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 so broad (eg: Tmax varying from 0.25–5.0h, CL/F spanning 1.6–22 L/h) that any attempt at a reliable dose-response relationship collapses under basic scrutiny; their p-values dance precariously around the threshold of significance. (There are many more)
If this is what’s guiding psychedelic research, we’re in serious trouble.
> 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 consent, but the study design sounds bad to me, to be honest. According to S1, seven of the subjects had never taken any psychedelic (LSD/psilocybin/MDMA). The study confined them for their first LSD experience, and likely multiple followups, in a hospital room, with a stranger who was not on LSD. And six sessions? LSD should not be used multiple times within 1 year, in my opinion, let alone 2 weeks apart, I think multiple rapid use unnecessarily increases the low-ish risk of psychosis. No matter how nice the room, this seems unethical to me for a few reasons. People shouldn't be experiencing their first psychedelics in a hospital room unless they can't physically leave a hospital bed. I just don't think the basic dose-response curve gains us much new science, this is exactly what most people would draw who have experimented with LSD doses between 25-200ug (though the BDNF effects are interesting as another commenter mentioned).
I guess this is a general problem for all psychedelic studies, though. There's no way to place all the necessary controls around the subject, without keeping them indoors and making them feel like a trapped mouse. The inability to change your own setting during a significant psychedelic trip can definitely induce or prolong major anxiety, much more for someone experiencing novel effects for the first time.
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 has precisely none of that.
It's good that they got data from first time users. It would be even better to get data from people who hadn't been set up with psychedelic culture expectations, but that jury pool is hopelessly tainted.
> I think multiple rapid use unnecessarily increases the low-ish risk of psychosis.
I don't think there's any good evidence that LSD affects the rate of psychosis, just the entirely expected outcome that people who have psychosis may be triggered to express that psychosis by LSD use, combined with the statistical fact that people try psychedelics at the same period of life as schizophrenics start showing their first symptoms (late teens to early 30s.)
>LSD should not be used multiple times within 1 year, in my opinion, let alone 2 weeks apart, I think multiple rapid use unnecessarily increases the low-ish risk of psychosis.
People regularly dose LSD dozens of times a year or even month without any issues.
> I think multiple rapid use unnecessarily increases the low-ish risk of psychosis.
Not that I disagree, but the 200ug dose is generally considered safe in a clinical setting, and most doses administered were smaller. Assuming individuals were screened for mental health risks before entering the study I don't think the risk was significantly elevated because of the dosing rate.
Very interesting to me that the BDNF effects were present with 5-HT2A blocked. Also interesting to see how much deeper they were at 200ug. Would be interesting to see a much longer temporal profile of the BDNF response. If this is also interesting to you, you might enjoy: https://pubmed.ncbi.nlm.nih.gov/29898390/
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 intake is also a fairy tale. I'm not trying to be incendiary, I am speaking from experience as a recovering alcoholic with 5 years sobriety.
Second of all, 10 day spacing between doses is insane, and dangerous. Having done this particular drug many times, I can tell you that it takes at least 2 days to feel "normal". And by that, I mean "as normal as you're ever going to feel." You see, LSD changes you... forever. Each time I took LSD I only ever "came down" 99.5%. That other 0.5% stays with you for years, if not forever. You never fully "come down" all the way. You're always just a little "less" than you were before.
Thirdly; this particular drug is not just mind altering, it is life altering. It unlocks things in your mind that permanently change your perception. I don't know anyone who's taken this drug who disagrees with this statement. This permanent altering of your consciousness is literally the thing you pay for and hope to receive.
Honestly science will probably never get LSD right. In order to do so the scientists would need to experience LSD first hand, several times before they could reasonably ever begin planning such an experiment. "You just don't know what you don't know."
"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.
I just disagree with the "little less" statement. Your experience of dependence maybe colors your language, I would use different but not less, as my psychedelics experiences have taught me so much about myself I don't feel diminished in any way after having them.
> 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 more suggestible, expectations picked up from social lore can dominate one's subjective experience, and the memory of it.
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 in street doses makes it unpredictable to work with if you don't have a way of measuring potency yourself (which I would argue disqualifies you from being a facilitator to begin with, but that's a separate topic...)
As for duration, this research indicates that lower doses are metabolized much faster (6.7 hours for 50ug vs 11+ hours for 200ug) which could help although the tradeoff is less 'good effect' even if 'bad effect' is minimized as well.
However, with respect to dose potency, a PSA for anyone new to this area -- go to the /r/LSD subreddit and read the pinned post on street dosages -- in short, street doses are on average ~100ug below what they claim.
So when this study says that 50ug produces such and such effects -- and the typical psychonaut on reddit might roll their eyes at such a 'light dose' -- keep in mind that an accurate "50ug" in a lab likely means "150ug" on the street which is a fairly typical dose sold. Of course the data shows an occasional over-dosed tab vs. the reported value, too.
Which leads to the most important PSA of all: please don't put any psychoactive substance into your body without having a lot of confidence in its actual composition and dose.
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-exploration and absolutely devoid of the kind of people who become psychedlic-assisted underground therapists.
> if you don't have a way of measuring potency yourself
>Why don't you display actual milligram quantitative amounts? #
> In short, we are not allowed to do so. In the United States, the handling of Schedule I substances (MDMA, LSD, Cannabis, etc) is restricted to those with a valid license. Forensic labs such as DDL and others require and obtain licensure in order to operate. An unpublished administrative rule stipulates that licensed labs are not allowed to provide quantitative data to the public, reportedly for fear of providing 'quality control' to dealers and suppliers of black market products.
In Europe, one can send samples to drug checking services and get information about potency, but here the US Government is basically admitting that it's artificially inflating the risk of overdose by denying consumers information they need to stay safe. They can point to these inflated harms as justification for continued persecution of individuals who use drugs.
monkburger|1 year ago
If this is what’s guiding psychedelic research, we’re in serious trouble.
nabla9|1 year ago
indiantinker|1 year ago
cypherpunks01|1 year ago
> 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 consent, but the study design sounds bad to me, to be honest. According to S1, seven of the subjects had never taken any psychedelic (LSD/psilocybin/MDMA). The study confined them for their first LSD experience, and likely multiple followups, in a hospital room, with a stranger who was not on LSD. And six sessions? LSD should not be used multiple times within 1 year, in my opinion, let alone 2 weeks apart, I think multiple rapid use unnecessarily increases the low-ish risk of psychosis. No matter how nice the room, this seems unethical to me for a few reasons. People shouldn't be experiencing their first psychedelics in a hospital room unless they can't physically leave a hospital bed. I just don't think the basic dose-response curve gains us much new science, this is exactly what most people would draw who have experimented with LSD doses between 25-200ug (though the BDNF effects are interesting as another commenter mentioned).
I guess this is a general problem for all psychedelic studies, though. There's no way to place all the necessary controls around the subject, without keeping them indoors and making them feel like a trapped mouse. The inability to change your own setting during a significant psychedelic trip can definitely induce or prolong major anxiety, much more for someone experiencing novel effects for the first time.
pessimizer|1 year ago
It's good that they got data from first time users. It would be even better to get data from people who hadn't been set up with psychedelic culture expectations, but that jury pool is hopelessly tainted.
> I think multiple rapid use unnecessarily increases the low-ish risk of psychosis.
I don't think there's any good evidence that LSD affects the rate of psychosis, just the entirely expected outcome that people who have psychosis may be triggered to express that psychosis by LSD use, combined with the statistical fact that people try psychedelics at the same period of life as schizophrenics start showing their first symptoms (late teens to early 30s.)
edm0nd|1 year ago
People regularly dose LSD dozens of times a year or even month without any issues.
6 times is no big deal imo.
hx8|1 year ago
Not that I disagree, but the 200ug dose is generally considered safe in a clinical setting, and most doses administered were smaller. Assuming individuals were screened for mental health risks before entering the study I don't think the risk was significantly elevated because of the dosing rate.
neom|1 year ago
unknown|1 year ago
[deleted]
zelon88|1 year ago
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 intake is also a fairy tale. I'm not trying to be incendiary, I am speaking from experience as a recovering alcoholic with 5 years sobriety.
Second of all, 10 day spacing between doses is insane, and dangerous. Having done this particular drug many times, I can tell you that it takes at least 2 days to feel "normal". And by that, I mean "as normal as you're ever going to feel." You see, LSD changes you... forever. Each time I took LSD I only ever "came down" 99.5%. That other 0.5% stays with you for years, if not forever. You never fully "come down" all the way. You're always just a little "less" than you were before.
Thirdly; this particular drug is not just mind altering, it is life altering. It unlocks things in your mind that permanently change your perception. I don't know anyone who's taken this drug who disagrees with this statement. This permanent altering of your consciousness is literally the thing you pay for and hope to receive.
Honestly science will probably never get LSD right. In order to do so the scientists would need to experience LSD first hand, several times before they could reasonably ever begin planning such an experiment. "You just don't know what you don't know."
cess11|1 year ago
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.
luckydata|1 year ago
pessimizer|1 year ago
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 more suggestible, expectations picked up from social lore can dominate one's subjective experience, and the memory of it.
unknown|1 year ago
[deleted]
corry|1 year ago
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 in street doses makes it unpredictable to work with if you don't have a way of measuring potency yourself (which I would argue disqualifies you from being a facilitator to begin with, but that's a separate topic...)
As for duration, this research indicates that lower doses are metabolized much faster (6.7 hours for 50ug vs 11+ hours for 200ug) which could help although the tradeoff is less 'good effect' even if 'bad effect' is minimized as well.
However, with respect to dose potency, a PSA for anyone new to this area -- go to the /r/LSD subreddit and read the pinned post on street dosages -- in short, street doses are on average ~100ug below what they claim.
So when this study says that 50ug produces such and such effects -- and the typical psychonaut on reddit might roll their eyes at such a 'light dose' -- keep in mind that an accurate "50ug" in a lab likely means "150ug" on the street which is a fairly typical dose sold. Of course the data shows an occasional over-dosed tab vs. the reported value, too.
Which leads to the most important PSA of all: please don't put any psychoactive substance into your body without having a lot of confidence in its actual composition and dose.
foobiekr|1 year ago
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-exploration and absolutely devoid of the kind of people who become psychedlic-assisted underground therapists.
krispyfi|1 year ago
>Why don't you display actual milligram quantitative amounts? #
> In short, we are not allowed to do so. In the United States, the handling of Schedule I substances (MDMA, LSD, Cannabis, etc) is restricted to those with a valid license. Forensic labs such as DDL and others require and obtain licensure in order to operate. An unpublished administrative rule stipulates that licensed labs are not allowed to provide quantitative data to the public, reportedly for fear of providing 'quality control' to dealers and suppliers of black market products.
https://www.drugsdata.org/about_data.php
In Europe, one can send samples to drug checking services and get information about potency, but here the US Government is basically admitting that it's artificially inflating the risk of overdose by denying consumers information they need to stay safe. They can point to these inflated harms as justification for continued persecution of individuals who use drugs.
killjoywashere|1 year ago
RIMR|1 year ago