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)
#2Thanks 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.
Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)
#3Very 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/
Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)
#4Skimmed this. Is it just me or does the data look a little too perfect?
Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)
#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 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.
Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)
#6Skimmed this. Is it just me or does the data look a little too perfect?
Can you elaborate on this? If you see something suspicious about this, maybe actually explain what you saw...
Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)
#7Skimmed this. Is it just me or does the data look a little too perfect?
Can you elaborate on this? If you see something suspicious about this, maybe actually explain what you saw...
Not op but: dose response curves shown in their figures are quite smooth, and ceiling effect at exactly 100ug for positive effects with anxiety &ego dissolution continuing to increase linearly above that, some might read that as narratively convenient? I think it's a byproduct of it being 8:8 subjects in a well controlled setting, it's Liechti lab after all, they know what they are doing.
Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)
#8Earlier quoted context omitted.
Can you elaborate on this? If you see something suspicious about this, maybe actually explain what you saw...
Not op but: dose response curves shown in their figures are quite smooth, and ceiling effect at exactly 100ug for positive effects with anxiety &ego dissolution continuing to increase linearly above that, some might read that as narratively convenient? I think it's a byproduct of it being 8:8 subjects in a well controlled setting, it's Liechti lab after all, they know what they are doing.
Am op, sorry haven't had my coffee yet. Yeah, agree with noem. These curves would be smooth for a 3000-subject phase 3 trial. For 16 people? The error bars are even weirdly tight. One general truism: all the normals are the same, but abnormals are increasingly different in different ways. That gets more true as people get older, they just accumulate more varied life experience. Just looking at the participants section,
> "eight men and eight women; mean age ± SD: 29 ± 6.4 years; range: 25–52 years"
> "The participants were asked to consume no more than 10 standard alcoholic drinks/week and have no more than one drink on the day before the test sessions."
> "Drug administration timing did not consider the menstrual cycle in females for practical reasons. Four women used a hormonal contraceptive and one was menopausal."
> "Six participants had previously used LSD (1–3 times), eight participants had used methylenedioxymethamphetamine (MDMA) (1–5 times), ten participants had previously used a stimulant, including methylphenidate (four participants, 1–2 times), amphetamine (six participants, 1–3 times), and cocaine (two participants, 1–2 times), and one participant had smoked opium (once)."
These are not your standard young, male athletes you'd typically desire for a tightly controlled result.
Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)
#9The 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.
Re: Dose-dependent effects of LSD in double-blind placebo-controlled study (2020)
#10Thanks 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-exploration and absolutely devoid of the kind of people who become psychedlic-assisted underground therapists.