> To be a dedicated fan of Nintendo's franchises is to be a masochist.
For example I am a Zelda and Metroid fan (by “fan” I mean “someone that enjoys playing those games”), but I don’t think I’ve ever cared about any video game to the point of actually subjecting myself to any suffering. I know even more diehard friends than me that happily use emulators for games that they can’t find/afford.
Maybe there is a masochistic style of being a fan that someone can choose to subscribe to, but it’s not clear that it’s Nintendo’s fault that one would make such a choice.
I’m glad to hear people discussing this! I love how most of the hippies that love “natural psychedelics” have a loophole for LSD. Just because a drug has a precursor found in nature doesn’t make the drug itself natural.
As somebody that experimented heavily with psychedelics when I was much younger, my opinion is that the 2C-B/E/I group have definite possible therapeutic value, and the main thing causing stagnation is the ridiculous hippy mindset that it’s ~synthetic~ and therefore bad. It’s ridiculous.
Over the past few years it’s been interesting watching polite society “discovering” psychedelics. I really can’t wait for these people to find the therapeutic value of smoked/IV DMT, especially considering that it’s WAY safer than ayahuasca.
I would love to see a study on the possible therapeutic value of dextromethorphan, but as far as I’ve seen it’s not really on the radar. I know it seems weird, but from subjective experience I found it to be very helpful a few times as a teenager. I used to jokingly call it “therapy in a bottle.” It’s a real shame that most DXM-containing products nowadays in the US come mixed with other compounds that make it dangerous to take at a recreational/therapeutic dose.
See also, Nuedexta, which is used to treat pseudobulbar affect (PBA.)
I agree with GP. If ketamine works for depression, there's no reason to think similar effects wouldn't occur with DXM. I've always found the 'next day' glow to be quite nice.
> I agree with GP. If ketamine works for depression, there's no reason to think similar effects wouldn't occur with DXM. I've always found the 'next day' glow to be quite nice.
From what I understand, ketamine's rapid antidepressant effect was once thought to have been mediated by NMDA antagonism. However, countless NMDA antagonists have been studied for depression, and their efficacy was nowhere near the S-enantiomer of ketamine, suggesting that NDMA antagonism alone isn't responsible for the full effect.
DXM acts as a dirty serotonin reputake inhibitor before it's metabolized into DXO, which is actually an NDMA antagonist like ketamine.
By combining DXM with bupropion, the bupropion prevents the DXM from rapidly metabolizing into DXO through enzyme inhibition, leaving more SSRI-like DXM in the blood to affect the brain. Bupropion itself is a potent inhibitor of enzymes that metabolize many pharmaceuticals.
So the idea behind combining DXM+bupropion to treat depression doesn't really come from the same mechanism of action that esketamine has. It's more about the SSRI-like properties DXM has in the body as long as it isn't metabolized into DXO.
Also, combining two medications that are off-patent for a new treatment means that you can patent the new combination as if it's a new drug. I suspect that's why it's being investigated. Both DXM and bupropion have pretty good safety profiles, they're cheap to manufacture, and the combination can be patented.
I don't think the SSRI effects are the primary goal. The appeal of esketamine is its rapid effect, the same thing being sought with DXM+bupropion (AXS-05). Studies with naltrexone and ketamine reduced the antidepressive effect, so maybe the mu opioid or sigma-1 are important. (https://www.cambridge.org/core/journals/cns-spectrums/articl...)
Interestingly, there's a small trial with just DMX (300mg - aka first/second plateau) to determine safety: https://clinicaltrials.gov/ct2/show/NCT04226352 The bupropion seems to be only useful for slowing the DXM->DXO to allow for lower doses. A full on 'robo-trip' may actually work as well as a full on ketamine trip.
I think there's an argument to be made that a working opioid system is central to the anti-depressant effect of any anti-depressant? I actually tried naltrexone for a condition related to depression and it made me feel much worse and unable to feel much pleasure in anything.
DMX is really a crappy drug with a half-life that is too long for frequent administration.
> I've always found the 'next day' glow to be quite nice.
I’m not sure I’ve ever experienced the afterglow in the way many people describe it. Next day I would just feel kinda drowsy, and a bit muted and dumbed down.
> One of the most valuable features for institutions is the Terminal’s Enterprise IB Chat.
This is essentially a Terminal-wide chat function that allows traders to chat with brokers, portfolio managers to talk with each other, or simply for intra-firm communication, perhaps to run something by compliance.
Devil’s advocate, hear me out (thought experiment), what if the economy is made up of people other than business owners? What if economic function needs both businesses and individuals to survive?
Where, out of curiosity, did you find the objective fact that the free money giveaway wasn’t meant to be welfare? It certainly helped a lot of people… fare… better?
Is it possible that a person could be made so averse to the idea of “welfare” through conditioning that, when they see it plainly in front of them, their knee-jerk reaction is to invent a whole new reality to justify making sure the biggest benefactors of society remains squarely “those who need it least“?
If you took your stimulus, or a PPP loan, or avoided eviction due to moratorium, or were in any way given a tiny sliver of help directly or indirectly using government funds, you are a welfare recipient. You can no longer claim having pulled yourself up by your bootstraps! Ever!
The thought is so painful to so many Americans that they literally would rather just starve at the feet of the rich out of some fever-dream version of earned righteousness.
This website is pretty easy to post on anonymously. It takes five seconds to make a throwaway and another three to post a name.
While I agree that there are frauds out there in academia and elsewhere, I have no reason to believe that you’re not yourself some sort of fraud. You’ve essentially posted “I have direct knowledge of [unspecified academic fraud in which somebody claimed to have direct knowledge of [unspecified academic fraudulent conclusion] but can’t back it up] but won’t back it up”
Your overall point is… what? Fraud of perpetuated by cowardice? Self interest? An overall sense of apathy towards the truth? Your comment could be construed as any of those.
There are people that love to spread fear, uncertainty and doubt without having to rely on being truthful. People that are intentionally misleading with the sole intent of leveraging people’s biases and emotions to confirm folks notions and whip people up into an artificially-created frenzy make statements yours.
Serious questions:
1. Do you actually give a shit about this big fraud you’ve brought up but not revealed?
And
2. Why did you post?
> 1. Do you actually give a shit about this big fraud you’ve brought up but not revealed?
To expose it directly here would likely have little effect generally, but would have an outsized effect personally (damaging trust). If it did have an impact it would likely expose those involved (many careers). I am not in the command chain, I have seen the evidence and it's overwhelming. But I'm not in a position to enact the requisite change.
That said, I don't actually give a shit about this particular case. It's widespread, insanely wide spread. Most studies / work cannot be replicated.
> 2. Why did you post?
As an anecdote to highlight something that I've seen. I also linked to several other informational pieces with public accounts (so don't trust mine, fine -- trust theirs).
> To expose it directly here would likely have little effect generally, but would have an outsized effect personally (damaging trust). If it did have an impact it would likely expose those involved (many careers). I am not in the command chain, I have seen the evidence and it's overwhelming. But I'm not in a position to enact the requisite change.
Sorry, I don’t mean to pick at you but… what?
If you were to anonymously post the name of an academic fraud, you personally would necessarily be found out, and it would ruin multiple careers?
The powers that be know who you are, know of the fraud and its nature and those involved? You’ve been privy to this big juicy secret that’s shared by many, but if its content were to be revealed, you would certainly be the one pointed out?
Are you the only person that could reasonably know about and publicly object to this fraud? If so, is it a necessary function of your social or professional life to cover up this fraud? If so, I’ll go back to “why did you post?” (“Sharing anecdotes” isn’t really an answer to “Why did you share this anecdote?”)
Not sure why people are that hostile. I'm sure that identifying someone also can identify you if the circle around the person is small enough, and if said person is powerful enough, people choosing to believe them over him would end careers, yes. He'd have to say "well, i worked on this particular study with him, and the data was made up vs actually collected."
I think its more "how dare you hint scientists are corrupt!" that kind of drives the outrage.
> This website is pretty easy to post on anonymously.
Correct me if I am wrong, but this website, and the owners are in U.S. of A. If so, an appropriate court order would force the disclosure of logs, IP addresses, accounts, etc. There are plenty of examples where sites had to disclose sufficient details to track an 'anonymous' writer down.
With multi-million (billion?) dollar endowments on the line, I would be worried to presume just a throw away account would work.
VPNs exists and are trivial to use. As is the TOR browser. Yes it's probably compromised already, but the FBI is not going to show their hand chasing a random libel case.
This is hilarious! I’m sure Elbert’s cutting wit and no-nonsense method of sniffing out true cinema mastery and creative rot saved dozens of eight year olds from watching this film, thus preserving their intellectual cinematic palate for better works, such as Das Boot.
> * Drinking alone helps you understand yourself better.
- No it doesn't. It distracts you from that endeavor. If you sit at a table with no TV or phone and do nothing, you will have a significantly more interesting and honest dialog with yourself if you are sober.
I don’t think that the fact that you disagree with a statement qualifies that statement as a syllogism.
I read those three statements as being distinct (for example “preferred cocktail” is a different subject from “comfortable silence”) though I will concede that all three statements do share a general theme of “the author enjoys drinking alone.” However, discussing various reasons for enjoying something does not qualify a statement as a syllogism.
While I also do not generally agree with the author, I’m not a big fan of “things I disagree with are Wrong in terms of fundamental logic. Anything I don’t like but Others do is wrong because those Others lack the fundamental Brain Power to Understand The World(tm) like me. To disagree with me is to commit an Aristotelian error of the highest order.”
It’s honestly an incredibly depressing attitude to come across, and it’s pretty much universally held by people that spend a lot of energy being “Not Mad” at not getting invited to parties.
Maybe you might feel differently about who is the arbiter of logic if you cracked open a nice beer?
For example I am a Zelda and Metroid fan (by “fan” I mean “someone that enjoys playing those games”), but I don’t think I’ve ever cared about any video game to the point of actually subjecting myself to any suffering. I know even more diehard friends than me that happily use emulators for games that they can’t find/afford.
Maybe there is a masochistic style of being a fan that someone can choose to subscribe to, but it’s not clear that it’s Nintendo’s fault that one would make such a choice.