7 ms·

I see so many studies trying to somehow distill trippy drugs into an isolated, side-effect free, take a pill and get back to work treatment. Maybe there's somet

I see so many studies trying to somehow distill trippy drugs into an isolated, side-effect free, take a pill and get back to work treatment. Maybe there's something to be found there, would be huge, but my hope is that we don't waste all the will and funding down this path without more fully exploring the path where we admit that yes, the trip helps, and we'll just need to deal with the lack of blinding.

tokai 3y ago
Literally the last line of the article: "Future studies of novel antidepressants with acute psychoactive effects should make stronger efforts to mask treatment assignment to minimize the effects of subject-expectancy bias." Instead of pondering if their method is at fault for their negative result, the conclusion is to double down and working even harder at masking the effects.
- mtlmtlmtlmtl 3y ago
  Well, what they're trying to do is provide better blinding. Doing proper blind studies of ketamine is quite hard because its subjective effects are far too noticable. That line just says people should do better at this in future to get more accurate results. It's not a statement about the ultimate form the treatment should take.
  - tokai 3y ago
    yes ofc, but if the treatment is the trip it will never work blinding it like this. If anything they should be looking for drugs that give comparable trips, with no potential for depression treatment.
    - mtlmtlmtlmtl 3y ago
      I agree in principle, though having tried most of the various types of trippy substances, I've yet to encounter one that hasn't showed potential for a short term antidepressant effect. I guess I haven't tried those weird delta opioid ligands(salvia divonorum). I guess deliriants(like diphenhydramine) would have about zero antidepressant effect too, but that would have possible negative effects, even being liable to cause trauma. I believe benzodiazepines have also been tried as an active placebo but I don't remember what the results were.
      - oaktrout 3y ago
        Small correction, the active ingredient in Salvia is a kappa opioid agonist.
        mtlmtlmtlmtl 3y ago
        You're right, thanks for the correction! Really should check more of these things and not just do it from memory.
      - tpm 3y ago
        Diphenhydramine as a first generation antihistamine acts on a large number of receptors and can even be used as a mild anxiolytic, so I'd guess it could very well have antidepressant effect. No idea about deliriants like atropine/scopolamine, but in low doses, they were traditionally used to spice up beer (hence Pilsen named for Bilsenkraut, black henbane), so I could imagine short antidepressant effect there too.
        natechols 3y ago
        > Diphenhydramine as a first generation antihistamine acts on a large number of receptors and can even be used as a mild anxiolytic, so I'd guess it could very well have antidepressant effect. It does, and this observation led to the development of dedicated antidepressant drugs. There are several such cases where interesting side effects turned out to open a world of possibilities, including an anti-TB drug that also led to antidepressants, and of course Viagra.
        tpm 3y ago
        Yeah, I vaguely remembered something like that. The anti-TB drug is isoniazid/iproniazid which is also a MAO inhibitor.
    - Spivak 3y ago
      You basically can't do science like this and prove anything useful outside of group A is the more effective than group B. And that's assuming your test subjects can't tell the difference. That would tell you that at minimum either A or B has a non-zero effect because they both can't do nothing and be different. But proving that A is an improvement over not A is the important bit. A and B could both be worse than nothing but A is just less bad. "find something that has a similar trip but does nothing" is actually equivalent to the original problem.
  - naasking 3y ago
    > That line just says people should do better at this in future to get more accurate results But it's also doubling down on the assumption that the subjective effects aren't the source of the benefit.
SiempreViernes 3y ago
One of the objections against the improvement observed that is mentioned in tfa is precisely that you can get "trips" from general anaesthesia: 'Schenberg points out that people often report dreamlike and visual, auditory, and affective experiences under anesthesia. “Maybe people who had dreamlike experiences during the anesthesia had more improvement than the people who didn’t,” he says.' So maybe the trip does indeed help, but evidently it is not necessary to be able to remember if you had one to get the reported benefits.
PragmaticPulp 3y ago
The problem is real, though. Drugs with overt recreational effects very frequently distract the patient from the therapeutic effect in unproductive ways. The recreational effects generally disappear quickly as tolerance develops, which can give patients the false impression that the medication “stopped working”. A common example would be ADHD stimulants, where the early stimulating and mood-boosting effects disappear over time while the concentration-enhancing effects mostly remain. This leads a lot of patients to assume the medication isn’t working because it doesn’t feel like those first few doses, which can lead to discontinuation or abuse. Ketamine has a similar story arc. The antidepressant effect doesn’t require full blown dissociation, but so many headlines and fame-seeking authors have hyped it as “psychedelic medicine” that some patients assume it isn’t working until they disassociate/hallucinate. This can create a sort of nocebo effect where patients may actually be improving but they think they’re not because they didn’t have the wild hallucinations they read about in some exaggerated internet article.
- vasco 3y ago
  I took LSD twice in my life only and it changed my outlook ever since. It's been almost 10 years. I wasn't depressed and had other benefits from it, but I can see how that experience could've fixed depression, and know of people who say it did for them even though I'm not in any hippy-like community or whatever. I think a possible reason why medical research prefers a pill that works forever for continued use is that if you buy something cheap twice in your life and it fixes whatever needs fixing the pharma industry can't make money off of you the same way they can put you on antidepressants for life. I'm not in the medical field so I'm just speaking out of my ass based on personal anecdotes though.
  - ativzzz 3y ago
    Or because it's not really medicine and person specific? I've taken LSD several times in varying doses and it's never been anything more than "a really really fun time". Nothing profound, but damn fun times, the same effect as any fun memorable party Perhaps if you are looking for something profound or want a change of mindset, psychedelics might be able to help you reach it - similar to how shamans used psychedelics to talk to their gods or whatever - but if you're just looking to have fun that's what you'll get
deleted 3y ago
[deleted]

tokai 3y ago

Literally the last line of the article: "Future studies of novel antidepressants with acute psychoactive effects should make stronger efforts to mask treatment assignment to minimize the effects of subject-expectancy bias." Instead of pondering if their method is at fault for their negative result, the conclusion is to double down and working even harder at masking the effects.

mtlmtlmtlmtl 3y ago
Well, what they're trying to do is provide better blinding. Doing proper blind studies of ketamine is quite hard because its subjective effects are far too noticable. That line just says people should do better at this in future to get more accurate results. It's not a statement about the ultimate form the treatment should take.
- tokai 3y ago
  yes ofc, but if the treatment is the trip it will never work blinding it like this. If anything they should be looking for drugs that give comparable trips, with no potential for depression treatment.
  - mtlmtlmtlmtl 3y ago
    I agree in principle, though having tried most of the various types of trippy substances, I've yet to encounter one that hasn't showed potential for a short term antidepressant effect. I guess I haven't tried those weird delta opioid ligands(salvia divonorum). I guess deliriants(like diphenhydramine) would have about zero antidepressant effect too, but that would have possible negative effects, even being liable to cause trauma. I believe benzodiazepines have also been tried as an active placebo but I don't remember what the results were.
    - oaktrout 3y ago
      Small correction, the active ingredient in Salvia is a kappa opioid agonist.
      - mtlmtlmtlmtl 3y ago
        You're right, thanks for the correction! Really should check more of these things and not just do it from memory.
    - tpm 3y ago
      Diphenhydramine as a first generation antihistamine acts on a large number of receptors and can even be used as a mild anxiolytic, so I'd guess it could very well have antidepressant effect. No idea about deliriants like atropine/scopolamine, but in low doses, they were traditionally used to spice up beer (hence Pilsen named for Bilsenkraut, black henbane), so I could imagine short antidepressant effect there too.
      - natechols 3y ago
        > Diphenhydramine as a first generation antihistamine acts on a large number of receptors and can even be used as a mild anxiolytic, so I'd guess it could very well have antidepressant effect. It does, and this observation led to the development of dedicated antidepressant drugs. There are several such cases where interesting side effects turned out to open a world of possibilities, including an anti-TB drug that also led to antidepressants, and of course Viagra.
        tpm 3y ago
        Yeah, I vaguely remembered something like that. The anti-TB drug is isoniazid/iproniazid which is also a MAO inhibitor.
  - Spivak 3y ago
    You basically can't do science like this and prove anything useful outside of group A is the more effective than group B. And that's assuming your test subjects can't tell the difference. That would tell you that at minimum either A or B has a non-zero effect because they both can't do nothing and be different. But proving that A is an improvement over not A is the important bit. A and B could both be worse than nothing but A is just less bad. "find something that has a similar trip but does nothing" is actually equivalent to the original problem.
- naasking 3y ago
  > That line just says people should do better at this in future to get more accurate results But it's also doubling down on the assumption that the subjective effects aren't the source of the benefit.

SiempreViernes 3y ago

One of the objections against the improvement observed that is mentioned in tfa is precisely that you can get "trips" from general anaesthesia: 'Schenberg points out that people often report dreamlike and visual, auditory, and affective experiences under anesthesia. “Maybe people who had dreamlike experiences during the anesthesia had more improvement than the people who didn’t,” he says.' So maybe the trip does indeed help, but evidently it is not necessary to be able to remember if you had one to get the reported benefits.

PragmaticPulp 3y ago

The problem is real, though. Drugs with overt recreational effects very frequently distract the patient from the therapeutic effect in unproductive ways. The recreational effects generally disappear quickly as tolerance develops, which can give patients the false impression that the medication “stopped working”. A common example would be ADHD stimulants, where the early stimulating and mood-boosting effects disappear over time while the concentration-enhancing effects mostly remain. This leads a lot of patients to assume the medication isn’t working because it doesn’t feel like those first few doses, which can lead to discontinuation or abuse. Ketamine has a similar story arc. The antidepressant effect doesn’t require full blown dissociation, but so many headlines and fame-seeking authors have hyped it as “psychedelic medicine” that some patients assume it isn’t working until they disassociate/hallucinate. This can create a sort of nocebo effect where patients may actually be improving but they think they’re not because they didn’t have the wild hallucinations they read about in some exaggerated internet article.

vasco 3y ago
I took LSD twice in my life only and it changed my outlook ever since. It's been almost 10 years. I wasn't depressed and had other benefits from it, but I can see how that experience could've fixed depression, and know of people who say it did for them even though I'm not in any hippy-like community or whatever. I think a possible reason why medical research prefers a pill that works forever for continued use is that if you buy something cheap twice in your life and it fixes whatever needs fixing the pharma industry can't make money off of you the same way they can put you on antidepressants for life. I'm not in the medical field so I'm just speaking out of my ass based on personal anecdotes though.
- ativzzz 3y ago
  Or because it's not really medicine and person specific? I've taken LSD several times in varying doses and it's never been anything more than "a really really fun time". Nothing profound, but damn fun times, the same effect as any fun memorable party Perhaps if you are looking for something profound or want a change of mindset, psychedelics might be able to help you reach it - similar to how shamans used psychedelics to talk to their gods or whatever - but if you're just looking to have fun that's what you'll get

deleted 3y ago

[deleted]