One thing I do for the did-I-take-it-or-not problem is to lay out the pills in advance. Either measure into pill cases for the week (did I take today’s dose? I can look!) or just put the pill next to a cup of water on my bedside table the night before, when I’m thinking more clearly.
I don’t know if that would work for other people, but those headaches sounded truly awful, so I thought it was worth mentioning just in case.
I take a daily pill early in the morning before breakfast. A simple way I found to remember if I took it is to leave a glass of water on the nightstand at bedtime, and finish the whole glass when I take the pill. This works because no matter how brain dead I was at 6am, empty glass = yes, you took your pill.
I tried a bunch of tricks and kept accidentally forgetting to reset the trick. Turns out you can buy little pill-bottle-cap stopwatches, with a clever pressure-sensitive assembly so they automatically reset when you open the bottle. Just look on the cap to see when the last time you opened the bottle was.
You can safely consume way more than 10 liters of water in a day. I have frequently consumed over 10 liters of water in a day when doing long distance bike rides. Water is very safe to consume.
I had a considerably shorter period than that in mind; let's say 1 hour. The ratio of a normal dose of say 1 litre to a fatal dose of say 8 liters is rather low compared to many substances considered dangerous.
You get water poisoning when you drink way too much, and drink it faster than your body can get rid of it. If you're just replacing what you sweat out, you're fine.
Death from drinking too much water is rare, because you have to keep drinking long past the point where your body tells you to stop.
I doubt it's the water, either, ill effects are probably just hyponatremia or something. If you drank lactated Ringer's I think you could probably do it until you literally explode.
Mmm that's kind of stretching the definition of "mechanism" in my book. You might as well say N2 is the mechanism by which hypoxia kills, or boiled beef is what gives you scurvy. The water is an innocent bystander, it's your failure to consume enough electrolytes along with the water that does the job.
Great post but I would caution using the terms "recreational user" and "abuser" interchangeably. There are a good many people who slip through the cracks with these studies because researchers have motive to show a big difference when publishing so they typically use abusers in their studies who are taking doses at the extremely high end, and clinical users are taking doses near the very low end. This is also the case in many in vitro and in vivo animal studies where doses and concentrations that far exceed what a normal recreational user might take or. There are likely many more recreational users that use drugs intermittently, say for concerts or outings with friends and may take in excess of what would be considered a therapeutic dose but are still well below the consumption rates of an abuser given that they don't take the drugs all the time. It's not at all clear that these users should be lumped in with "abusers", nor should they expect the same level of side effects.
I parsed "mislabel molly as meth" to mean that a bottle labeled "methamphetamine" contained MDMA. In case anyone else read it the same way, the linked article is about the reverse situation, where a study indicating neurological damage from MDMA was actually dosing animal subjects with meth by accident.
"molly" is the direct object of "mislabel. It's the thing that had the action performed upon it. "meth" is the indirect object of "mislabel". It is preceded by a preposition, and indicates the natures of the action. Your reading is the correct one. "Mislabel molly as meth" means that molly is the thing that actually exists and was mislabeled, and meth is the thing that describes how it was mislabeled.
3g of ketamine a day is a lot even by my standards and I’ve been around the block a few times. What addict has the cash for that? My heroin abusing pals, at their height were doing maybe 15 grams every week or two. I might be misremembering and didn’t do heroin enough to know, but I don’t think it came anywhere close to 3g a day at least for anyone I knew. I suppose Sid Vicious or Lane Staley might have been up there but in my day to score smack someone still had to make a desperate trip to the worst part of the ghetto just to get ripped off half the time, which always made a score fraught with danger. To do it everyday you had to be all in and off be very curious where the line is between those people and others.
“ The average crystal meth addict uses about 500 mg a day.”
One minor point - as far as I can tell thats the average for someone who thinks they have enough of a problem to seek treatment. I would say the average dose is more like a gram a week. Coke and meth are expensive. The average users needs to hold down a job.
Per the study: “One hundred and eighty-three stimulant users from a longitudinal cognitive study (120 MA and 63 cocaine) were included in this study. One hundred and fifty-three of them were enrolled in treatment in either the Matrix Rancho Cucamonga Clinic in San Bernardino County California, or the UCLA Integrated Substance Abuse Programs’ Torrance Clinic in Los Angeles County”
My understanding is the prices per gram are roughly the same but cocaine is much shorter acting so you need to use more to stay high. At half a gram a day you’d be looking at $1500/month. That’s hard to sustain on multiple levels.
Meth and coke have similar per gram prices but meth is much cheaper per kilogram. This is the markets way of saying that dealers require extra compensation to have to deal to meth users.
Re: your comment in section II. Many organic chemicals have completely different functions when modified slightly, such as nicotine and nicotinic acid (niacin); one is a toxin and the other is vitamin B-3. Also, chlorophyll and hemoglobulin; one converts carbon dioxide and water to oxygen and simple sugars, the other transports oxygen and carbon dioxide. This is because evolution doesn't usually create uniquely new structures, whether morphological or chemical, but more typically modifies existing ones.
That's true, on the other hand you've only changed half the molecule. My point was was about evolution really; morphological adaptations are more obvious than chemical adaptations.
"Although ketamine might seem like a promising antidepressant that could relieve treatment refractory depressive symptoms, the induction of memory impairments in the longer term is of concern"
I take legal, cheap, widely-prescribed antipsychotics that leave me with the memory of a goldfish and do much worse. Where are these people when it comes to that? Or do older drugs with bad side effects get grandfathered in?
I mean, ketamine also got approved eventually. Usually you weigh cost vs. benefits and approve things if the benefits outweigh the costs. I think we prescribe antipsychotics less than we would if they didn't have these kinds of side effects (though we still overprescribe them). Now we're debating how often to prescribe ketamine, these kinds of considerations are coming up, and I support being more liberal with them because I think this only happens in people taking them at high doses.
Also, everyone should know that Paracelsus is the reason Robert Boyle recommended dried human excrement, blown into the patient's eyes as a powder, as a treatment for cataracts.
Most of my concerns* about occasionally using nicotine gum as a nootropic went away when I realized just how much nicotine a typical smoker is getting. A pack/day is like 300mg/week or something, whereas a few pieces of gum per week is like 10-15mg.
*that is, my concerns that remained after learning that nearly all of the risk from tobacco has nothing to do with stimulants
That makes sense. Gwern has the willpower and self-control to not go overboard, but I'm not sure how I would do. Anecdotally, I had a cousin get addicted to the strips fairly quickly. Enough to say "I don't feel anything from them", and also going through 10 strips before breakfast. Gwern I believe was doing <2mg per dose. The strips my cousin uses are 2.5mg each, just massive differences is usage amounts. This reminded me of your blog on the dosage differences for melatonin.
Btw, the typical melatonin dose being 10x higher than optimal lends itself to a neat lifehack - I can split the pill in 8 parts and get a more efficient drug at 12.5% cost. Take that, big pharma!
A cheap pill splitter is very effective at getting pretty exact halves, and pretty good at converting those halves into quarters. Eighths seem a bit more finicky, but I bet you could stay within 20% accuracy? But given how cheap melatonin is, I don't know that it's worth the 1-2 cents of profit to perform a third division.
Yeah, I know a few people who are clearly dependent on it, so I'm pretty strict about having a specific amount that I allow myself to use every week, and I've been successful staying within that amount for several years now.
I don't know about your social circles, but even ten years ago when everyone when everyone in the UK smoked a pack a day was considered the stereotypically amount for "too much", an almost obscene amount. You would say it as an exaggeration "He must smoke a pack a day!" And from my own personal experience even a pack every two days is kind of pushing it. I'm pretty sure that most people smoke far less than that.
So now the trick is to get some test subjects to go from zero to 100,000 mg of some drug over the course of some months and see if we can identify the break point.
This wouldn't make sense because there would be accumulation of harm. You would want to have cohorts of ascending doses 10mg , 100mg , 1000 mg, 10,000 mg, 100,000 mg. You would find a point at which it harms the cohort. However, I'm pretty sure that type of study would be illegal. You're not supposed to ascend until you intentionally inflict harm on subjects.
I think this sort of thing should be legal provided the person knows the risks involved and feels appropriately compensated. Is it ethical? This would depend on a lot of factors. Doing it for fun would seem unethical. Being misleading to subjects in anyway would be very unethical. And the obvious other caveats.
I hope some country does an experiment where they make literally every drug available over the counter to adults, but in low-dose pills so that it's hard to take enough to do harm. Prescription gating sometimes feels like a jobs program for very expensive rubber stamps.
Possibly a dumb question: When I was living in the UK, I found it annoying that all the drugs I bought (including very safe things like ibuprofen) came in blister packs. Is this to control self-dosing? I'll admit it might have made me slightly more likely to take a single tablet when I was on the fence between one tablet or two.
It seems like it would have that effect. If everything came in blisterpacks of low-dose pills, it would take an annoyingly long time to take too much, and this would push people towards taking less.
One patient encounter of mine involved someone who opened up 3 months-worth of prescription medication blister packs and took them all at once. Not only is it theoretically possible, I've seen it happen!
One reason (perhaps the main reason) is that every blister pack comes embossed with its own use-by date. I think you must agree this is a sensible arrangement.
Isn't that simply the cheapest way to package it? Light, doesn't take up much space, keeps each pill packaged until use, and cheap. The alternatives, where pills would be in a plastic bottle seem to be useful only when a pharmacy does the packaging and the pills are moved in bulk.
That's probably not something that pharmacies carry around here. It could be due to legal limitations, maybe simply beacuse those big packs are absolutely not subsidized, or maybe I just haven't checked.
After a looking for ibuprofen 500 pieces here, I found a big bucket of 100 pieces of paracetamol 1g pills on sale. (0.11 USD/piece, the small box that has only 25 pieces just costs a bit more per pill.) Completely crazy, a few of these is deadly :o
So ... it seems the blister pack is simply the cheapest for that amount. (10-30, in a box) But above a certain amount the bucket/bottle is the economical one.
I believe it's to discourage suicide. I'm told it works, compared to the time when you could open your jar of pills and swallow the whole lot in almost one go.
Numbers of tablets per pack of paracetamol and salicylates decreased markedly in the year after the change in legislation on 16 September 1998. The annual number of deaths from paracetamol poisoning decreased by 21% (95% confidence interval 5% to 34%)
The UK has (correctly) a high level of concern about paracetamol overdosing. Unfortunately, the legislation on this was actually written to apply to all painkillers, so the same rules apply to ibuprofen and aspirin for no good reason.
Because such a large fraction of the drugs people buy over the counter include painkillers, the pharma companies find it easier to operate a supply chain of everything in blister packs than to have a separate chain for bottles.
Quite right. Unfortunately for acetaminophen (as we colonials call it) the difference between the therapeutic dose and the dose that starts working over your liver is not as great as onewould hope.
Numbers of tablets per pack of paracetamol and salicylates decreased markedly in the year after the change in legislation on 16 September 1998. The annual number of deaths from paracetamol poisoning decreased by 21% (95% confidence interval 5% to 34%) and the number from salicylates decreased by 48% (11% to 70%). Liver transplant rates after paracetamol poisoning decreased by 66% (55% to 74%). The rate of non-fatal self poisoning with paracetamol in any form decreased by 11% (5% to 16%), mainly because of a 15% (8% to 21%) reduction in overdoses of paracetamol in non-compound form. The average number of tablets taken in paracetamol overdoses decreased by 7% (0% to 12%), and the proportion involving >32 tablets decreased by 17% (4% to 28%). The average number of tablets taken in salicylate overdoses did not decrease, but 34% fewer (2% to 56%) salicylate overdoses involved >32 tablets. After the legislation mean blood concentrations of salicylates after overdose decreased, as did prothrombin times; mean blood concentrations of paracetamol did not change.
When tables are sold in bottles containing hundreds people are likely to take more. In the UK you can buy a maximum of two packs or 100 tablets, as this reduces the risk of abuse and use for suicide.
Portugal didn't quite do this, but it (and a few other countries I can't remember — Uruguay?) have decriminalized personal use of all drugs, and the results have been what you might expect (that is: entirely positive).
Decriminalizing is not the same thing as making them available OTC in your local Walgreens. If one has to source it on the street (which I think is still the situation in Portugal and Uruguay), the potency and purity is uncertain, and this probably increases overdoses and other negative side effects by a lot.
The list of harms caused by drug prohibition is staggering. The obvious ones, like "cartels control the supply" or "no quality control" can be seen even by the slow-witted; a little thought reveals a myriad of other negative details, like variable dosage being dangerous in terms of both overdose *and* reinforcement, high prices incentivizing criminal behavior and self-neglect, shame and illegality *dis*-incentivizing education and support, etc etc etc.
High prices and variable doses incentivize polydrug abuse and injection, as well, both of which make overdosing easier — it's surprisingly difficult to fatally OD on heroin alone, for example, to take perhaps the most infamous culprit. In fact, in all my years of personal and professional experience, I can't think of any case (off the top of my head) wherein an individual fatally overdosed on an opioid alone without either ingesting other drugs as well or choosing IV as the RoA (or both, staggeringly).
I don't believe most of these individuals would have felt the need to stretch their supply by mixing in benzos or alcohol (the most common suspects: nearly always ____ and alprazolam, it seemed), or injecting rather than snorting/eating, if a source of opioids had been readily available.
Man, I could just keep going and going... but most people here already agree, I think, heh.
No, not really. The thing with heroin is rapid tolerance reversal. The overdoses are often cases where people havent used for awhile, then use a dose they were using with no problem before.
Even setting can affect this. People who dose in new places dont have their body prepare for it and the rush of sedative effect can overwhelm the nervous system. You are correct that it is hard to od if someone is using chronically and increasing their dose relative to their tolerance levels.
Absolutely. I merely meant to suggest that if decriminalization didn't result in a spate of overdoses, drug tourism, and addiction, making drugs available OTC would probably be pretty good too.
The study of the safety and efficacy of the vast majority of drugs is so profoundly inadequate as to be criminal. Even"gold standard" designed and executed clinical trials are too short term, too small and subject to statistical manipulation as to be near useless. Post marketing studies are few a far between and adverse event reporting a joke.
Physicians are left to "ask around" and spend time most don't have searching for literature that many are ill equipped to judge. Most don't bother and shy away from drugs that might help and prescribe based on pharmaceutical advertising consumed by either themselves or their patients.
What little system there is is vastly inadequate, economically driven and morally corrupt.
Can you give some evidence for this, or explain it further?
I think we know a lot about most drugs. It's not perfect, but the amount of studies we would have to do to make it perfect would make medicine impossible. What changes would you propose?
I think that your description of what you've gone through to be able to make some sort of intelligent informed decision about prescribing Ketamine illustrates most of what I'm saying. Shouldn't the FDA be the ones doing the sort data collection an analysis you've done, and making it part of the prescribing information?
The current system is not great, but assuming what you said (I tend to agree), it's still pretty good at weeding out bad stuff and finding useful things. I mean just look at how completely useless nutrition science is in comparison. (Even after adjusting for budgets/expenses.)
Of course there's plenty to improve on it, but that'd require cutting out a lot of middleman (and not just the middlemen, but the middlewoman and middlechildren too - sorry). And like the replication crisis this is kind of ongoing with placebo and SSRI studies. But as long as we lack meaningful alternatives we'll unlikely to pour more money into this whole system just to get very similar results.
It is all on the PI for Spravato. Here's the relevant paragraph:
5.9 Ulcerative or Interstitial Cystitis
Cases of ulcerative or interstitial cystitis have been reported in individuals with long-term off-label use or misuse/abuse of ketamine. In clinical studies with SPRAVATO nasal spray, there was a higher rate of lower urinary tract symptoms
(pollakiuria, dysuria, micturition urgency, nocturia, and cystitis) in SPRAVATO treated patients than in placebo-treated patients [see Adverse Reactions (6)].
No cases of esketamine-related interstitial cystitis were observed in any of the
studies, which included treatment for up to a year.
Monitor for urinary tract and bladder symptoms during the course of treatment
with SPRAVATO, and refer to an appropriate healthcare provider as clinically
I haven't been able to find any long term studies of stimulant effects for ADHD treatment in adults or children. A quick search shows https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473329/ which is a 12 month study in primates. Previously the longest term studies Ive found are 6 weeks.
Considering that ADHD is a life long diagnosis for adults it seems like some rigorous longitudinal studies would be appropriate. Adderall was approved in 2002. Where are the 20 year studies?
Adderall was approved in 2002, but amphetamine and dextroamphetamine have been studied extensively and in regular use since the 1930s. They have a much longer history of use and a much larger body of knowledge surrounding them than most drugs that are currently in use.
Aren't Biostatisticians designing studies to be adequately powered with large enough n? What sort of manipulation is going on that renders clinical trials useless? And what is a joke about adverse event reporting?
Imagine a world where the most ruthless drug dealers cut their drugs so hard that they end up curing their customers' depression and turn them into diligent straight-A students.
This reminds me of when I decided to stay on my ADHD meds through my pregnancy (baby is fine). I was sent to the maternal fetal medicine doctor for an assessment and the guy rolled his eyes and told me "the data we have on amphetamines and pregnancy is from meth users, so everyone is going to act like you're on meth when they talk about risks. You're not, you're basically here for my blessing, and you have it."
So much else in pregnancy advice follows this pattern. I was told not to eat lemongrass when I was pregnant, and decided to chase down the science behind that advice. There was one study 30 years ago where mice were fed some compound found in lemongrass in increasing amounts until it caused measurable fetal harm. The required dose for a human would be equivalent to a brick-sized chunk of pure compound.
You’d need to eat a truckload of lemongrass daily for weeks to replicate this. But pregnancy makes a lot of us want “do this not that” advice, and this is the rare foodstuff that has even a single study describing effects on fetuses, so it ends up on a blurry photocopy of Foods To Avoid handed out at OBGYNs for the next 30 years. This seems harmless until researching this advice takes you to a few forums, and you realize there are women in this world who believe they caused their own miscarriages by inadvertently eating Thai food. That made me incredibly sad.
Maybe that's a little too cryptic. If you take a look at the risks these people take, in terms of spending 18 months with a $50 million lawsuit hanging over your head, by people who expected childbirth in 2021 ought to go perfectly, rainbows and unicorns every single time, regardless of maternal risk or behavior, or the bad luck of genetics, then it would become a little clearer why these people are often intensely paranoid and never ever err on the side of rational risk, but always on the side of if there is any conceivable way someone can get upset because I didn't warn her of X or Y absurdly tail risk I better do it.
I’m not sure this really makes sense from a legal perspective. Why lemongrass then and why not a million other things? Why was I not specific cautioned to avoid rue or fenugreek or driving? There’s stronger science for an awful lot of omissions that could stand up better in court than lemongrass.
I'm not saying people run through the entire gamut of weird things you could do and rank them in order of risk (to you or their 401(k)) and then warn you about the top 100. What I suspect happens is that whenever they run across something, because it pops up in the news, or someone asks about it, they reflexively take the path of ticking the box that says "I warned her that this coffee is hot, and she should not pour it into her lap."
And also that I totally get why they do that. Obstetrics is inherently a weird field, because people don't instinctively feel like their health is at risk when they get pregnant the way they do when diagnosed with cancer or even high blood pressure (although it totally is). So their natural expectations are sky-high, whereas I would guess if you stumble into the oncologist's office with a Stage 4 lung cancer diagnosis, your expectations are so low that if he or she merely offers you the chance to extend your days by 6 months you're ready to weep with gratitude, and certainly not angrily demand why it isn't 9 months like your step-aunt June Cleaver got.
From a *legal* perspective no one should ever take any chance at all, and you should live in a stainless steel box and communicate with the world only through typewritten notes vetted by your lawyer. The legal system is a giant field of antipersonnel and occasionally antitank mines through which we stroll every day, gaily unaware of the risk simply because of the fairly wide spacing between people getting their legs blown off. The existence of the legal system is one of the better arguments against the existence of a merciful God.
No, eating a mouse that ate out of the garbage or even rolling around in some catnip now and then will not make your litter of kittens stillborn, but I might as well have been talking in Chinese.
I think dehydration is the main problem for recreational Ketamine users as well.
I think taking 3g every day for long periods of time while following harm reduction practices (and the main practice is DRINK A LOT OF WATER) is relatively safe and less dangerous than taking 1g once a week without any harm reduction.
I've heard that dodgy nightclubs would sometimes turn the heating up and not supply tap water in order to sell more drinks to clubbers who were on e or ket.
The main reason of death for ecstasy users is overheating thought.
Also, overheating/dihydration is not an issue for "social" dosages of Ketamine. But it may be an issue for "I want to be almost unconscious for many hours" kinds of dosages.
I wonder how this relates to anabolic steroid usage. Every slightly academic source I've ever read on steroids always says 'of course, we know that IRL users are consuming much much larger quantities than standard dosing'. Could it be possible that smaller steroid cycles are..... not as bad for you? Testosterone prescription is now a thing (yes I know there's a distinction between test and actual anabolic roids).
Anecdotally, I know several people who said that they consumed steroids in their youth for a decade or longer, just not in huge quantities. They all, I dunno, seem to be in fine health in their 50s & 60s? The two guys that I'm thinking of in particular both have a full head of hair, in addition to seeming like normal, highly fit older folks
Most users are not only taking steroids, but many other things as well. The side effects are very dose dependant. 2g of testosterone will affect a 140Kg bodybuilder very differently from a 75Kg guy who doesn't train.
You can build a lot of muscle really fast with Xmg a week for 10 weeks then taking 10 weeks off. Then you have people who are huge taking 50xmg/week and having all kinds of problems. A little is good a lot is bad.
I wanted to try, but then someone told me that my body won't produce as much testosterone on its own forever after, that I'll get dick shrinkage and moobs if I don't take estrogen blockers at the same time, and that it will cause my thick, luxuriant hair, that hasn't thinned one whit since my youth, to begin doing just that. Horrifying...
What's the evidence say, anyone aware off the top of their head?
I don't know much about bodybuilding per se, but when it comes to specifically testosterone they tend to take several times what trans men do (in addition to what they have endogenously), and anecdotally trans men only rarely encounter any problems health-wise.
A while back I was researching phenibut to see if I should take it for anxiety. The first things I see when I google are recreational users talking about how horrible it is, how quickly you build up a tolerance, how easy it is to get addicted, and how terrible withdrawal is. I finally found one that talked about how much he was taking--14 grams three times a week! Yikes! Even the lower-dosage users were taking several grams at a time at least, multiple times a week.
So I decided I'm not at all worried about taking 250 mg, or even 500mg, every few weeks when I need it.
Don't Air Force pilots sometimes take amphetamines to fly for so many hours straight? Is this why they also don't seem to have problems? Is it why they are not likely to get addicted to them?
I don't think this has been mentioned yet. The book "Blitzed: Drugs in Nazi Germany" by Norman Ohler is both relevant here and excellent. Long-term outcomes of the broader population and also military personnel that used methamphetamine aren't entirely clear, but short-term outcomes were really well understood.
Amphetamines can impair judgement making military pilots too ebullient resulting in attacks on allies. I would guess they would prefer something like modafinal.
Am I off in believing that the opioid epidemic is a result of doctors generously/carelessly prescribing opioids? That doesn't mesh with the idea that clinical doses are overly safe and clinical prescribers are overly cautious.
Part of the harm with those prescriptions is supposed to be that people got addicted, so after the authorities clamped down many switched to heroin & fentanyl. Additionally, there were anti-abuse treatments to the various *contins which worked initially to spread out the dose over a long time rather than producing the sharp peak addicts want... but addicts eventually figured out ways around those. As far as I'm aware the most recent reformulation of oxycontin still works to curb abuse, and the result has been addicts switching to more dangerous street drugs.
My understanding (which I admit is just based on half-remembered blog posts so I'm happy to be corrected) is that the "legit prescription -> opioid addict" pipeline is mostly a myth, and that the vast majority of opioid addicts are simply people who started off abusing them recreationally.
People love to make excuses for drug addicts that put the blame everywhere except on the addict themselves.
I thought it was because the drug companies lobbied to make it legal to prescribe opioids for chronic pain, when they were not really intended for long term use in the first place.
Yeah, this is what I concluded, after looking into it — although this was a few years ago and I don't know if any new data has come out.
(I became interested because, after reading about the legit script --> addiction "pipeline" so much, I realized that all the opioid abusers I knew — myself included, at the time — *started off* abusing them. The only people with legit prescriptions we knew were selling them to us, not taking them.)
Although there are definitely bad apples who are litlte more than DEA-licensed dealers, my impression is that addicts score these in various less obvious ways, e.g. acquiring prescriptions from several docs who don't know about each other, or visiting an ER (per week) with nonspecific belly pain that is TOTALLY a 10 out of 10...er...and I'm allergic to whatever you offer me other than oxy, sorry.
It's multi-factorial. While there certainly were poor prescribing practices, they seem to be responsible for a minority of the problems. Drug trial issues (big one for me), sales practices, and crisis of Lack of Meaning are all a bigger problem.
That's the standard narrative, usually with a side order of "...and the doctors did it because the marketing reps from Evil Big Pharma tricked them into it". Conveniently, the standard narrative gives us a wholly unsympathetic villain to blame.
To the extent that clinical use of opioids is relevant to the great opioid epidemic, I think it is mostly that a legitimate pain-management prescription gives people who Are Totally Not Low-Life Drug Addicts, What Sort Of Person Do You Think I Am, a cheap convenient and socially legitimate opportunity to experiment with opioids. Some of the like it for reasons that go beyond pain management, and some of those like it more than alcohol or anything else in their lives at the moment, and they want more.
Eventually, the doctor will cut off their Vicodin or Percocet, but there will be someone to step in and offer them fentanyl at that point.
I think my favorite kind of example of this personally was having coca tea in Peru, in comparison to the awful energy drinks I usually go with. The boost with the coca tea was so smooth, so much less "buzzy" than with caffeine, that it seems criminal it's not legal in the US. I know, apples and origins, but very mild, low-dose coca seems really great, and too much caffeine seems kind of bad.
Yes, I came here to say this. If you used caffeine powder the way people use cocaine powder, it would be equally extreme (or maybe much more so?). If you use coca tea the way people use coffee or tea, it's equally mild.
Wikipedia tells me that a typical cup of coca tea has about 4.2mg of cocaine in it while a line of cocaine has about 30mg (ymmv. Harder addicts have been known to do a gram per *dose*!). A moderately addicted person might do 30 lines in a day, adding up to 900 mg, or about 220 cups worth. A typical cup of coffee has, say 100mg of caffeine, and 220 cups of coffee, that is, 22g of caffeine, will kill you.
On the flip side, 8 cups of coca tea add up to about a single small recreational dose, so I quite believe you when you say coca tea used like coffee is mild.
I am all for legalizing cocaine, but the obvious problem with legalizing coca tea for the mild effects is that people would just drink the 8 cups to get a full recreational dose.
It says making Chifir breaks down caffeine into adenine and guanine. What do those chemical do to you when you drink them? I can't find anything suggesting that they're drugs.
That sounds like complete bullshit. You can't make either adenine or guanine from caffeine without some tricky organic chemistry, it's certainly not going to happen by merely heating the stuff up to 100C.
In Russian version, which should be considered in this case more authoritative, as it's mostly Russian phenomenon, and unlike the English version, it is sourced, there's no mention of caffeine breakdown. I think somebody is either copy-pasting some unreliable info or playing the game of "how long could I have some BS on Wikipedia before anyone notices".
We used to do this. Ever heard of Vin Mariani? It was a sweet red wine laced with coca, one of the most popular drinks of the 19th century. Huge numbers of people in the US and Europe drank this stuff for a few decades. Some ads for it featured a testimonial from *the Pope*. Three small glasses a day contained something like the equivalent of 3-4 lines of cocaine.
Coca Cola was actually developed in part as a substitute for Vin Mariani in response to the rise of the temperance movement. Drinking the cocaine wine was less and less acceptable because it was *wine*. Kind of hard to wrap our heads around that one these days.
wikipedia: "Coca-Cola once contained an estimated nine milligrams of cocaine per glass. (For comparison, a typical dose or "line" of cocaine is 50–75 mg.[73]) In 1903, it was removed.[74]"
The dose was so low it was probably mostly harmless.
This is just not true. Caffeine and cocaine have totally different mechanisms of action. Notably cochise has a far more direct action on dopamine levels which makes it much more addictive and euphoric.
The difference (I assume, having tried large doses of caffiene but never having taken cocaine) is that using caffine powder the way a banker with suspenders uses cocaine is not a recipe for a fun time.
You just end up an anxious nauseated mess and never drink that much coffee at once again. It's neither recreational nor productivity-boosting.
Which is kind of similar to what people were saying about adderall vs meth.
Maybe we need a dimensionless quantity, like therapeutic index, except that it's the ratio between a dose that does long-term damage and a dose that makes you have a really bad time. A higher index would mean there's less of a risk of it being abused in a dangerous way.
I commented elsewhere recently about how nutmeg falls into this category. It will get you high, but you’ll also wish you were dead. Someone responded that “nutmeg high = weed + the flu”. So no thanks on the nutmeg.
This excellent post reminds me of the standard admonition against supplementing liberally with vitamin D, which says that doing so will give us all kidney stones and soft tissue calcification.
All the published evidence I have been able to find on this is old, and it mostly documents food fortification mishaps of the kind that result in a litre of milk containing 1,000,000 IU. Those stories do not have anything remotely to do with vitamin D as it would be used in any reasonable supplementation regime, but they sure are effective in scaring everybody, closing minds and shutting down inquiry.
"Throughout my preparation of this review, I was amazed at the lack of evidence supporting statements about the toxicity of moderate doses of vitamin D. Consistently, literature citations to support them have been either inappropriate or without substance. The statement in the 1989 US nutrition guidelines that 5 times the RDA for vitamin D may be harmful (3) relates back to a 1963 expert committee report (5), which then refers back to the primary reference, a 1938 report in which linear bone growth in infants was suppressed in those given 45–157.7 μg (1800–6300 IU) vitamin D/d (119). The citation is not related to adult nutrition and it does not form a scientific basis for a safe upper limit in adults. The same applies to the statement in the 1987 Council Report for the American Medical Association that “dosages of 10,000 IU/d for several months have resulted in marked disturbances in calcium metabolism…and, in some cases, death.” Two references were cited to substantiate this. One was a review article about vitamins in general, which gave no evidence for and cited no other reference to its claim of toxicity at vitamin D doses as low as 250 μg (10000 IU)/d (120). The other paper cited in the report dealt with 10 patients with vitamin D toxicity reported in 1948, for whom the vitamin D dose was actually 3750–15000 μg (150000–600000 IU)/d, and all patients recovered (121). If there is published evidence of toxicity in adults from an intake of 250 μg (10000 IU)/d, and that is verified by the 25(OH)D concentration, I have yet to find it."
This post shows that this kind of unconsidered overreaction is a more general problem. I guess I'm relieved?
Come on...Just one article I want to read "This is definitely medical advice and these drugs are really fun so go nuts"
Reminds me of psychedelic therapy. Is anybody going to be getting a massive dose legally, or will clinical doses be so much smaller that they are qualitatively different drugs? There is a major difference in experience between ketamine abusers and patients being prescribed ketamine by a doctor. If you read trip reports from massive ketamine doses, you can see there is much more going on. I would expect ketamine abusers to be less depressed, all else equal, but curious if there is actual data on that.
The dosage used in many of John Hopkins trials is equivalent to 5g of mushrooms, which is a large dose, though not massive. Microdosing typically uses .1g doses and 1g - 2g is a small recreational dose.
The difference with psychedelic therapy (to my understanding) is that the treatment is actually moreso the radical mystical experience you undergo during the trip, rather than any chemical effects of the drug itself. For that to happen, you need a large dose.
This reminded me of a long time ago when I was reading about lean, a drink combining prescription cough syrup with sprite and jolly ranchers. I cannot find the exact dosage currently, but I believe I read it was around 25 times the prescribed dosage. I'm sure there is a wide range. It would seem that one would quickly run out of cough syrup.
I am not sure if there is the same phenomenon with lean. People don't seem to have much qualms with taking cough syrup but a lot of rappers have died or had health problems as a result of lean usage.
Yes, this is right. Lean is usually using prescription drugs. It appears that sometimes people use over-the-counter according to wikipedia: "but over-the-counter cold medicine that lists dextromethorphan as the active ingredient has also been used, as it can produce similar effects and eliminate the need for a doctor's visit."
Also, wikipedia says: "Lean is often used in combination with alcohol and/or other drugs"
That's very misleading on the part of Wikipedia. Dextromethorphan is nothing like codeine. A high dose is like a fever dream, and a low dose is like being mildly impaired and confused. Codeine is like a warm hug that injects you with pure happiness.
Well, thank you for being so nice about it! I feel like I didn't actually provide that much detail, so if you are truly interested I'll expand a little.
I don't doubt that the article is correct in that people attempt to substitute DXM for codeine, because it's much easier to acquire; however, I'd bet they only do it once.
DXM is only considered a recreational drug in high doses — low ones are about as recreational as NyQuil! — but in high doses, the best I can compare it to really is a fever dream. Nothing makes sense and reality comes at you in brief, confusing flashes. I did not personally consider it recreational at all, in truth.
Meanwhile, I may be biased by my extreme love for all opioids, but it's generally conceded that codeine & co. provide euphoria, and are often described as "draping you with a warm blanket" or the like.
Categorizing drugs by effect rather than chemical structure, DXM is a dissociative like ketamine; codeine, of course, an opioid.
I think this case is a bit of an outlier, because "lean" is so retarded and, in a way, complicated.
0) "lean" syrup is usually promethazine-codeine syrup, but is/was often used interchangeably to mean hydrocodone-containing syrup as well. It's hard to overdose on codeine, easier on hydrocodone (but still hard unless you add in other factors, as you allude to; see below, also).
1) "lean" users generally dump a bunch of the syrup, unmeasured, in a drink, then sip on it — a great way to have no control over how much you're actually taking. Spreading the dose out over time like this might help, but actual amount of delay before the entire dose is consumed would obviously be highly variable.
2) "25x" sounds bad, but codeine is very weak; the amount in a regular dose of cough syrup (10mg) would only touch a completely opioid-naive person, and even then not very much so. Conversely, 10mg of oxycodone will have a strong effect even on someone who has developed a small tolerance, and 60mg will still get most experienced users high (although because opioids are otherwise so benign, tolerance can reach ungodly levels in a few cases).
3) codeine also has a ceiling effect at around 200-250mg, if I recall correctly. A user might therefore continue imbibing in frustration, and since
4) most "lean" syrups contain promethazine as well, which increases CNS depressant effects, this ain't so good; and
4) polydrug abuse is generally much more dangerous and likely to lead to overdose than using codeine (for example — or hydrocodone) alone would, so adding in alcohol and other drugs is now even more likely to cause complications.
*****
So I think the difference is not only the dosage — although it's certainly part of it — but also the confusion between different types of cough syrup, wildly varying doses, and the effects of concomitantly administered drugs like alcohol and promethazine.
DJ Screw makes lean worthwhile. How many drugs have a single artist who dedicated his life to that drug and redeemed it? Sure, plenty have tried. DJ Screw is probably the greatest success story when it comes to making art out of a bad drug.
Relevant clip from a superb film, 32 Short Films About Glenn Gould (this is film #23). GG took all these— a drug user who took a *lot* of drugs. https://www.youtube.com/watch?v=7eBotiHABdo
It's a much shorter list of drugs, but I like the repeated drug scene in All That Jazz (1979), the autobiographical film by Bob Fosse. https://youtu.be/L2e9acreKmQ?t=26
This reminds me of a friend who read that nutmeg is hallucinogenic, so he ate a tablespoon of nutmeg to get high. He said all he could taste for two weeks was nutmeg.
My dad used to work in a lab, and another guy got some pure nicotine on his skin. He would have died if they hadn't gotten him to the hospital right away.
related: alcohol is a much more social drug than a lot of pills and other such things, because you take your full dose in sips over several hours. Allows you to manage your level of intoxication via feedback. Whereas a tab of LSD or a pill can really fuck you up for hours and there's an expectation you should just take the whole thing at once. LSD would probably be much more popular if it came highly dilute and you could have a wee bit at a time (have I just reinvented microdosing, maybe.)
I'd say that microdoses are around 1/6th of a trip dose. The psychedelic equivalent of having a single beer vs the psychedelic equivalent of downing six.
I'm way out of my wheel house here as a non-biologist and non-drug user (I rarely even drink, pretty much stick to caffeine and sugar), but could this be read not just as an explicit argument against medical dosing guidelines, but also tacit argument *for* microdosing? Like, you're not wealthy, you don't have great insurance, but you need antidepressants, so you buy street drugs and then carefully stretch them out to a hundred doses?
From what I understand, street drugs vary in strength so you don't know exactly what dose you're getting, and sometimes it's not even the kind of drug that the dealer says it is.
"A lot of our impressions of drugs, what side effects they have, and how dangerous they are, get shaped by the recreational users, not the patients."
I'd suggest a variation on this: our impression of drugs is shaped by their mode of delivery, which in recreational contexts tends to be a mode that delivers a faster rate of onset and/or higher peak plasma. I think this matters more than the total dose.
So I can ingest vast quantities of caffeine in the form of coffee every day and still enjoy moral superiority vs. someone who injects the same quantity of stimulant at the weekend.
Of course they are probably getting a totally different high and side-effect profile too so it's not as if the moral stereotype is baseless. But I suspect it does feed into sub-optimal public-health outcomes. See: vaping.
Still confusing to me as a non-English speaker: in Dutch we have two words: "drugs" are recreational (sometimes illegal) substances that change your mood or cognition, medicijnen are physician prescribed substances. This makes reading a piece like at times confusing:"Which of the two is he talking about now?"
Well, he's talking about literally the exact same chemical substance, in the first part ketamine, C13H16ClNO arranged thusly: http://www.chemspider.com/Chemical-Structure.3689.html . Using two different words to describe the exact same substance depending on who sold it to you, seems like the confusing part. In English, a "drug" is a substance intended to alter the biochemistry of the human body to produce a desired effect. It's the same word, and often the same substance, whether the desired effect is medical or recreational.
If who sold it to you makes a significant difference - like, just as an example, whether you get put in prison vs being on solid legal footing and maybe even getting your drug paid for by insurance, I wouldn't call using different words "confusing".
Although I personally do prefer the way it works in English, with "drug" covering both, partly because it allows talking about things like illicit ketamine, lsd, etc. without reinforcing the framing as "bad, illegal, criminal substances that are bad for you because bad"... at least, not nearly as much as happens in a language like Dutch or, very similarly, German (my first language).
In German, "Droge" (drug, duh) also refers to the illegal kind. Although in the law, they're classified as "Betäubungsmittel" (~numbing agent, basically "narcotics"), as is quite common, I believe, because that's how the international war on drugs treaties etc call them.
The German language generally errs on the side of eliminating ambiguity & words or phrases having many possible meanings, and creating more specific categories. Makes it a great language for precise technical instructions, engineering and natural science talk; less great for art.
Minor nitpick (7 months after you wrote that): drugs in English (even restricted to those used to treat humans) aren't only substances intended to alter the biochemistry of the *human* body; often the target is other organisms within that body, like with antibiotics or antiparasitic medications. Ivermectin targets the biochemistry of invertebrates, for example.
In English, the word "drug" is often ambiguous. It normally has a strong suggestion of being the recreational (and usually illegal) kind, but it is used both ways (as in "Food and Drug Administration" and the phrase "prescription drugs"). "Medicine" is only used for chemicals taken for medical purposes (sometimes prescribed, but sometimes just over the counter, like aspirin, acetaminophen/paracetamol, etc.).
In English when the distinction should be made and context doesn't supply it, we usually add one of several adjectives, e.g. "recreational drugs," "illegal drugs," "illicit drugs."
I guess the other point is that the ambiguity is useful to the point Scott is making, because he's pointing out that the very same molecule can have beneficial or deleterious effects, depending on the dosage and pattern of administration -- and even the underlying reason, since e.g. I believe there is evidence that suggests even opiates need not be addictive *if* they are actually being used to moderate severe pain and at appropriate levels.
So in this case maybe English has an advantage over Dutch, in that our language already includes this ambiguity, so the fact that the effect of a "drug" is contingent on circumstances may require less of a conceptual step for the English speaker.
As others have pointed out, it's unfortunate that you seem to be using some of the terms interchangeably which leads to casual drug users and drug abusers being conflated.
Obviously taking a large vs small quantity of a drug has differing effects but so does taking the drug daily vs occasionally. This is especially true given that the examples used seem to mostly refer to long term, frequent abuse. Most recreational drug users do not use so frequently.
In terms of meth, I think you're also missing some important confounds
[accidentally prematurely posted] if frequent meth abusers have much worse dental health than medicinal Adderall users, do we really have to believe that it's due to meth itself? I would expect you might find large differences in terms of diet, dental hygiene and several other factors between the two.
I have a friend who used to take a lot of recreational ketamine. (This is a friend, not a "friend" ;-P ) He had a sports injury and wound up in the ER. When the anesthetic they gave him didn't work, they gave him more. Then they asked him if he took recreational ketamine, lol! He kinda demurred but was like, "Yeah, well, kinda..." Bottom line: recreational drug users take a lot of drugs!
"They find that severe abusers, who are taking an average of 60,000 mg/month, experience cognitive problems. But mild abusers, who take more like 3,500 mg/month, don't. Again, psychiatric patients are taking about 280 mg/month. I think this is pretty strong evidence that the psych patients shouldn’t worry that much."
I remember a post you made a while back about melatonin having greater effects at lower doses. Is this a possibility for ketamine?
Melatonin has *better* effects at lower doses, but that's different from saying it has *stronger* effects (which it doesn't). From the Lorien Psych page (https://lorienpsych.com/2020/12/20/melatonin/):
"A meta-analysis of dose-response relationships concurred, finding a plateau effect around 0.3 mg, with doses after that having no more efficacy, but worse side effects (Brzezinski et al, 2005)."
My biggest issue with s-ketamine is its broad agonist on over 30 receptors. While it’s dissociative properties are why I would use it in a pinch, I prefer pharmaceuticals that are much more targeted. Also, I think the literature supports more novel psychedelic treatments such as psylocibin and MDMA as better effective depression and addiction treatments than ketamine - which has a very short duration of efficacy and is just about one step better than ECT.
I’d also like to add, I suspect the bladder dysfunction likely stems from ketamine’s affinity for Mu receptors. Ketamine has a the strongest preferential affinity for NMDA receptors, but number two and three on the list are Mu-1 and Mu-2 opioid receptors. This is what gives the analgesic benefit to ketamine administration. Urinary retention secondary to inability to relax the urinary sphincter and contract the detrusor muscle is a side effect - along with pupillary contraction - that you cannot grow a tolerance to with chronic opioid use. Again, ketamine is a “dirty” drug in that it has affinity for so many receptors, and therefore is more of a very niche drug, akin to Demerol’s widespread use for rigoring - even though dexmedetomidine works better with less side-effects for that specific scenario.
Very interesting, thanks. To set against this, perhaps, one suspects the more targeted drugs might in general have pharmacokinetics that pose more risks -- the more generic the molecule, the more pathways there probably are for its degradation, and the more likely that the intermediate metabolites are benign.
I have friends who use ketamine and those doses are on the extreme high end. I would say the average dose for a normal non-addict ketamine user would be a gram every 1-2 weeks. Still higher than the therapeutic dose buy not by such an extreme margin
Every so often I see an article about how e.g. soldiers in WW2 were on amphetamines all the time-- now I'm curious where their dosage fell between "Adderall" and "recreational drug user".
I find it hard to believe that frequent ketamine users take around 3g/day. Just from a financial perspective, 3g/day equates to £2100/month (~$3000) at £25/gram. Given how disabling K is, I don't think that the kinds of people that are doing 3g/day could afford it. I had a quick look at the Morgan et al. paper, and although it says the frequent group uses about 3 grams, it doesn't specify over what time period. Perhaps they mean 3grams per week or month? Happy to be proven wrong here if I've missed it. The chinese paper does specifically say 3g per day though, so maybe my instincts are wrong. Anecdotally, I've heard of bladder issues in people that wouldn't be consuming more than a gram a month.
So.... Why don't we prescribe Adderall to just anyone who wants it at those low dosages? Or do we? Does this same kind of logic apply to steroids? Sure, body builders take huge dosages and can do damage to themselves. Can relatively low dosages work as treatment for obesity?
Right up until that last paragraph I was really considering taking a micro-dose of DNP. Maybe I still should, but I would feel bad doing it without your blessing!
Could one call this phenomenon “replicability crisis two: electric boogaloo”? Sure seems the thrust here is that a large portion of drug studies won’t replicate in clinical settings, which feels like a big deal? And also implies we can’t really understand a drug’s risk unless we legalize it medically first and then study possible side effects?
I understand the point you're trying to make here, but as a recreational ketamine user I just want to let you know that 3g/day figure is way too high and nobody is taking those kind of doses, most certainly not everyday for a month. To get an idea of how much a typical recreational user is taking, you can refer to this harm reduction website. https://drugsand.me/en/
This site states that heavy dose for oral ingestion of ketamine is around 500mg which is also referred to as the K-hole dose. K-hole is the term used among users to refer to the state of total dysfunctionality when you take a large enough dose of ketamine. Going by these numbers it just seems absurd to believe that an average ketamine user is dysfunctional everyday over months.
Moreover the LD50 for ketamine for a 70 kg human is 4.2 grams. There's no way an average ketamine user is steering so close to the levee all the time.
Is there any evidence at all that energy drinks are harmful in low doses? I'm suspecting the entire stigma comes from case series where people took too much or had pre-existing heart problems.
Also I saw a review paper where a weight loss supplement providing -2kg over 3 months was described as "not clinically significant", but 1.33 pounds per month is a lot of weight loss. If that could be safely extrapolated over a long time it adds up. Adding it to the water supply might reduce obesity rates by more than half. Again I suspect thermogenic supplements have a bad name because of people who take too much.
"and you wouldn't believe how many hoops the psych patients have to jump through to get their 280, or how terrified their doctors are that something could go wrong"
This is pretty much why I gave up trying to get medications that I actually NEED to treat my ADHD and depression; it's actually less work to just go unmedicated and be mostly-functional than it is to deal with all the bullshit involved with getting stimulants and ketamine.
There's bits of this all over pharmacy lore. Metronidazole is the only antibiotic you're supposed to actually not take with alcohol because there's a theoretical disulfiram-like reaction (disulfiram is normally used to treat alcohol addiction does so by severely magnifying its effects so any tiny amount with have you throwing up like you went on a full bender) but I was told once (tbh I've not personally looked into this one) that there's straight up never been a case study of this actually happening.
Recreational users of non-meth amphetamine also take huge doses like 500-1,000mg on a single day. So it seems surprising they don't seem to get the same health problems and addiction. Though to be fair they probably don't take this every day. But that also suggests the addiction potential for non-meth amphetamine is lower. (Maybe because it can't be smoked?)
It is well known fact that ketamine high make urination difficult. It's not really a physical difficulty, but rather you forget how to contract and relax appropriate muscles. Also, having full bladder stops being so unpleasant on ketamine.
So I guess if you do lots of ketamine, then you're high most of the time and may hold your urine for long periods of time - and that can cause UTI and bladder injury.
One thing I do for the did-I-take-it-or-not problem is to lay out the pills in advance. Either measure into pill cases for the week (did I take today’s dose? I can look!) or just put the pill next to a cup of water on my bedside table the night before, when I’m thinking more clearly.
I don’t know if that would work for other people, but those headaches sounded truly awful, so I thought it was worth mentioning just in case.
I take a daily pill early in the morning before breakfast. A simple way I found to remember if I took it is to leave a glass of water on the nightstand at bedtime, and finish the whole glass when I take the pill. This works because no matter how brain dead I was at 6am, empty glass = yes, you took your pill.
I tried a bunch of tricks and kept accidentally forgetting to reset the trick. Turns out you can buy little pill-bottle-cap stopwatches, with a clever pressure-sensitive assembly so they automatically reset when you open the bottle. Just look on the cap to see when the last time you opened the bottle was.
This has solved a lot of issues for me.
Source please?
Excellent post. Just the right dosage of all the ingredients for a splendid article. No side effects!
Just be careful reading the back catalog.
Drink water and stay healthy. Drown in water and die. #DosageMatters
Or drink 1 litre of water and stay healthy; drink 10 litres of water and die of water poisoning.
You can safely consume way more than 10 liters of water in a day. I have frequently consumed over 10 liters of water in a day when doing long distance bike rides. Water is very safe to consume.
I had a considerably shorter period than that in mind; let's say 1 hour. The ratio of a normal dose of say 1 litre to a fatal dose of say 8 liters is rather low compared to many substances considered dangerous.
Yeah but drinking 10L of water in an hours is...difficult. Consuming 10x the therapeutic dose of any number of drugs is easy.
You get water poisoning when you drink way too much, and drink it faster than your body can get rid of it. If you're just replacing what you sweat out, you're fine.
Death from drinking too much water is rare, because you have to keep drinking long past the point where your body tells you to stop.
I doubt it's the water, either, ill effects are probably just hyponatremia or something. If you drank lactated Ringer's I think you could probably do it until you literally explode.
Hyponatremia is the mechanism by which water kills.
Mmm that's kind of stretching the definition of "mechanism" in my book. You might as well say N2 is the mechanism by which hypoxia kills, or boiled beef is what gives you scurvy. The water is an innocent bystander, it's your failure to consume enough electrolytes along with the water that does the job.
The dangers of dihydrogen monoxide.
(puts on cape) This looks like a job for... (takes off cape, puts on suit and tie) ...the FDA.
There should be a website where Scott recommends studies/clinical trials and university students carry them out and publish results.
I know I know I know! A *prediction market*!
Great post but I would caution using the terms "recreational user" and "abuser" interchangeably. There are a good many people who slip through the cracks with these studies because researchers have motive to show a big difference when publishing so they typically use abusers in their studies who are taking doses at the extremely high end, and clinical users are taking doses near the very low end. This is also the case in many in vitro and in vivo animal studies where doses and concentrations that far exceed what a normal recreational user might take or. There are likely many more recreational users that use drugs intermittently, say for concerts or outings with friends and may take in excess of what would be considered a therapeutic dose but are still well below the consumption rates of an abuser given that they don't take the drugs all the time. It's not at all clear that these users should be lumped in with "abusers", nor should they expect the same level of side effects.
and sometimes they just mislabel molly as meth, lol.
https://www.wired.com/2003/09/ecstasy-study-botched-retracted/
I parsed "mislabel molly as meth" to mean that a bottle labeled "methamphetamine" contained MDMA. In case anyone else read it the same way, the linked article is about the reverse situation, where a study indicating neurological damage from MDMA was actually dosing animal subjects with meth by accident.
"molly" is the direct object of "mislabel. It's the thing that had the action performed upon it. "meth" is the indirect object of "mislabel". It is preceded by a preposition, and indicates the natures of the action. Your reading is the correct one. "Mislabel molly as meth" means that molly is the thing that actually exists and was mislabeled, and meth is the thing that describes how it was mislabeled.
3g of ketamine a day is a lot even by my standards and I’ve been around the block a few times. What addict has the cash for that? My heroin abusing pals, at their height were doing maybe 15 grams every week or two. I might be misremembering and didn’t do heroin enough to know, but I don’t think it came anywhere close to 3g a day at least for anyone I knew. I suppose Sid Vicious or Lane Staley might have been up there but in my day to score smack someone still had to make a desperate trip to the worst part of the ghetto just to get ripped off half the time, which always made a score fraught with danger. To do it everyday you had to be all in and off be very curious where the line is between those people and others.
“ The average crystal meth addict uses about 500 mg a day.”
One minor point - as far as I can tell thats the average for someone who thinks they have enough of a problem to seek treatment. I would say the average dose is more like a gram a week. Coke and meth are expensive. The average users needs to hold down a job.
Per the study: “One hundred and eighty-three stimulant users from a longitudinal cognitive study (120 MA and 63 cocaine) were included in this study. One hundred and fifty-three of them were enrolled in treatment in either the Matrix Rancho Cucamonga Clinic in San Bernardino County California, or the UCLA Integrated Substance Abuse Programs’ Torrance Clinic in Los Angeles County”
I thought much of the point of meth was that it is relatively cheap (aka "redneck cocaine") when compared with cocaine?
My understanding is the prices per gram are roughly the same but cocaine is much shorter acting so you need to use more to stay high. At half a gram a day you’d be looking at $1500/month. That’s hard to sustain on multiple levels.
Meth is far cheaper than cocaine. Typically between $20-$30/gram. Cocaine costs $90-$110 per gram.
https://dhs.saccounty.net/BHS/Documents/SUPT/Methamphetamine/Coalition-2020/MA-ADS-2020-02-13-Methamphetamine-Trends-in-the-Sacramento-County-Probation-Department.pdf
https://www.addictioncenter.com/drugs/how-much-do-drugs-cost/
Meth and coke have similar per gram prices but meth is much cheaper per kilogram. This is the markets way of saying that dealers require extra compensation to have to deal to meth users.
I suppose the ones who seek treatment are the ones who appear in the studies.
"One hundred and fifty-three of them were enrolled in treatment in either the Matrix Rancho Cucamonga Clinic in San Bernardino County California,"
Let me tell you, that is an exceptionally appropriate location for a meth addiction clinic.
Re: your comment in section II. Many organic chemicals have completely different functions when modified slightly, such as nicotine and nicotinic acid (niacin); one is a toxin and the other is vitamin B-3. Also, chlorophyll and hemoglobulin; one converts carbon dioxide and water to oxygen and simple sugars, the other transports oxygen and carbon dioxide. This is because evolution doesn't usually create uniquely new structures, whether morphological or chemical, but more typically modifies existing ones.
Forgive me if you’re not new here, but it’s sort of taken as read that Scott knows that and his audience knows that.
Here’s a quick list of entries from his previous blog where he talks (often in some detail) about racemic mixtures of a variety of compounds, for example: https://www.google.com/search?q=site%3Aslatestarcodex.com+racemic&rlz=1CDGOYI_enUS949US949&oq=site%3Aslatestarcodex.com+racemic&aqs=chrome..69i57j69i58.12054j1j7&hl=en-US&sourceid=chrome-mobile&ie=UTF-8
Sorry, you're right. I am new and should have realized this. I not used to blogs where the participants have so much expertise.
No worries! Welcome! Plenty of enthusiastic amateurs as well, myself included.
Personally, I didn't know that!
The difference between nicotine and nicotinic acid is hardly slight. If nothing else, the first is an amine and the second an acid.
That's true, on the other hand you've only changed half the molecule. My point was was about evolution really; morphological adaptations are more obvious than chemical adaptations.
"one is a toxin"
Not really https://www.gwern.net/Nicotine
Well, it's a toxin to insects. That's why the plants produce it.
It has interesting effects in humans. Especially for ADHD people.
"Although ketamine might seem like a promising antidepressant that could relieve treatment refractory depressive symptoms, the induction of memory impairments in the longer term is of concern"
I take legal, cheap, widely-prescribed antipsychotics that leave me with the memory of a goldfish and do much worse. Where are these people when it comes to that? Or do older drugs with bad side effects get grandfathered in?
I mean, ketamine also got approved eventually. Usually you weigh cost vs. benefits and approve things if the benefits outweigh the costs. I think we prescribe antipsychotics less than we would if they didn't have these kinds of side effects (though we still overprescribe them). Now we're debating how often to prescribe ketamine, these kinds of considerations are coming up, and I support being more liberal with them because I think this only happens in people taking them at high doses.
Everyone should know the paraphrase of Paracelsus: the dose makes the poison.
Also, everyone should know that Paracelsus' actual name was Philippus Aureolus Theophrastus Bombastus von Hohenheim. No lie!
Also, everyone should know that Paracelsus is the reason Robert Boyle recommended dried human excrement, blown into the patient's eyes as a powder, as a treatment for cataracts.
Also, everyone should know that immunotherapy and intestinal matter therapies are really cool.
Most of my concerns* about occasionally using nicotine gum as a nootropic went away when I realized just how much nicotine a typical smoker is getting. A pack/day is like 300mg/week or something, whereas a few pieces of gum per week is like 10-15mg.
*that is, my concerns that remained after learning that nearly all of the risk from tobacco has nothing to do with stimulants
I think the main risk with nicotine gum is that you get addicted to nicotine and then start taking more like 300 mg/week.
That makes sense. Gwern has the willpower and self-control to not go overboard, but I'm not sure how I would do. Anecdotally, I had a cousin get addicted to the strips fairly quickly. Enough to say "I don't feel anything from them", and also going through 10 strips before breakfast. Gwern I believe was doing <2mg per dose. The strips my cousin uses are 2.5mg each, just massive differences is usage amounts. This reminded me of your blog on the dosage differences for melatonin.
Btw, the typical melatonin dose being 10x higher than optimal lends itself to a neat lifehack - I can split the pill in 8 parts and get a more efficient drug at 12.5% cost. Take that, big pharma!
Maybe you should snot it as well, doubling the peak plasma level is literally a 50% discount!
Do you have a good way to do that division in a controlled way?
A cheap pill splitter is very effective at getting pretty exact halves, and pretty good at converting those halves into quarters. Eighths seem a bit more finicky, but I bet you could stay within 20% accuracy? But given how cheap melatonin is, I don't know that it's worth the 1-2 cents of profit to perform a third division.
Yeah, I know a few people who are clearly dependent on it, so I'm pretty strict about having a specific amount that I allow myself to use every week, and I've been successful staying within that amount for several years now.
I don't know about your social circles, but even ten years ago when everyone when everyone in the UK smoked a pack a day was considered the stereotypically amount for "too much", an almost obscene amount. You would say it as an exaggeration "He must smoke a pack a day!" And from my own personal experience even a pack every two days is kind of pushing it. I'm pretty sure that most people smoke far less than that.
Looks like the average American smoker smokes .7 packs per day, down from .85 packs per day in 2005: https://www.cdc.gov/media/releases/2018/p0118-smoking-rates-declining.html
So now the trick is to get some test subjects to go from zero to 100,000 mg of some drug over the course of some months and see if we can identify the break point.
Pay me $200 a day, I’ll volunteer as tribute.
This wouldn't make sense because there would be accumulation of harm. You would want to have cohorts of ascending doses 10mg , 100mg , 1000 mg, 10,000 mg, 100,000 mg. You would find a point at which it harms the cohort. However, I'm pretty sure that type of study would be illegal. You're not supposed to ascend until you intentionally inflict harm on subjects.
I think this sort of thing should be legal provided the person knows the risks involved and feels appropriately compensated. Is it ethical? This would depend on a lot of factors. Doing it for fun would seem unethical. Being misleading to subjects in anyway would be very unethical. And the obvious other caveats.
I hope some country does an experiment where they make literally every drug available over the counter to adults, but in low-dose pills so that it's hard to take enough to do harm. Prescription gating sometimes feels like a jobs program for very expensive rubber stamps.
Possibly a dumb question: When I was living in the UK, I found it annoying that all the drugs I bought (including very safe things like ibuprofen) came in blister packs. Is this to control self-dosing? I'll admit it might have made me slightly more likely to take a single tablet when I was on the fence between one tablet or two.
It seems like it would have that effect. If everything came in blisterpacks of low-dose pills, it would take an annoyingly long time to take too much, and this would push people towards taking less.
Or else you'd just create a cottage industry of slicing open blister packs and repackaging the pills in bottles.
It may take too long to peel it apart with your fingers, but be no big deal if you use a utility knife.
One patient encounter of mine involved someone who opened up 3 months-worth of prescription medication blister packs and took them all at once. Not only is it theoretically possible, I've seen it happen!
One reason (perhaps the main reason) is that every blister pack comes embossed with its own use-by date. I think you must agree this is a sensible arrangement.
I'm not sure I understand the difference between this and a date on the bottle?
Pills from different bottles can get mixed up. Not likely perhaps, but possible.
Isn't that simply the cheapest way to package it? Light, doesn't take up much space, keeps each pill packaged until use, and cheap. The alternatives, where pills would be in a plastic bottle seem to be useful only when a pharmacy does the packaging and the pills are moved in bulk.
It depends on the quantity. I have a 500 tablet bottle of 200mg ibuprofen, and I doubt it would have been cheaper to package that in a blister pack
:o
That's probably not something that pharmacies carry around here. It could be due to legal limitations, maybe simply beacuse those big packs are absolutely not subsidized, or maybe I just haven't checked.
After a looking for ibuprofen 500 pieces here, I found a big bucket of 100 pieces of paracetamol 1g pills on sale. (0.11 USD/piece, the small box that has only 25 pieces just costs a bit more per pill.) Completely crazy, a few of these is deadly :o
So ... it seems the blister pack is simply the cheapest for that amount. (10-30, in a box) But above a certain amount the bucket/bottle is the economical one.
Have you not learned that Americans love to buy in bulk? Hell, even our single-serving portions are designed to scratch the buy-in-bulk itch.
I believe it's to discourage suicide. I'm told it works, compared to the time when you could open your jar of pills and swallow the whole lot in almost one go.
Results
Numbers of tablets per pack of paracetamol and salicylates decreased markedly in the year after the change in legislation on 16 September 1998. The annual number of deaths from paracetamol poisoning decreased by 21% (95% confidence interval 5% to 34%)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC31616/
I now feel much better about the illegal drugs I buy coming individually wrapped. Someone out there cares about me!
The UK has (correctly) a high level of concern about paracetamol overdosing. Unfortunately, the legislation on this was actually written to apply to all painkillers, so the same rules apply to ibuprofen and aspirin for no good reason.
Because such a large fraction of the drugs people buy over the counter include painkillers, the pharma companies find it easier to operate a supply chain of everything in blister packs than to have a separate chain for bottles.
Interesting, thanks. Do you know if there's evidence that the policy had the desired effect?
There was a big drop in deaths from paracetamol poisoning, see Jason Murphy's comment below for more details.
Quite right. Unfortunately for acetaminophen (as we colonials call it) the difference between the therapeutic dose and the dose that starts working over your liver is not as great as onewould hope.
it's proven to reduce suicides.
Numbers of tablets per pack of paracetamol and salicylates decreased markedly in the year after the change in legislation on 16 September 1998. The annual number of deaths from paracetamol poisoning decreased by 21% (95% confidence interval 5% to 34%) and the number from salicylates decreased by 48% (11% to 70%). Liver transplant rates after paracetamol poisoning decreased by 66% (55% to 74%). The rate of non-fatal self poisoning with paracetamol in any form decreased by 11% (5% to 16%), mainly because of a 15% (8% to 21%) reduction in overdoses of paracetamol in non-compound form. The average number of tablets taken in paracetamol overdoses decreased by 7% (0% to 12%), and the proportion involving >32 tablets decreased by 17% (4% to 28%). The average number of tablets taken in salicylate overdoses did not decrease, but 34% fewer (2% to 56%) salicylate overdoses involved >32 tablets. After the legislation mean blood concentrations of salicylates after overdose decreased, as did prothrombin times; mean blood concentrations of paracetamol did not change.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC31616/
When tables are sold in bottles containing hundreds people are likely to take more. In the UK you can buy a maximum of two packs or 100 tablets, as this reduces the risk of abuse and use for suicide.
Portugal didn't quite do this, but it (and a few other countries I can't remember — Uruguay?) have decriminalized personal use of all drugs, and the results have been what you might expect (that is: entirely positive).
Decriminalizing is not the same thing as making them available OTC in your local Walgreens. If one has to source it on the street (which I think is still the situation in Portugal and Uruguay), the potency and purity is uncertain, and this probably increases overdoses and other negative side effects by a lot.
The variation in potency might also make it more addictive, like variable-ratio reinforcement in skinner boxes.
The list of harms caused by drug prohibition is staggering. The obvious ones, like "cartels control the supply" or "no quality control" can be seen even by the slow-witted; a little thought reveals a myriad of other negative details, like variable dosage being dangerous in terms of both overdose *and* reinforcement, high prices incentivizing criminal behavior and self-neglect, shame and illegality *dis*-incentivizing education and support, etc etc etc.
High prices and variable doses incentivize polydrug abuse and injection, as well, both of which make overdosing easier — it's surprisingly difficult to fatally OD on heroin alone, for example, to take perhaps the most infamous culprit. In fact, in all my years of personal and professional experience, I can't think of any case (off the top of my head) wherein an individual fatally overdosed on an opioid alone without either ingesting other drugs as well or choosing IV as the RoA (or both, staggeringly).
I don't believe most of these individuals would have felt the need to stretch their supply by mixing in benzos or alcohol (the most common suspects: nearly always ____ and alprazolam, it seemed), or injecting rather than snorting/eating, if a source of opioids had been readily available.
Man, I could just keep going and going... but most people here already agree, I think, heh.
No, not really. The thing with heroin is rapid tolerance reversal. The overdoses are often cases where people havent used for awhile, then use a dose they were using with no problem before.
Even setting can affect this. People who dose in new places dont have their body prepare for it and the rush of sedative effect can overwhelm the nervous system. You are correct that it is hard to od if someone is using chronically and increasing their dose relative to their tolerance levels.
Absolutely. I merely meant to suggest that if decriminalization didn't result in a spate of overdoses, drug tourism, and addiction, making drugs available OTC would probably be pretty good too.
I believe that Russia and Bulgaria already do this, I don't know the details though.
The study of the safety and efficacy of the vast majority of drugs is so profoundly inadequate as to be criminal. Even"gold standard" designed and executed clinical trials are too short term, too small and subject to statistical manipulation as to be near useless. Post marketing studies are few a far between and adverse event reporting a joke.
Physicians are left to "ask around" and spend time most don't have searching for literature that many are ill equipped to judge. Most don't bother and shy away from drugs that might help and prescribe based on pharmaceutical advertising consumed by either themselves or their patients.
What little system there is is vastly inadequate, economically driven and morally corrupt.
Can you give some evidence for this, or explain it further?
I think we know a lot about most drugs. It's not perfect, but the amount of studies we would have to do to make it perfect would make medicine impossible. What changes would you propose?
I think that your description of what you've gone through to be able to make some sort of intelligent informed decision about prescribing Ketamine illustrates most of what I'm saying. Shouldn't the FDA be the ones doing the sort data collection an analysis you've done, and making it part of the prescribing information?
The current system is not great, but assuming what you said (I tend to agree), it's still pretty good at weeding out bad stuff and finding useful things. I mean just look at how completely useless nutrition science is in comparison. (Even after adjusting for budgets/expenses.)
Of course there's plenty to improve on it, but that'd require cutting out a lot of middleman (and not just the middlemen, but the middlewoman and middlechildren too - sorry). And like the replication crisis this is kind of ongoing with placebo and SSRI studies. But as long as we lack meaningful alternatives we'll unlikely to pour more money into this whole system just to get very similar results.
It is all on the PI for Spravato. Here's the relevant paragraph:
5.9 Ulcerative or Interstitial Cystitis
Cases of ulcerative or interstitial cystitis have been reported in individuals with long-term off-label use or misuse/abuse of ketamine. In clinical studies with SPRAVATO nasal spray, there was a higher rate of lower urinary tract symptoms
(pollakiuria, dysuria, micturition urgency, nocturia, and cystitis) in SPRAVATO treated patients than in placebo-treated patients [see Adverse Reactions (6)].
No cases of esketamine-related interstitial cystitis were observed in any of the
studies, which included treatment for up to a year.
Monitor for urinary tract and bladder symptoms during the course of treatment
with SPRAVATO, and refer to an appropriate healthcare provider as clinically
warranted.
https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf
So you should get a telephone-book-thick stack of reprints of papers with each bottle of the drug?
I will add that I worked in an academic setting as both a data manager as well as a clinical trial coordinator in pediatric psychopharmacology.
I haven't been able to find any long term studies of stimulant effects for ADHD treatment in adults or children. A quick search shows https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473329/ which is a 12 month study in primates. Previously the longest term studies Ive found are 6 weeks.
Considering that ADHD is a life long diagnosis for adults it seems like some rigorous longitudinal studies would be appropriate. Adderall was approved in 2002. Where are the 20 year studies?
Here is a study I worked on:
https://pubmed.ncbi.nlm.nih.gov/17023867/
Awaiting someone with a spare $10 million to fund them?
Adderall was approved in 2002, but amphetamine and dextroamphetamine have been studied extensively and in regular use since the 1930s. They have a much longer history of use and a much larger body of knowledge surrounding them than most drugs that are currently in use.
Aren't Biostatisticians designing studies to be adequately powered with large enough n? What sort of manipulation is going on that renders clinical trials useless? And what is a joke about adverse event reporting?
Your intense skepticism is piquing my interest.
"The dose makes the poison" --Paracelsus, Swiss physician, alchemist, theologian, and philosopher of the German Renaissance
Imagine a world where the most ruthless drug dealers cut their drugs so hard that they end up curing their customers' depression and turn them into diligent straight-A students.
Nice. Even though it is mostly unrelated it reminded me of this SMBC:
https://www.smbc-comics.com/comic/drugs-3
This reminds me of when I decided to stay on my ADHD meds through my pregnancy (baby is fine). I was sent to the maternal fetal medicine doctor for an assessment and the guy rolled his eyes and told me "the data we have on amphetamines and pregnancy is from meth users, so everyone is going to act like you're on meth when they talk about risks. You're not, you're basically here for my blessing, and you have it."
So much else in pregnancy advice follows this pattern. I was told not to eat lemongrass when I was pregnant, and decided to chase down the science behind that advice. There was one study 30 years ago where mice were fed some compound found in lemongrass in increasing amounts until it caused measurable fetal harm. The required dose for a human would be equivalent to a brick-sized chunk of pure compound.
You’d need to eat a truckload of lemongrass daily for weeks to replicate this. But pregnancy makes a lot of us want “do this not that” advice, and this is the rare foodstuff that has even a single study describing effects on fetuses, so it ends up on a blurry photocopy of Foods To Avoid handed out at OBGYNs for the next 30 years. This seems harmless until researching this advice takes you to a few forums, and you realize there are women in this world who believe they caused their own miscarriages by inadvertently eating Thai food. That made me incredibly sad.
Maybe take a look at malpractice insurance premiums for OB/GYN specialists.
Maybe that's a little too cryptic. If you take a look at the risks these people take, in terms of spending 18 months with a $50 million lawsuit hanging over your head, by people who expected childbirth in 2021 ought to go perfectly, rainbows and unicorns every single time, regardless of maternal risk or behavior, or the bad luck of genetics, then it would become a little clearer why these people are often intensely paranoid and never ever err on the side of rational risk, but always on the side of if there is any conceivable way someone can get upset because I didn't warn her of X or Y absurdly tail risk I better do it.
I’m not sure this really makes sense from a legal perspective. Why lemongrass then and why not a million other things? Why was I not specific cautioned to avoid rue or fenugreek or driving? There’s stronger science for an awful lot of omissions that could stand up better in court than lemongrass.
I'm not saying people run through the entire gamut of weird things you could do and rank them in order of risk (to you or their 401(k)) and then warn you about the top 100. What I suspect happens is that whenever they run across something, because it pops up in the news, or someone asks about it, they reflexively take the path of ticking the box that says "I warned her that this coffee is hot, and she should not pour it into her lap."
And also that I totally get why they do that. Obstetrics is inherently a weird field, because people don't instinctively feel like their health is at risk when they get pregnant the way they do when diagnosed with cancer or even high blood pressure (although it totally is). So their natural expectations are sky-high, whereas I would guess if you stumble into the oncologist's office with a Stage 4 lung cancer diagnosis, your expectations are so low that if he or she merely offers you the chance to extend your days by 6 months you're ready to weep with gratitude, and certainly not angrily demand why it isn't 9 months like your step-aunt June Cleaver got.
From a *legal* perspective no one should ever take any chance at all, and you should live in a stainless steel box and communicate with the world only through typewritten notes vetted by your lawyer. The legal system is a giant field of antipersonnel and occasionally antitank mines through which we stroll every day, gaily unaware of the risk simply because of the fairly wide spacing between people getting their legs blown off. The existence of the legal system is one of the better arguments against the existence of a merciful God.
I tried telling a pregnant female this.
No, eating a mouse that ate out of the garbage or even rolling around in some catnip now and then will not make your litter of kittens stillborn, but I might as well have been talking in Chinese.
As always, the danger is the dose. Which is why water poisoning is a thing.
Maybe the difference is dosage, but there are lots of other differences. I think the main problem with recreational meth users is dehydration.
How much did various thinkers choose to use? Erdős and Auden used about 20mg/day, but Sartre used 500mg/day.
I think dehydration is the main problem for recreational Ketamine users as well.
I think taking 3g every day for long periods of time while following harm reduction practices (and the main practice is DRINK A LOT OF WATER) is relatively safe and less dangerous than taking 1g once a week without any harm reduction.
I've heard that dodgy nightclubs would sometimes turn the heating up and not supply tap water in order to sell more drinks to clubbers who were on e or ket.
This usually didn't kill any patrons.
The main reason of death for ecstasy users is overheating thought.
Also, overheating/dihydration is not an issue for "social" dosages of Ketamine. But it may be an issue for "I want to be almost unconscious for many hours" kinds of dosages.
So is this post tacitly saying that we should be less afraid of meth? I think thats accurate
I wonder if there is a population of people who take meth recreationally but a lower dose and more responsible and therefore fly under the radar.
Which is to say nothing about the fed gov grants making perverse incentives for exagerrating the very real negative effect of drugs.
I wonder how this relates to anabolic steroid usage. Every slightly academic source I've ever read on steroids always says 'of course, we know that IRL users are consuming much much larger quantities than standard dosing'. Could it be possible that smaller steroid cycles are..... not as bad for you? Testosterone prescription is now a thing (yes I know there's a distinction between test and actual anabolic roids).
Anecdotally, I know several people who said that they consumed steroids in their youth for a decade or longer, just not in huge quantities. They all, I dunno, seem to be in fine health in their 50s & 60s? The two guys that I'm thinking of in particular both have a full head of hair, in addition to seeming like normal, highly fit older folks
Most users are not only taking steroids, but many other things as well. The side effects are very dose dependant. 2g of testosterone will affect a 140Kg bodybuilder very differently from a 75Kg guy who doesn't train.
You can build a lot of muscle really fast with Xmg a week for 10 weeks then taking 10 weeks off. Then you have people who are huge taking 50xmg/week and having all kinds of problems. A little is good a lot is bad.
What about side effects?
I wanted to try, but then someone told me that my body won't produce as much testosterone on its own forever after, that I'll get dick shrinkage and moobs if I don't take estrogen blockers at the same time, and that it will cause my thick, luxuriant hair, that hasn't thinned one whit since my youth, to begin doing just that. Horrifying...
What's the evidence say, anyone aware off the top of their head?
I don't know much about bodybuilding per se, but when it comes to specifically testosterone they tend to take several times what trans men do (in addition to what they have endogenously), and anecdotally trans men only rarely encounter any problems health-wise.
A while back I was researching phenibut to see if I should take it for anxiety. The first things I see when I google are recreational users talking about how horrible it is, how quickly you build up a tolerance, how easy it is to get addicted, and how terrible withdrawal is. I finally found one that talked about how much he was taking--14 grams three times a week! Yikes! Even the lower-dosage users were taking several grams at a time at least, multiple times a week.
So I decided I'm not at all worried about taking 250 mg, or even 500mg, every few weeks when I need it.
Don't Air Force pilots sometimes take amphetamines to fly for so many hours straight? Is this why they also don't seem to have problems? Is it why they are not likely to get addicted to them?
I don't think this has been mentioned yet. The book "Blitzed: Drugs in Nazi Germany" by Norman Ohler is both relevant here and excellent. Long-term outcomes of the broader population and also military personnel that used methamphetamine aren't entirely clear, but short-term outcomes were really well understood.
Amphetamines can impair judgement making military pilots too ebullient resulting in attacks on allies. I would guess they would prefer something like modafinal.
https://www.google.com/amp/s/www.independent.co.uk/news/world/americas/us-pilots-in-friendly-fire-case-were-given-amphetamines-125456.html%3famp
James Bond used them as a smart/brave drug in an Ian Fleming novel.
In Moonraker, Fleming describes Bond as stirring Benzedrine, a type of amphetamine, into his drink before downing it in "one long swallow".
https://en.wikipedia.org/wiki/No-go_pill#Go_pill
Am I off in believing that the opioid epidemic is a result of doctors generously/carelessly prescribing opioids? That doesn't mesh with the idea that clinical doses are overly safe and clinical prescribers are overly cautious.
Part of the harm with those prescriptions is supposed to be that people got addicted, so after the authorities clamped down many switched to heroin & fentanyl. Additionally, there were anti-abuse treatments to the various *contins which worked initially to spread out the dose over a long time rather than producing the sharp peak addicts want... but addicts eventually figured out ways around those. As far as I'm aware the most recent reformulation of oxycontin still works to curb abuse, and the result has been addicts switching to more dangerous street drugs.
My understanding (which I admit is just based on half-remembered blog posts so I'm happy to be corrected) is that the "legit prescription -> opioid addict" pipeline is mostly a myth, and that the vast majority of opioid addicts are simply people who started off abusing them recreationally.
People love to make excuses for drug addicts that put the blame everywhere except on the addict themselves.
I thought it was because the drug companies lobbied to make it legal to prescribe opioids for chronic pain, when they were not really intended for long term use in the first place.
I don't think that's it at all. "Opioids for chronic pain" has a long history, mostly because they're often the only things that work.
Yeah, this is what I concluded, after looking into it — although this was a few years ago and I don't know if any new data has come out.
(I became interested because, after reading about the legit script --> addiction "pipeline" so much, I realized that all the opioid abusers I knew — myself included, at the time — *started off* abusing them. The only people with legit prescriptions we knew were selling them to us, not taking them.)
Although there are definitely bad apples who are litlte more than DEA-licensed dealers, my impression is that addicts score these in various less obvious ways, e.g. acquiring prescriptions from several docs who don't know about each other, or visiting an ER (per week) with nonspecific belly pain that is TOTALLY a 10 out of 10...er...and I'm allergic to whatever you offer me other than oxy, sorry.
It's multi-factorial. While there certainly were poor prescribing practices, they seem to be responsible for a minority of the problems. Drug trial issues (big one for me), sales practices, and crisis of Lack of Meaning are all a bigger problem.
That's the standard narrative, usually with a side order of "...and the doctors did it because the marketing reps from Evil Big Pharma tricked them into it". Conveniently, the standard narrative gives us a wholly unsympathetic villain to blame.
To the extent that clinical use of opioids is relevant to the great opioid epidemic, I think it is mostly that a legitimate pain-management prescription gives people who Are Totally Not Low-Life Drug Addicts, What Sort Of Person Do You Think I Am, a cheap convenient and socially legitimate opportunity to experiment with opioids. Some of the like it for reasons that go beyond pain management, and some of those like it more than alcohol or anything else in their lives at the moment, and they want more.
Eventually, the doctor will cut off their Vicodin or Percocet, but there will be someone to step in and offer them fentanyl at that point.
Isn't the same thing true of the papers that claimed salt is bad for you? Something like 3000x the normal daily dose?
I'm having difficulty imagining this - the sodium RDA is about a teaspoon, which would make a 3000X dose a little less than 4 gallons (40ish pounds).
I think my favorite kind of example of this personally was having coca tea in Peru, in comparison to the awful energy drinks I usually go with. The boost with the coca tea was so smooth, so much less "buzzy" than with caffeine, that it seems criminal it's not legal in the US. I know, apples and origins, but very mild, low-dose coca seems really great, and too much caffeine seems kind of bad.
Yes, I came here to say this. If you used caffeine powder the way people use cocaine powder, it would be equally extreme (or maybe much more so?). If you use coca tea the way people use coffee or tea, it's equally mild.
Wikipedia tells me that a typical cup of coca tea has about 4.2mg of cocaine in it while a line of cocaine has about 30mg (ymmv. Harder addicts have been known to do a gram per *dose*!). A moderately addicted person might do 30 lines in a day, adding up to 900 mg, or about 220 cups worth. A typical cup of coffee has, say 100mg of caffeine, and 220 cups of coffee, that is, 22g of caffeine, will kill you.
On the flip side, 8 cups of coca tea add up to about a single small recreational dose, so I quite believe you when you say coca tea used like coffee is mild.
I am all for legalizing cocaine, but the obvious problem with legalizing coca tea for the mild effects is that people would just drink the 8 cups to get a full recreational dose.
That's a risk with tea: https://en.wikipedia.org/wiki/Chifir
It says making Chifir breaks down caffeine into adenine and guanine. What do those chemical do to you when you drink them? I can't find anything suggesting that they're drugs.
That sounds like complete bullshit. You can't make either adenine or guanine from caffeine without some tricky organic chemistry, it's certainly not going to happen by merely heating the stuff up to 100C.
In Russian version, which should be considered in this case more authoritative, as it's mostly Russian phenomenon, and unlike the English version, it is sourced, there's no mention of caffeine breakdown. I think somebody is either copy-pasting some unreliable info or playing the game of "how long could I have some BS on Wikipedia before anyone notices".
We used to do this. Ever heard of Vin Mariani? It was a sweet red wine laced with coca, one of the most popular drinks of the 19th century. Huge numbers of people in the US and Europe drank this stuff for a few decades. Some ads for it featured a testimonial from *the Pope*. Three small glasses a day contained something like the equivalent of 3-4 lines of cocaine.
Coca Cola was actually developed in part as a substitute for Vin Mariani in response to the rise of the temperance movement. Drinking the cocaine wine was less and less acceptable because it was *wine*. Kind of hard to wrap our heads around that one these days.
wikipedia: "Coca-Cola once contained an estimated nine milligrams of cocaine per glass. (For comparison, a typical dose or "line" of cocaine is 50–75 mg.[73]) In 1903, it was removed.[74]"
The dose was so low it was probably mostly harmless.
This is just not true. Caffeine and cocaine have totally different mechanisms of action. Notably cochise has a far more direct action on dopamine levels which makes it much more addictive and euphoric.
The difference (I assume, having tried large doses of caffiene but never having taken cocaine) is that using caffine powder the way a banker with suspenders uses cocaine is not a recipe for a fun time.
You just end up an anxious nauseated mess and never drink that much coffee at once again. It's neither recreational nor productivity-boosting.
Which is kind of similar to what people were saying about adderall vs meth.
Maybe we need a dimensionless quantity, like therapeutic index, except that it's the ratio between a dose that does long-term damage and a dose that makes you have a really bad time. A higher index would mean there's less of a risk of it being abused in a dangerous way.
I commented elsewhere recently about how nutmeg falls into this category. It will get you high, but you’ll also wish you were dead. Someone responded that “nutmeg high = weed + the flu”. So no thanks on the nutmeg.
This excellent post reminds me of the standard admonition against supplementing liberally with vitamin D, which says that doing so will give us all kidney stones and soft tissue calcification.
All the published evidence I have been able to find on this is old, and it mostly documents food fortification mishaps of the kind that result in a litre of milk containing 1,000,000 IU. Those stories do not have anything remotely to do with vitamin D as it would be used in any reasonable supplementation regime, but they sure are effective in scaring everybody, closing minds and shutting down inquiry.
From Reinhold Veith's 1999 paper on vitamin D safety (https://doi.org/10.1093/ajcn/69.5.842):
"Throughout my preparation of this review, I was amazed at the lack of evidence supporting statements about the toxicity of moderate doses of vitamin D. Consistently, literature citations to support them have been either inappropriate or without substance. The statement in the 1989 US nutrition guidelines that 5 times the RDA for vitamin D may be harmful (3) relates back to a 1963 expert committee report (5), which then refers back to the primary reference, a 1938 report in which linear bone growth in infants was suppressed in those given 45–157.7 μg (1800–6300 IU) vitamin D/d (119). The citation is not related to adult nutrition and it does not form a scientific basis for a safe upper limit in adults. The same applies to the statement in the 1987 Council Report for the American Medical Association that “dosages of 10,000 IU/d for several months have resulted in marked disturbances in calcium metabolism…and, in some cases, death.” Two references were cited to substantiate this. One was a review article about vitamins in general, which gave no evidence for and cited no other reference to its claim of toxicity at vitamin D doses as low as 250 μg (10000 IU)/d (120). The other paper cited in the report dealt with 10 patients with vitamin D toxicity reported in 1948, for whom the vitamin D dose was actually 3750–15000 μg (150000–600000 IU)/d, and all patients recovered (121). If there is published evidence of toxicity in adults from an intake of 250 μg (10000 IU)/d, and that is verified by the 25(OH)D concentration, I have yet to find it."
This post shows that this kind of unconsidered overreaction is a more general problem. I guess I'm relieved?
Come on...Just one article I want to read "This is definitely medical advice and these drugs are really fun so go nuts"
Reminds me of psychedelic therapy. Is anybody going to be getting a massive dose legally, or will clinical doses be so much smaller that they are qualitatively different drugs? There is a major difference in experience between ketamine abusers and patients being prescribed ketamine by a doctor. If you read trip reports from massive ketamine doses, you can see there is much more going on. I would expect ketamine abusers to be less depressed, all else equal, but curious if there is actual data on that.
The dosage used in many of John Hopkins trials is equivalent to 5g of mushrooms, which is a large dose, though not massive. Microdosing typically uses .1g doses and 1g - 2g is a small recreational dose.
The difference with psychedelic therapy (to my understanding) is that the treatment is actually moreso the radical mystical experience you undergo during the trip, rather than any chemical effects of the drug itself. For that to happen, you need a large dose.
This reminded me of a long time ago when I was reading about lean, a drink combining prescription cough syrup with sprite and jolly ranchers. I cannot find the exact dosage currently, but I believe I read it was around 25 times the prescribed dosage. I'm sure there is a wide range. It would seem that one would quickly run out of cough syrup.
I am not sure if there is the same phenomenon with lean. People don't seem to have much qualms with taking cough syrup but a lot of rappers have died or had health problems as a result of lean usage.
Are there restrictions on how much cough syrup a person can buy?
If you mean with codeine, in the US I think a prescription is required.
Yes, this is right. Lean is usually using prescription drugs. It appears that sometimes people use over-the-counter according to wikipedia: "but over-the-counter cold medicine that lists dextromethorphan as the active ingredient has also been used, as it can produce similar effects and eliminate the need for a doctor's visit."
Also, wikipedia says: "Lean is often used in combination with alcohol and/or other drugs"
That seems so bad for you.
That's very misleading on the part of Wikipedia. Dextromethorphan is nothing like codeine. A high dose is like a fever dream, and a low dose is like being mildly impaired and confused. Codeine is like a warm hug that injects you with pure happiness.
a high dose (of DXM)*
I didn't know it was so categorically different. Interesting. Thank you.
Well, thank you for being so nice about it! I feel like I didn't actually provide that much detail, so if you are truly interested I'll expand a little.
I don't doubt that the article is correct in that people attempt to substitute DXM for codeine, because it's much easier to acquire; however, I'd bet they only do it once.
DXM is only considered a recreational drug in high doses — low ones are about as recreational as NyQuil! — but in high doses, the best I can compare it to really is a fever dream. Nothing makes sense and reality comes at you in brief, confusing flashes. I did not personally consider it recreational at all, in truth.
Meanwhile, I may be biased by my extreme love for all opioids, but it's generally conceded that codeine & co. provide euphoria, and are often described as "draping you with a warm blanket" or the like.
Categorizing drugs by effect rather than chemical structure, DXM is a dissociative like ketamine; codeine, of course, an opioid.
I think this case is a bit of an outlier, because "lean" is so retarded and, in a way, complicated.
0) "lean" syrup is usually promethazine-codeine syrup, but is/was often used interchangeably to mean hydrocodone-containing syrup as well. It's hard to overdose on codeine, easier on hydrocodone (but still hard unless you add in other factors, as you allude to; see below, also).
1) "lean" users generally dump a bunch of the syrup, unmeasured, in a drink, then sip on it — a great way to have no control over how much you're actually taking. Spreading the dose out over time like this might help, but actual amount of delay before the entire dose is consumed would obviously be highly variable.
2) "25x" sounds bad, but codeine is very weak; the amount in a regular dose of cough syrup (10mg) would only touch a completely opioid-naive person, and even then not very much so. Conversely, 10mg of oxycodone will have a strong effect even on someone who has developed a small tolerance, and 60mg will still get most experienced users high (although because opioids are otherwise so benign, tolerance can reach ungodly levels in a few cases).
3) codeine also has a ceiling effect at around 200-250mg, if I recall correctly. A user might therefore continue imbibing in frustration, and since
4) most "lean" syrups contain promethazine as well, which increases CNS depressant effects, this ain't so good; and
4) polydrug abuse is generally much more dangerous and likely to lead to overdose than using codeine (for example — or hydrocodone) alone would, so adding in alcohol and other drugs is now even more likely to cause complications.
*****
So I think the difference is not only the dosage — although it's certainly part of it — but also the confusion between different types of cough syrup, wildly varying doses, and the effects of concomitantly administered drugs like alcohol and promethazine.
Two fours. I drank too much lean, sorry.
great comment. Thanks Nasiskuurt.
DJ Screw makes lean worthwhile. How many drugs have a single artist who dedicated his life to that drug and redeemed it? Sure, plenty have tried. DJ Screw is probably the greatest success story when it comes to making art out of a bad drug.
He died from it, no? Isn't that a precautionary story.
Relevant clip from a superb film, 32 Short Films About Glenn Gould (this is film #23). GG took all these— a drug user who took a *lot* of drugs. https://www.youtube.com/watch?v=7eBotiHABdo
It's a much shorter list of drugs, but I like the repeated drug scene in All That Jazz (1979), the autobiographical film by Bob Fosse. https://youtu.be/L2e9acreKmQ?t=26
A couple big spoonfuls of pure caffeine powder can be lethal
This reminds me of a friend who read that nutmeg is hallucinogenic, so he ate a tablespoon of nutmeg to get high. He said all he could taste for two weeks was nutmeg.
My dad used to work in a lab, and another guy got some pure nicotine on his skin. He would have died if they hadn't gotten him to the hospital right away.
Always fun remembering that the plants make nicotine in the first place to kill insects. It's a nerve poison, more-or-less.
Why does the poppy make opioids?
The question is how much more likely you are to start doing recreational megadoses eventually if you get a prescription.
related: alcohol is a much more social drug than a lot of pills and other such things, because you take your full dose in sips over several hours. Allows you to manage your level of intoxication via feedback. Whereas a tab of LSD or a pill can really fuck you up for hours and there's an expectation you should just take the whole thing at once. LSD would probably be much more popular if it came highly dilute and you could have a wee bit at a time (have I just reinvented microdosing, maybe.)
Is there a similar dosage delta between people who "microdose" LSD or other psychedelics and those who take more typical recreational doses?
Typical microdose for mushrooms is .1g, typical recreational doses can be between 2g - 5g (or higher). unsure of LSD.
I'd say that microdoses are around 1/6th of a trip dose. The psychedelic equivalent of having a single beer vs the psychedelic equivalent of downing six.
Hey dude, what if you just fuck off?
This was a fun article to read! (That was true and kind ;)
One thing I was repeatedly told as a child (from a non-medical family!) was: Only the dose makes it poison.
I'm way out of my wheel house here as a non-biologist and non-drug user (I rarely even drink, pretty much stick to caffeine and sugar), but could this be read not just as an explicit argument against medical dosing guidelines, but also tacit argument *for* microdosing? Like, you're not wealthy, you don't have great insurance, but you need antidepressants, so you buy street drugs and then carefully stretch them out to a hundred doses?
From what I understand, street drugs vary in strength so you don't know exactly what dose you're getting, and sometimes it's not even the kind of drug that the dealer says it is.
It seems to be a standard practice to greatly big up the risks of taking any medication with recreational/abuse potential.
Well, you know cf. guns or studies of human intelligence. It's not like drugs are treated specially in this regard.
"A lot of our impressions of drugs, what side effects they have, and how dangerous they are, get shaped by the recreational users, not the patients."
I'd suggest a variation on this: our impression of drugs is shaped by their mode of delivery, which in recreational contexts tends to be a mode that delivers a faster rate of onset and/or higher peak plasma. I think this matters more than the total dose.
Morally: oral ingestion > inhalation > insufflation > intravenous injection.
So I can ingest vast quantities of caffeine in the form of coffee every day and still enjoy moral superiority vs. someone who injects the same quantity of stimulant at the weekend.
Of course they are probably getting a totally different high and side-effect profile too so it's not as if the moral stereotype is baseless. But I suspect it does feed into sub-optimal public-health outcomes. See: vaping.
Only users lose drugs.
3g of ketamine is by no way recreational, that's hardcore addicted in my book.
Still confusing to me as a non-English speaker: in Dutch we have two words: "drugs" are recreational (sometimes illegal) substances that change your mood or cognition, medicijnen are physician prescribed substances. This makes reading a piece like at times confusing:"Which of the two is he talking about now?"
Well, he's talking about literally the exact same chemical substance, in the first part ketamine, C13H16ClNO arranged thusly: http://www.chemspider.com/Chemical-Structure.3689.html . Using two different words to describe the exact same substance depending on who sold it to you, seems like the confusing part. In English, a "drug" is a substance intended to alter the biochemistry of the human body to produce a desired effect. It's the same word, and often the same substance, whether the desired effect is medical or recreational.
If who sold it to you makes a significant difference - like, just as an example, whether you get put in prison vs being on solid legal footing and maybe even getting your drug paid for by insurance, I wouldn't call using different words "confusing".
Although I personally do prefer the way it works in English, with "drug" covering both, partly because it allows talking about things like illicit ketamine, lsd, etc. without reinforcing the framing as "bad, illegal, criminal substances that are bad for you because bad"... at least, not nearly as much as happens in a language like Dutch or, very similarly, German (my first language).
In German, "Droge" (drug, duh) also refers to the illegal kind. Although in the law, they're classified as "Betäubungsmittel" (~numbing agent, basically "narcotics"), as is quite common, I believe, because that's how the international war on drugs treaties etc call them.
The German language generally errs on the side of eliminating ambiguity & words or phrases having many possible meanings, and creating more specific categories. Makes it a great language for precise technical instructions, engineering and natural science talk; less great for art.
Minor nitpick (7 months after you wrote that): drugs in English (even restricted to those used to treat humans) aren't only substances intended to alter the biochemistry of the *human* body; often the target is other organisms within that body, like with antibiotics or antiparasitic medications. Ivermectin targets the biochemistry of invertebrates, for example.
In English, the word "drug" is often ambiguous. It normally has a strong suggestion of being the recreational (and usually illegal) kind, but it is used both ways (as in "Food and Drug Administration" and the phrase "prescription drugs"). "Medicine" is only used for chemicals taken for medical purposes (sometimes prescribed, but sometimes just over the counter, like aspirin, acetaminophen/paracetamol, etc.).
In English when the distinction should be made and context doesn't supply it, we usually add one of several adjectives, e.g. "recreational drugs," "illegal drugs," "illicit drugs."
I guess the other point is that the ambiguity is useful to the point Scott is making, because he's pointing out that the very same molecule can have beneficial or deleterious effects, depending on the dosage and pattern of administration -- and even the underlying reason, since e.g. I believe there is evidence that suggests even opiates need not be addictive *if* they are actually being used to moderate severe pain and at appropriate levels.
So in this case maybe English has an advantage over Dutch, in that our language already includes this ambiguity, so the fact that the effect of a "drug" is contingent on circumstances may require less of a conceptual step for the English speaker.
As others have pointed out, it's unfortunate that you seem to be using some of the terms interchangeably which leads to casual drug users and drug abusers being conflated.
Obviously taking a large vs small quantity of a drug has differing effects but so does taking the drug daily vs occasionally. This is especially true given that the examples used seem to mostly refer to long term, frequent abuse. Most recreational drug users do not use so frequently.
In terms of meth, I think you're also missing some important confounds
[accidentally prematurely posted] if frequent meth abusers have much worse dental health than medicinal Adderall users, do we really have to believe that it's due to meth itself? I would expect you might find large differences in terms of diet, dental hygiene and several other factors between the two.
Is it fine if I dont mention you to the cops?
I have a friend who used to take a lot of recreational ketamine. (This is a friend, not a "friend" ;-P ) He had a sports injury and wound up in the ER. When the anesthetic they gave him didn't work, they gave him more. Then they asked him if he took recreational ketamine, lol! He kinda demurred but was like, "Yeah, well, kinda..." Bottom line: recreational drug users take a lot of drugs!
"They find that severe abusers, who are taking an average of 60,000 mg/month, experience cognitive problems. But mild abusers, who take more like 3,500 mg/month, don't. Again, psychiatric patients are taking about 280 mg/month. I think this is pretty strong evidence that the psych patients shouldn’t worry that much."
I remember a post you made a while back about melatonin having greater effects at lower doses. Is this a possibility for ketamine?
Melatonin has *better* effects at lower doses, but that's different from saying it has *stronger* effects (which it doesn't). From the Lorien Psych page (https://lorienpsych.com/2020/12/20/melatonin/):
"A meta-analysis of dose-response relationships concurred, finding a plateau effect around 0.3 mg, with doses after that having no more efficacy, but worse side effects (Brzezinski et al, 2005)."
My biggest issue with s-ketamine is its broad agonist on over 30 receptors. While it’s dissociative properties are why I would use it in a pinch, I prefer pharmaceuticals that are much more targeted. Also, I think the literature supports more novel psychedelic treatments such as psylocibin and MDMA as better effective depression and addiction treatments than ketamine - which has a very short duration of efficacy and is just about one step better than ECT.
I’d also like to add, I suspect the bladder dysfunction likely stems from ketamine’s affinity for Mu receptors. Ketamine has a the strongest preferential affinity for NMDA receptors, but number two and three on the list are Mu-1 and Mu-2 opioid receptors. This is what gives the analgesic benefit to ketamine administration. Urinary retention secondary to inability to relax the urinary sphincter and contract the detrusor muscle is a side effect - along with pupillary contraction - that you cannot grow a tolerance to with chronic opioid use. Again, ketamine is a “dirty” drug in that it has affinity for so many receptors, and therefore is more of a very niche drug, akin to Demerol’s widespread use for rigoring - even though dexmedetomidine works better with less side-effects for that specific scenario.
Very interesting, thanks. To set against this, perhaps, one suspects the more targeted drugs might in general have pharmacokinetics that pose more risks -- the more generic the molecule, the more pathways there probably are for its degradation, and the more likely that the intermediate metabolites are benign.
I have friends who use ketamine and those doses are on the extreme high end. I would say the average dose for a normal non-addict ketamine user would be a gram every 1-2 weeks. Still higher than the therapeutic dose buy not by such an extreme margin
Every so often I see an article about how e.g. soldiers in WW2 were on amphetamines all the time-- now I'm curious where their dosage fell between "Adderall" and "recreational drug user".
Can I have my cocaine back now please?
"The dose makes the poison"
~ Paracelsus
I find it hard to believe that frequent ketamine users take around 3g/day. Just from a financial perspective, 3g/day equates to £2100/month (~$3000) at £25/gram. Given how disabling K is, I don't think that the kinds of people that are doing 3g/day could afford it. I had a quick look at the Morgan et al. paper, and although it says the frequent group uses about 3 grams, it doesn't specify over what time period. Perhaps they mean 3grams per week or month? Happy to be proven wrong here if I've missed it. The chinese paper does specifically say 3g per day though, so maybe my instincts are wrong. Anecdotally, I've heard of bladder issues in people that wouldn't be consuming more than a gram a month.
So.... Why don't we prescribe Adderall to just anyone who wants it at those low dosages? Or do we? Does this same kind of logic apply to steroids? Sure, body builders take huge dosages and can do damage to themselves. Can relatively low dosages work as treatment for obesity?
"one (1)" has an astounding comedy-to-character-count ratio.
Right up until that last paragraph I was really considering taking a micro-dose of DNP. Maybe I still should, but I would feel bad doing it without your blessing!
Could one call this phenomenon “replicability crisis two: electric boogaloo”? Sure seems the thrust here is that a large portion of drug studies won’t replicate in clinical settings, which feels like a big deal? And also implies we can’t really understand a drug’s risk unless we legalize it medically first and then study possible side effects?
I understand the point you're trying to make here, but as a recreational ketamine user I just want to let you know that 3g/day figure is way too high and nobody is taking those kind of doses, most certainly not everyday for a month. To get an idea of how much a typical recreational user is taking, you can refer to this harm reduction website. https://drugsand.me/en/
This site states that heavy dose for oral ingestion of ketamine is around 500mg which is also referred to as the K-hole dose. K-hole is the term used among users to refer to the state of total dysfunctionality when you take a large enough dose of ketamine. Going by these numbers it just seems absurd to believe that an average ketamine user is dysfunctional everyday over months.
Moreover the LD50 for ketamine for a 70 kg human is 4.2 grams. There's no way an average ketamine user is steering so close to the levee all the time.
Is there any evidence at all that energy drinks are harmful in low doses? I'm suspecting the entire stigma comes from case series where people took too much or had pre-existing heart problems.
Also I saw a review paper where a weight loss supplement providing -2kg over 3 months was described as "not clinically significant", but 1.33 pounds per month is a lot of weight loss. If that could be safely extrapolated over a long time it adds up. Adding it to the water supply might reduce obesity rates by more than half. Again I suspect thermogenic supplements have a bad name because of people who take too much.
"and you wouldn't believe how many hoops the psych patients have to jump through to get their 280, or how terrified their doctors are that something could go wrong"
This is pretty much why I gave up trying to get medications that I actually NEED to treat my ADHD and depression; it's actually less work to just go unmedicated and be mostly-functional than it is to deal with all the bullshit involved with getting stimulants and ketamine.
There's bits of this all over pharmacy lore. Metronidazole is the only antibiotic you're supposed to actually not take with alcohol because there's a theoretical disulfiram-like reaction (disulfiram is normally used to treat alcohol addiction does so by severely magnifying its effects so any tiny amount with have you throwing up like you went on a full bender) but I was told once (tbh I've not personally looked into this one) that there's straight up never been a case study of this actually happening.
Recreational users of non-meth amphetamine also take huge doses like 500-1,000mg on a single day. So it seems surprising they don't seem to get the same health problems and addiction. Though to be fair they probably don't take this every day. But that also suggests the addiction potential for non-meth amphetamine is lower. (Maybe because it can't be smoked?)
It is well known fact that ketamine high make urination difficult. It's not really a physical difficulty, but rather you forget how to contract and relax appropriate muscles. Also, having full bladder stops being so unpleasant on ketamine.
So I guess if you do lots of ketamine, then you're high most of the time and may hold your urine for long periods of time - and that can cause UTI and bladder injury.