Dose-response relationships of LSD-induced subjective experiences in humans | Hacker News Reader

Dose-response relationships of LSD-induced subjective experiences in humans

nature.com

83 pointsorhmeh0930 comments

Love seeing more research done on LSD. Hopefully the more we can prove its positive effects will lead to broader acceptance and safer use by all who are interested. I feel that most "bad experiences" can be avoided by education and ensuring the proper "set and setting", and the more we know about the substance's effects the better.

Yeah. People who have bad trips are often in bad places at bad times to take such a powerful substance. Or, they have a lot of pent-up fear or anxiety that the LSD simply unmasks and smacks them with.

I've had a bad trip exactly once, and it was when I had no control over my surroundings and was in an inopportune spot at the wrong time. The times when I was in a controlled environment of my own design with zero distractions, extremely low probability of bad things happening, etc... it was great.

Do it in your own home, when you have a full day of time and zero obligations to anyone including yourself, and you're around as few people as possible.

Agree with everything you're saying here, I'll add what might be obvious: it's generally best if the first doses aren't too large.

I first took LSD back in 2014 I believe, after researching everything surrounding the topic for a year. My wife was completely on board and we allocated a three day weekend.

All of the research indicated that it was completely safe from a physical perspective and for a stable and fairly well adjusted person like me, with a very informed and willing helper, fairly psychologically safe.

Me being me, I decided to go big on the first dose. I took well over 600μg.

I won't say this was a mistake for me, but it was a rather rigorous experience that lasted most of three days.

All of the trip was interesting. Most of it was a range between neutral and amazing, but there were definitely some bad trip elements.

About once a year since then I've taken a much smaller dose. At the moment I don't have a desire to repeat the huge experience, but I won't rule it out for the future.

Very briefly: during the worst of the bad trip parts I lost the ability to understand and produce language, which was scary for both my wife and I, though we understood that the impact would be temporary. This happened about 8-12 hours after the trip started.

None of my subsequent trips (all between 50μg and 200μg) had any big bad effects.

And yes, the whole experience was a big win. While I as doing pretty well beforehand, there were some areas of tunnel vision that greatly improved.

How on earth do you do research for a year and end up taking 600ug for your first time?

This is an understandable reaction and question.

Fundamentally LSD is physically safe at most any reasonable dose. What remains is psychological safety, which is quite important. I've always been a well grounded person, and with the serious measures we took to prepare, I felt like it was most likely safe for me. And it was, nothing bad came out of the experience, even though there were some scary parts.

To be clear, the intensity of the trip wasn't a surprise. My wife and I knew that we were getting into a 'serious situation'.

When I said 'me being me' above, it's a personality trait: when something I'm interested in, that is potentially useful, and that is very safe comes up, I tend to go all in.

In general I strongly recommend people start very low and work up from there.

I mostly feel bad for your wife looking after you for three days!

(I'm sure she signed up for that, it's just a long time to be responsible for another person who may do erratic things. And I say that as the parent of two small kids.)

Hah thanks. It was actually not too bad. The only really challenging part was the few hours of aphasia which came up in the middle of the night.

Overall it was a nice 'shared adversity' kind of experience.

For context on what an appropriate dose is, this article seems to suggest that the intensity of most effects start to flatten out as you go past 100ug. The effects that continue to get more pronounced past that level seem to be negative effects such as anxiety or potentially difficult to navigate such as disembodiment.

Seems like 100ug is likely a sweet spot for most first timers.

i do not know if i would actually agree with this as general advice, even for first timers (assuming healthy and safe settings) -- Strassman [0], paraphrasing as it has been a while, mentions in his findings the difference between psychotic and psychedelic thresholds. psychotic thresholds ~<= 300 mcgs tend to be more stimulant-like with an increased heart rate, and it is my opinion he contends this can be more anxiety inducing than a psychedelic dose, which depresses breathing and eases the heart rate/is less stimulating.

my anec-data is most people taking small doses, while enjoyable, seem to experience more anxiety overall than those who have taken a little more of a plunge (myself included in this) -- increased heart rate can really send people through some weird feedback loops, especially on peak.

perhaps mileage varies.

[0]: Dr. Rick Strassman, DMT: The Spirit Molecule -> this is mostly a clinical study on the effects of DMT but Strassman does have general observational commentary on psychedelics such as LSD.

I agree that 100 is a good starting point, or even less.

Dosage is very important, and also be extra cautious if you have a history of acute mental illness in your family.

Only once you’ve lost your marbles do you realize how important they actually are and that traumatic event will likely leave a chasm in your mind for a long time

Counter hypothesis. "Bad trips" work just like "the giggles". Its not anyone's fault nor something you did wrong, nor something you can hope to control. it just one of k prominent means that our brains tend to become.

I have no stake either way. No gigles, no bad trips.

Also isn’t most of what’s sold as lsd these days anything but? Nbomd, various 2cs, that sort of thing.

There were a couple of years in the early "research chemicals" scene when this was true in some areas but LSD itself is now in ample supply in most places.

Not really. I know this is anecdata, but : I always test my stuff, and I've never gotten anything but LSD.

NBOMe was super popular in the early 2010s. I'd be willing to bet that on my college campus 90+% of "LSD" was some sort of NBOMe during that time.

No idea what's going on nowadays but plenty of gray market LSD analogous will test positive as LSD (Al-LAD, Pro-LAD, Eth-LAD, 1P-LSD, idk what else is available now). I wouldn't be shocked if people get those without realizing.

I really loved how this paper shared the r-syntax of the analysis, along with the consolidated data they used. The interactive webpage summarizing their results is fantastic. Loading the full charts of individual questionnaires took a little bit of time, but the way in which the results are displayed is exceptional. It was slower on mobile, but it was still useful.

https://dose-response-lsd.asdb.info/

Chuckled @ the radar chart diligently quantifying "ineffability"

Thought that was great too - check out the questionnaire https://www.trippingly.net/lsd-studies/2018/5/22/the-mystica...

Those radar charts looked like spiderwebs to me. Trippy.

It does not plateau at 100mcg...

> Overall, full mystical-type experiences seem unlikely to be induced with doses below 200 µg

I thought that was the point. Did I read this article right, and there are essentially no modern studies of LSD use in the 200-500µg range?

Oh there's modern studies alright.

I thought there was already data on this, this paper doesn't seem to be adding anything we didn't know before to the science. Can someone explain if that's actually the case or not?

It's a so-called meta-analysis, looking at a bunch of other studies and trying to create a baseline of known knowledge which will inform future individual focused studies.

> "The established dose-response relationships may be used as general references for future experimental and clinical research on LSD to compare observed with expected subjective effects and to elucidate phenomenological differences between psychedelics."

Having this kind of body of curated knowledge means, for example, that a funding agency might be more willing to sponsor further specific research, i.e. you could say 'here's our plan for giving subjects doses of x amounts to study the threshold where visual perception becomes strongly altered, based on this prior work' and so on.

As photochemsyn previously mentioned, a meta-analysis looks at previous research in order to see if there are any interesting conclusions to draw the combined data. As an example, the analysis found that no appropriate studies have been done on doses between 20 - 50 μg, or over 200 μg.

Their notes on how set and setting, and whether or not the participants had ever used psychedelics before affects the experience can also be interesting for a scientist working with LSD. The study also observes that "No direct experimental comparison of the bioequivalence of the two formulations has been made to date", meaning that we simply do not know if LSD base is stronger or weaker than LSD tartrate, or how the ingestion method affects the experience.

This information in tandem with the graphs can be used as inspiration for what kind of experiment to do next in order to better understand how LSD interacts with the brain.

A meta-analysis is a good tool for taking a step back and trying to see if there are any blind spots in the research field.

Sometimes scientists cover the same stuff as other scientists in the interest of checking reproducibility or finding new data. Sometimes new stuff is discovered, sometimes not.

This adds to the body of evidence around the subject, especially if it reproduces, fails to reproduce, or builds on previous findings -- an important part of science.

What's wrong with more data?

I confirm!

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