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Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)

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Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)

#21

Post by cess11 »

zelon88 wrote: post #14

As someone who's done most of the substances listed in the article; none of this matters. First of all, you can't take 16 people with the drug-taking profiles listed and reliably account for their drug and alcohol intake. 100% of their sample came into the lab as drug seeking individuals. Expecting them to only take drugs under your supervision is a fairy tale. Expecting them to tell the truth about their alcohol int…

"Thirdly; this particular drug is not just mind altering, it is life altering."

Why do you think that? In my experience most people that have used LSD changed little in their lives because of it. Looking back at the sixties, a lot of the people who dosed heavily then went on to work for the man or otherwise become very ordinary citizens.

Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)

#22

Post by nabla9 »

monkburger wrote: post #9

The most egregious limitation is the absurdly small sample size (n=16), which utterly cripples its statistical power. The authors throw around p-values without any serious correction for multiple comparisons.. Their confidence intervals (CIs) are embarrassingly wide in several places, making many of their so called significant findings borderline meaningless. For example, their pharmacokinetic (PK) values show ranges…

There was 96 experiments total. 16 participants, each going trough 6 sessions separated by at least 10 days.

Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)

#23

Post by lm28469 »

pessimizer wrote: post #16
cypherpunks01 wrote: post #5

> Sixteen healthy subjects > Six participants had previously used LSD > The sessions were conducted in a calm hospital room. > Standardized lunches and dinners were served at 1:30 p.m. and 6:00 p.m > The subjects were never alone during the first 16 h after drug administration > The study included a screening visit, six 25 h test sessions (each separated by at least 10 days) I understand the concept of informed conse…

This all sounds like warmed-over hippie-lore. I would have loved for my first time to take LSD to have been in a completely safe, clean environment filled with treats, doctors, and other people who were attending to me. The worst parts of the first experience for most people are fear of police, fear that one is having a medical problem, and fear that one is being a problem for the people they're with. This experience…

> doctors, and other people who were attending to me

I did my fair share and this sounds like absolute hell on earth. But then again my first trip was alone deep in the middle of the woods, still my best drug related experience so far, and that was more than a decade ago

Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)

#24

Post by corry »

foobiekr wrote: post #10
corry wrote: post #2

Thanks for sharing, although I'm curious what prompted this to be posted in 2025? I've heard from a few underground psychedelic facilitators that LSD is one of the best 'medicines' for therapy of various kinds, but (a) the duration is often uncomfortably long, (b) the social/political stigma hangover from the 60s adds undesirable connotations which can 'prime' the participant in negative ways, and (c) the variability…

You forgot (d) which is that the people involved are often terrible people. The issue of people on mind-altering substances being involved with "facilitators"/therapists who use that power for their own ends showed up even in the recent MAPS trial with alleged professionals. LSD and other psychedelics like mushrooms of mescaline are best used with someone who actually cares about you in a setting you control for self…

I hear you, and it's a good warning, but I think the word "often" in your first sentence requires some qualification or maybe nuance.

It's no different from any other potential for abuse from someone with power - the way to mitigate it isn't merely to try pick good people (of course, start there), it's to wrap the vulnerable elements in protective practices and institutional controls to prevent abuse if an individual actor fails to live up to the standard.

For example, in the biggest abuse scandal of our generation (sexual abuse by Catholic priests), it's not just that the priests did great individual evil but also that the institution itself utterly failed to do anything about it or even abetted it.

However, the illicit nature of psychedelics makes those kinds of controls or institutions impossible or very hard to put in place.

Finally, for the abuse in the MAPS MDMA trial (which was 1 patient out of 200 participants) to be used as evidence that psychedelic therapy is more prone to abuse, you'd have to look at the rate of abuse among therapists and psychologists as a whole to know if it's par for the course or something extraordinary.

Bad actors will try to take advantage of the vulnerable -- and these drugs put you in a more vulnerable position than otherwise -- so your warning still stands. I just don't think these issues are unique to this stuff other than the legal status.

Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)

#25

Post by [deleted] »

zelon88 wrote: post #14

As someone who's done most of the substances listed in the article; none of this matters. First of all, you can't take 16 people with the drug-taking profiles listed and reliably account for their drug and alcohol intake. 100% of their sample came into the lab as drug seeking individuals. Expecting them to only take drugs under your supervision is a fairy tale. Expecting them to tell the truth about their alcohol int…

[deleted]

Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)

#26

Post by foobiekr »

corry wrote: post #24
foobiekr wrote: post #10

Earlier quoted context omitted.

You forgot (d) which is that the people involved are often terrible people. The issue of people on mind-altering substances being involved with "facilitators"/therapists who use that power for their own ends showed up even in the recent MAPS trial with alleged professionals. LSD and other psychedelics like mushrooms of mescaline are best used with someone who actually cares about you in a setting you control for self…

I hear you, and it's a good warning, but I think the word "often" in your first sentence requires some qualification or maybe nuance. It's no different from any other potential for abuse from someone with power - the way to mitigate it isn't merely to try pick good people (of course, start there), it's to wrap the vulnerable elements in protective practices and institutional controls to prevent abuse if an individual…

I think you’re basically ignoring the history. I cited the MAPS example specifically because it was a highly observed study where the people involved were incredibly aware of what had gone wrong in the past with psychedelic-assisted therapy and even given that still couldn’t keep it out of a single trial.

The history of psychedelic use in therapy is part of how we got here in the first place. The therapists in the 50s and 60s were engaging in inappropriate behavior with their patients with regularity.

I am very pro psychedelics but the 60s provides an almost endless array of examples of how it can go wrong. Psychedelics basically do not belong in a therapist to patient context because the therapists attracted to that approach have a tendency self-select.

A lot of the modern day gurus and shamen have exactly the same problem.

Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)

#27

Post by monkburger »

indiantinker wrote: post #19
monkburger wrote: post #9

The most egregious limitation is the absurdly small sample size (n=16), which utterly cripples its statistical power. The authors throw around p-values without any serious correction for multiple comparisons.. Their confidence intervals (CIs) are embarrassingly wide in several places, making many of their so called significant findings borderline meaningless. For example, their pharmacokinetic (PK) values show ranges…

Agreed. I mean n=16 and its on nature.

The blinding? Functionally useless UNLESS the researchers genuinely believe subjects couldn't tell whether they were in a psychedelic fugue state or on a placebo. The ketanserin condition? A self-congratulatory exercise in proving that a known 5-HT2A antagonist blocks 5-HT2A-mediated effects. Stunning. rolls eyes

Then there’s the pharmacokinetics section, breathlessly confirming that LSD is absorbed, peaks, and is metabolized..just like every other small-molecule drug with hepatic clearance. The BDNF findings? A biochemical footnote with no functional correlation (tossed in for faux mechanistic depth)

Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)

#28

Post by corry »

foobiekr wrote: post #26
corry wrote: post #24

Earlier quoted context omitted.

I hear you, and it's a good warning, but I think the word "often" in your first sentence requires some qualification or maybe nuance. It's no different from any other potential for abuse from someone with power - the way to mitigate it isn't merely to try pick good people (of course, start there), it's to wrap the vulnerable elements in protective practices and institutional controls to prevent abuse if an individual…

I think you’re basically ignoring the history. I cited the MAPS example specifically because it was a highly observed study where the people involved were incredibly aware of what had gone wrong in the past with psychedelic-assisted therapy and even given that still couldn’t keep it out of a single trial. The history of psychedelic use in therapy is part of how we got here in the first place. The therapists in the 50…

Fair points! I guess I have more optimism for the modern incarnation, but history does indeed suggest otherwise.

Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)

#29

Post by zelon88 »

cess11 wrote: post #21
zelon88 wrote: post #14

As someone who's done most of the substances listed in the article; none of this matters. First of all, you can't take 16 people with the drug-taking profiles listed and reliably account for their drug and alcohol intake. 100% of their sample came into the lab as drug seeking individuals. Expecting them to only take drugs under your supervision is a fairy tale. Expecting them to tell the truth about their alcohol int…

"Thirdly; this particular drug is not just mind altering, it is life altering." Why do you think that? In my experience most people that have used LSD changed little in their lives because of it. Looking back at the sixties, a lot of the people who dosed heavily then went on to work for the man or otherwise become very ordinary citizens.

That's true, and those people probably went on to live happier, more full, more wholesome lives than if they had never taken LSD.

The first time I took LSD it unlocked a level of thinking that I was not capable of before. For example, other people's perspectives. I fell down such a deep rabbit hole of contemplating other people's feelings and perspectives that I could literally (in that moment) FEEL other people's feelings. Obviously that is the drugs talking, and it didn't really happen like that. But in the same way that I really did see the wood grain in my coffee table bubbling like a witches cauldron, I also really did have a deep, meaningful, impactful thinking session about other people's perspective.

So when you "come down" you kind of get to keep that fullness of appreciation. The need to now consider other people is there, and your brain is fully aware how important it is now. The experience of appreciating things deeply stays with you somehow.

Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)

#30

Post by zelon88 »

pessimizer wrote: post #20
zelon88 wrote: post #14

As someone who's done most of the substances listed in the article; none of this matters. First of all, you can't take 16 people with the drug-taking profiles listed and reliably account for their drug and alcohol intake. 100% of their sample came into the lab as drug seeking individuals. Expecting them to only take drugs under your supervision is a fairy tale. Expecting them to tell the truth about their alcohol int…

> this particular drug is not just mind altering, it is life altering. It unlocks things in your mind that permanently change your perception. I agree, but to 100x less of a degree than learning French, or becoming very good at chess. One thing we need to pay attention to is the degree to which this chemical, and this class of chemicals, have been romanticized by the culture. Especially because these drugs make you m…

The psychadelic effects of this particular drug is so overwhelmingly, convincingly powerful that it's hard for me to imagine anyone who actually took it describing it as "romanticized". Words cannot accurately describe how convincingly powerful the visual hallucinations are. None of the T-shirts or album covers do the actual experience justice.

To your point about expectations; Related story: One time me and my friends got some and we were supposed to wait for a friend to get out of work before we all took it together. We couldn't wait, and passed around the tin foil containing the stuff and we each took our hits. I was last, I bought 2 hits and there were 2 tabs on the foil. So I took both of them and threw the empty foil away. 20 minutes later someone comes to me looking for the foil, because it supposably still contained 2 tabs for my friend who was on his way. It turns out that I accidentally took the 2 hits that I bought AND the 2 hits that my friend bought (the 2 tabs in the foil represented 4 hits total). I still had his tab on my tongue, so I removed it and put it back in the foil. It was totally cooked. When my friend came over, we didn't tell him and he took the his empty tabs and insisted all night that he was tripping sack, sometimes embarrassingly so. Meanwhile I was rocked out of my gourd.

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