6 ms·

The problem with psychoactive drugs, as I understand it, is not the lack of positive results. There are plenty of well recognized cases. The problem is the the

by GuB-42 5d ago

The problem with psychoactive drugs, as I understand it, is not the lack of positive results. There are plenty of well recognized cases. The problem is the the unpredictability, because there are plenty of catastrophic results too, and we don't really know why. We can't tell "in your case you should take this dose, the risks are quantified and acceptable, and this is what we should do if things go wrong". And it is not for the lack of trying. People tend to forget that LSD is a product of "big pharma" and they definitely tried to make a safe and effective treatment out of it, so that they could make money out of their patent. The "war on drugs" certainly didn't help, but research never really stopped, but we are struggling to turn these drugs into treatments that up to modern standards. And by the way, many controlled substances are used in mainstream medicine: heroin, fentanyl, amphetamines (incl. meth), cocaine, ketamine,...

jareklupinski 5d ago
> The problem is the the unpredictability, because there are plenty of catastrophic results too, and we don't really know why. i can think of a way to find out :) we'll have to take it in stages https://en.wikipedia.org/wiki/Clinical_trial https://en.wikipedia.org/wiki/Clinical_trial
Aurornis 5d ago
> The problem with psychoactive drugs, as I understand it, is not the lack of positive results. There are plenty of well recognized cases. There is a long way to go toward solid research on this topic. The studies that exist have small sample sizes and usually very limited monitoring periods after the dose, which makes them extremely prone to placebo effects. There’s no real blinding in a study with powerful psychedelics, so long-term comparisons against active comparators (therapy, other antidepressants) are needed. There is a lot of reporting that would make the studies seem like slam-dunk, case closed results, but every study I’ve read so far has felt very weak compared to traditional antidepressant studies. That’s expected for early stage research, but it’s going to take a lot more to quantify the treatment effects. > The problem is the the unpredictability, because there are plenty of catastrophic results too, and we don't really know why. The studies go to great lengths to have controlled circumstances like therapists monitoring and guiding the situation for hours, including integration sessions afterward in a lot of the studies. This helps control the situation for those studies, but it’s hard to translate that to real world practices. If the current proliferation of poorly-run ketamine clinics by cash grabbing providers is a clue, it would be really hard to ensure the level of trained therapist oversight that happens in these studies if this every becomes mainstream. There’s also the big problem of occasional majorly negative outcomes, as you noted. There are a lot of reports around the internet of even seasoned psychonauts who eventually had a trip that left them depressed or dissociated for months. For the longest time these anecdotes were dismissed as having triggered an underlying mental health disorder as a way to avoid blaming the drug. The advice was always that people with mental health problems shouldn’t take the drugs. Well now that we’re talking about using these as antidepressants (maybe) then it would be exclusively people with severe mental health conditions taking them. I don’t think it would take very many severely negative public cases to shut it down or at least severely restrict it.
999900000999 5d ago
The War on Drugs only serves to give law enforcement unlimited extra constitutional powers. Even the bizarre murder of Central American fishermen is justified by someone somewhere having a dime bag or something. Who needs trials , or evidence. Drugs are bad. Government good. Drugs bad.
- daseiner1 5d ago
  i don't dispute that the "War on Drugs" was (is?) pretty much just a glorified jobs program for law enforcement but nevertheless some drugs are very bad. ironically enough alcohol, despite being the most readily available drug after caffeine, is probably the worst drug of all in terms of societal destruction.
  - klrefg 5d ago
    > is probably the worst drug of all in terms of societal destruction. We are yet to observe a society where the overwhelming majority of the population regularly uses fentanyl, crack cocaine or meth-amphetamine. I bet that if we try comparing apples to oranges alcohol would end up being relatively harmless.
    - mitxela 5d ago
      Not fentanyl, but it used to be normal to get methamphetamine as a cough treatment from any pharmacy, and it worked out okay.
      - kakacik 4d ago
        Heroine and cocaine too, coke was full of... coke at the beginning
    - 999900000999 5d ago
      If Crack was legal today would you light up a pipe ? Maybe right after filing your taxes ? The most dangerous part of any illegal substance is the illegal economy existing to support it. Drug dealers generally can’t sue each other so they resolve disputes via other means. Law Enforcement has the right to suspend all your so called rights because someone you may or may not know might have an unauthorized substance. Set the legal drug age to whatever the enlistment age is. I’d argue 21 for both.
bitexploder 5d ago
We have pretty strong indications of when and why things go wrong. Openness vs rigid thinking are an axis that are very strong correlative factors. A lot more nuance but there is a lot we do know about risk factors so it isn’t a complete question mark.
- RangerScience 4d ago
  Anecdotally / personally experienced; bad trips happen “when you get stuck”. The #1 thing to do in such a situation is to change the music. The #2 thing to do is, quite literally, go to the bathroom and take a shit. It’s extremely analogous to anything that would make a normal day into a bad day.
  - bitexploder 4d ago
    That makes sense. I think I have approached becoming stuck. I reached a kind of extreme disassociated state once where I felt like I didn't exist and part of my brain started to panic. I meditate a lot. I reminded the part of me that was becoming anxious that we are okay because we are somehow still observing ourselves so we must still exist. That was apparently adequate to calm it lol. It is truly weird to negotiate with some part of your brain and see it work in real time. I think it was a particularly sticky day for my DMN and or some particular loop it was hanging on to? It is always hard to say.
whakim 5d ago
> The "war on drugs" certainly didn't help, but research never really stopped. This is false. The scheduling of psychedelics such as psilocybin and LSD was catastrophic for medical research in the United States (as well as in many other countries) from the early 1970s until the mid-2000's. Even today, research on psychedelics is challenging. > but we are struggling to turn these drugs into treatments that up to modern standards The elephant in the room is that psychedelics don't really fit into our existing framework around development of psychiatric drugs. For example, you can't really run a RCT, because it's completely obvious to the patient whether they've received the drug or a placebo. The concepts of set and settings, and the importance of "guides" in trials, prove challenging as they introduce highly subjective elements. I would frame this as more of a mismatch than a case of "modern standards being better" - the jury is still out on whether psychedelics will prove effective, and we're still trying to figure out how to "prove" that.
- heavenlyblue 4d ago
  That's really wrong though: it's really hard to not feel effects of fentanyl, opioids, ketamine either.
  - ttoinou 4d ago
    But we only use those as sedative. Or how ? Except ketamine therapies are being done right now with low doses where the effects are lighter than psychedelics
  - whakim 4d ago
    Sure; total blinding is an issue with many drugs (however active placebos which can make you feel dizzy/sedated/whatever can help); opiods/fentanyl/etc sometimes have to make do with imperfect blinding. The fact remains that the psychedelic state is so distinct from normal consciousness that the challenge is qualitatively different.
- vikramkr 4d ago
  There are plenty of other cases (e.g. ultra rare diseases) where we don't do RCTs for various practical reasons. So it's not really a problem of the existing framework - there's a ton of room for "we can't do an rct because like, duh they know they're tripping." But as other comments pointed out were really hampered by the lack of understanding of how and why these do or don't work - why some people get positive outcomes and why some get negative (preferably we'd like to know before prescribing broadly!) a ton of this basic research/mechanistic understanding etc has not been possible because of the war on drugs. If research had been possible we would be in a much better place of understanding how they could be regulated and used today - even with the more limited technology available a couple decades ago more openness around this could have at least enabled e.g. more and larger observational studies that could elucidate things today but we're stuck with a very fragmented and incomplete picture
grensley 5d ago
The way I think of them is as a mulligan in a trading card game like Magic. Sometimes you have a hand you can't keep, and it's better to draw a new hand with one fewer card. Don't want to do that too many times, or you will almost certainly have a losing hand.
zer00eyz 5d ago
> but we are struggling to turn these drugs into treatments that up to modern standards. We are struggling to pay for the research that would result in these being effective treatments (not subscription medicines) that would start out as generic drugs. > ketamine Great example, SPRAVATO, is a brand name patent protected version of this drug (enantiomer) that as a dose cost over 500 bucks.
- pstuart 5d ago
  Meanwhile my at home treatment used Braun 250mg lozenges, which probably cost ~ $4 a pop (wholesale) and for many 2-3 are enough for a treatment session. It's not like it's a novel drug -- the gatekeeping is ridiculous. Fuck the DEA.
- GuB-42 4d ago
  You just gave your own counter argument. If they find a promising way to use psychedelics for instance, they are not going with straight LSD, they will find some analogue that they show is 0.1% better and patent it. Just like that special ketamine. Or all these ADHD medicine that is just tweaked and patented amphetamine.

by GuB-42 5d ago

jareklupinski 5d ago

> The problem is the the unpredictability, because there are plenty of catastrophic results too, and we don't really know why. i can think of a way to find out :) we'll have to take it in stages https://en.wikipedia.org/wiki/Clinical_trial https://en.wikipedia.org/wiki/Clinical_trial

Aurornis 5d ago

> The problem with psychoactive drugs, as I understand it, is not the lack of positive results. There are plenty of well recognized cases. There is a long way to go toward solid research on this topic. The studies that exist have small sample sizes and usually very limited monitoring periods after the dose, which makes them extremely prone to placebo effects. There’s no real blinding in a study with powerful psychedelics, so long-term comparisons against active comparators (therapy, other antidepressants) are needed. There is a lot of reporting that would make the studies seem like slam-dunk, case closed results, but every study I’ve read so far has felt very weak compared to traditional antidepressant studies. That’s expected for early stage research, but it’s going to take a lot more to quantify the treatment effects. > The problem is the the unpredictability, because there are plenty of catastrophic results too, and we don't really know why. The studies go to great lengths to have controlled circumstances like therapists monitoring and guiding the situation for hours, including integration sessions afterward in a lot of the studies. This helps control the situation for those studies, but it’s hard to translate that to real world practices. If the current proliferation of poorly-run ketamine clinics by cash grabbing providers is a clue, it would be really hard to ensure the level of trained therapist oversight that happens in these studies if this every becomes mainstream. There’s also the big problem of occasional majorly negative outcomes, as you noted. There are a lot of reports around the internet of even seasoned psychonauts who eventually had a trip that left them depressed or dissociated for months. For the longest time these anecdotes were dismissed as having triggered an underlying mental health disorder as a way to avoid blaming the drug. The advice was always that people with mental health problems shouldn’t take the drugs. Well now that we’re talking about using these as antidepressants (maybe) then it would be exclusively people with severe mental health conditions taking them. I don’t think it would take very many severely negative public cases to shut it down or at least severely restrict it.

999900000999 5d ago

The War on Drugs only serves to give law enforcement unlimited extra constitutional powers. Even the bizarre murder of Central American fishermen is justified by someone somewhere having a dime bag or something. Who needs trials , or evidence. Drugs are bad. Government good. Drugs bad.

daseiner1 5d ago
i don't dispute that the "War on Drugs" was (is?) pretty much just a glorified jobs program for law enforcement but nevertheless some drugs are very bad. ironically enough alcohol, despite being the most readily available drug after caffeine, is probably the worst drug of all in terms of societal destruction.
- klrefg 5d ago
  > is probably the worst drug of all in terms of societal destruction. We are yet to observe a society where the overwhelming majority of the population regularly uses fentanyl, crack cocaine or meth-amphetamine. I bet that if we try comparing apples to oranges alcohol would end up being relatively harmless.
  - mitxela 5d ago
    Not fentanyl, but it used to be normal to get methamphetamine as a cough treatment from any pharmacy, and it worked out okay.
    - kakacik 4d ago
      Heroine and cocaine too, coke was full of... coke at the beginning
  - 999900000999 5d ago
    If Crack was legal today would you light up a pipe ? Maybe right after filing your taxes ? The most dangerous part of any illegal substance is the illegal economy existing to support it. Drug dealers generally can’t sue each other so they resolve disputes via other means. Law Enforcement has the right to suspend all your so called rights because someone you may or may not know might have an unauthorized substance. Set the legal drug age to whatever the enlistment age is. I’d argue 21 for both.

bitexploder 5d ago

We have pretty strong indications of when and why things go wrong. Openness vs rigid thinking are an axis that are very strong correlative factors. A lot more nuance but there is a lot we do know about risk factors so it isn’t a complete question mark.

RangerScience 4d ago
Anecdotally / personally experienced; bad trips happen “when you get stuck”. The #1 thing to do in such a situation is to change the music. The #2 thing to do is, quite literally, go to the bathroom and take a shit. It’s extremely analogous to anything that would make a normal day into a bad day.
- bitexploder 4d ago
  That makes sense. I think I have approached becoming stuck. I reached a kind of extreme disassociated state once where I felt like I didn't exist and part of my brain started to panic. I meditate a lot. I reminded the part of me that was becoming anxious that we are okay because we are somehow still observing ourselves so we must still exist. That was apparently adequate to calm it lol. It is truly weird to negotiate with some part of your brain and see it work in real time. I think it was a particularly sticky day for my DMN and or some particular loop it was hanging on to? It is always hard to say.

whakim 5d ago

> The "war on drugs" certainly didn't help, but research never really stopped. This is false. The scheduling of psychedelics such as psilocybin and LSD was catastrophic for medical research in the United States (as well as in many other countries) from the early 1970s until the mid-2000's. Even today, research on psychedelics is challenging. > but we are struggling to turn these drugs into treatments that up to modern standards The elephant in the room is that psychedelics don't really fit into our existing framework around development of psychiatric drugs. For example, you can't really run a RCT, because it's completely obvious to the patient whether they've received the drug or a placebo. The concepts of set and settings, and the importance of "guides" in trials, prove challenging as they introduce highly subjective elements. I would frame this as more of a mismatch than a case of "modern standards being better" - the jury is still out on whether psychedelics will prove effective, and we're still trying to figure out how to "prove" that.

heavenlyblue 4d ago
That's really wrong though: it's really hard to not feel effects of fentanyl, opioids, ketamine either.
- ttoinou 4d ago
  But we only use those as sedative. Or how ? Except ketamine therapies are being done right now with low doses where the effects are lighter than psychedelics
- whakim 4d ago
  Sure; total blinding is an issue with many drugs (however active placebos which can make you feel dizzy/sedated/whatever can help); opiods/fentanyl/etc sometimes have to make do with imperfect blinding. The fact remains that the psychedelic state is so distinct from normal consciousness that the challenge is qualitatively different.
vikramkr 4d ago
There are plenty of other cases (e.g. ultra rare diseases) where we don't do RCTs for various practical reasons. So it's not really a problem of the existing framework - there's a ton of room for "we can't do an rct because like, duh they know they're tripping." But as other comments pointed out were really hampered by the lack of understanding of how and why these do or don't work - why some people get positive outcomes and why some get negative (preferably we'd like to know before prescribing broadly!) a ton of this basic research/mechanistic understanding etc has not been possible because of the war on drugs. If research had been possible we would be in a much better place of understanding how they could be regulated and used today - even with the more limited technology available a couple decades ago more openness around this could have at least enabled e.g. more and larger observational studies that could elucidate things today but we're stuck with a very fragmented and incomplete picture

grensley 5d ago

The way I think of them is as a mulligan in a trading card game like Magic. Sometimes you have a hand you can't keep, and it's better to draw a new hand with one fewer card. Don't want to do that too many times, or you will almost certainly have a losing hand.

zer00eyz 5d ago

> but we are struggling to turn these drugs into treatments that up to modern standards. We are struggling to pay for the research that would result in these being effective treatments (not subscription medicines) that would start out as generic drugs. > ketamine Great example, SPRAVATO, is a brand name patent protected version of this drug (enantiomer) that as a dose cost over 500 bucks.

pstuart 5d ago
Meanwhile my at home treatment used Braun 250mg lozenges, which probably cost ~ $4 a pop (wholesale) and for many 2-3 are enough for a treatment session. It's not like it's a novel drug -- the gatekeeping is ridiculous. Fuck the DEA.
GuB-42 4d ago
You just gave your own counter argument. If they find a promising way to use psychedelics for instance, they are not going with straight LSD, they will find some analogue that they show is 0.1% better and patent it. Just like that special ketamine. Or all these ADHD medicine that is just tweaked and patented amphetamine.