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GuB-42yesterday at 11:42 PM5 repliesview on HN

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,...


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whakimtoday at 4:19 AM

> 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.

bitexplodertoday at 2:13 AM

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.

Aurornistoday at 12:51 AM

> 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.

jareklupinskitoday at 12:43 AM

> 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

999900000999today at 2:05 AM

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.

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