Yep, all very good points. Neuropsychopharmacology is extremely and recursively complicated. It's turtles all the way down. Just take one component in all this, the receptor. One might want to think of a receptor as just a switch triggered by a chemical. But autoreceptors are a thing, as you mention. Receptors do different things in different areas of the brain. Receptors form complexes with eachother(e.g 5-HT-2a and D2), and we have essentially no idea why? Receptors have all sorts of different modes of interaction both with ligands and cell internals. Agonism, partial agonism, antagonism, inverse agonist, positive/negative allosteric modulation. The GABA-A receptor is not really one receptor, it's more like a family of receptors made up of a varying constellation of subunit proteins. Different constellations appear in different parts of the brain, and have different allosteric binding sites, which is why benzos vary widely in qualitative effects despite all being "GABA-A PAMs". NMDA receptors don't just bind to glutamate, but also glycine, and magnesium needs to be around? And NMDA triggers an intracellular cascade that regulates membrane expression of AMPA receptors. This is thought to be involved in memory. Cannabinoid receptors are expressed presynaptically carry signals in reverse, so that's weird. And there are 5 identified cannabinoid receptors. We only sort of understand what 2 of them even do. The other 3 are still quite mysterious(last time I checked). Most of the well studied neurotransmitters have not one, but many different receptors they interact with. 5-6 dopamine receptors, I can't even remember all the serotonin receptors, etc. Many of them are still poorly understood.
And of course, neurotransmitter systems talk to eachother. Serotonin so much so that it's also been called a neuromodulator. Because it very often regulates release of other neurotransmitters(including itself).
It's a field that, the more I dig into it, the more confused I get, honestly.
So when I see someone say herp derp, serotonin hypothesis is false, therefore SSRIs are ineffective, the only conclusion I can make is they haven't even tried to dig into it.
I've noticed that most submissions involving anything that might invite the slightest criticism of Musk routinely get flagged. My conclusion has been that there's an army(or just a handful of people with too much time on their hands) of Elon fanboys patrolling the site, flagging stuff that causes them cognitive dissonance.
Doesn't even have to be political. I've seen it over and over with submissions about cybertruck recalls, twitter related stuff, etc.
I believe they're bots. Easy enough to do a negative sentiment analysis with an llm. Positive sentiment Tesla astroturfing is also everywhere on facebook and instagram.
Makes sense if you’re worth billions and billions yet still need to cheat at video games so you can pretend on a livestream that you are one of the best at some random video game.
I find the idea of Trump playing "3D/4D/5D/6D chess" frankly hilarious. Hell, the man probably can't even play 2D chess. I honestly doubt he even has the patience to learn the rules. He's the kind of person who would get checkmated in 4 moves, flip the opponent's king over, claim victory, and walk away bragging about his genius victory.
It's certainly true that simply explaining it in terms of "neurotransmitter levels" is an oversimplification. ADHD is a neurodevelopmental disorder which is predominantly genetic in origin. In other words, ADHD is not just a matter of the brain's state at the time of diagnosis, but the development of the brain from the very beginning. Brain structure is heavily involved here. It's been shown that prefrontal cortex is significantly smaller in ADHD, along with certain other brain regions, like the hippocampus.
But the implication of neurotransmitters in causing ADHD is not merely hypothetical. ADHD is polygenic, i.e involving many sifferent genes. But in genetic studies, many of the genes found to he most correlated with ADHD were directly involved in monoamine neurotransmission, and many of those relate to dopamine. These include the genes for the D4 and D5 receptors, the dopamine transporter(DAT), which is responsible for dopamine reuptake(and also one of the targets for ritalin), TAAR1, which regulates synaptic monoamine release(this is targeted by amphetamine), and various enzymes involved in monoamine metabolism or synthesis(MAO-A, COMT, DBH).
There's also some involvement of serotonin and noradrenaline related genes like SERT, the serotonin 1b receptor(which, big surprise, is involved in mediating dopamine in PFC), the adrenergic alpha 2a receptor(which is targeted by the adhd meds clonidine and guanfacine), and some more enzymes.
So the genetic evidence for the involvement of dopamine is quite strong. There's also some evidence from brain imaging studies, showing that long-term treatment with central stimulants(which primarily act on dopamine and noradrenaline) leads to reduced abnormalities in brain structure. In addition there's mountains of evidence for the effectiveness of stimulants in managing the symptoms of ADHD.
In conclusion, the role of dopamine ADHD is backed up by a lot of empirical data. Doesn't make it the only factor involved, but it's certainly an important one, and not merely hypothetical.
Been running Linux on the A770 for about 2 years now. Very happy with the driver situation. Was a bit rough very early on, but it's nice and stable now. Recommend at least Linux 6.4, but preferably newer. I use a rolling release distro(Artix) to get up to date kernels.
ML stuff can be a pain sometimes because support in pytorch and various other libraries is not as prioritised as CUDA. But I've been able to get llama.cpp working via ollama, which has experimental intel gpu support. Worked fine when I tested it, though I haven't actually used it very much, so don't quote me on it.
For image gen, your best bet is to use sdnext(https://github.com/vladmandic/sdnext), which supports Intel on linux officially, and will automagically install the right pytorch version, and do a bunch of trickery to get libraries that insist on CUDA to work in many of the cases. Though some things are still unsupported due to various libraries still not supporting intel on Linux. Some types of quantization are unavailable for instance. But at least if you have the A770, quantisation for image gen is not as important due to plentyful VRAM, unless you're trying to use the flux models.
I also have an A770. Don't use it for AI, but it runs fine for general 3D use (which mostly means either Minecraft, other similarly casual games, or demoscene shaders). I'm pretty sure I'm not utilizing it fully most of the time.
My main complaint is that the fan control just doesn't work. They stay at low speed or off no matter how hot the card gets, until it shuts down due to overheating. Apparently there's a firmware update to fix this, but you need Windows to flash it. You can zip-tie a spare fan somewhere pointing at the card...
Secondary complaint is that it's somehow not compatible with Linux's early boot console, so there's no graphical output until the driver is loaded. You'd better have ssh enabled while setting it up.
It's also incompatible with MBR/BIOS boot since it doesn't include an option ROM or whatever is needed to make that work - so I switched to UEFI (which I thought I was already using).
When I ran a shader "competition" some people's code with undefined behaviour ran differently on my GPU than theirs. That's unavoidable regardless of brand and not an Intel thing at all.
Swartz wasn't the kind of person to accept a plea bargain from an overzealous prosecutor who was indicting him on 13 felony charges with a possible sentence up to 35 years along with a $1 million fine. I assume he wanted a trial because he wanted to continue his fight for open access. And maybe he thought he might lose, but wouldn't lose on all counts, and would make the prosecution look unreasonable in the public eye. Was that decision rational from a self-interest point of view? Maybe not.
And then you might ask, if he wanted a trial, why did he kill himself? Obviously no one knows what was going through his head when he did it. He left no note. But the prospect of being locked in a cell until he was an old man probably had something to do with it.
You can certainly argue it was his own fault for not pleading down, but even if that's your view, that doesn't absolve the prosecutor. Ortiz has a lot of blame in this too, and the fact she still hasn't acknowledged it over a decade later speaks volumes to the kind of person she is.
His criminality is one matter, but the full weight of the Federal Government on him was an entirely separate matter. A federal prosecutor's job is to jail you regardless of whether it is for downloading a file from a server or for trafficking in humans, and they will come at you with the same vigor regardless of the crime. And nothing has changed about that.
Treating a human trafficker and someone who downloaded some files from a server the same is not in the job description of a prosecutor. What an absurd statement. It's very much the job of a prosecutor to make judgements about the severity of the crime and how to respond. And in this case, the prosecutor showed incredibly poor judgement. There wasn't even a particular reason why the case should go federal in the first place. The state prosecutor saw things very differently.
That is complete bullshit as evidenced by the federal criminal sitting president.... The ONLY time I ever see this argument is to try and paint over blatant police and state injustice and tyranny.
"A federal prosecutor's job is to jail you regardless of whether it is for downloading a file from a server or for trafficking in humans, and they will come at you with the same vigor regardless of the crime."
You have to be malicious to put forward this statement in the current environment. Or you are so propagandized you think it's true? Either one is very frightening
If you want to stop the flow of hyperpotent opioids like fentanyl and nitazenes, legalise opium and heroin. As drugs, the only advantage of these compounds is that their potency makes them easier and cheaper to smuggle. I've asked a lot of opioid addicts about this and not one of them has described an all-things-equal preference for these drugs. I'm sure some people do exist, but they're likely a very small minority. Most people don't even know what they're using, they just take whatever's available to get a fix.
This is a completely artificial problem, created by the war on drugs. Just like the waves of PMMA deaths in europe caused by safrole seizures. Western nations have no one to blame for this but themselves.
This rings true with my experiences. The people who I've known to become addicted usually started with something prescribed and then graduated to heroin. When heroin became harder to find, smuggle in, or too expensive, fentanyl happily stepped up to meet demand.
Addicts literally carry around fent testing kits so they can _avoid_ this synthetic opioid.
> Addicts literally carry around fent testing kits so they can _avoid_ this synthetic opioid.
Choosy addicts choose...is something I never thought I'd read. I'd suggest they weren't addicting right if they are choosy. When you can find your fix of choice, you just fix with what's available.
If your comment were accurate, fent sales would plummet and the problem would fix itself. This is clearly not the case.
None of what you've described is how any of this works in the real world.
There's an entire world of behaviour from a seller's perspective for every drug and an entire set of behaviour from a user's perspective. They match closely to how 'legal' alcohol production and consumption works. Biggest profits are from the biggest addicts of alcohol and their suppliers are all on the stock exchange for everyone to see. Beer almost never kills anyone, same with the production from large reputable companies. but if you find a great deal of homemade hard liqour make sure you test for ethanol and methanol. Thats simply how addicts die no matter the product they are using.
'some white powder' could literally be anything and everything. Idiots could cut it up wrong and what previously got you high just fine might potentially be a lethal dose right in front of you in the form of a powdery white line with no way to tell. Theres the mostly harmless chemicals used to reduce dose to cut the dealer more profit but could still not be mixed properly so new users wouldn't be able to notice. Then theres the nitazenes and other stuff that most tests only detect 'presence of' but not the dose so you would still have to throw everything out even though it might be mixed and dosed properly. And then theres the less addicted group who doesn't even bother with anything ever and only wants the pure stuff in large single batches in order to test fully and properly. Those people never get screwed over because thats what they pay for.
That's true to an extent. But we can also reduce the incidence of opioid addiction by prescribing them only for really severe pain, and in smaller quantities. This is already happening. Back in 2007 an oral surgeon gave me a prescription (which I never filled) after a minor procedure but today that probably wouldn't happen.
We did legalise opium by way of oxycontin and I'm not sure that helped reduce the scope of the problem. Arguably a lot more people got hooked on opium than ever before because something legalized has less stigma attached and is more easily accessible. Society has waffled repeatedly on the legality of opium and the effects of opium are a bit different than less destructive narcotics where legalization makes more sense.
> Arguably a lot more people got hooked on opium than ever before because something legalized has less stigma attached
Growing up in the 70s and 80s, I know that by the 80s heroin had a bad stigma attached to it even by other drug users, and it was rarely seen in the circles I knew. Coke, pot and meth did not have that at the time.
OxyContin was de-facto legalized. You could go to certain doctors, complain of pain, and walk out with a prescription. Just like you could do with medical marijuana in California. Legalization made the problem much worse because it increased demand markedly.
There is already some compelling anecdata that warrants studying.
Rat park is one, and the doctor who prescribed heroin in the 60s is another.
The jist of it was that addicts stopped abusing when there was something better to live for. In the absence of community, opportunity, and hope, abuse abounded.
The reality of some people's experiences though is that while euphoric in the beginning, long term use leads to an unpleasurable mental haze. The lack of clarity becomes its own hell.
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The potential solution is likely unpopular and likely difficult to implement. Investing into communities that promote community along with incentives for economically depressed areas to be rebuilt, IMO would likely reduce opioid abuse.
But that's not nearly as popular as the moral displacement schadenfreude the people get by being able to point the finger at the drug abusers.
Seriously, it feels like society has drifted too far away from the idea of small, local communities. So much of modern life separates people either physically or technologically. Though I would like to blame modern marketing and consumerism, I think these problems have been brewing for centuries.
From a sociological perspective, I do see the benefits of small conservative communities that effectively serve as a guarding or protective mechanism, shielding the more vulnerable from potentially destructive influences.
That's very true. The drug issue is a very complex problem, and I was only addressing a very narrow aspect of it, namely the root cause for the proliferation of hyperpotent opioids in black/grey markets.
The legal side of it is just that; one side. It's important, yes, but just legalising opium won't automagically solve the opioid crisis on its own. We also need to address societal causes of opioid addiction. At least in the US, overprescription from doctors corrupted by big pharma(especially purdue), is one major contributing factor that's been thoroughly exposed in recent years. Obviously the role of money in medicine needs to be changed.
The deeper issue though is that more people are becoming vulnerable to developing addiction. Speaking as an addict myself, one of the root causes of addiction at an individual level can be untreated mentall illness. Drugs can often provide a temporary reprieve from mental illness, and unfortunately is often more easily available than good treatment options. In many western countries, funding for mental health treatment programs has been reduced. This is contributing to a rise in unmanaged mental health issues.
I think spending a ton more on mental health, especially in youth, is essential to reducing the prevalence of addiction.
Other issues include poverty, unemployment, housing. The thread through all of this is that more people lead miserable lives, and that makes drugs more tempting.
But let me circle back to the legalisation issue and why it's so important. The main health risks with opioids are overdose in the short term, infections(hepatitis, HIV, endocarditis) from dirty needles and organ damage from dirty drugs in the longer term. Legalisation can address all of these things. Any addict will tell you the main reason overdoses are so common is there's no consistency to the potency of their drugs. Even when it was still heroin, the constant battle with LE meant the purity would fluctuate wildly. Add to that synergistic adulterants, and now these hyperpotent drugs, and you get addicts dying like flies. Legalising the drugs would allow regulating them and providing consistent dosages, eliminating harmful adulterants, and mandating that doses be sold alongside clean user equipment. This would greatly limit the health impact of these drugs on its users. It's obvious that recovering from addiction would be a lot easier if your body hadn't been destroyed by it before you even enter a treatment programme.
In addition, remember what I said about funding for mental health declining? How much money is spent futilely fighting the war on drugs? I haven't done the tedious task of adding up federal, state and police budgets for the US, but the budget for the DEA alone is in the billions, so it's safe to assume once you do the math it'll be in the tens of billions for LE alone. And that's without accounting for the courts, prisons, and all the money being funneled away from the legitimate economy by criminal gangs. This is money that should be spent elsewhere. On mental health and addiction treatment, housing, social programmes. But instead it's essentially being piled up and lit on fire.
So at least for me, that's why I keep saying "let them take drugs".
If I were to become a drug addict, I would also choose opium and heroin. I do see interviews on YouTube with folks who seek out fentanyl. But as other commenters mention, this may be a minority, and likely more so if safe and pure opium and heroin were accessible.
Dumbest thing I’ve heard. You’d have large swathes of the population (at least 15%) addicted to them within the year. Any country where it’s freely available ends up having a large number of addicts (20th century China, modern day Afghanistan and Pakistan etc.)
This argument is too dismissive for me to bother spending time on it except to say this: try to think about other factors than just availability, because it's not the only thing that matters.
Here's an exercise for you to do just that. Alcohol is legal and extremely available in the west. It has an even stronger addiction potential than opioids do. And the majority of people in the west drink at varying rates. But the rate of addiction is generally under 5%(in the west). Why do you think that is?
> It has an even stronger addiction potential than opioids do. And the majority of people in the west drink at varying rates. But the rate of addiction is generally under 5%(in the west). Why do you think that is?
I conclude that... alcohol doesn't actually have an even stronger addiction potential than opioids do?
Artix Linux does this. Arch sans systemd, and you have a choice between openrc, runit, s6, dinit, or even some combination of the 4. Any daemon type package will have a -runit/s6/dinit/openrc variant that includes the relevant scripts/configs.
