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Full disclosure, I have severe clinical depression. Multiple comments here have asked for double blind placebo trials. But you can't really do that with someth

Full disclosure, I have severe clinical depression. Multiple comments here have asked for double blind placebo trials. But you can't really do that with something psycho active, at least not ethically. I can appreciate wanting high standards, but that doesn't mean banning everything that doesn't fit the neat mold we use in other cases. Also, suicide is the leading cause of death for multiple age/sex demographic groups in most of the western world. Literally number 1 killer. Current anti depressants are about the least effective medicines used in the Western world. So there is a good public health arguement to accept that we're in an emergency and try things without necessarily having 10 years of statistically significant results and followup and debate.

PragmaticPulp 6y ago
> Multiple comments here have asked for double blind placebo trials. But you can't really do that with something psycho active, at least not ethically. There are no ethical barriers to including a control group. The idea that double-blind, placebo-controlled trials are impossible with psychoactive medication is a strawman argument, because obviously we can still have a control group. The control group doesn't even need to receive placebo. In a study like this one, they could have easily and ethically had one group receive therapy and a second group receive therapy plus mushrooms. Or the first group could have received therapy plus traditional SSRIs. The placebo response rate in antidepressant studies is extraordinarily high. There is no good reason to omit a control group in studies like these, other than perhaps if the researchers were too underfunded to make it work.
- LatteLazy 6y ago
  The reason you cannot have a double blind study is that you can tell you've been given mushrooms. So, I expect, can the therapist and the researcher etc. The moment anyone knows it's no longer double blind. I'm happy to be corrected if there is some clever way around this. I have heard people suggest you give "control" group members so other psychoactive substance (MDMA was suggested). But that doesn't have the same effect as mushrooms. And also, it's ethically merky to give people other drugs they're not expecting/consenting to. Plus then you don't really have a control group, you have Mushrooms vs Other Drugs...
  - tasty_freeze 6y ago
    People have attempted controls in the past, and often it is a high dose of niacin. It causes flushing and increased HR. To someone who has experience with mushrooms they won't be fooled. To someone naive, they can think they got the real deal.
    - LatteLazy 6y ago
      I guess (I'm no expert) we would want a little of both: A blind, Niacin trial that is not placebo controlled AND a Placebo controlled but not blind trial? I wonder what Tim Ferriss has gotten up to recently on this...
    - esperent 6y ago
      But how can you tell if someone has been fooled or is just saying they've been fooled? When a drug has a very clear and obvious psychoactive effect, double blind simply doesn't work.
  - meetups323 6y ago
    Perhaps at low doses in total darkness?
    - raunakdag 6y ago
      Darkness won’t affect it. You’ll probably be able to tell either way. Microdosing probably wouldn’t make for an effective study, as it’s currently being touted as a way to increase “productivity”.
  - austinjp 6y ago
    Indeed. Other trial designs may also be appropriate such as crossover or waiting lists. Depends on the aims of the study. Double blind RCT simply isn't feasible or appropriate in every circumstance.
    - jdietrich 6y ago
      >waiting lists I'd be careful with that - waiting lists may have a nocebo effect, exaggerating the benefits of the treatment under test. https://onlinelibrary.wiley.com/doi/abs/10.1111/acps.12275 https://onlinelibrary.wiley.com/doi/abs/10.1111/acps.12275
- ultimape 6y ago
  They're not taking mushrooms, they're taking raw psilosybin sans any of the other active components in the mushrooms such as the bits that act as MAOIs. That seem to help reduce the chance of having a bad experience while tripping. This is why the therapist needs to be involved. If you start seeing demons or negative other hallucinations and can't calm yourself down it can be a traumatic experience.
bigphishy 6y ago
In the correct setting, psychedelics can critically alter one's view on the world and themselves. This is very powerful, but very unknown. We must tread on light ground when approaching these substances. So, more research must be done under the right trip settings, but not in haste.
- LatteLazy 6y ago
  I mean, there should be at least some haste here. 50k healthy people a year die from suicide in the US alone. And that's the official number, it supposedly missed a lot of people who "fall" off of bridges and crash cars alone at very high speed into stationary, well lit obstacles while sober and healthy... For comparison, AIDS kills about 13k. About 16k people died from (non suicide) handgun injuries. Even All Cancers caused 600k deaths. Curing depression would be the same as curing 1/12th of all cancers...
  - bigphishy 6y ago
    I agree, regardless of the numbers, there is a problem, but if SSRI's are not the problem, maybe getting people the help they need is the problem. Perhaps instead, many of those people hypothetically are chronic alcoholics, or maybe they are recovering opioid addicts who cannot deal with withdrawal and don't have the help they need ( Actually, psychedelics work wonders when trying to beat addictions ) . My point is, you can't associate a rising number of suicide cases and believe there's a definite cause and solution. It is not a black and white problem, and for that matter imho nether is "suicide and depression." Those two things are caused by so many infinite externalities in life, we cannot point to a solution with any sort of confident conviction. In essence I see that and hear this: "Oh look, that suicide statistic is caused by "XXX", and "YYY" is the solution. It's more like... "Oh look, that suicide statistic is caused by problems "X&$Y#", "DLKJER)(", "DOEKDHT&", "$%&DHTJ" ETC., and there are a ton of solutions for each problem. TLDR: we should legalize psychedelics for recreational use, not limited to medical purposes
Balgair 6y ago
Hey, just want to say, thanks for the comment. I hope you are getting the help you need. It's not easy these days, even for us 'normal' nerds, so thanks for being here.
- LatteLazy 6y ago
  Thanks, that means a lot. :)
stjohnswarts 6y ago
I don't see how it's unethical if you don't know if the drug even works or not. Sure if you were trying to figure out which of two wildly successful depression meds is more successful vs a placebo for a group of suicidal teenagers clearly there's some ethical violations, but if you don't even know if a medication is useful or not how is it unethical to do a double blind study?

PragmaticPulp 6y ago

> Multiple comments here have asked for double blind placebo trials. But you can't really do that with something psycho active, at least not ethically. There are no ethical barriers to including a control group. The idea that double-blind, placebo-controlled trials are impossible with psychoactive medication is a strawman argument, because obviously we can still have a control group. The control group doesn't even need to receive placebo. In a study like this one, they could have easily and ethically had one group receive therapy and a second group receive therapy plus mushrooms. Or the first group could have received therapy plus traditional SSRIs. The placebo response rate in antidepressant studies is extraordinarily high. There is no good reason to omit a control group in studies like these, other than perhaps if the researchers were too underfunded to make it work.

LatteLazy 6y ago
The reason you cannot have a double blind study is that you can tell you've been given mushrooms. So, I expect, can the therapist and the researcher etc. The moment anyone knows it's no longer double blind. I'm happy to be corrected if there is some clever way around this. I have heard people suggest you give "control" group members so other psychoactive substance (MDMA was suggested). But that doesn't have the same effect as mushrooms. And also, it's ethically merky to give people other drugs they're not expecting/consenting to. Plus then you don't really have a control group, you have Mushrooms vs Other Drugs...
- tasty_freeze 6y ago
  People have attempted controls in the past, and often it is a high dose of niacin. It causes flushing and increased HR. To someone who has experience with mushrooms they won't be fooled. To someone naive, they can think they got the real deal.
  - LatteLazy 6y ago
    I guess (I'm no expert) we would want a little of both: A blind, Niacin trial that is not placebo controlled AND a Placebo controlled but not blind trial? I wonder what Tim Ferriss has gotten up to recently on this...
  - esperent 6y ago
    But how can you tell if someone has been fooled or is just saying they've been fooled? When a drug has a very clear and obvious psychoactive effect, double blind simply doesn't work.
- meetups323 6y ago
  Perhaps at low doses in total darkness?
  - raunakdag 6y ago
    Darkness won’t affect it. You’ll probably be able to tell either way. Microdosing probably wouldn’t make for an effective study, as it’s currently being touted as a way to increase “productivity”.
- austinjp 6y ago
  Indeed. Other trial designs may also be appropriate such as crossover or waiting lists. Depends on the aims of the study. Double blind RCT simply isn't feasible or appropriate in every circumstance.
  - jdietrich 6y ago
    >waiting lists I'd be careful with that - waiting lists may have a nocebo effect, exaggerating the benefits of the treatment under test. https://onlinelibrary.wiley.com/doi/abs/10.1111/acps.12275 https://onlinelibrary.wiley.com/doi/abs/10.1111/acps.12275
ultimape 6y ago
They're not taking mushrooms, they're taking raw psilosybin sans any of the other active components in the mushrooms such as the bits that act as MAOIs. That seem to help reduce the chance of having a bad experience while tripping. This is why the therapist needs to be involved. If you start seeing demons or negative other hallucinations and can't calm yourself down it can be a traumatic experience.

bigphishy 6y ago

In the correct setting, psychedelics can critically alter one's view on the world and themselves. This is very powerful, but very unknown. We must tread on light ground when approaching these substances. So, more research must be done under the right trip settings, but not in haste.

LatteLazy 6y ago
I mean, there should be at least some haste here. 50k healthy people a year die from suicide in the US alone. And that's the official number, it supposedly missed a lot of people who "fall" off of bridges and crash cars alone at very high speed into stationary, well lit obstacles while sober and healthy... For comparison, AIDS kills about 13k. About 16k people died from (non suicide) handgun injuries. Even All Cancers caused 600k deaths. Curing depression would be the same as curing 1/12th of all cancers...
- bigphishy 6y ago
  I agree, regardless of the numbers, there is a problem, but if SSRI's are not the problem, maybe getting people the help they need is the problem. Perhaps instead, many of those people hypothetically are chronic alcoholics, or maybe they are recovering opioid addicts who cannot deal with withdrawal and don't have the help they need ( Actually, psychedelics work wonders when trying to beat addictions ) . My point is, you can't associate a rising number of suicide cases and believe there's a definite cause and solution. It is not a black and white problem, and for that matter imho nether is "suicide and depression." Those two things are caused by so many infinite externalities in life, we cannot point to a solution with any sort of confident conviction. In essence I see that and hear this: "Oh look, that suicide statistic is caused by "XXX", and "YYY" is the solution. It's more like... "Oh look, that suicide statistic is caused by problems "X&$Y#", "DLKJER)(", "DOEKDHT&", "$%&DHTJ" ETC., and there are a ton of solutions for each problem. TLDR: we should legalize psychedelics for recreational use, not limited to medical purposes

Balgair 6y ago

Hey, just want to say, thanks for the comment. I hope you are getting the help you need. It's not easy these days, even for us 'normal' nerds, so thanks for being here.

LatteLazy 6y ago
Thanks, that means a lot. :)

stjohnswarts 6y ago

I don't see how it's unethical if you don't know if the drug even works or not. Sure if you were trying to figure out which of two wildly successful depression meds is more successful vs a placebo for a group of suicidal teenagers clearly there's some ethical violations, but if you don't even know if a medication is useful or not how is it unethical to do a double blind study?