Well first you’re not supposed to be inhaling amphetamines if you’re using them for non-recreational purposes. I’m sorry for your friend, but it sounds like their use went far beyond therapeutic use cases.
Not sure why are all the comments here discussing stimulants. The drug in this study is a derivative of something called GLP-2 which seems to have some completely novel mechanism of action (if it indeed works).
Spravato is a stupid attempt to make money off of depressed people. They isolated one isomer of ketamine so they could patent it. Tested against placebo but not against generic ketamine... It's almost ten times the price of ketamine too.
I was excited for this until I read it's from Japan.
Before you downvote me or call me names, let me explain.
Japan is known for having an enormously toxic work culture -- I think we've all heard about the people having to sit 16 hours in the office just so they seem like they are working hard, or how they nap in the toilet, and many other such horrors.
So Japan inventing a very quickly working anti-depressant seem more like paving the way to a nightmare cyberpunk dystopia to me... imagine an operator going through the cameras and an AI warns them: "Employee T-4214 looks to be emotionally distressed or apathetic. Administer countermeasures immediately". And then the person gets a serotonin / dopamine boost and starts working their meaningless awful job with a creepily wide smile on their face.
But hey, if the rest of us who are not slaves and genuinely need some help sometimes can benefit, I am still all for it. I just question the motives of this particular team. Hopefully I am wrong!
In the end it's all circling back to the guns argument: guns can be used for doing evil, and guns can be used for doing good. It's all on us the humans, not on the implement itself.
I think you're massively underestimating the lengths of work-related cruelty that happens here (everywhere except Japan). Obviously there are varying types of cruelty, but an Amazon warehouse worker who is not allowed to go to the restroom past their time limit or an office worker who puts in ridiculous overtime to fulfill the expectations their boss "subtly" gaslighted into them are subject to the exact same situation you're describing.
I don't think this has anything to do with Japan, their work culture just shows what capitalism does to everyone more explicitly. They say the quiet part out loud.
I agree completely. Sorry that I didn't include other prominent examples.
It's true what you say: we're witnessing the endgame of capitalism. What was a cyberpunk dystopia before and was meet with laughter -- "crazy fantasy, man" -- is now the reality of tens or hundreds of millions of people.
---
My post was mostly just expressing skepticism about the seemingly benevolent nature of this research. People who are as strongly set in their ways as the elderly Japanese wealth-holders are, will IMO first launch a nuclear strike before they give their employees better working conditions. So putting my tinfoil hat on, I'd theorize this research has been funded by Japanese big business owners.
1. When we figured out fossil fuels can be used to drive vehicles we did not realize until recently the cost of using it on our environment
2. When we figured out plastic has versatile uses we did not realize until recently that plastic will end up in ocean as micro plastic which will then become part of food chain.
I can come up with more examples like this. I am not questioning the efficacy of the drug. I am only wondering what if this has adverse effects on other parts of brain which we might discover too late.
When we figured out that some Diseases come from little living creatures we wash our hands before operating patients and are able to create vaccines, and medicine.
I can come up with more examples like this too, but yes looking into the future is not easy, but much easier when not depressive ;)
With vaccines, we do extensive testing to ensure it does not have side effects and that it does not pose a threat to health of next generation.
But I am not so sure if that same analogy can be used with everything else which is not directly impacting human health. Companies invent things, they get greedy and lose the foresight of consequences of their actions. They lobby politicians to defend their own shady practices. The general public ends up paying the price.
A substantial amount of folks suffering with depression have situational depression, e.g. depression from living (for them) and unfulfilled life, relationship problems, stress, substance abuse etc. I can see a 20 minute fix with no effort to address the root cause, just creating more issues.
One of the worst things with depression is that might be in a negative spiral until a person becomes totally apathetic. Breaking that negative spiral and instead putting a person in a positive spiral (going to the gym becomes more fun, socialising becomes more fun, removing the need for a big amount of willpower) is essential to living a fulfilled life. An empathic doctor will know when it is time to wean the person away from it.
I've seen my brother waste his life completely, becoming a shut in, he has never hurt a fly but he has zero confidence and absolutely zero optimism even though he was in the top 2% in our version of SAT, which made him be able to pick any university he wanted, but having no optimism, he didn't go to school. He is nearly 50 now and the family (including me) has basically given up on him having a job or a girlfriend, or a bunch of friends for that matter (he is very kind but a pessimist, you are not going to hear him cracking a joke). For most people, they can't even phantom being able to get that high score and not choosing to study/work, because they haven't been apathetic.
Medicine (subscribed by specialists) are the cheat code of life, done sparingly and well. Just look at the amount of people who changed their life with ADHD medication saying they couldn't even have energy for mowing the lawn before taking it.
From what I've seen, I just can barely see anything riskier than a life of depression.
I personally believe that source of depression is purely physical.
Some physical factor affects the mood and it affects behavior that may further degrade physical condition that progresses the depression.
So the root cause is not the way people live, or percive their world but some defect in their brains and you always need to start with that. Improving behavior comes next. Same way that walks might help your broken leg heal, but only after you properly put in together and secured with some screws and plates and a cast.
People thought stomach ulcers were caused by stress and lifestyle until they discovered it's actually helicobacter pylori.
So before that people advocated that if you have ulcers you should improve your life to stress less. Which ultimately had very limited effect because no matter how little you stressed and how well you ate you were still infected with the bacteria.
And the solution turned out to be just the right antibiotic which looked like cheating because people didn't improved their lifestyle just took some pills, got rid of ulcers and still mostly lead the same "wrong" lives.
Another explanation for depression I've heard from Mark Solms. Or partial explanation. He thinks it may be a dysfunctional or pathologised form of mourning. There are two relevant emotional needs which all mammals possess:
1. Seeking. This is ongoing energetic and curious engagement with the world.
2. Attachment. The need for connection with others, especially to parents.
These two rarely come into conflict but when they do system 1 may be switched off.
e.g. A rat pup is separated from its mother and becomes anxious. It commences to squeak for a brief period in order to attract her attention. It then goes quiet; its brain switches off seeking. It experiences mourning and despair.
The evolutionary rationale for this built-in mechanism is to prevent vulnerable infants from attracting predators.
Obviously humans are more complicated. Perhaps the same shutdown process is triggered in response to the breaking of other kinds of attachment, e.g. attachment to ideas about what to do.
I think you're right that "situational depression" is a thing, probably moreso than ever with the way we live nowadays.
I think it's also worth noting that some people appear to "have it all" (and would even claim so themselves), but can still be depressed - situationally, things are great, but feelings of depression persist.
The issue with depression is it often makes it impossible to address the root concerns. It is almost like a catch-22 in a lot of ways, and it is why it is such an awful thing.
This is the sort of thing that bothered me about some "stress management" approaches that seemed to be largely about treating the symptoms of stress while ignoring the root causes.
For example, were you to ask university students about what would relieve their stress, they might provide concrete suggestions like more flexible grading policies, better teaching, advising and mentoring, less punitive discipline, better housing options, better food, lower fees, etc., but university mental health staff generally have zero power to put any of these suggestions into practice, and such changes are generally opposed by the faculty and administration. Much of the stress experienced by students is directly caused and incentivized by the university, yet somehow counselors are supposed to fix it?
The root causes of stress for the population at large might include the many horrors and dangers of modern life. Problems such as horrible work, horrible school, lack of affordable housing/health care/education, constant financial insecurity, stifling and isolating social environment, lack of opportunity, lack of purpose, existential dread, mortality, political and social strife, environmental pollution, impending doom from global warming, pandemics, wars, etc.) are often very hard (if not impossible) to change, so perhaps just trying to treat the symptoms makes sense.
Interesting stuff. Most (basically all??) of our existing psychiatric drugs are small molecules. I presume this is related to how much of a pain getting proteins into the brain is - which is exactly what this research helps enable. They show that by grafting on specific structures into a protein (GLP-2) they can drastically increase its speed and effectiveness at delivering into the brain.
I don't put much hope into GLP-2 being anywhere close to useful for actually treating anything in humans - I think it's just a nice model to demonstrate the technique.
It's interesting, and I think the article does a great disservice because:
a) This technique doesn't seem extendible to our existing drugs, which means this technique can't help mitigate some of the challenges of our existing drugs (one of them off the top of my head is that it just takes a long time for them to fully saturate your system, meaning its a total pain to figure out dosing). I feel like this should have been commented on.
b) This technique potentially opens up an entire category of candidates that were previously ruled out. I feel like this should also been commented on directly.
For those wondering, the nmda receptor which is in charge of motor function seems to have anti-depressant potential. This is what ketamine and other nmda medications activate. And it seems like this novel peptide interacts with that as well in some way.
Not a scientist but have experimented with a ton of compounds trying to relieve feelings of dread brought on by being raised in the lower class of society due to a father who was disabled. And later on rejection from jobs because of lack of education and being forced to work for extremely low wages. Messes up your self respect after awhile.
Anyways,
Drugs won’t solve anything for longer than a few weeks or months, but what nmda drugs I have tried seemed to have the biggest breakthrough from serious depression. So ymmv
Have you programmers ever tried to fix a problem with your program by trying random things? Did it work?
I am so tired of hearing about some random thing that supposedly helps with mental illness as if trial and error without understanding was a reasonable method.
What mental illness is, is an ordinary illness that occupies a social niche where it's exempt from normal scientific or medical study. It evades our social immune system the way retroviruses evade our physical immune system.
The sane, rational, reasonable approach would be to put everything into developing tools and measurement techniques to establish what mental illnesses are.
Depression, mania, and psychosis need, above all else, tools like blood sugar tests and A1C provide for diabetes.
99% of solving any problem is describing it. Administering random treatments to suffering people and lab animals is not progress, it is a tragic waste, cargo cultism, part of the disease that transcends the actual victims.
The only thing I know of that's really seemed like progress in ages is opto-genetics.
Just...develop tools because without them there is no evaluating treatments. Stop using surveys.
I would like to think that researching mental illness would lead to ways of enhancing normal cognition that would help everyone. I would expect that people would think of this possibility, and therefore there would be plenty of funding available. But it doesn't seem to work that way.
38 comments
[ 3.2 ms ] story [ 75.0 ms ] threadJust don't do it, kids. Amphetamines can mess with you, I've lost a friend who couldn't stop using it
Before you downvote me or call me names, let me explain.
Japan is known for having an enormously toxic work culture -- I think we've all heard about the people having to sit 16 hours in the office just so they seem like they are working hard, or how they nap in the toilet, and many other such horrors.
So Japan inventing a very quickly working anti-depressant seem more like paving the way to a nightmare cyberpunk dystopia to me... imagine an operator going through the cameras and an AI warns them: "Employee T-4214 looks to be emotionally distressed or apathetic. Administer countermeasures immediately". And then the person gets a serotonin / dopamine boost and starts working their meaningless awful job with a creepily wide smile on their face.
But hey, if the rest of us who are not slaves and genuinely need some help sometimes can benefit, I am still all for it. I just question the motives of this particular team. Hopefully I am wrong!
In the end it's all circling back to the guns argument: guns can be used for doing evil, and guns can be used for doing good. It's all on us the humans, not on the implement itself.
A gram is better than a damn.
I think you're massively underestimating the lengths of work-related cruelty that happens here (everywhere except Japan). Obviously there are varying types of cruelty, but an Amazon warehouse worker who is not allowed to go to the restroom past their time limit or an office worker who puts in ridiculous overtime to fulfill the expectations their boss "subtly" gaslighted into them are subject to the exact same situation you're describing.
I don't think this has anything to do with Japan, their work culture just shows what capitalism does to everyone more explicitly. They say the quiet part out loud.
It's true what you say: we're witnessing the endgame of capitalism. What was a cyberpunk dystopia before and was meet with laughter -- "crazy fantasy, man" -- is now the reality of tens or hundreds of millions of people.
---
My post was mostly just expressing skepticism about the seemingly benevolent nature of this research. People who are as strongly set in their ways as the elderly Japanese wealth-holders are, will IMO first launch a nuclear strike before they give their employees better working conditions. So putting my tinfoil hat on, I'd theorize this research has been funded by Japanese big business owners.
https://news.ycombinator.com/newsguidelines.html
2. When we figured out plastic has versatile uses we did not realize until recently that plastic will end up in ocean as micro plastic which will then become part of food chain.
I can come up with more examples like this. I am not questioning the efficacy of the drug. I am only wondering what if this has adverse effects on other parts of brain which we might discover too late.
I can come up with more examples like this too, but yes looking into the future is not easy, but much easier when not depressive ;)
But I am not so sure if that same analogy can be used with everything else which is not directly impacting human health. Companies invent things, they get greedy and lose the foresight of consequences of their actions. They lobby politicians to defend their own shady practices. The general public ends up paying the price.
That's a political problem not a technical one.
A substantial amount of folks suffering with depression have situational depression, e.g. depression from living (for them) and unfulfilled life, relationship problems, stress, substance abuse etc. I can see a 20 minute fix with no effort to address the root cause, just creating more issues.
I've seen my brother waste his life completely, becoming a shut in, he has never hurt a fly but he has zero confidence and absolutely zero optimism even though he was in the top 2% in our version of SAT, which made him be able to pick any university he wanted, but having no optimism, he didn't go to school. He is nearly 50 now and the family (including me) has basically given up on him having a job or a girlfriend, or a bunch of friends for that matter (he is very kind but a pessimist, you are not going to hear him cracking a joke). For most people, they can't even phantom being able to get that high score and not choosing to study/work, because they haven't been apathetic.
Medicine (subscribed by specialists) are the cheat code of life, done sparingly and well. Just look at the amount of people who changed their life with ADHD medication saying they couldn't even have energy for mowing the lawn before taking it.
From what I've seen, I just can barely see anything riskier than a life of depression.
Do you think your choice to disrespect his privacy might play a role in your relationship?
Some physical factor affects the mood and it affects behavior that may further degrade physical condition that progresses the depression.
So the root cause is not the way people live, or percive their world but some defect in their brains and you always need to start with that. Improving behavior comes next. Same way that walks might help your broken leg heal, but only after you properly put in together and secured with some screws and plates and a cast.
People thought stomach ulcers were caused by stress and lifestyle until they discovered it's actually helicobacter pylori.
So before that people advocated that if you have ulcers you should improve your life to stress less. Which ultimately had very limited effect because no matter how little you stressed and how well you ate you were still infected with the bacteria.
And the solution turned out to be just the right antibiotic which looked like cheating because people didn't improved their lifestyle just took some pills, got rid of ulcers and still mostly lead the same "wrong" lives.
1. Seeking. This is ongoing energetic and curious engagement with the world.
2. Attachment. The need for connection with others, especially to parents.
These two rarely come into conflict but when they do system 1 may be switched off.
e.g. A rat pup is separated from its mother and becomes anxious. It commences to squeak for a brief period in order to attract her attention. It then goes quiet; its brain switches off seeking. It experiences mourning and despair.
The evolutionary rationale for this built-in mechanism is to prevent vulnerable infants from attracting predators.
Obviously humans are more complicated. Perhaps the same shutdown process is triggered in response to the breaking of other kinds of attachment, e.g. attachment to ideas about what to do.
I think it's also worth noting that some people appear to "have it all" (and would even claim so themselves), but can still be depressed - situationally, things are great, but feelings of depression persist.
This is the sort of thing that bothered me about some "stress management" approaches that seemed to be largely about treating the symptoms of stress while ignoring the root causes.
For example, were you to ask university students about what would relieve their stress, they might provide concrete suggestions like more flexible grading policies, better teaching, advising and mentoring, less punitive discipline, better housing options, better food, lower fees, etc., but university mental health staff generally have zero power to put any of these suggestions into practice, and such changes are generally opposed by the faculty and administration. Much of the stress experienced by students is directly caused and incentivized by the university, yet somehow counselors are supposed to fix it?
The root causes of stress for the population at large might include the many horrors and dangers of modern life. Problems such as horrible work, horrible school, lack of affordable housing/health care/education, constant financial insecurity, stifling and isolating social environment, lack of opportunity, lack of purpose, existential dread, mortality, political and social strife, environmental pollution, impending doom from global warming, pandemics, wars, etc.) are often very hard (if not impossible) to change, so perhaps just trying to treat the symptoms makes sense.
I don't put much hope into GLP-2 being anywhere close to useful for actually treating anything in humans - I think it's just a nice model to demonstrate the technique.
It's interesting, and I think the article does a great disservice because:
a) This technique doesn't seem extendible to our existing drugs, which means this technique can't help mitigate some of the challenges of our existing drugs (one of them off the top of my head is that it just takes a long time for them to fully saturate your system, meaning its a total pain to figure out dosing). I feel like this should have been commented on.
b) This technique potentially opens up an entire category of candidates that were previously ruled out. I feel like this should also been commented on directly.
Not a scientist but have experimented with a ton of compounds trying to relieve feelings of dread brought on by being raised in the lower class of society due to a father who was disabled. And later on rejection from jobs because of lack of education and being forced to work for extremely low wages. Messes up your self respect after awhile.
Anyways,
Drugs won’t solve anything for longer than a few weeks or months, but what nmda drugs I have tried seemed to have the biggest breakthrough from serious depression. So ymmv
I am so tired of hearing about some random thing that supposedly helps with mental illness as if trial and error without understanding was a reasonable method.
What mental illness is, is an ordinary illness that occupies a social niche where it's exempt from normal scientific or medical study. It evades our social immune system the way retroviruses evade our physical immune system.
The sane, rational, reasonable approach would be to put everything into developing tools and measurement techniques to establish what mental illnesses are.
Depression, mania, and psychosis need, above all else, tools like blood sugar tests and A1C provide for diabetes.
99% of solving any problem is describing it. Administering random treatments to suffering people and lab animals is not progress, it is a tragic waste, cargo cultism, part of the disease that transcends the actual victims.
The only thing I know of that's really seemed like progress in ages is opto-genetics.
Just...develop tools because without them there is no evaluating treatments. Stop using surveys.
I would like to think that researching mental illness would lead to ways of enhancing normal cognition that would help everyone. I would expect that people would think of this possibility, and therefore there would be plenty of funding available. But it doesn't seem to work that way.