I thought an individual atom has been imaged before, at least roughly. Anyway, this is fantastic science. I'm excited to see how imaging atoms affects our understanding of quantum mechanics and atomic structure in general.
I think they mean that this is the first time individual atoms have been imaged using this specific type of electron microscope. Individual atoms have of course been imaged as early as the 1980s using scanning tunneling microscopy. [1]
Last year, Aricescu’s team used cryo-EM to map the protein to 2.5 ångströms. But with the new kit, the researchers attained a 1.7-ångström resolution, with even better resolution in some key parts of the protein. “It was like peeling off a blur over your eyes,” Aricescu says. “At this resolution, every half ångström opens up a whole universe.”
I'm kind of hoping this puts the nail in the coffin with researchers trying to separate the psychedelic effects from the anti-depressant effects so that they can turn it into some kinda pill people have to take every day.
> they can turn it into some kinda pill people have to take every day.
I feel like this model is a perfect example of how the incentive structure of the pharmaceutical industry runs counter to pursuit of the best outcomes.
From what I understand anecdotally, psilocybin taken in moderate doses can have beneficial effects on depression and anxiety which last for weeks or months after the dose. This would be an amazing result by all accounts. A treatment which can be done every 6 weeks and still be effective would mitigate a lot of risks, like possible dependency and any toxicity which might be related to prolonged exposure. It seems to me that gets much closer to what we would refer to as a cure than a treatment.
But it seems like most of the clinical research is going into micro-dosing: i.e. how to make this something you would take every day to alleviate symptoms. I just don't understand the benefit of this approach other than the fact that it might be a better business model.
Moderate does trips aren't for everyone. The HN crew is full of novelty-seeking, curious, open-minded explorers, already drawn to this sort of experience. Your average, vanilla soccer mom who is largely okay with life but struggles with panic attacks because her brain isn't great at damping the amygdala-cortical loop, may not necessarily be ready/interested in a trip through psychedelic space.
I think the answer to that is to slowly increase the dose over a number of sessions. Starting out with microdosing to get used to the body feeling, then getting used to visual disturbances and the altered mental state, and then graduating to a level that can unlock new perspectives on self and the world. This absolutely has to be done by a trained professional with personal experience with the substance and who has assisted with other guided sessions. It's not going to be a prescription that a doctor can throw at the patient and then check up on in a few weeks time.
> This absolutely has to be done by a trained professional with personal experience with the substance and who has assisted with other guided sessions. It's not going to be a prescription that a doctor can throw at the patient and then check up on in a few weeks time.
That's pretty much how every treatment, for almost anything, should be.
Unfortunately, in most professional services (not just doctors), the people providing the service just have a few "recipes" on how to solve certain types of problems and then they just prescribe that. If your problem doesn't fall into any of their predefined categories, then good luck.
The typical interaction is: you have an initial session/interview where you describe your issue, then they immediately diagnose you (unless they require some additional info - documents/exams), and finally they provide their predefined solution. They never observe you in your daily routine to see what's actually going on, they don't study you to provide a personalized solution.
It's as if programmers would never debug a program, only get told by someone what the issue is and then they provide some library/api/piece of code that deals with what appears to be the issue from the outside.
> This absolutely has to be done by a trained professional with personal experience with the substance and who has assisted with other guided sessions. It's not going to be a prescription that a doctor can throw at the patient and then check up on in a few weeks time.
Seems like a bang-up business model, along with all sorts of other regular-meetings-with-the-professional therapies. Biologics on the pharm side, or just plain old therapy on the practitioner side.
Industry has plenty of practice with "every month or two" doses, so I wouldn't be so cynical in the attempts to remove the side effects. "Can you do it without getting high" is something that would greatly expand the audience and give people a better experience.
Hm, could you elaborate on that please? Do you mean the separate as in stereoisomer-wise? Or do you mean that ketamin has multiple effects on the brain or central nervous system, and one is the antidepressant effect and the other is the tripping balls effect? (And obviously pharma would like to find out what's going on exactly in the first case or ... how to block the second case while still having the first effect happen?)
* the stereo-isomers have differing effects: s-ketamine being more inebriating and less anti-depressant, while r-ketamine is less inebriating and has a stronger anti-depressant effect.
* The inebriant effect can be modulated without altering the anti-depressant effect, at least in lab rats. Cannabis is one drug that does this.
* The pharmaceutical company that ran the clinical trials for esketamine likely did so because it is actually the least effective anti-depressant of the two entanomers, and less effective than regular ketamine. By trialing and patenting the less effective one first, they can then patent the more effective one later, and make money longer, by dragging their feet. Esketamine is currently a few hundred dollars a dose (every three days). My ketamine is $70 for ~6 week supply. Capitalism is wonderful.
* fwiw, ketamine triggers other pathways in the brain, including ones that are involved in attention deficit and wakefulness. It has the same effect as amantadine - an ADHD medication. I can't take it after 10 am or so, if I am going to get a decent night's sleep.
Off-label use is great, doctors love it, but ... trials don't show much.
" [...] esketamine’s results are at least as bad as any SSRI’s. If you look at Table 9 in the FDA report, ketamine did notably worse than most of the other antidepressants the FDA has approved recently – including vortioxetine, an SSRI-like medication."
> Another possibility is that everyone made a huge mistake in using left-handed ketamine, and it’s right-handed ketamine that holds the magic. Most previous research was done on a racemic mixture (an equal mix of left-handed and right-handed molecules), and at least one study suggests it was the right-handed ketamine that was driving the results. Pharma decided to pursue left-handed ketamine because it was known to have a stronger effect on NMDA receptors, but – surprise! – ketamine probably doesn’t work through NMDA after all.
I think pharma pursued left-handed ketamine because they could patent it and charge a king's ransom for it, whereas your dog's vet has a bottle of right-handed ketamine for $5.
Meditation has similar effects - some people will have a single mind-blowing experience and a lot of their problems go away at once. Others practice for years and slowly whittle away at the sharper corners of their mind.
The problem is, you may not know what type of person you are going to be till ten years in. I suspect the same is true of psychedelic dosing: some of those soccer moms may need a strong depersonalization experience to get any real benefit from it. In some psychonauts it's going to trigger psychosis. I'm glad there's finally research being done in this area, the possibilities are certainly very exciting.
"The problem is, you may not know what type of person you are going to be till ten years in."
Very true. I used to fancy myself a psychonaut, then i got careless with 5-meo-dmt. Now i'm a teetotaler. Upon reflection i can't say i ever really liked tripping.
That’s probably true some of the time, but I think there’s a mode of mental health issues that I’ve experienced personally and seen in others who approach life with one foot on the gas and one foot on the brake. Basically, my hypothesis is that some people have contradictory impulses of desire and fear of stimulation and calm at the same time. You don’t have two groups of people (novelty-seeking HN crew vs vanilla soccer moms), but one type of person who is both and in conflict with themselves.
That's me. Easily overstimulated, yet drive myself to exhaustion because everything is too damn exciting. If you ask me it's a combination of high dopamine and high neural excitability/high connectivity. I think many programmers are like this and exist in a semi-permanent state of exhaustion.
This is a bad assumption on both ends (HN comments are most definitely not a bastion of free thought and expression.) but If people affected by PTSD can re-experience their trauma in controlled therapeutic settings using psychedelic compounds, so to can most others. Psychedelics are not for everyone, but they are certainly also not limited to chosen ones.
As a mini-side rant, I've found that people in the psychedelic community (defined as those that purposefully use psychedelics vs more spur of the moment usage) have pumped them selves up on their own identities as these "open minded explorers". I've actually found them to be belligerently dug in when faced with new evidence, information, and perspectives.
Source: I helped run a major city psychedelic community for a couple years
I honestly don't understand what happens to some people they trip. When I trip I get torn apart and question everything I believe in. After my first trip I thought wow if only everyone could experience this people would open their minds.
Then in time I met more and more people who regularly use psychs who were stuck in dogma. Recently I saw an interview with Dennis McKenna of all people who regularly trips (like his brother) and he just came across really disconnected like a dogmatic liberal like he was repeating what he had been told rather than thinking for himself.
It's been bothering me for a long time trying to understand it. I think the conclusion I have come to so far is that it opens your mind but only above whatever baseline you came from. The other thing is because the experiences have a feeling of being profound people who are not that open minded end up worshiping it and just fit themselves into that niche.
There's a long rant here, but it'll be pages worth of text. The short of it is that the so called leaders of the community are often accidental, untrained, uneducated, and largely unchecked. They say the right things and every one coalesces around them even if it's unsubstantiated gibberish (Terrance was the master of this and a total nut to be honest). It is very reminiscent of political dogma and zealotry (lets not pretend this is just a "dogmatic liberal" thing). Not to mention the big money they're pulling in from it now too (looking at you Bill Richards.)
There's no reason to continually trip, to take large doses, to try multiple psychedelics, etc. It's up to the individual to decide on what feels right for them. It is one of the most subjective and personal experiences you can have. Benchmarking against others is just...destructive really. No one in the community is saying that right now. It's just spiraling group think.
Yes essentially the leaders become like religious leaders. The problem is there is usually a kernel of truth to what they are saying which makes it easy to buy into if you're not thinking critically about it.
> But it seems like most of the clinical research is going into micro-dosing: i.e. how to make this something you would take every day to alleviate symptoms. I just don't understand the benefit of this approach other than the fact that it might be a better business model.
Could be because it's supposedly quite prevalent in Silicon Valley, so it's a cheap way to study its effects in a largish population that's self-medicating. Research is expensive!
I think it might just be a hangover from the view that "you're missing X from what we consider a normal neuro-chemistry so we'll give you a constant dose of Y to make some changes to the level of X"
This has always felt like it was treating the wrong thing. The way that neurons operate seems to be much more complex than just the changes made by neurotransmitter levels and flooding the entire network with higher levels of a neurotransmitter probably has all kinds of unintended consequences. I think this approach is often applied because its something that can be done quickly and easily and has immediate effect rather than spending months and years retraining the patient's brain. I hope that we see a revolution in clinical treatment that combines guided psychedelic therapy and daily practice. We need a more compassionate approach than just twisting a knob and nailing it in place.
this may not be entirely what you were getting at, but for the "daily pill" vs. "once a month" or "once every 6 months" - the business models already have precedents for this - there are psychiatric, migraine, autoimmune disease, and oncological drugs that are dosed monthly, every 3 months, every 6 months etc.
Unless I'm misunderstanding you completely, what's wrong with that idea? Currently, anti-depressants are a very hit and miss science, leaving many people further frustrated by therapy that was supposed to help them instead. Anything that can move towards better medicine in the future should be a good thing, no?
What's wrong is psychedelics already work as-is, but due to stigma around "fun" alterations of consciousness possibly being beneficial (along with desire for a patentable compound that can get through FDA regs), most of the focus has been on how we can go about removing the wetness from water while preserving water's essential useful properties. Regardless of how many years go by and self-reporting along with scientific evidence accumulates that water's wetness is mostly the entire point, and all while people are being thrown in jail for water possession.
I agree with your statement on principle that we should make these drugs widely available when we find efficacy.
I disagree that we shouldn't try to separate psychedelic effects from therapeutic action. There is a body of research on ketamine metabolites. Some of these metabolites may have less psychedelic effects and more anti-depressant action.
I need to take ketamine almost every day. This means there are several hours when my ability to read, think, and remember things is impaired. I hope we are able to discover better drugs.
> This means there are several hours when my ability to read, think, and remember things is impaired. I hope we are able to discover better drugs.
I don't think people give this enough consideration. Tripping on mushrooms might be enjoyable to some, but having it as a regimented treatment means you are losing a lot of time where you cannot be productive, cannot enjoy the company of your sober friends and family, etc.
The current research into psychedelic medicine is better described as intense therapy with a psychedelic adjunct for some sessions.
They aren't just giving people psychedelics and hoping everything turns out okay. The psychedelic dosing is combined with therapy, and the sessions are both preceded by and followed with additional therapy without psychedelics.
It's a mistake to assume that the psychedelic drugs are curing depression on their own. In fact, many people experience worsening depression or derealization if they take psychedelics without professional guidance while suffering from mental illness.
> They aren't just giving people psychedelics and hoping everything turns out okay. The psychedelic dosing is combined with therapy, and the sessions are both preceded by and followed with additional therapy without psychedelics.
And historically, that's exactly the way psychedelics have been used, for thousands of years. A shaman/guide would provide the medicine and help the people go through the experience, usually in a tight community where there's follow up and support.
Unfortunately that was suppressed, first by the Catholic Church when the Spanish arrived to America, and now more recently by making psychedelics illegal.
The idea of psychedelics being some sort of party drug is a problem of the current state of affairs, politically and culturally, where we have abandoned or forgotten their origins.
It's not "stigma". People treated from clinical depression hope to be able to function in their normal day lives at work and at home, not just be on a never-ending psychedelic trip.
This is exactly the stigma psychedelic enthusiasts have in mind. Psychedelic-assisted therapy doesn't need to rely on patients being administered psychedelic doses on a daily basis.
What's actually happening (either in trials or by underground practictioners) is that the super-malleable/open to self-analysis mental states that can be induced by psychedelics can be a catalyst for significant long-term shifts in perspectives and thinking patterns.
An amazing book to give you a cursory understanding of the state of the field is How to Change Your Mind: The New Science of Psychedelics by Michael Pollan. It'll give you a good understanding of what psychedelic research may be able to achieve (and what it's achieved so far).
> This is exactly the stigma psychedelic enthusiasts have in mind. Psychedelic-assisted therapy doesn't need to rely on patients being administered psychedelic doses on a daily basis.
Why does it have to include the psychedelic component though (even sub-trip-levels)? Some seem to think that you absolutely must not divide the psychedelic qualities from other qualities, even if you could. As if "you only deserve to enjoy the anti-depressant benefits if you embrace the trippy potential of it". That sounds too religious to me.
I find that a weird stance, and I'm very pro-psychedelics and would like to see them regulated but legally available. But I wouldn't want to keep depressed people who are afraid of the psychedelic experience from the benefits just because it won't help with legalization efforts.
Again, I'm not suggesting that you can split them into "trip drug" and "anti-depressant drug". But if you could, I'm absolutely for doing so. I'll still take the trip drug, but people who are afraid of tripping can take the safe one and still get benefits.
I believe the sentiment most people are expressing when they say you cannot separate the "trip" from the beneficial effects is that they both have the same origin or causative agent. Personally I'm in the "neural annealing" camp and it makes sense to me from personal experience that the benefits are due to psychedelics being a drug that essentially induces a state that you would normally only experience during profound and meaningful experiences. Those are the only other circumstances where I have felt the same as I have with psychedelics, experiencing a deep connection with the awesome scale and complexity of the natural world, falling in love, reading a life changing book, being transported emotionally and mentally by a symphony, getting caught up in the experience of a great movie, the physical rush of pushing yourself to your limits when exercising. We have drugs that seem to be able to produce the same life altering experiences that they can on demand. That's why it seems perverse to many people when it's argued that we should distill just the dregs of chemicals that produce the change without realizing that the actual mental and physical journey, the story that you weave around that experience that includes yourself, your thoughts, your environment and the people around you is probably the most important part. You can't just be happy all the time without having a reason to be happy, you can't be in love without someone to love and if you could it would seem more like a nightmare than an improvement.
I completely agree that the profound experiences you can have during psychedelic trips can be life-altering. I don't know whether it's the experience that leads to the other benefits, and if it doesn't, I see no reason why one would have to get them bundled.
The OP's comment reminded me of a some people I've come across that were into meditation and were anti-psychedelics, and to me it seemed like their main issue was that you could get these very deep experiences like ego-death but you didn't earn it, you didn't sit and quiet yourself for months and years, you just popped something into your mouth, experienced a bit of nausea and were teleported into a different dimension. It always seemed to me that they felt cheated because they took the hard road and felt that it's unfair that others took a short cut. Needless to say that it was even weirder given that they also tend to talk about compassion and inner peace a lot.
I totally understand if you believe that you simply cannot separate the psychedelic from other parts because it is what gives the benefits. I did get the feeling that that's not quite it though, that there's a lot of "and you shouldn't try to", and that feels like "you shouldn't get the benefits without embracing the experience, potentially encountering your demons etc", or a religious practice surrounding it.
>> You can't just be happy all the time without having a reason to be happy, you can't be in love without someone to love and if you could it would seem more like a nightmare than an improvement.
What you are describing is the state of enlightenment, and those who have had sustained experiences with it would disagree.
> I believe the sentiment most people are expressing when they say you cannot separate the "trip" from the beneficial effects is that they both have the same origin or causative agent.
Perhaps I've swallowed too much propaganda, but this seems like a testable belief. What if it's not true? What if psychadelic-assisted therapy is just one of multiple viable psychadelic-assisted treatment approaches? What if people want to be able to use store-bought neurotransmitters to regulate their minds without going through the trip-induced emotional or spiritual experience that they may not want?
Would achieving a deeper understanding of the relevant neurochemistry and allowing people to make their own choices be so bad? Would more treatment options be a negative?
I don't oppose the research or having more treatment options, I'm sure they would be necessary in many cases. My perception of it is a bit negative though at least when imagined to be an easy to access option for everyone, it's the same sort of opposition I feel towards the idea of taking steroids to promote muscle growth.
the psychedelic effect is simply (so to speak) the outcome of shutting down your executive function (that one that creates your internal monologue and gives you the perception of the self) so that the rest of your brain function that normally are "kept together and normalized" become more accessible for analysis and introspection.
Psychedelics are not anti-depressant, are just a potent accelerator for discovering WHY you're depressed. The psychedelic experience is necessary to the therapy. If you ever did a dose once you would understand exactly what I'm talking about, it's pretty hard not to understand what's happening once you experience it, just as it is essentially impossible before doing it.
> If you ever did a dose once you would understand exactly what I'm talking about, it's pretty hard not to understand what's happening once you experience it, just as it is essentially impossible before doing it.
Sorry, that sounds religious. I've experimented with psychedelics quite a bit, I've had very different intense experiences on them that have strongly affected me for long periods of time. That said, psychedelics do not unveil truths to you, not about the universe, not about yourself, but it can absolutely feel like it. You don't discover "why" you're depressed (as if there was a why, and understanding it would magically take the weight off of your shoulders; it's not a Hollywood movie).
That's just mysticism and naive religious interpretation imho.
You understood very little of what I was saying and it looks on purpose. If you like to go around feeling morally superior to people of faith (I’m not one of them btw) then leave me out of that please.
This is not how psychedelics for treatment resistant depression is tested. The most common treatment protocol is a single psychedelics session assisted by 2 therapists (preceded by a few therapy sessions and some follow-ups). Overwhelmingly the evidence point to very significant effects lasting months after the session.
This is far from "a never-ending psychedelic trip". If you follow the evidence for the most researched treatment protocol, this would involve a session every year or half-year.
> The most common treatment protocol is a single psychedelics session assisted by 2 therapists (preceded by a few therapy sessions and some follow-ups).
Ketamine is approved by the FDA for depression and also has a history, albeit shady, of being prescribed off-label at IV clinics. This is far more common than psychotherapy while taking medication and much less expensive too.
> If you follow the evidence for the most researched treatment protocol, this would involve a session every year or half-year.
In this small survey 60% of patients returned once a month or more for maintenance infusions.
Psychotherapy is seen as prohibitively expensive because of the way it is currently practiced where the patient must see the therapist on an ongoing basis. This isn't necessarily a bad thing, it's a lot like seeing a personal trainer on a regular basis but it's certainly an expensive way to stay fit. Psychedelic therapy seems to be an option that helps make a much smaller number of sessions "stick". If you only have to do 3 sessions a year then it means the therapists can see a much larger number of patients and the overall cost for each patient could go down.
My opinion is that most people could handle (small) group therapy as well which could further reduce cost and might actually have a number of benefits for those involved.
It doesn’t affect the same receptors as “classic” psychedelics (LSD, DMT, Mescaline) but dissociatives aka dissociative psychedelics are wildly psychedelic at high doses. It seems ludicrous to insist otherwise. Is Salvinorin-A not a psychedelic?
I think you have it a little backwards. IME, psychedelics give dissociative effects along with the psychedelic experience and the dissociative experience is solely dissociative on its own.
I think there's a lot of confusion on what a psychedelic experience is and it gets confused with a hallucinogenic experience, which both classes of substance can offer.
I’ve been following this stuff since the mid 90s and am familiar with the terminology.
What do you assert is the difference between a psychedelic experience and a hallucinogenic experience then? Dissociative I agree only partially overlaps with psychedelic on a venn diagram but hallucinogen and psychedelic I understand as synonymous.
Hallucinations are pretty concretely defined, medically. Seeing stuff that isn't there. Hearing stuff that isn't there. Things moving when they aren't.
For me, the psychedelic experience is more about the "Ah hah! we're all in this together! We're all the same thing! I've removed the veil and barriers I've built up all my life and can finally see clearly what it's All About." I'm sure it's different for others, but I don't experience that "oneness" or "connection" on dissociative. It feels like I am born again, free to be vulnerable and experience the world without the lenses that society and myself have placed over my eyes.
Research has focused on long-term (months to years/permanent) benefits from just one or a small handful of psychedelic experiences. It would even be difficult to find marginally responsible "psychonauts" who would recommend attempting a "never-ending psychedelic trip", which regardless wouldn't be physically plausible due to how rapidly the short-term tolerance increases.
In short, perhaps do more research on this topic because you're arguing against a position no one has taken.
"Life is the never-ending psychedelic trip, maaaan"
On a serious note, this isn't what GP is referring to. Generally psychedelics in the work day are self-limiting. A microdose that is more of a mesodose makes for some interesting Zoom meetings. People learn the right dose to get a boost without excess distraction/warping. Fadiman's research [0] suggests the best dose is well below the threshold of "trip" effects. So there's no risk of never-ending daytrips, unless one desires that thing. So why limit access?
Aspects of American culture have a strong stigma against "fun", euphoria, and to an extent, any effect beyond "restoring normal". eg nootropics are popular in young, hip crowds like HN, but kinda sketch among many MDs, from "I don't think these are safe" to "why do you need that?" It's a "if it feels good, stop" sentiment that runs as an undercurrent through American history and you can see signs of it in Protestant work ethic, Prohibition (of alcohol and cannabis), and of course the war on drugs.
Keep in mind, LSD and MDMA were very hotly researched back in the day, but when subcultures started associating them with parties, that's when things started getting the kabash.
"But addiction bad" - this would be a fair argument if it weren't for the near lack of correlation between DEA schedule and addiction potential [1], as well as the rapid action to ban analog drugs without any consideration to addiction potential. This is the fate of most Shulgin compounds, many exhibiting the typical rapid tolerance of psychedelics.
That leaves the theraputic dose. These are typically administered in a guided setting, either in the clinical sense, or trip-sitters/sherpas, in the informal. This is the best mitigation against trips that leave lasting psychological harm (the term "bad trip" is very loaded, as it doesn't distinct "hard lesson trips" from "no this actually messed them up long term"). If the concern is really "harm trips", then the solution is logically harm-reduction, not prohibition.
Daily medication, which must be taken without fail in order to have a normal life, is a liability. It can be lost, stolen, or missed. It must be obtained on a regular basis, and carried around on trips. It can be expensive. It can stop working, from tolerance. It can have unpleasant side effects.
A one-time, permanent cure is clearly superior. And your closing sentence was unnecessarily combative.
No research points to psychedelics being a one-time, permanent cure. That's an extreme misrepresentation of the science.
In fact, the current psychedelic research revolves around a series of intense therapy sessions, a small number of which involve psychedelics. They aren't just giving people psychedelics to take at home and hoping for the best.
And again, no serious researchers are suggesting that depression is cured permanently, let alone with a single ad-hoc dose. This should be common sense, as many people who used psychedelics recreationally still suffer from depression. Indeed, psychedelics can worsen depression for some people.
Properly replicating these psychedelic-assisted therapy sequences is going to be expensive. I'm sure the vast majority of people would prefer a daily pill that has no cognitive distortions.
I never suggested that the dose be ad-hoc, nor implied that we should just give people psychedelics to take home and hope for the best.
"One time cure" is indeed not accurate, today, but as a shorthand it captures the promise of psychedelic treatments. A single session can give benefits lasting many months, and some people may remit entirely. This is why more research is needed.
>I'm sure the vast majority of people would prefer a daily pill that has no cognitive distortions.
These don't exist. Existing psychological medication, not unsurprisingly, often comes with severe cognitive distortions - far worse than a single psychedelic trip every few months.
Psychedelic trips aren't a permanent cure for depression though. They have really good long-term effects on remission, but that still means nearly half won't remit.
> At a follow-up appointment after three months, 5 out of 12 patients were still in remission and 7 out of 12 showed a continued response
It often shines a light on the causes, but sometimes the causes are intractable/ongoing, or the only resolution is to learn to accept.
>Daily medication, which must be taken without fail in order to have a normal life, is a liability. It can be lost, stolen, or missed. It must be obtained on a regular basis, and carried around on trips.
I doubt these are a real problem for people who have a modicum of conscientiousness.
>A one-time, permanent cure is clearly superior
If you think that big bad pharma companies are keeping people from taking one-time cures for depression, by all means come up with a one-time cure on your own. How do you think one pill can create a permanent structural change in the brain that makes the just-so changes necessary to cure depression forever?
> I doubt these are a real problem for people who have a modicum of conscientiousness.
What does conscientiousness have to do with it?
You might need to travel or transit through a country which prohibits carrying them. Now you have to cancel the trip or go without the medicine.
> by all means come up with a one-time cure on your own
This is not helpful. People have the right to ask questions without being asked to devote a lifetime to develop some arbitrary authority (which would then in any case bias them to look for positive results).
Yes. You need to get permission to take a vast number of medications into UAE, including opioids and even common antidepressants.
I went through this process before COVID, with the intention of travelling to Dubai, and they knocked back my request about 10 times for spurious reasons, and were adament that I couldn't enter Dubai with a single pill more than was required for the duration of my time in Dubai. Which of course is completely unrealistic - I'd need some for travelling back, and a small buffer because of flight delays or whatever.
Honestly, travelling with certain medications is a major PITA.
Please have your strawman back as I said nothing about the feasibility of a one-time cure. I was backing up dTal's right to say that a one-time cure would be superior, without suffering a pointless ad-hominem rejoinder that why don't they find one if they're so clever.
One-time cures may be a sci-fi dream but they are highly desirable, as anyone who needs regular/prophylactic treatment for any severe ongoing condition knows.
> Now you have to cancel the trip or go without the medicine.
International travel is a minuscule thing to give up if you get effective depression (or pretty much any chronic condition) treatment in exchange. Heck most people can't justify the expense of international travel in the first place and the number of people who do it regularly for work and have depression is very small compared to the number of people who have depression. Practically nobody is going to let a chronic condition that affects their daily life go untreated because there's a short list of countries they can't have that treatment in.
What exactly are you arguing? That people should be happy with the flaws of the status quo, and that we should not follow up on promising new treatments that don't have those flaws, because...?
I thought my point was fairly clear and I'm not sure how you managed to derive the "people should be happy with the status quo and not follow up on promising new treatments with less flaws" from what I said. I'm arguing that "prevents international travel in some cases" is an inconsequential side effect for anything that treats an often debilitating chronic illness that is not even within the realm of consideration for the overwhelming majority of patients and that likewise "no negative effects on international travel" is not really a meaningful improvement over the status quo of treatments (all else being equal). Basically, if your biggest gripe with a treatment for a chronic illness is that you can't travel internationally then that's a pretty small gripe.
It was one example to illustrate one of the potential problems.
A much bigger issue is as pointed out by harimau777: prescriptions often don't get filled on time and sometimes not at all. Plenty of people run out of pills on holidays and have to suffer withdrawals, with suicidal ideation and actions being one of the symptoms of acute withdrawal from benzos.
Daily medication that requires a prescription is a huge problem for people that actually have to take it. What if they can't afford it at some point? What if their physician changes and the new physician doesn't want to prescribe it?
Why are we even defending daily medication? If there is any possibility of a permanent cure, obviously that is a much better choice of treatment.
His biggest gripe is that the pill has to be taken every day or very frequently. There are loads of circumstances which make that less desireable than taking a pill a few times a year instead. You've latched onto the travel example he gave.
> I doubt these are a real problem for people who [have good mental health]
Yeah. Funny thing about that. You're generally prescribed as low of a dose as is feasible, so by the time you're due to take your ADHD meds, antidepressants, antipsychotics, or whathaveyou, the last dose has worn off (especially first thing in the morning) and you're liable to miss a dose. So you get a pill minder, and fill it weekly, so at least you can check to make sure you don't forget and double-dose yourself. Chances are, you're taking several meds, so you have a highly detail-oriented chore you need to succeed at once a week on a specific day. If that's a bad day, you might not be able to muster the motivation and that throws off the whole week. Or you get most of the pills in but accidentally miss a day or a whole week's worth of a drug because you're juggling a handful of bottles and you're only human. Phone apps sound great, but depend on you being near your pills and your (charged) phone at a specific time of day, which has all sorts of failure modes.
And then there's the uncontrollable shit. You pack for a trip out of town. You're only supposed to be gone for a week, so you diligently pack a week's meds. Your ride home flakes, flight gets cancelled or whatever, and suddenly you're S.O.L. Or, your bag gets rifled by luggage inspectors at the airport and they pocket the goods (I've lost a nice pocket knife that way), it's stolen by hotel cleaning staff, pickpockets, or whatever. Good luck getting your prescription filled in a different country.
And once you miss a pill, you might hit a spiral that lasts a week or longer before you get back on track. It's a fucking liability.
At least for controlled substances, it is definitely not that simple. Patients can run into situations where pharmacies refuse to tell them if they are able to fill a prescription until it is actually written for them. However, if they are not able to fill it, the doctor is hesitant to write a new prescription for a different pharmacy because it could look like they are writing the patient multiple prescriptions for the same drug.
I found myself irritated enough to talk about conscientiousness.
I have a permanent medical condition which calls for a somewhat antique medication. It is typically used "as needed," certainly not every day. I have had a regular prescription for over a decade and it has certainly improved my quality of life. I refill like clockwork, I am responsible about using it. It comes time for a refill and ... my pharmacist at Walgreens regrets to inform me that they cannot seem to get it, and that the manufacturer has stopped making it.
This is worrisome. I remember life before the medication. I dig through the FDA databases, locating every organization which has applied to make the medication and been issued an NDC (National Drug Code) identifier. Each organization is tracked down: are they still in existence? Have they been bought out and if so, by what other company? I discover buyouts, shutdowns, press releases saying that they are "exiting" some market. I make phone calls, I send emails, and, when no other contact information is available, I send letters with self-addressed stamped envelopes. Almost everyone who has ever made it has stopped or been stopped in one fashion or another. Meanwhile, I begin to canvass the distributors: McKeeson, Cardinal, AmeriSourceBergen. Are there any remaining in stock? If so, which pharmacies in my area do they work with? Most pharmacies have a single distributor. These are organizations who do not like to be contacted by the hoi polloi, and I have quite a lot of "How did you get this number?" conversations.
At last, a hit: someone has just started manufacturing it. Out of all of them, there's only one. I dutifully take this to Walgreens. After a few go-rounds, they cannot seem to get ahold of it. They suggest Walmart. I have to hassle my poor doctor's office, now in COVID-panic like everyone else, to move my script, which one required a special paper. Walmart swears they have it, they have contacted their distributor, they have bottles in stock. Wonderful. And it does not arrive, they call again, and it does not arrive, and they call again. Finally, they shrug and give up. Right!
I call CVS; they are sure they can get it. I transfer the script, again. Off I go to CVS. CVS says that, yes, it is in stock at their distributor. Similar to Walmart, after a few weeks, they cannot get it. The pharmacist has called the corporate offices and only knows that there is a "corporate block" on it and that, despite being able to submit an order for a bottle of pills which are present at a distributor, they will never ever arrive. I am disappointed, and, out of a little curiosity, I submit a letter to CVS corporate (again with the self-addressed stamped envelope to remove barriers to reply) asking just what this block is ... not that I ever get a reply.
I try a small, local shop. I wince at having to call my doctor to have the script transferred yet again. Surely they will try harder rather than giving me the brush-off you can so often get from large organizations. No dice. The dance is now familiar to me.
Armed with yet more research and NDC codes and distributor phone numbers, I approach my original pharmacy again. Another script transfer, with all of the pain entertained in moving something with a low Schedule number around. With the new information I have gathered and a great deal of persistence, they manage to obtain it. The head pharmacist tells me that the sole other patient on it will be relieved, and that he has never had to work this hard to get a prescription before.
By the end of this two month period, I had lost approximately twenty pounds and was clumsily knocking things over due to my coordination degrading. Finally, I managed to fall hard enough that I was still limping two months later.
The moral of the story is this: being conscientious does not guarantee availability. One can do all of the right things and still not have it on hand. Being dependent on a medication, even weekly, can be a burden, even if you attend to the situation quite closely. I urge you not to be quite so flippant about it.
Most people I've met who solved their problem in this way seemed, as a side-effect, to have distorted their personalities in noticeable ways. (I am not claiming that this tradeoff is never worth it, but something rarely considered, and usually not noticed by the person taking the medication.)
To be more specific in the kind of distortion I noticed: lack of empathy, shorter attention span, lowered curiosity.
I would say if the symptoms reappear when you stop taking a medication, your problem isn't solved so much as the symptoms are being managed. Given that mood disorders can be due to some underlying conflict within the person's psyche, simply alleviating all negative symptoms seems at odds with the goal of getting as many people as possible to self-actualization.
"Given that mood disorders can be due to some underlying conflict" - that is an interesting assumption. It is one of those things that is impossible to prove or disprove. My position is most complex organ systems have biological abnormalities that are prone to dysfunction, such as diabetes, albinoism, genetic predisposition to heart disease and cancers, I'm not sure why the brain would be different in that regard.
Assuming there is an underlying conflict driving things, then medication might be simply masking the symptoms, which is a perfectly valid approach in dire situations, no use seeking out the underlying conflict if the symptoms kill you before you come to a conclusion.
However, if there is no underlying conflict and this is just a twist of fate, searching for an underlying conflict can be aggravating and misleading. If waves of negative emotion occur randomly (or semi-randomly), as has been my experience, and you assume there is always some valid reason for these feelings, the tendency is to re-arrange your life searching for a solution, if that solution does not exist because there is no underlying problem, constant rearrangement can blow up your support system and the routines that help maintain your daily living.
I did say 'can be'. The soldiers with PTSD whose depression has improved with small numbers of treatments did not simply suffer from a biological abnormality - their brains changed in response to stimulus, which is after all what we'd expect brains to do.
I do think brains should be viewed as different from most organs when we describe medical intervention, they are plastic to a degree other organs are not. If a diabetic could simply 'mutate' their pancreas to function normally with a single intervention, I think most would prefer that to taking insulin all their lives, even if the one intervention was distressing.
Brains actually can change in very dramatic ways. Most are for the worse of course, and we instinctively avoid any change in our mentality, but they are times when it is actually preferable.
>Given that mood disorders can be due to some underlying conflict within the person's psyche
Couldn't be further from the truth. I know where you're going with this and I think we are in agreement on the majority of mental illnesses (as the brain's best response to stress), but mood disorders are in a different category entirely. Mood disorders and schizophrenia do not respond to therapy. They are never cured or recovered from. All you can do is manage the symptoms.
> I take a prescribed ketamine lozenge every day. I don't experience any psychedelic effects and I'm fine with that.
Many of the researchers and clinics are gravitating toward ketamine regimens that avoid hallucinations entirely, like your current treatment regimen.
Ketamine has some inherent anti-depressant effects that don't depend on hallucinating. Unfortunately, many psychedelic proponents have tried to push the narrative in the opposite direction to emphasize the trip.
It's unrealistic to expect depressed people to routinely go on psychedelic trips to keep their depression at bay. It's also unrealistic to expect people to trip frequently and not have part of the population start to accumulate weird, irrational ideas from their trips.
A medicine that captures the anti-depressant effects without causing a psychedelic trip or really any cognitive distortions at all would be far better than expecting people to trip regularly. I don't understand the aversion to pharmaceutical companies pushing the research in this direction.
I’m very curious about how much you take daily and the effects. I’ve read about the super high dosage therapy, and that made a lot of sense to me. Are you just ever so slightly dissociated at all times?
I dunno about them but, but I get by on 20mg taken weekly. If I miss a dose, it's usually ok. If I miss two, suicidal ideation is my dominant thought pattern. As for effects, I'm a little dizzy for about 30 minutes and I prefer to spend this time napping or in a hot bath.
All medications have two kinds of effects: therapeutic effects, and any number of side effects.
The "problem" with compounds that can alter our state of mind is that, by definition, they can be fun/weird/recreational if taken in meaningful doses. And this, of course, scares the government and the pharmaceutical industry. They are not allowed to sell things which can be used for disorder (read: "recreation").
So the pharma industry must select against these compounds. What we're left with is medication where the active, psychoactive effect is so small that it's of the same magnitude as the side effects. This prevents "abuse".
Hence why antidepressants are basically constipation/headache/libido killing pills that kinda maybe change your frame of mind.
The profit motive would clearly prioritize finding an expensive medication that must be taken regularly and indefinitely. Psychedelic research up to now is pointing to small numbers of uses having lasting positive effects. There is a fear that research driven by a profit motive will try to not just not investigate this further but actively gloss over this potential medicine.
> The profit motive would clearly prioritize finding an expensive medication that must be taken regularly and indefinitely.
The idea that pharmaceutical companies are deliberately avoiding one-time treatments is a myth.
If you assume profit is the ultimate motive, there's nothing stopping a pharmaceutical company from charging $10,000 for a long-lasting depression treatment.
It's not like pharmaceutical companies are going to stumble upon a perfect treatment and then decline to patent it.
Also, patents don't last forever. Common SSRI anti-depressants are available for $4-5/month.
Everyone I've known who took such medication have altered their personalities in noticeable (unpleasant) ways. It may be worth it for the person in question, but one should be aware of it.
This may be true, but even in the cases that I mention the experience of those taking the medication was positive, it is just other people who noticed the shift in personality.
that's not how it works. The anti-depressant, anti-addiction effect can only be achieved through the psychedelic effect since ego dissolution IS what you experience. Through that effect, you get to analyze the "parts" of your psyche without the executive function hiding the discrete parts and that's integral to WHY a psychedelic drug helps with those issues.
I don't believe this will ever be a once a week treatment.
I wonder what's the correlation between this and people being underpaid. I'm fortunate enough to have my own house after graduation so I don't have to pay rent. But I have friends that don't have this luxury and man, they are struggling. Besides eating and rent they can't afford anything else in a month. No question here what's giving them these feelings
I live in Denmark, where we lift a lot of the burden of civilisation together, to give everyone access to education, health/elderly/child care as well as a solid security system for those who get unemployed.
And here society is hard enough these days, pressing more and more people beyond their limits. I really wonder how you all do it in America.
A lot of Americans think they can make it themselves without help from others. Smart people don’t believe that and make the government subsidize their stuff left and right. Often while deluding themselves into thinking that they are “self made”. And then you have the people who constantly vote against their own interests while enduring the hardships the system imposes.
The United States and Denmark are very different countries.
The U.S. has nearly 4x as fast population growth, 2x as many immigrants, 10x the incarceration rate, much greater religious and racial diversity, 100x more billionaires, 17% less GDP per capita, and 3x as much debt/GDP.
I'll refrain from opining as to what is cause and what is effect, but the differences are many.
Denmark has a dramatically greater household debt to income ratio than the US, and is one of the most indebted countries in the world. They're in horrible debt shape. Their household debt as a percentage of disposable income is 282%, the worst in the world; that contrasts with 105% for the US, which is only slightly worse than Germany at 95%. Denmark's quality of life is coming at the expense of the future, as they load up massively on debt today to fake their standard of living.
>Denmark's quality of life is coming at the expense of the future, as they load up massively on debt today to fake their standard of living.
It's probably worth it in the end. How much longer do we have to endure low quality of life for the sake of some future? Let's say you endured and now your son becomes an adult. Is that now the time to start improving things and enjoying a better quality of life? Probably not, people will say it isn't time yet and we aren't ready, therefore your son will have to sacrifice his happiness and wellbeing too, for his children.
The average person in Denmark will probably die of natural cause, after a relatively happy and fulfilling life. Doesn't seem like they're getting any worse either for it.
What do we have to show for our sacrifices? Nothing it seems. The powers that be will cry about muh inflation all day and won't bail out people, but they're ready to bend over and print money if the corporations and ultra rich need it though.
> And here society is hard enough these days, pressing more and more people beyond their limits. I really wonder how you all do it in America.
It's all relative. Someone in the US is looking at failed states in Central America and Africa and thinking the same thing. One day, people will look at Denmark and think the same.
Objectively people may be having a better or worse time in different places at different times, but how you personally feel about your situation is all relative at the end of the day.
I don't know whether there's a large correlation, but I believe it would mostly be in the severity of outcomes. Depression isn't "because life is hard", but life being hard makes dealing with depression harder than life being easy.
I know people who are very wealthy who struggle with depression, I know people who are very wealthy who don't even really understand the term because they've never experienced anything remotely close. And I know both types who are not wealthy at all. From my personal experience, money doesn't matter in that regard. But it's definitely better to struggle with depression without the added stress of keeping up with the bills, and when you've gotten through it, you're having a good life if you've been rich before, and you're going to have to pick up the pieces and try to glue them back together if you haven't.
On top of that, I wonder how much these statistics are influenced by the ridiculous student debt burdens the U.S. education system saddles their youth with. Getting a master's degree will easily have you graduating with six figures in student loan debt. In a sibling comment I see a mention of Denmark - a country where not only is higher education free, the government actually pays students a monthly stipend to help cover basic living expenses.
The U.S. is an extremely backwards country when it comes to taking care of its people, with city streets literally lined up with tents of homeless people in some of its biggest cities. No universal healthcare, low social mobility, it's not the least bit surprising to me that a third of the country is depressed. It's just sad that our government does nothing about it while our president is busy tweeting conspiracy theories.
I guess they are playing for a portfolio approach. With investments in a bunch of different companies, in-house drones, and robotics research. Very interested in how they integrate them into Amazon, if at all.
All jokes aside, the Theremin is actually quite a remarkable instrument when played correctly. Also remarkable is his listening device, "The Thing", hung for seven years in plain view in the US Ambassador's Moscow office and Soviet agents eavesdropped on secret conversations. Used the same principles as RFID.
Here's the notorious video of her performing the Ecstasy of Gold with voice, theremin, and a looper pedal (that's how she load in multiple sounds and layers them).
It's relatively limited as a standalone instrument (people can make remarkable music with it, don't get me wrong), but really opens up as a CV controller for other instruments. It also makes a really nice source for a talkbox.
I have one and can confirm it's a very complicated instrument to play well. It's a phenomenal piece of early electronic tech.
2) Don't make any claims about effect size (i.e. correlation strength & predictive strength)
You can basically make this point about literally any substance with enough studies on it. Ranging from melatonin to insulin, to idk... probably not mercury? So I guess that's a strike against 1 and 2 being fully generalizable.
