11 ms·

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 ca

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.

varjag 6y ago
Why are you hoping for that? Is non-hallucinogenic anti-depressant a bad thing in some way?
- SuoDuanDao 6y ago
  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.
  - PragmaticPulp 6y ago
    > 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.
- new2628 6y ago
  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.
  - werber 6y ago
    Maybe I’m too self involved, but I’ve never noticed someone microdosing psychedelics til they have told me
  - PragmaticPulp 6y ago
    Selection bias. Plenty of people take SSRIs with positive experience. They're just not advertising it to the world. People who have bad experiences are much, much more likely to communicate this to other people.
    - new2628 6y ago
      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.
Etheryte 6y ago
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?
- themgt 6y ago
  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.
  - varjag 6y ago
    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.
    - themgt 6y ago
      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.
    - erispoe 6y ago
      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.
deathgrips 6y ago
If you take an anti-depressant pill everyday and it solves your problem, why is that bad? Are you hostile to medication in general?
- dTal 6y ago
  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.
  - deathgrips 6y ago
    >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?
    - kranner 6y ago
      > 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).
      - 6y ago
ketamine__ 6y ago
I take a prescribed ketamine lozenge every day. I don't experience any psychedelic effects and I'm fine with that.
- werber 6y ago
  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?
  - garbageket 6y ago
    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.
  - GordonS 6y ago
    Not the OP, but I'm prescribed ketamine for chronic nerve pain. Prescription is for 25mg orally 4-6 times a day, but I find 15mg as effective as 25mg, but with no side effects at all. At 25mg I do feel slightly dizzy for an hour or so. Ketamine has a small, but noticeable effect on the pain - but has had a huge effect on my ability to deal with the pain.
- PragmaticPulp 6y ago
  > 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.
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?
el_nahual 6y ago
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.
- lostlogin 6y ago
  > And this, of course, is what scares the government and the pharmaceutical industry. The opioid epidemic has shown that not all pharmaceutical companies feel constrained in this way.
  - el_nahual 6y ago
    This is an excellent point and seems to torpedo my entire argument.
luckydata 6y ago
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.

varjag 6y ago

Why are you hoping for that? Is non-hallucinogenic anti-depressant a bad thing in some way?

SuoDuanDao 6y ago
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.
- PragmaticPulp 6y ago
  > 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.
new2628 6y ago
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.
- werber 6y ago
  Maybe I’m too self involved, but I’ve never noticed someone microdosing psychedelics til they have told me
- PragmaticPulp 6y ago
  Selection bias. Plenty of people take SSRIs with positive experience. They're just not advertising it to the world. People who have bad experiences are much, much more likely to communicate this to other people.
  - new2628 6y ago
    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.

Etheryte 6y ago

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?

themgt 6y ago
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.
- varjag 6y ago
  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.
  - themgt 6y ago
    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.
  - erispoe 6y ago
    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.

deathgrips 6y ago

If you take an anti-depressant pill everyday and it solves your problem, why is that bad? Are you hostile to medication in general?

dTal 6y ago
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.
- deathgrips 6y ago
  >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?
  - kranner 6y ago
    > 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).
    - 6y ago

ketamine__ 6y ago

I take a prescribed ketamine lozenge every day. I don't experience any psychedelic effects and I'm fine with that.

werber 6y ago
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?
- garbageket 6y ago
  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.
- GordonS 6y ago
  Not the OP, but I'm prescribed ketamine for chronic nerve pain. Prescription is for 25mg orally 4-6 times a day, but I find 15mg as effective as 25mg, but with no side effects at all. At 25mg I do feel slightly dizzy for an hour or so. Ketamine has a small, but noticeable effect on the pain - but has had a huge effect on my ability to deal with the pain.
PragmaticPulp 6y ago
> 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.

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?

el_nahual 6y ago

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.

lostlogin 6y ago
> And this, of course, is what scares the government and the pharmaceutical industry. The opioid epidemic has shown that not all pharmaceutical companies feel constrained in this way.
- el_nahual 6y ago
  This is an excellent point and seems to torpedo my entire argument.

luckydata 6y ago

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.