6 ms·

> 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 pharma

by skohan 6y ago

> 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.

kortex 6y ago
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.
- pharke 6y ago
  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.
  - vajrabum 6y ago
    Ketamine is being used to good effect these days in major depression. I wonder if they ramp up the doses like that when using it?
    - WalterSear 6y ago
      They don't. Fwiw, the psychedelic effect of ketamine is separate from its antidepressant effect.
      - pas 6y ago
        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?)
        WalterSear 6y ago
        * 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.
    - 6y ago
- flatline 6y ago
  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.
  - pasquinelli 6y ago
    "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.
- mrxd 6y ago
  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.
  - plutonorm 6y ago
    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.
- beepboopbeep 6y ago
  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
  - partyboat1586 6y ago
    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.
    - beepboopbeep 6y ago
      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.
pharke 6y ago
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.
deleted 6y ago
[deleted]
caycep 6y ago
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.
naasking 6y ago
> 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!

by skohan 6y ago

kortex 6y ago

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.

pharke 6y ago
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.
- vajrabum 6y ago
  Ketamine is being used to good effect these days in major depression. I wonder if they ramp up the doses like that when using it?
  - WalterSear 6y ago
    They don't. Fwiw, the psychedelic effect of ketamine is separate from its antidepressant effect.
    - pas 6y ago
      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?)
      - WalterSear 6y ago
        * 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.
  - 6y ago
flatline 6y ago
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.
- pasquinelli 6y ago
  "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.
mrxd 6y ago
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.
- plutonorm 6y ago
  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.
beepboopbeep 6y ago
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
- partyboat1586 6y ago
  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.
  - beepboopbeep 6y ago
    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.

pharke 6y ago

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.

deleted 6y ago

[deleted]

caycep 6y ago

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.

naasking 6y ago

> 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!