes but without them I would be much worse off.

For performance anxiety, try asking a doctor for propranolol.

Propranolol blocks the physical symptoms of anxiety. It stops your hear rate and blood pressure from rising. It stops those uncomfortable adrenaline rushes. It stops stress-induced trembling / shaking.

It's completely safe, any doctor will happily prescribe it, it's not addicting, and unlike benzos, it doesn't affect your cognition.

Thanks but I've tried beta blockers and a couple of SSRIs and diazepam is the only thing that touches my anxiety. When I walk in public the vigilance to perceived threat is is what I would expect walking through 1980s Beirut, it's a primitive fear response that manifests through symptoms that are more mental than physical in nature - heart rate and sweating in particular are issues but seem to me to be at the bottom of the chain.

How can it be "completely safe" if it's affecting your heart rate and blood pressure? Those are pretty basic systems to tamper with and altering them in ways contrary to what signals your brain is sending is inherently going against the normal functioning of your body.

This is exactly me

This whole discussion is making me feel better than ever for choosing cannabis edibles (legal in Canada) to address stress-induced insomnia and other sleep issues for which the root cause was not something I was in a position to immediately address.

I take it a few times a week as needed, small doses (2-5mg) and I feel that I am in control of it and could go off any time.

The thing with most addictions is that as long as you are taking a substance and don't try to stop you feel that you are in control. As long as you have not tried to stop you will never know

Fair, fair. I think the main thing is that I'm not taking it in response to a craving, but rather in recognition that my mental state in the early evening is fragile and I'm going to be more susceptible to an anxiety attack when trying to sleep. I'm also well aware of the root causes of my mental state, so if it ever became bad enough that I did feel like I was losing control (upping the dose, taking during the day, etc), then I would treat that as a sign that it was time to start thinking more seriously about exiting the situation that is the main root cause.

I think it also helps that edibles take 60-90 mins to kick in, vs smoking which is pretty immediate gratification.

I use benzo to reduce anxiety, not for sleeping. In some situations, I'm so anxious that I'm not able to work properly (e.g. giving an important talk, dealing with stressful situation at work). Benzo magically removes the anxiety and let me function properly.

This isn't my experience with cannabis: it does relieve anxiety but it also makes me unable to get anything done, which defeats the purpose.

There's a fine line sometimes with edibles and anxiety with many people, I observe.

Doctor's job is to quickly find a solution in the 10 minute appointment that insurance will cover optimizing for higher pay. A doctor runs a business.

If you have been taking benzos for 20 years you might have an addiction. Parent poster was talking about cravings a year later.

Most doctors don't run a business.

Private practices in the US have been declining for decades. Most Doctors today are employed by a hospital or other provider network. This trend has only accelerated since the pandemic as well. As a result of this Doctors have had no choice but to run their practices as a business. This is why they now require you to have a credit card on file, why there's cancellation fees, and why you don't actually see the Doctor until almost an hour after your appointment. They are simply triple and quadruple-booked. They can not choose their volume. This trend has been well-documented. See:

https://www.ama-assn.org/press-center/press-releases/ama-ana...

https://www.healthcarefinancenews.com/news/nearly-70-us-phys...

https://www.webmd.com/health-insurance/news/20210527/more-an...

> easier said than done

Yes but easier comes with a greater cost.

This is widely true for broader society where we are all busy taking the convenient solution over the harder, proper way, because screw long-term.

Sometimes, you have to realise that what pharma companies list as 'side effects' are not that at all, they're effects. Think about that.

Yes but easier comes with a greater cost.

It isn't like we are choosing easier because we are lazy. The reason it is easier to say is because with a lot of diseases and afflictions, we simply do not know the cause or do not know how to treat it. And honestly, it is Much better to treat symptoms than to treat nothing at all. Heck, sometimes it might mean death - like in the case of diabetes - or more suffering and disability - like with MS.

It isn't just because we are taking the convenient solution, in other words, and I find it disingenuous not to remember that we have a lot of holes in our medical knowledge and to realize that our imperfect knowledge leads to much of this.

And redefining side effects isn't really helpful. Sure, the medicine causes them, but it isn't like any researcher or doctor is trying to make you have unwanted effects. They are there because we don't yet know how to do the treatment without unwanted effects, and we still do it because sometimes those are better than the disease.

I don't think "big pharma" is innocent, mind you, but it doesn't help anyone to focus on conspiracy theories when you could be looking at things that actually happen and including other organizations that allow the abuse to continue (for profit medicine, for example).

Yeah, I've been diagnosed with chronic insomnia and benzos are the only thing that can reliably put me to sleep if I desperately need them. I reserve them for emergency situations, but just knowing I have them as an option is comforting.

I think literally everything from learning to play tic tac toe to quantum computing is easier said than done…

It’s harder to clear trauma, teach emotional regulation and to build a life that is healthy, yes. And, it’s a path worth walking down.

> that's the doctor's job to assess whether the benefits outweigh the cost, considering the patient and their problems.

Have you been hiding under a rock? American doctors are completely corrupt and in the pockets of "big pharma". They've gotten millions of Americans addicted, and caused countless deaths and unimaginable human suffering.

> You can’t generalize your experience

Would that not mean the same to your own?

To anyone curious about phenibut:

Don't. Just don't. Please.

Just a few weeks of usage can cause dependence. It is notorious for causing compulsive redosing. Withdrawal can make you unable to sleep for days, with lingering effects like panic attacks and anhedonia for weeks and weeks. Withdrawal from larger quantities can cause auditory and visual hallucinations and seizures and can even KILL you. Avoiding serious symptoms requires an excruciating taper that can take months. The effects of long term abuse are poorly understood.

"But it's totally legal, and with responsible dosing can be a potent nootropic. I'm not a drug addict, I'm a biohacker. I'm not after a high."

Yeah, That was my thinking too, and in hindsight that was immensely stupid. Please just look at r/quittingphenibut before doing anything.

Be kind to your GABA receptors.

I take phenibut about 1x/week, I have been for about 2 years now. I think it's generally pretty OK for me, though I've started to worry that it impacts my memory a touch, at the edges.

Do not take drugs every day. For real. I don't want to victim-blame but it is wild that you expected to be able to be able to take drugs daily for weeks without withdrawals. As a rule of thumb, unless you intend to be on it forever (e.g. caffeine), you should never take anything more than maybe 2 days out of 7 in the week. Psychoactive drugs are not like aspirin, where you dabble a bit as necessary.

Phenibut is serious stuff. Nobody would say "I had only been drinking a pint of vodka every day for a few weeks before I realized I might have to deal with withdrawals."

> I take phenibut about 1x/week, I have been for about 2 years now. I think it's generally pretty OK for me, though I've started to worry that it impacts my memory a touch, at the edges.

You're addicted, you just don't know it.

> it is wild that you expected to be able to be able to take drugs daily for weeks without withdrawals

If you're referring to benzos, the doctor said it would be fine. If you're referring to phenibut, I wasn't taking it every day. Maybe every few days or maybe once a week.

> You're addicted, you just don't know it.

I smoked cigarettes for ~10 years and I went to rehab for cocaine as a teenager, I am pretty familiar with addiction. I have never exceeded 1x/weekly phenibut and I've taken weeks off for travel, studying, etc, with no problems. I use some other substances recreationally with various cadences, set according to my understanding of how the body reacts to them (e.g. LSD never more often than every 2 weeks).

It's shocking to me that some people can smoke the occasional cigarette without getting hooked, but the fact of the matter is that the psychological impact of drug use varies quite a lot according to the (person + substance) in question. Nicotine is something that happens to appeal to me a lot more than it seems to appeal to other people.

> If you're referring to phenibut, I wasn't taking it every day

I'm replying to phenthrowAway, who said he used phenibut for "just a few weeks" before getting dependent.

This is why we can't have nice things.

I'm sorry, but you fucked up, with the focus being on "you". Phenibut is notorious for building tolerance fast, and having bad withdrawal.

I really really dislike it when people try dangerous things in obviously wrong ways, then act like it's society's fault that they were available. No, it's not. I've tried a lot of things over the years, and I've been properly paranoid with most of them. I'm extremely creative with treating my insomnia but guess what: I have two doctors I check with. I don't care when they laugh at me (like when I told them I'm taking 1/60 mirtazapine pill), or when they shrug. I keep checking for the moments when they say "no, that's a really bad idea", and I keep doing that even if they keep saying nothing for 10 years at a time. Because even one "no, that's stupid" makes it worth it.

Well that's frightening. I tried it out recently and didn't really feel anything that would get me hooked on it but maybe that's naive.

My advice: Don't underestimate the substance, but also don't give too much importance to stories of people that overdid it and had a terrible time. People have been using Phenibut for long periods of time without getting dependent -- provided they space out the "Phenibut days" enough. Of course that requires some self-knowledge: If you are the kind of person who would have trouble keeping it to "not more than twice a week maximum (ideally not more than once a week) at reasonable dosages", then Phenibut can easily turn into a slippery slope to physical dependence, with horrible withdrawals.

If you know yourself enough not to overdo it, it's not _that_ terrible a thing; though your individual response to it will of course vary, which is where the "self-knowledge" comes in again.

If you have "Phenibut days", you're addicted. You may space it out, but your body is adjusting to it being in your system. It is that absolutely powerful. I was like you before things got bad.

Phenibut is horrific and should be banned. I thought I could control it, but I couldn't.

I tried it once years ago.

Amazingly potent. I considered finding applications for it, but alas, I had no use for it.

Seems like a WW2 drug like amphetamines: Sure works wonders if you’re patching up people, going through horrors like a breeze. But it ain’t a peace-time nootropic with minimal downside.

Never more than two non consecutive days in a week — this isn’t a mystery.

Because you have no self control a substance should be banned.

Cool world that would be to live in.

These drugs chemically change the brain, so your brain might fall into a state where you lose control.

Drugs often get pulled decades after being approved, usually because the safety studies were not expansive enough to give a complete picture of the danger. For example: Varenicline.

I've heard of people going through withdrawals after just a single week of use. Nuts that it's sold as a supplement at all.

Interestingly enough, a suspected GABA prodrug that supposedly passes the blood-brain barrier called picamilon has been banned by the FDA, yet phenibut is still on shelves.

picamilon is banned? That's dumb, soon they will ban l-theanine and taurine? I really don't think you can get addicted to picamillon like phen or benz

Some supplements are basically unregulated medications.

I found out the hard way that L-Theanine does not mix well with bipolar disorder. I suspect it inactivated the mood stabilizer I was on.

The FDA's argument is that it isn't a naturally occurring substance like an amino acid: https://en.wikipedia.org/wiki/Picamilon#Regulation

It's much the same with chronic alcohol usage, and a very similar pathway. Both alcohol and benzodiazepines bind to GABA receptors, and through several difference mechanisms (desensitization, downregulation through gene expression, degradation), these receptors become less sensitive.

GABA receptors are critical to sleep. After prolonged usage of alcohol, or benzos, sleep often becomes impossible without an ever-larger dosage.

These sleeping difficulties sometimes persist for quite a while, and sleep disturbances are one of the primary causes of relapse in alcoholics. People learn that alcohol helps them to fall asleep. Even if the quality of sleep is poor, it's substantially better than no sleep at all, as anyone who has gone through what you did surely knows.

Someone close to me has long been addicted to both alcohol and Ambien (sleeping pills).

I'd never considered that alcohol could trigger the need for Ambien. I'd presumed it was a lifestyle thing for someone who was used to being out all night.

Did you tell your doctor you were taking phenibut when they prescribed you benzos? It seems like something you definitely shouldn't mix.

I completely agree that benzos are bad news unless you truly need them. In my relatively uneducated opinion, I don't think they should be a first-line treatment and it's kind of a joke that they're considered schedule 4 (at least compared to things that are schedule 2 - I don't think really anything should be "scheduled"). Benzos and other gaba-ergics may not be as pleasurable as other drugs, but they're very addicting and have the most harmful withdrawal process of any class of drugs.

Phenibut and the prevalence of RC benzos (which aren't subject to the federal analogue act since benzos are schedule 4) are another phenomenon. I think people underestimate the risks of this stuff due to how easy it is to get them - especially phenibut which is sold in a lot of more "legit" websites.

They are considered a first line treatment because they are fast acting whereas other anxiety medications like SSRIs can take weeks to start working.

That makes complete sense for something like panic attacks. I guess I’m thinking more of GAD - I don’t know if they’re formally first line treatments but I know it’s definitely possible to get started with a long-acting benzo

> Did you tell your doctor you were taking phenibut when they prescribed you benzos?

I mentioned it the old doctor, but they didn't know much about it. The newer doctor researched it and was horrified by it.

Mixing them is terrible and should be avoided at all costs.

> 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.

Do you ever wonder if maybe something about your situation might be different from most other people prescribed benzos? For example, the concurrent phenibut use.

> Do you ever wonder if maybe something about your situation might be different from most other people prescribed benzos? For example, the concurrent phenibut use

Absolutely, but benzos are a temporary fix regardless of anything else. They can't fix underlying causes. Obviously people can pop a xanax every once in a while and not go crazy like me, but if you're doing that, perhaps you should look into other treatments like modern SSRI's.

First, I want to acknowledge your situation so I don't want to belittle what you went through in any way, but I had a catastrophic series of events happen in my life almost 9 years ago, and Xanax was literally a life saver for me.

Taking the Xanax allowed to me relax enough to do the work to figure out how to relax naturally. Before the Xanax I was having crippling panic attacks 24/7.

My only point is, you're a data point of one, I'm a data point of one we both had very different experiences. I don't tell people to take, or not to take benzos when they ask me, I just give my objective experience and let them make their own decision.

I'm glad they worked for you. And yes, in extreme cases, yes, a relatively mild benzo like Xanax can really help. But doctor's give them out like candy and people don't really understand what's happening when you take them so they keep taking them. I give out that warning just to be safe because most people don't research things enough.

“I once went three days without sleep.”

This is just a side note, but I’ve never heard of anything like this happening before with such a short course of benzos.

That doesn’t mean it’s not happening, and it doesn’t mean that it’s not the benzos, but because it’s an unusual outcome, have you considered looking into other possible causes?

You were taking the benzos for sleep, after all, could a different underlying cause have gotten worse or been exacerbated by the benzos?

To be clear, this isn’t to diminish or invalidate your experience, it’s genuine concern from another human.

It was two 15mg Temazepam capsules every night. Temazepam is a very powerful benzo. One night I actually took 60mg total without understanding what I was doing. So its very different from a Xanax, which is what people usually think of when they think of benzos.

Anxiety was the underlying cause of all of this, and I was dealing with a lot of stuff in life at the time that was causing me anxiety. So yes, it wasn't just the benzos and the phenibut. My body simply couldn't handle any anxiety and I was putting myself in situations that caused it.

Of the common legal drugs, benzos are by far the most dangerous to quit.

And you get addicted in like a week.

Be very careful.

There was a tea bar in my neighborhood that would put kratom in one of the teas.

It didn't make me feel particularly euphoric, but I did find myself craving it the next day. Shit is fucking weird and scary.

It isn't a terribly difficult drug to quit but it is addictive. Some people use it to wean themselves off of opoids.

> Of the common legal drugs, benzos are by far the most dangerous to quit.

Not sure if that's right. Alcohol withdraw can actually kill you.

They're the same withdrawal... Benzos are just far more potent, so the dependence can happen MUCH faster, in like days.

By the time you've developed alcohol dependence you've most likely gained more than a few comorbidities. That doesn't happen in a week.

Which comorbidities? I am just curious.

Benzo withdrawal can as well.

Oh, I didn't know.

I took it for two months for sleep and had no issues quitting it besides a few nights of taking longer to fall asleep.

Somewhat germane:

https://pubmed.ncbi.nlm.nih.gov/22371848/

Conclusions: Receiving hypnotic prescriptions was associated with greater than threefold increased hazards of death even when prescribed <18 pills/year. This association held in separate analyses for several commonly used hypnotics and for newer shorter-acting drugs. Control of selective prescription of hypnotics for patients in poor health did not explain the observed excess mortality.

Just putting this in here. If you are suffering from insomnia, one possible alternative is to look into CBTI (cognitive behavioral therapy for insomnia). Its one of the only clinically proven non-drug-related treatments for insomnia. If you are struggling, google it and try to find a CBTI counselor to help. Don't try it on your own - its quite challenging. It literally saved my life a few years ago.

I don't think they're meant to be taken that way.

I've had the same bottle of Xanax around for 5 years. It's more like a "break the glass in case of emergency" type thing. Usually reserved for going to funerals or weddings of people I hate, when I can't tie my tie because I'm in a cold sweat. As the kind of alcoholic who never turns down a drink, it surprises me how strongly I don't want to touch diazepam, how little inclination I've ever had to take it recreationally, even though I enjoy it and know it can provide short-term comfort. On a lot of occasions, having the bottle in my pocket just in case has been enough.

Then again, that might be because of how strongly it reacts with alcohol, which is a given in most situations where I'd break out the Xanax...

I learned about benzo alcohol reactions the hard way. I took one or two decent doses (purple footballs) of Xanax with a lot of alcohol. I some how made it home and then fell into a cycle of sleep sessions where I would sleep for four hours, wake up for 15 minutes, and then fall back asleep. This happened several times, wiping out an entire day of my life.

I was finally roused to go help my brother who had done the same thing but instead of sleeping he wrecked my motorcycle and bounced his face off a tree (helmet on, he was ok).

A few minutes down the road my uncle had done the same thing but was already home--he managed to total my cousin's car (his son's car) in the driveway....in reverse.

After that I was done with benzos forever. My brother and uncle weren't though. As a result they are both in an early grave.

There is more to the story but benzos we're always central to dangerous addiction, raging drug abuse, and heroine use. Around that time my brother almost died by drowning in a bowl of fruit loops on a benzo bender. His girlfriend found him face down in the bowl and saved him--and subsequently left him afterward.

My dad (also dead from addiction) was on benzos for many years...very small dose. He was an alcoholic and the benzo+alcohol mix (I found to be a very common self medication and recreational outlet) literally destroyed his life.

I have a pretty negative and reactionary stance against the whole range of pills that people deal in. Though, my experience is one where I have never seen anyone be helped by them.

I'm kind of ridiculously qualified to speak on this subject. I've been taking phenibut off and on for over 6 years now. lol back when it was known online as the "crazy russian drug" lol. Before that I was on gabapentin. It's a type of drug known as a gabapentinoid. Phenibut has a reputation, but it is basically just gabapentin/neurotin/ or lyrica/pregaba(Honestly, you might have been able to solve your problem with a perscription to gabapentin. There probably is a cross tolerance.). I was also prescribed benzodiazapines for years. I quit several times basically cold turkey(don't ever do that). I didn't find benzodiazapines in any way psychologically addictive. They are physically addictive. REALLY physically addictive! I feel like all the issues caused by benzodiazapines went away with time. Short term, there were a ton of problems. The human brain is good at adapting to things. Benzos makes you tired and hungry... That isn't recreational to me. I was basically taking benzos because I was so miserable I didn't want to exist anymore. It wasn't recreational, it was self medicating... COCAINE is a recreational drug. I also dont get how people have problems with phenibut. You get a tolerance faster than any drug I have ever taken. You end up having to double the dosage almost everyday... I've had several psychiatrists literally try and diagnose me with bipolar disorder while i was on VERY large dosages of gabapentanoids. The "high" is the most chaotic thing I have ever experienced. Why would you want to feel like that everyday? Anecdotally, I had a very different experience from you. Phenibut also just does crazy, crazy things to your libido. Seriously... It turn's you into a sex maniac... It takes 5 hours to kick in... It doesn't even make since as a solution to the problem you were trying to solve! Take it and maybe you will go to sleep in 5 hours... I'm literally on it right now. Maybe i'm approaching things more from the perspective of an addict. I guess it's understandable that maybe you have had a different experience than me. I'm on seroquel for sleep issues. Maybe give that a try. At low dosages seroquel functions as an antihistamine not a antipsychotic. It's solved my sleep problems better than anything I have ever taken. I've had a very, very different experience from you. The Phenibut for sleep thing doesn't make since. I'm messed up on the stuff atm. I took it yesterday. 24 hours ago! Don't take it for sleep. Maybe take it at gym if you really need to kill it.

I have to disagree with the "any reasons" part. First is if it's a psychiatric emergency administered by a nurse for psychosis but I doubt we're really talking about that.

But I think they're a valid last-resort treatment for panic attacks if we're talking less then twice a month-ish range. Reason being is that they will reliably work every time, and for many people including myself just knowing we have it can prevent panic attacks. But you still need to be treating your anxiety with therapy and/or other medications (but especially therapy) - its only a last resort.

And I mean using it very sparingly, I only take it once every few months, and only the lowest dose (klonopin @0.5mg max) to take the edge off so I can work through it, not enough to remove all the anxiety.

EDIT: Oh and anyone with addiction issues should stay away from these. They work _every time_ which is so tempting to use for just mild anxiety and my understanding is higher doses then what I take are euphoric so stay clear.

> But you still need to be treating your anxiety with therapy and/or other medications (but especially therapy) - its only a last resort.

Most people ignore this part.

> I tell everyone to never take benzos for any reasons.

You tell people having a panic attack not to take a sublingual benzodiazepine?

A panic attack is not a normal reaction. There's an underlying cause to them, and I tell people that they should get that treated. Benzos are a temporary fix.

A friend of mine has panic attacks all the time. He should be on SSRI's but refuses because his anxiety is telling him that they'll destroy him. Can't do any worse than his existing anxiety though.

> Treat the cause, not the symptoms.

By all means comrade, supply UBI, universal healthcare, and quality housing for free.

The reason I was stressed in college is because I didn’t have those things and I needed to work exceptionally hard in a cutthroat stack ranked program to stay afloat. Once I was making $100k+ (I was living in SV) and had a financial cushion instead of barely scraping by - I didn’t have as severe of sleeping issues. Same with getting a partner. It was nice to share the bed with someone instead of being alone for 26 years.

Doctors prescribe stuff because that shit isn’t possible to fix by them or nearly anyone else on an individual level. It requires systematic changes to our entire economy (and dating economy for the relationship part).

>There were months where I maybe got an hour or two of sleep a night.

I feel like this is very easy to gloss over while reading, but in actuality is quite an intense experience to have gone through. This would drive me actually insane, I don't know how to coped with it

It was utter torment. I had to run a team at work all the while. I was able to do it, but only through sheer willpower. I had to constantly reiterate to myself what was happening and the timeline for it to be over to be able to deal with it. It increased my mental toughness dramatically. My life is actually much better now because of the entire experience.

Doctors prescribe benzos for sleep issues and tell you they are safe? Do you live in the US?

Yes. Some doctors do; some don't. My new doctor was horrified when I told her what I was prescribed. She's young, and she said the first thing they say in medical school nowadays is, "Benzos are bad." My first doctor was much older and clearly from a different era of medical school.

My doctor is young and gave me a limited prescription for ten doses of lorazepam while I was adjusting to duloxetine, which often exacerbates anxiety in the first couple weeks. I was experiencing regular panic attacks before starting so he wanted to be sure they didn't become disabling. Benzos are safe when the amount and duration are carefully controlled. The problem is chronic usage, which is more or less contraindicated these days.

is that a question? Benzos are not safe despite what many doctor believe. I'm in EU.

In my opinion doctors underestimate the danger of benzos. They also often don't know that there is a black market for benzos (like there is for any other drug). Patients will be able to find benzos if they look for them even if they don't have a prescription.

I had a friend who wanted to stop smoking cannabis and got alprazolam prescribed for that by his doctor (it was in EU). In my opinion it would be better to stick to cannabis than switch to Xanax.

I myself tried talking with my family doctor about my benzo addiction. I was addicted to etizolam, a RC benzo popular at the time. He seemed not to believe me that it was possible to get benzos without a prescription, and told me that I was wrong and couldn't have a benzo addiction.

Weird this can happen in the EU to be honest.

In Germany these things are really difficult to come by for these minor reasons (it's probably different for the critically ill but I wouldn't know).

Briefly, doctors have to have special permissions to prescribe potentially addictive or mentally altering substances and it's only with a special, bureaucratic kind of prescription ("BtM-Rezept").

That's why I always wonder how this can happen so casually. If I'd ask my GP for benzos for sleep problems I'd most certainly not get them even if he'd be allowed to prescribe them and reckless prescription in this case could lose him his license.

they're saying they wouldn't be so easily prescribed in the US

Actually the opposite. Pharma making people addicted: Opioid epidemic and all.

is that a joke? I'd be very surprised if doctors were'nt abusing benzo prescriptions for GAD

Wow, 1. who tf gave you phenibut before gabapentin/pregabalin? Phenibut is notoriously hard to quit. It takes at least a few weeks of gradual tapering down. 2. Together with a benzodiazepine? Wew, lad. Should've also taken a few shots of vodka before sleep for the insanity trifecta.

Edit: sorry, I always assume other people have access to medication. I don't so I shouldn't have laughed.

Yeah, so there are a few gabapentinoids/gabaergics out there, and they can help a lot.

But please read everything you can before deciding on something.

Just a couple of pages of Phenibut experiences have convinced me to not try it because there are better alternatives with fewer side effects.

He probably gave himself phenibut. It's not a prescription drug. You can just buy it online.

I bought it online under the name Somatomax. But you can get it from plenty of other places easily. Actually, a different doctor recommended it to me much earlier. "Just take a break every once in a while," she said. Ok, doc!

it's less frequent but people can get addicted to pregabalin too.

I mean, a lot if not most drugs are addictive - if not physically, then mentally. It's all down to whether it helps you more than it harms you.

Hell, I can make the same argument about exercise - is it worth the risk of physical injury, something that most people don't even consider? I'd say yes, the beneficial effects outweigh the negative ones.

I've used gabapentinoids (and am using a gabaergic right now) to great positive effects. The downsides are there but they are minor. On that note, I have been using alphaPVP for ADHD management and am happy to report it is nowhere near as scary as the media makes it out to be. A shorter lasting version of methylphenidate, basically, and better than cocaine for the purpose.

Gabapentin and pregabalin withdrawal can be scary at first, but once you know the effects and learn to taper off, they're rather harmless. In fact, the biggest danger is in not being able to buy them because the medical system won't allow it, leaving you to quit cold turkey. Second biggest danger is from the police (illegal to possess without a prescription).

I have not tried any benzodiazepines or phenibut, but I'd bet they can be managed pretty well.

I think it’s dangerous to say you should never take benzos. People and their mental states are different.

For people with anxiety and panic attacks, benzo’s are literal lifesavers.

There were times when I abused them. I had a pretty bad withdrawal that gave me a seizure. Now I take them to give me munchies. For that of course I must not take it for longer than 2 weeks. My depression and anxiety is treated in a different way. Benzodiazepines messes with my memory and cognition. Lorazepam seems to be the worst on memory, for me. Useful for dental appointments though.

Was your use monitored by a doctor? It doesn't sound like it. Klonopin was very helpful for me to pull me out of an episode of severe anxiety and constant extreme panic attacks. It was a bridge med until the SSRIs kicked in. My dose was never that high and I wound off them slowly after two months. Stopping abruptly after 3 weeks sounds like a bad idea. Im very grateful for that drug.

I’ve taken benzos for half my life but I space them out in a way so they aren’t damaging like that. Yeah it can be bad how people don’t realize how damaging they can be. I’m really grateful for them, and they’ve saved me from burning out at my job multiple times (hypersensitive, social anxiety, likely autism)

I think they're quite dangerous nightly/daily, but from what I've seen 1-2X a week for sleep can be restorative versus perpetual insomnia.

> 3 weeks of using large doses of the benzos every night

Is this literally what the doctor prescribed?

I recommend trying clonidine . It was a life saver for me

Just use Marihuana and stop taking synthetic shit.

there can be legitimate uses for acute exceptional benzo use for e.g. panic attacks but yeah for anxiety or sleep they are a slippery slope that ruin lives. As I said in my other comment, there exist effective, saner solutions.

I have a small pack of prescribed diazepam in my backpack in case I have a panic attack. Haven't used any of them so far, but just having them there makes me a lot less anxious.

That’s a classic strategy. I had a brief period of panic attacks that benzos really helped with that helped me gradually have less and less. I don’t particular like the feeling of the benzo, luckily, so it wasn’t appealing to take outside of acute need. My doctor did seem to want to monitor refills and asks me how often I take them (almost never now), so he was aware of the dependence issue. I do carry one around just in case, and very rarely, do in fact need it.

Same here with klonopin/clonazepam . I take .5mg max which is generally the starting dose, and very, very sparingly - like .5mg every few months max.

Benzos can absolutely decimate anxiety reliably - and half of my panic is the fear of not being able to control a panic attack (thus the self-feedback loop into panic). The amount I take only takes the edge off which is all I need, just knowing I have it is such a massive help at preventing panic attacks it's crazy.

My eventual treatment for my underlying anxiety was Lexapro. It's worked wonders. I can't say enough good things about it - as long as you stick with it. Old SSRI's are terrible, but newer ones work like they're supposed to. At least in my opinion.

SSRIs do not work for everyone. It's good that they work great for you.

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.”

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.

>"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."

The loss of a spark can happen regardless of drug use. Work in an unsupportive environment over a long period of time, a breakup, or the failure to achieve a long-sought goal can cause a person to change over time. In addition, the underlying condition that the medication is treating may cause the effect, which could have been worse had the medication not been prescribed.

It's plausible that medications may have understudied long-term effects, but there are too many confounding causes to attribute a behavioral change to long-term medication use.

As someone who has had a long time relationship with Xanax, it quite literally saved my life. I was prescribed it for chronic nausea, and was 40lbs below my ideal weight.

I've never been tempted to take any more than my prescribed dose, and so it's been a "healthy" relationship, but I'm working to discontinue my prescription for reasons other than this article.

Not to be one of those "well, I use it and I'm fine and aren't tempted", on the contrary - I understand fully why people would feel the tugs of addiction.

It's hard because I know I have an uphill battle to go. I use therapy and have seen benefits from psychedelics and medicinal cannabis, but it's literally a "pick your poison" battle.

But also, it's hard to have a spark when you're not able to live a normal life without assistance.

But in hindsight, I can see that this route has had it's costs and I'm excited to see who I am independent of it.

> His "medical degree" and insurance demands that he "treats" his patient.

Completely lost me here. Why does the doctor have air quotes around their medical degree? And what’s wrong with treating disease? Or are you saying insurance requires unnecessary prescriptions? Because that’s definitely not the case, insurance would prefer no prescriptions financially at least and the doc is paid the same either way. Overall I think you just have an axe to grind against medicine for some reason. It’s not a perfect system but I don’t think you really know what you’re talking about and are concerned with the wrong things.

The reality is that many doctors these days will not prescribe large amounts of benzos, certainly not just willy nilly.

I'm not just talking about benzos, but also anti psychotics, amphetamines, statins, and basically the whole gamut. My brother is a pharmacist, and is constantly shocked by the prescriptions that healthy people bring in to get filled. The medical field has been unjustly given too much prestige.

> My brother is a pharmacist, and is constantly shocked by the prescriptions that healthy people bring in to get filled.

While I definitely agree with your general point, how does your brother know that they’re healthy or don’t need to take the medication? I’ve never had any discussion with a pharmacist (in the US or Canada) where I’ve revealed this information.

15-ish years ago, when I was twenty, I was foolish enough to see a psychiatrist. I walked away with a prescription for an SSRI, a typical antipsychotic, a mood stabilizer and some Xanax to take as needed.

What I really needed was my father not being dead when it mattered.

What I mean is a mother of 4, with no medical history, is feeling stressed and worn out. Maybe she has trouble focussing. All of a sudden she comes in with an amphetamine prescription. A year later, she's a full blown dependent on a serious drug. She was actually just burned out and probably just needed a break from her kids and a vacation. Very common. There's no transparency, no public understanding of doctors who are prescribing like this. It's only in a pharmacy do you get a birds eye view.

If they're healthy, couldn't that be because of the medicine?

A lot of people have conditions that medicine treats so well you wouldn't even know they had a condition at all.

I know many people who have taken antipsychotics, amphetamines, and statins for decades and it was perfectly fine for them. I also personally know some judgmental pharmacists too. All I'll say is, there's a reason pharmacists and doctors are distinct professions.

> If they're healthy, couldn't that be because of the medicine?

It's very likely. This actually has to be explained to a lot of people with chronic diseases like hypertension and type 2 diabetes. Way too many of them just stop taking their medication after their condition improves.

I believe blaming this on doctors only is way to easy. I believe many people demand medication when they go to the doctor. If they go because of a cold they don't accept being told to rest for a week, but demand antibiotics, if they feel depressed they don't want to be told to exercise, but want a quick medication etc.. I definitely see this since coming to Sweden, where it's difficult for doctors to prescribe antibiotics and lots of expats complain that they went to the doctor and were told to rest for a week. They feel they are not taken seriously if they don't get medication (that is not to say that there are no problems with how healthcare is done here, but restrictive prescriptions of antibiotics is not one of them).

Your brother is not a clinician, definitely not those people's clinician.

And how does he know they are healthy?

If your brother told you that with this exact framing, he's in the wrong industry.

Health, and especially not mental health is very much not visible or even obvious. Just ask any disabled person that is not bound to a wheelchair 100 percent of the time.

antipsychotics are horrifying. do therapeutic doses of stimulants cause problems other than heart disease over the long term?

Benzodiazepines are not even first line treatments for anxiety though. More like a last resort. They are very useful in aborting panic attacks and that says a lot about the intensity of symptoms necessary to justify their use.

SSRIs and SNRIs have a much better risk/benefit profile. Sertraline in particular is a really effective drug. I don't really understand why other doctors prescribe benzodiazepines so frequently but I'm not doing it.

SSRI-like drugs and drugs like buspirone are considered the gold standard for anxiety disorders now. They do not act like benzodiazepines at all in the brain.

How do they act? I just started taking buspirone for crippling social anxiety and I’m not sure if it’s helping or not.

SSRIs are speculated to work via activation and downregulation of certain serotonin receptors, in particular 5HT1A, an autoreceptor responsible for regulating release of other neurotransmitters in the brain. Buspirone acts directly on 5HT1A as an agonist, I believe, which is more direct than the shotgun approach of SSRIs. In theory, activation of 5HT1A and its downregulation can help with depression and anxiety. Buspirone also blocks some dopamine receptors, but not any that are associated with dopamine blockade from antipsychotics, so their serious dopamine-related side effects aren't something to worry about, but the blocking might also contribute to anxiolytic effects.

Newer SSRI-like drugs that block the serotonin transporter and activate 5HT1A also exist, combining the actions of both drugs.

It typically takes serotonin receptors about two weeks to downregulate, and possibly even months to see any effects on depression and anxiety. Buspirone is not like benzodiazepines that work pretty much instantly, but it doesn't come with any of the risks benzodiazepines do.

You are speaking beside his point.

You're taking a very specific article about benzos and making unsubstantiated leaps about medicine in general.

You've got a dangerous level of confidence.

If you look closer at others, you'll notice they have a new spark. But "new medication" won't be your first thought.

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.

Propranolol does almost, but not quite nothing for me. It does, however, put me on a daily(!) withdrawl cycle where when I'm on it, it does a small amount which is right up near the level of noticing, and when it wears off amplifies my normal symptoms.

Xanax was the only thing I ever took that did more than took the edge off (or some things which just made me loopy, sleepy, and/or high), it could at appropriate dosages simply turn my symptoms off and I went about doing normal productive human things that I wanted to.

But the state that I live in, and every doctor that I've met since I moved across the country has wanted to try every other drug in the book (again) before even considering, and none have thought raising the dosage beyond the literal smallest dose (despite me being 6'2" >200lbs). It is extremely frustrating.

I recommend working out, it helped me a ton with anxiety. It basically cured it (I don't work out much anymore but a short intense few months of hard workouts seems to have almost removed it from my system years afterwards).

Interestingly working out is a trigger for my anxiety. I'm currently trying graded exposure therapy for exercise, but so far it's not working.

Was about to say this.

Do you also trigger while trying to exercise? I have had pretty intense panic attacks while trying to work. to the point of having dizziness, weakness, closing throat feelings, the works! Pretty shitty stuff. 15 minutes later, you are absolutely normal and feeling bummed and sometimes embarrassed as well.

I would also not wish a panic attack to my worst enemy.

What I'm trying to do now is short walks and getting more 'confidence'. I think what gets us/me is the "what if I trigger" thing.

So, going slow helps build a little of confidence. That's my current plan, at least. I know an attack is bound to happen, and I will not win every time, but I'm not gonna be deterred by it. I know exercise helps a ton.

Thank you for this reply and wish you well!

This was the case for me too! :) I really hated running at the start because it triggered anxiety. In the end it turned out to be a blessing because it provided me with basically a safe (not socially connected etc) way to activate it at my own comfort and degree I was comfortable with and basically feel like my twisted up brain connections got smoothed out by doing it for a while. (Basically exposure therapy as you mention.) Lions mane may have been part of helping too but idk.

There are sources of anxiety without clear solutions. I have a stalker. There's low-level harassment continuously, but every few months, she does something crazy, and my life is completely disrupted. I have no idea what to do about it.

It's nearing a decade....

Can police help?

Alternatively, (non-violent) retaliation? Seems like there's no downside for this person to be harassing you. Creating a downside might make her think twice next time.

Sounds awful. My cause was definitely more caused by developmental period weird wiring, so definitely different. Hope you find some way to resolve it one day somehow.

Mindfulness meditation totally cured my anxiety. People don’t believe me and say I’m making it up, but it’s true. How do I know? Before if I smoked weed I would panic, now I can have a bong hit and be fine. I don’t think there’s a clearer indicator than that. It was easy to, I just had to learn to mindfully see the moment my anxiety arises and let it go. On the other hand, depression has been much harder to deal with

Yes, it's unfortunate that exercise is not prescribed more for these issues as there are tons of studies showing the benefits of working out against depression, anxiety etc.. I think we should really be seeing a mechanism where doctors can prescribe time off for exercise to deal with mental or physical issues, without repercussions for the employee. Maybe it's too much of a hope to see that in the US, but at least in Europe.

Just a warning to anyone who has asthma, propranolol is a older beta blocker from the 1960s and has made asthma worse in various trials.

My doctor and psychiatrist recommended I use other classes of medications.

Yes. Asthma is treated with beta agonists. Beta blockers will block the effect of the asthma medication.

Yup. Newer, more specific beta-blockers are supposed to be safer, but I’m not really interested testing that. :)

Yeah. Asthma is treated with beta-2 agonists. Newer beta blockers such as metoprolol are beta-1 selective and so have "almost no effect" on beta-2 receptors. Older beta blockers like propranolol are not selective at all.

Not interested in taking unnecessary risks either since there are better and safer drugs for general anxiety disorder.

Most drugs that actually work are terrible. If you're gonna abuse stimulants for relaxation, it's obvious to everyone but you that it will be a very bad time, for example.

That said, the recommended dosages are basically bullshit. For anything, I'd say take 1/2 or 1/3 of what they recommend in the first few days/weeks and taper up.

But please use your own brain when taking advice from strangers.

I take a benzo ICE as needed, but was on them for a while and never really noticed degenerative affects though I’m young though. Should I be worried?

From the article:

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

I think you’ll be okay.

That’s good, I’m conflicted because they’ve helped me but they are nasty little drugs. I’ve only ever been prescribed would never take them recreationally.

I was on them daily for a while and eventually, even though I never really worried or got anxious, other emotions where muted as well. I felt like I didn’t need it anymore and my doctor didn’t tapper me off them correctly so for two weeks strait I barely slept and had terrible withdrawal symptoms. Having them ICE is nice but I would never recommend them to people to take daily they are just to intense.

Another happy propranolol user!

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..

>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.

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.

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.

The first time I took Xanax I cleaned my kitchen and it went from mildly embarrassing to quite presentable in an hour or two. I could actually execute the things I wanted to do without fighting though ridiculous feelings.

I am treated like an addict or ridiculous when I tell doctors I'd rather not "try SSRIs" or a series of strange sedating substances because they're all so afraid of prescribing something with addiction potential (and the regulators trying to stop them).

I've been on multiple prescriptions for depression/anxiety/panic attacks (had a lot of traumatic events happen in close succession to one another). Combinations of different SSRIs and whatnot but the one thing that had an immediate and hugely beneficial effect was Xanax. I truly felt like my problems were solvable and I could see how to go about making the necessary changes. It was truly life changing for me because up until that point I could no longer believe that sich relief was possible. I haven't ever had a prescription though, and most doctors will refuse if asked. So I just have that one experience where it was given to me during a panic attack emergency, but knowing that it is even possible to feel like things can get better was a huge help to remember what to keep fighting for.

Wouldn't you be afraid? Patients who get addicted to benzodiazepines are likely to end up taking them their whole lives, even in old age, in ever escalating dosages due to tolerance. Elderly patients on these drugs are at higher risk of losing their balance, falling, fracturing a femur and entering a fragile state after losing their functionality and independence. If anything doctors aren't afraid enough. Polypharmacy is one of the geriatric giants and iatrogenic complications are common.

I have a healthy respect for substances and try to understand the things they do with me, but have never had any problems at all with addiction. I'm not saying other people shouldn't make their own assessments for themselves.

> I am treated like an addict or ridiculous when I tell doctors I'd rather not "try SSRIs"

If you’re willing to take Xanax but you’re not willing to try SSRIs, you have probably been severely misled about the relative risks of each.

Seriously, the internet misinformation machine is terrible for SSRIs.

One thing to keep in mind when reading online reports of drugs is that they tend to correlate quite heavily with the liking effect of a drug. Patients will rate drugs with rewarding effects significantly higher because they literally trigger the neurons in your brain that say “this is good and you want it now”.

My primary disinterest with SSRIs is first hand experience with people taking them and going on and off them. I don’t want to go into it or discourage anyone from taking them, but my experiences and reading papers reporting side effects results in a hard no for me.

I was prescribed some after a severe accident and it really helped me, both during while dealing with the pain and stress, and after to get over the trauma and anxiety attacks.

I've always been fervently anti-meds but sometimes when you're in a tough spot they are magical and going without is the worse alternative.

For what it's worth after 2 years of occasional use, I have no addiction at all. I've been tracking my use daily for the past year and as my anxiety has waned I've stopped taking them entirely.

When I am having a bad panic attack and take 1 Ativan, if I am lucky I go from being convinced I am dying to able to function with some difficulty. Lotsa brains, lots of different reactions to the drug.

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...

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.

>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.

Seroquel is an anti-psychotic for bipolar, schizophrenia, and other disorders.

Maybe it makes you sleepy, but that doesn't feel like a safe alternate course. Not quite as aggressive as MJ taking propofol to sleep, I'll give you.

They work. Other things don’t always.

Yes, in rare cases of idiopathic insomnia antihistamines and other types of cns depressants may not work, but a benzo should very rarely be the first choice when trying to treat it. (Various stages of mania may be exceptions, and generally only short term until any underlying issues are addressed)

From personal experience, in periods of high stress and other things going wrong, nothing but benzos could reliably allow me to choose to fall asleep. Short term (for me it was just a few times a month) I’m sure the side effects were harmless. A handful of other things simply did not work.

Having a strong lever to push my sleep schedule back towards healthy even when I had, say, taken a five hour afternoon nap, was extremely useful.

Being given other things that not only didn’t make me fall asleep but let me lethargic most of the rest of the next day… and having to wait months while doctors experimented with “safer” things was extremely frustrated and led to worse effects than were feared from avoiding benzos.

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.

You already had the answer to that for years.

Now here's the answer for mice.

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

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.

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.

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

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.

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.

> dementia in old age.

Spoke to a psychiatrist on this one. He was saying The Lancet longitudinal study was bunk and that Xanax use was not one of concern.

I'm not saying he's correct, but he literally laughed at my objection to Xanax, including it's now very long history of use with an average dose of 6mg/day.

Xanax use is cause for concern in general. Acutely it is safe, but chronic administration is definitively not, and not something to laugh about or take lightly.

this man laughed at you for suggesting this? Xanax is a "benzo" wikipedia tells me.. Consider the source

doctors often laugh at their own ignorance and pride

Had some anxiety issues in France and a doctor that I met with (who I had trouble speaking to) prescribed daily benzos for a month. Towards the end of the month it felt like my body NEEDED the pills. It was scary.

Your brain chemistry acclimates to using a GABA agonist every day and will get out of whack if you stop taking it :( like anxiety will be WAY WORSE when going through withdrawal.

I still use a benzo (lowest dose lamictal) but only about once a month when I need hit the panic button. It's really not meant to be a daily use drug, scared me when a friend was prescribed it as a daily medication.

Lamictal is an anticonvulsant, not a benzo. I take it daily as a mood stabilizer for bipolar disorder.

I take Temazepam with no ill effects, I take it nightly except sometimes when I forget, its been a game changer for me.

Lamictal is not a benzo and must be used consistently (daily) to prevent SJS as it requires titration. Generally, those who need it (epileptic patients or those with bipolar disorder) must use it for the duration of their life.

Daily use of benzos gave me sleep paralysis, false awakenings and made me sleep walk.

Not saying that proves anything, but it was scary.

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.

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.

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...).

As zolpidem is associated with drug tolerance and substance dependence, its prescription guidelines are only for severe insomnia and short periods of use at the lowest effective dose [1].

Zolpidem increases risk of depression, falls and bone fracture, poor driving, suppressed respiration, and has been associated with an increased risk of death [2].

I would recommend you to seek a second opinion from another medical professional about whether this family member should perhaps slowly taper off of the Zolpidem.

[1] https://www.nice.org.uk/guidance/ta77/chapter/1-Guidance

[2] https://escholarship.org/content/qt08d9f3d5/qt08d9f3d5.pdf?t...

From skimming the article, it seems they've linked this effect to benzos interacting with a specific protein in microglia. This is not the interaction benzos share with Z-drugs, which is modulation of the GABA-A receptor. So it seems unclear whether this can be extrapolated to Zolpidem.

However, Z-drugs(and benzos as a sleep aid) generally should not be used daily for longer than a few weeks until a better solution is found. Unfortunately, doctors often do this anyway, following the path of least resistance, I suppose.

I wouldn't worry about any kind of brain damage, but I would recommend reviewing their options, maybe seeing another doctor. Lots of people can manage just fine with something like extended release melatonin, or indeed nothing.

Z drugs are better than benzodiazepines but not by much. Their pharmacodynamics are similar: they act on the same GABA receptors.

Zolpidem is best used for a couple to regularize sleep patterns and help establish proper sleep hygiene. Trazodone at lower doses is better for long term use, especially in older patients.

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

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.

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.

In mice

https://twitter.com/justsaysinmice?s=09

Ok, we've inmiced the title above.

I had to add the c-word, though ("causes"). The article uses it several times, so I suppose it's ok for the title. Please let's not repeat the usual "C is not C" business.

You know what else causes brain damage? Anxiety

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.

I take 5mg about once a week which I thought was pretty harmless :(

You’re not taking high doses every day, which is what the article is about.

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.

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.

Thank you for informing us of the fact that you take benzos with alcohol in your system.

Self PSA that probably nobody should take your opinions seriously.

Benzo after drinking? Jesus...

I've heard of doctors taking benzos after drinking. It's a potentially lethal combination, as you can stop breathing in your sleep. However, if you wait until the alcohol has metabolized in your system and becomes a stimulant (when your BAC is about 0.05, or about 4 hrs after moderate drinking), a short-acting benzo in a low dosage can counteract the stimulant effect of alcohol and let you sleep. I have done it before, and works very well, but that's because I have a breathalizer, very low dosage Xanax, and I am responsible with my health. I would never recommend this to anyone, as a wrong calculation can result in death; that's how many hollywood and rock stars have died.

Yeah this is what I did. It was at least 2 hours after the last drink and I wasn’t super drunk to begin with. I always get terrible sleep after drinking, but it helped a lot.

Overall doesn’t seem to be worth it though.

That's quite a lot, especially mixed with alcohol.

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.

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

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.

I have a good friend who had grand mal seizures about once per month for 6months+ after coming off them... Very scary.

take magnesium lthreonate for an effective synapse recovery

In many people the alternative to benzodiazepine use is suicide.

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.

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.

I researched long term impairment in humans for benzos and was only able to find very mild (i.e. on the edge of measurability) cognitive impairment which was mostly recoverable after a period of abstinence.

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?

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

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.

FYI - The idea that stimulant response can be used as a diagnostic tool for ADHD is a myth. No researcher or professional who studies the subject actually takes that seriously.

Nobody should be interpreting their response (or a child’s response) to stimulants as a diagnostic indicator for ADHD. It’s also worth noting they caffeine isn’t an effective ADHD treatment (it had been studied) and caffeine and Adderall don’t actually overlap as much as people seem to think.

You say it's a myth, and yet I have direct knowledge of a case where it went that way. To be clear though, the stimulant response was not by itself the only diagnostic criteria. They we're engaged with a process of trying to determine a correct diagnosis. The child's response to a stimulant was one piece of data, and happened to be the one that made everything else click into place. If there is a myth here, it is only the idea that a response to a stimulant by itself is sufficient for a diagnosis. It's not.

Also, yes-- caffeine isn't a great treatment here either. With respect to ADHD there are more effective methods.

Related research:

https://pubmed.ncbi.nlm.nih.gov/6110701/#:~:text=The%20admin....

https://psychcentral.com/blog/adhd-millennial/2018/06/when-s...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617411/

https://www.psychiatryadvisor.com/home/topics/child-adolesce...

> You say it's a myth, and yet I have direct knowledge of a case where it went that way.

Anecdotes like this are purely coincidental. Parents think they notice one thing, then later get an ADHD diagnosis and assume they’re both related.

Like I said, caffeine and ADHD medications don’t actually substitute for each other and have drastically different effects. Caffeine is not an effective ADHD medication, so it’s not relevant to the studies you’re linking.

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.

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

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...)

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

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

Benzos disrupt REM sleep. Eventually you will go mad.

I thought this was well known as Peterson effect.

We now know what happened to jordan b peterson

The effects it mentions in humans are not new.

I take .5 mg Klonopin for sleep every night.

Not a great idea in the long run.

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.

He claimed he had no idea what they were.

Someone that identifies as a neuroscientist.

He knew very well but thought he was special.

The only thing special is that he went cold turkey (extremely dangerous) and had to be placed into an induced coma in Russia because no one else would do it.

It's also pretty obvious that he is cognitively impaired.

Peterson is a verified idiot with nonexistent self-control. Not the slightest modicum of it.

Basing anything off of his antics is asinine. So weird to see people who put him on a pedestal on HN.

& benzos aren’t “horrible drugs”

People who don’t know how to manage themselves and their usage of them are horrible people though, especially when they try to cut down others who have no issues using them responsibly, which sometimes literally saves their entire lives.

> which sometimes literally saves their entire lives.

considering how benzos came into existence barely half a century ago, i highly doubt not having benzos as part of one's pharmaceutical cocktail is the fundamental difference maker to one's life or death. so even to those who are now dependent on them, their long-term health will almost certainly be better served by getting to the root cause of their health issues. not saying that's an easy thing to do, but that's still the reality.

> i highly doubt not having benzos as part of one's pharmaceutical cocktail is the fundamental difference maker to one's life or death. so even to those who are now dependent on them, their long-term health will almost certainly be better served by getting to the root cause of their health issues. not saying that's an easy thing to do, but that's still the reality.

Dude, I've spent my entire 20s in therapy while trying various "safe" drugs to get ahold of my anxiety issues. Nothing worked. I was offered electroconvulsive therapy or daily benzos. I went with benzos. I've been taking them for years now and my life is infinitely better as a result. I've changed careers, gotten married, and traveled the world. Before benzos I was living with parents, too anxious to go across the street to get the mail.

I really don't think it's right to dismiss a whole class of highly effective and generally safe medication that can have life-altering benefits for some people. I'm okay with being slightly more retarded in my later years if it means I actually get to live a life outside my parents' basement.

  > Basing anything off of his antics is asinine. So weird to see people who put him on a pedestal on HN.

not sure if its putting him on a pedestal as much as an example of what some prescribed drugs can do to people when they aren't careful...

Sorry, the pedestal bit was not aimed at the parent comment.

I’ve just seen a confusing amount of HN users who do speak of him in such a manner & thought I would make reference to that for context.

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.

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

I have a hard time believing that while the current status quo is suboptimal, there's some little known compounds that are, as you say, revolutionary and with little side effects. Pharmacological research is a constantly moving target, there is no scientific nor economic reason that a supposedly "perfect" remedy remains unknown. Sounds too much like thinly veiled conspiracy, or perhaps they're not as perfect as you're suggesting.

That said, it's not my area of competence, so if you know _why_ opipramol and guanfacine are ignored compared to benzos and other anxiolytic, you should probably explain that.

EDIT: re: guanfacine, I know it's a second-line treatment for ADHD, it was previously used to treat hypertension, but this is the first time I hear it might be applicable as an anxiolytic. It does certainly have side effects, though not as bad as being neurodegenerative like benzodiazepines.

https://en.wikipedia.org/wiki/Guanfacine

> I have a hard time believing that while the current status quo is suboptimal, there's some little known compounds that are, as you say, revolutionary and with little side effects.

Your suspicions are correct. The parent comment is an example of a trend among people who know just enough about pharmacology to be dangerous: Exaggerating the benefits of less popular medications while demonizing mainstream medications. Add a dose of conspiracy theory ("pharmaceutical industrial complex") and it's a recipe for contrarian exaggeration.

The parent comment strangely missed the actual mainstream, effective treatments for anxiety: SSRIs and Buspirone are widely used for long-term anxiety treatment with significant success. They’re not perfect and you can find horror stories if you search the Internet long enough, but people tend to get fooled into thinking mainstream medications are worse than obscure ones because mainstream medications will naturally have a higher absolute number of negative reviews online than rarely-prescribed medications.

In practice, it would be rare for a doctor in the United States to prescribes benzos as a first-line and long-term treatment for chronic anxiety. They are prescribed for panic attacks and short-term anxiety (e.g. a difficult court case with an end date) but SSRIs are the mainstream treatment.

You should probably read about the pharmaceutical industrial complex to balance out your wildly biased and one-sided, unbalanced perspective.

Are you honestly going to claim that the many multi-billion dollar pharmaceutical industry doesn't have a financial incentive to lead people toward 1) daily use medications that gives the industry a monthly recurring revenue stream, 2) where many people on them long-term because many of them have severe withdrawal symptoms so they are very hard to get off of?

And then something like 80% of ad revenue of mainstream media in the US comes from the pharma industry - so how do you suppose that influences what news and narratives are shared or allowed to be shared to the majority of a population on the mainstream-mass media channels?

You conveniently also forgot to mention that SSRIs, for example, actually increase the rate of suicide (along with suicidal ideation) - so you're more likely to kill yourself if you take them then if you didn't take them; that is from their clinical trials. It's the elephant in the room that's been mostly suppressed from conversation for some reason, somehow - probably in large part look at my previous paragraph for one mechanism used.

Are you also claiming then you know "more than just enough about pharmacology" in order to give a more credible response? Or are you perhaps arrogant thinking you're more competent to respond - but perhaps instead you're just indoctrinated into a biased perspective? Do you work in the medical profession, perhaps even one that prescribe medications? Consumers are bombarded by propaganda, and professionals even more so.

In reality you probably don't actually have any idea what level of knowledge nor experience the person you're responding to, saying that their response is dangerous.

Reality is more complex than you're currently aware of.

On the inertia and the gap between what the research/newest drugs and what is prescribed day to day: it is very real.

And there’s tons of reasons for that, ranging from:

- doctors that cling to the treatment they know to work (“the devil you know”)

- sheer lack of knowledge (not their speciality so they’re not up to date by a long shot)

- waiting for a few more years to have long term real world data

- pharma companies effectively bribing them by any means so they don’t look elsewhere

- propaganda put out by competing pharma companies to smear newer medications or create distrust of them

- pharma companies who spend more to get the lion's share of ad time keep their brand at the forefront of consumers, consumers then ask for those medications and then don't know about alternatives because they've been drowned out

- arguably some of most effective drugs have been illegal the past 40+ years as part of the "war on drugs" (did pharma industry help make those illegal?): marijuana, psilocybin/DMT, MDMA, and even cocaine will knock people out of a depression - where it could be taken weekly or less (arguably potentially more addictive than other medications, but SSRIs with severe withdrawal symptom is arguably equivalent to addiction, the aversion to the withdrawal symptoms) - but pharma can't patent any of those, so they can't gain exclusive rights to a brand they advertise to manipulate people to buy or trust their brand over something else (so patented drugs can captured more revenue and have more profit to pay more for ad time to drown out cheaper, more effective competitors).

- etc.

I have personal experience with Guanfacine (and Clonidine), beta blockers (Propanolol/Labetalol), Etifoxine, Phenibut, and a myriad of benzos.

Long history of RX for anxiety disorders, which I eventually tapered off of and quit due to dependence.

Can attest to Etifoxine being effective without side effects, guanfacine and clonidine being mildly effective. Beta blockers never did much for me but YMMV.

After all of those, what did you settle on for managing anxiety long term? Was it the Etifoxine?

Anecdotally, I can attest to the surprising efficacy of alpha blockers. I have used prazosin as a sleep aid for the last decade, a few times a month.

There were some limited studies that suggest it is effective in helping sleep quality in people with nightmares and PTSD. Now, I don't have PTSD, but I do have a mind that will not shut off at night, running in useless circles that jolt me back awake. It does nothing for the racing mind, but my body's physiological reaction to my emotional state is lessened. I physically relax, quite literally in smooth muscle activation terms, and apparently that lets me get to sleep.

Beta blockers are probably a bit more heavy duty, but they do appear to be quite effective at treating performance-related anxieties from another small study. Shakes? Chills? Dizziness and blood pressure spikes? From the discussion I had with my psychiatrist, I think the working hypothesis is that treating the physical symptoms of anxiety is an effective intervention here, as the discomforting experiences that the initial anxiety triggers, creates a feedback cycle. (Oh god, now I'm sweating and flushed, everyone's gonna notice...!)

Propranolol is very commonly prescribed for anxiety in the UK. I take it as needed and it works wonders, but it does make me a bit lethargic. It doesn't completely eliminate the low level anxiety but it stops it ending up in a viscous panic cycle.

To me it seems like it helps with some of the physical symptoms of anxiety, but not so much the anxiety itself. So, it's efficacy depends a lot on the pathology of a specific individual's anxiety. For many people the physical symptoms of anxiety become self reinforcing, and short circuiting them can stop the anxiety. For folks whose anxiety takes a different path it may still be slightly effective but not quite as much.

Widely used for anxiety in my country as well but not an optimal choice due to the cardiovascular effects. As you noted, it can cause fatigue.

High blood pressure and anxiety can both cause similar symptoms. Tightness in the chest, for example. Your body tends to mistake one for the other.

Treating high-blood pressure with an ACE inhibitor (which does not treat anxiety) can reduce anxiety simply by relieving symptoms that feel like anxiety.

Beta blockers have the nice effect of directly treating both anxiety and high blood pressure.

Good to hear! Glycine 3 gram before sleep can be useful as a combination. it relaxes the body too and relaxe the mind also. There are interesting studies showing positive effects on sleep and no tolerance.

magnesium l threonate before sleep, the lthreonate variant penetarte the brain far more than regular magnesium, and it acts as a mild NMDA antagonist, which means it decrease maximal excitation. it is also a great synaptotrophic.

> the lthreonate variant penetarte the brain far more than regular magnesium

How is this possible? Don't the magnesium ions fully dissociate once they come in contact with water, so that there's just free floating Mg+ and threonate?

Etifoxine can be purchased from other countries and has studies showing comparable effects to classic benzodiazepines for acute panic attacks, but without being addictive.

Personal experience, it doesn't have noticeable psychoactive effects like benzos do but does block stress response + panic.

https://en.wikipedia.org/wiki/Etifoxine

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

"Mother's little helper" was a term coined during the 60s and 70s (Diazepam - aka Valium)

Emoxypine doesn't seem to have any English studies, or has incredibly few. So it may or may not be useful, but I sure as heck can't tell.

here's 438 studies for you https://pubmed.ncbi.nlm.nih.gov/?term=Emoxypine&sort=date the marketing name is mexidol. Emoxypine is a wonder drug for health, it is one of the most potent superoxide antioxidant and has an incredible range of body protective effetcs see e.g. https://en.wikipedia.org/wiki/Emoxypine#Mechanism_of_action

look at the pictures and admire the amount of saved brain volume https://www.researchgate.net/publication/221738761_Evaluatio...

Interesting. What's the quality of Russian medical research versus western? What journals are considered prestigious? (Not trying to troll -- I honestly have no idea and can't judge it accurately).

I've been seeing your comments on HN and you seem very well-read. Is there a drug/supplement stack you recommend or use? I've seen you recommend magnesium l-threonate and skq1 several times and I was wondering if there are more drugs/supplements that are worth mentioning.

Not sure what the parent post would recommend, but l-theanine is supposedly well tolerated and moderately effective as an anxiolytic. Annecdotal personal experience supports this.

Opipramol is a weird one. It's among the most prescribed anti-depressants in Germany (and other European countries), yet apparently non existent in the US.

> Sustainable, non addictive and non neurotoxic anxiolytics exists: the #1 being opipramol

You misspelled kava.

don't forget buspirone!

buspirone works great, when it works.. which is for what ? 20% of the population?

remedies and compounds that work widely have a name: medicine.

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.

anyone knows wether ghb is neurotoxic?

xan not workib

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

Like, no shit?

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