Acute Effects of LSD on Amygdala Activity During Processing of Fearful Stimuli | Hacker News Reader

Acute Effects of LSD on Amygdala Activity During Processing of Fearful Stimuli

nature.com

84 pointsdpflan53 comments

So if I am reading this right, LSD reduced fearful reactions. I initially mis-read it as a correlation between LSD and fear.

Part of the reason psychedelics is kept away from treatment is because of those occasional bad reactions. You never know who might get a bad trip and for what reason. I wish psychedelics were researched without the baggage of "possible treatment". This would allow for the study for it's own sake, imho.

If anyone is interested in reading some first time experiences of random first time users here is a link. [0]

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[0] https://erowid.org/experiences/subs/exp_LSD_First_Times.shtm...

Definitely agree with you about the possibility of an unexpected reaction: I had to experience my friend losing touch with reality, taking off his clothes, running around my dormitory almost naked, and finally pulling the fire alarm. He was last seen that day being handcuffed and put into an ambulance. In case you're wondering, he took about 200 ug of real LSD.

Had an almost identical experience with a somewhat seasoned tripper. More blood though.

I've never really understood these stories of people completely dissociating and doing crazy things. At high doses I can barely walk.

I've started avoiding any thread on Reddit where LSD comes up.

People talk about taking a milligram of it and walking around the city enjoying fractals while their friend repeats the phrase "I see Candyland" for 12 hours straight, and their other friend thought he was a chicken and started flapping his arms, "bok bok bok!" And everyone in the comments laughs and says "yeah, isn't acid crazy?"

With defenses like "drugs affect everyone differently!" or "acid is known to cause insanity, albeit rarely!" invoked whenever you roll your eyes.

Too cringeworthy for me. Starting to see it on HN now as well.

... I joined HN because Reddit was starting to piss me off ;) . But I really stand by what I said, it was real LSD, and his experience was a minority and extreme case. I'm just trying to say LSD does not affect everybody the same way.

I don't understand how this is possible. I find it almost legitimately impossible to ever act in this way.

This feels more like they got some bad stuff.

That sentiment is tempting, but unfortunately the "good stuff" does actually occasionally cause insane reactions in some people, even in people who have had perfectly nominal trips on exactly the same batch of substance.

Hmm. This suggest that 200ug is a relatively strong dose[1] (the dose used in this study is 100ug). It's worth noting that a lot of things - alcohol, marijuana, even Robitussin (DXM) - can have very unpleasant side effects when the dose is too large. Drugs like caffeine and alcohol also have a much greater toxicity than LSD, for what it's worth.

[1] https://www.reddit.com/r/LSD/comments/2hg6io/different_dosag...

200ug are a pretty high dose[1], 10 to 20 times the threshold and your friend's reaction is not really typical even for a bad trip: In most cases people just want to reduce the amount of auditory or visual input they have to process when it is too much - so nothing like starting a fire alarm. Are you sure it was LSD?

[1] https://erowid.org/chemicals/lsd/lsd_dose.shtml

200ug is not high...?

Starting a fire alarm etc. just means the guy was using the reduced inhibition to go ballastic. Just stupid really. Don't go blame the stuff for that.

>400 is high. up to 150/200 is low - can function normally. between 200/400 is hard to function normally. above 400 you really kinda can't, best just lie down and let the colors wash over.

High for what barrier?

200µg is certainly enough to perceive the world radically differently—so, very high to a sober person. However, it's very low on the scale of LSD you can safely ingest.

Either way, the dude had more going on than an acid trip that day.

I share your skepticism. Part of the problem with the War on Drugs is that forcing science underground basically puts us in a medieval situation, where we have to rely on word of mouth and personal experiences.

It doesn't sound like LSD to me either, but all I can say for sure is that I took a whole bunch of stuff which people told me was LSD, back in the day, and that it affected me differently.

edit: skepticism significantly increased, now that people are talking about LSD causing reduced inhibitions. seen and experienced extraordinary counterexamples. it's not alcohol, folks.

It was bought off of the dark web with a seller with a very high rating, and was taken by multiple other friends who had a true LSD experience. He was the only one who had a "crazy" reaction. I'm hundred percent sure it was LSD. Talking to him after the event, I remember him saying that he believed he could do anything. Mind you, watching him felt like seeing a toddler in a grown mans body. I'm not sure if LSD necessarily lowers inhibition, but it did seem to confirm that different brain chemistries exist.

That doesn't sound at all strange to me, the drug makes you lose touch with reality (sort of by definition) and taking of your clothes is a common LSD trope, pulling the fire alarm is unfortunate but not so serious. Describing this like it's some sad event and a huge deal is weird to me, I hope the guy didn't have to suffer too much prejudice afterwards.

'Possible treatment' is almost a requirement to publish to these journals. Its usually some fluff added for that effect. Besides, one can easily make a connection to disease, however remote

> "So if I am reading this right, LSD reduced fearful reactions. I initially mis-read it as a correlation between LSD and fear."

Not really, the results were a bit more subtle and technical than that. They just found that there was a (fairly small) negative correlation on left amygdalar BOLD signal in the active group. They did not measure subjective fear, nor did they make any explicit claims about it. Just because blood oxygen levels changed does not mean the participants necessarily experienced less fear or anything different from the placebo group (in terms of fear at least).

The authors also mention toward the end of the paper that this was a fairly small dose, and that larger doses would likely induce more anxiety than placebo:

"Third, we can only provide data about one moderate dose. Higher doses of psychedelics are possibly difficult to use with fMRI, because they are more likely to induce anxiety,45 although the overall effects are still described as positive in the higher doses investigated.2, 45 The observed anxiolytic effect probably also depends on personal and environmental factors and might thus be different in the mentally ill or in uncontrolled settings."

Yeah, psychedelics in general seem to be a useful tool for understanding consciousness, whether or not they're clinically useful.

Erowid are currently asking for donations to keep running:

https://erowid.org/donations/donations.php

Anyway who has used them over the years and hope they are around for future generations, consider giving as they are more important than ever with the explosion in RCs and analogues where a slight mishap in dosage can result in death

Erowid stopped my experimental teenage years from becoming disastrous/addiction/overdose years and I know it's done the same for thousands if not millions.

This is a little disappointing considering that their conclusions can be summarized with the sentence "These data suggest that acute administration of LSD modulates the engagement of brain regions that mediate emotional processing". Not particularly surprising to anyone who has ever tried or read anything about LSD

A lot of the psychedelics literature is similarly unexciting unfortunately, but the reason is this "obvious" groundwork hasn't been done yet in a scientific context. So give it time and support and hopefully researchers' will have the opportunity to get to the more interesting bits!

Research 101 is about measuring and documenting results, even if they agree with popular knowledge.

It is what separate anecdote from data.

I'd love to know how the trial could remain double blinded after administration of the LSD or placebo...

The team looking at the fMRI might not be aware of which scans came from LSD Vs placebo.

That's only single-blind (experimenters are blinded to test vs control, but subjects are not). It's impossible to keep subjects unaware of whether or not they were given acid, for obvious reasons.

The paper includes a caveat at the end: "Our study has several limitations. First, although the trial was formally double-blinded, assignment to placebo or LSD was unavoidably unblinded by the obvious psychedelic effects caused by the dose used."

Yea, I'd love to see the placebo group. "Nope... still in this universe..."

In some studies they use other drugs that illicit similar but different feelings, e.g ecstasy

"similar but different feelings" - it can only be one or the other...

They are similar but different. They both are a departure from being sober. I think in one study about ecstasy they used an amphetamine as the placebo, because both get you wired but in different ways.

They are nowhere near similar in any capacity. It's like claiming that smoking and drinking produce similar effects

FYI, the correct spelling is "elicit". "Illicit" means forbidden or illegal, ironically in this context.

Haha whoops. Thank you for that!

You do raise an interesting point: would there be any value in emulating (some of) the subjective effects of a psychedelic to 'increase' blinding. Perhaps have all study participants wear VR headsets piping in video from their surroundings, then randomly assign a 'trippy' filter across groups so that some of the placebo group might (mistakenly) think that they were tripping?

It's been done before. The marsh chapel experiment had an active control -- participants who didn't get psylocibin got niacin instead, which causes some short-term physiological changes.

It isn't perfect, but it's probably as close as you could get.

https://en.wikipedia.org/wiki/Marsh_Chapel_Experiment

Not quite the same, but my dad did an alcohol study once where the blinding was achieved by giving the test group a strong vodka-and-orange, and the control group a glass of orange juice into which had been poured a small amount of vodka over the back of a spoon, so that it floated on top. Both drinks therefore smelled strongly of alcohol.

It's trickier with substances where the dose is undetectably tiny, but it seems there's certainly value in making people feel "trippy" so that they think they've had the active substance.

Yeah it's pointless to even use that methodology when the psychoactivity of LSD is already well documented, and the effects are self-evident to the user. It might be appropriate in a microdosing trial or something but not in one where an active dose is being administered.

Interesting. I would have come to the oppisite conclusion, namely that lsd would increase the response to fearful stimuli. It makes sense. My friends who have had bad trips weren't triggered by fearful, external stimuli. They were caused mostly by repressed emotions or thoughts that lsd or mushrooms brought to the fore.

From my experience and observations, bad trips can be powerful experiences that have a positive effect, forcing you to face that which you have hidden away. Of course, it can be damaging as well.

This may be interesting to those in this thread: https://www.reddit.com/r/Drugs/comments/63p20e/why_billionai... (Why billionaires should be intrigued by psychedelic research)

A commenter here said, [this only measured a small chemical effect and did not make any claims about real fear]

Let me add some color for you, it's absolutely real. I predict the drug will eventually be validated as one of the most powerful and useful therapeutic substances discovered to date.

>>impaired recognition of fearful faces, while it did not significantly affect recognition of neutral, happy and angry faces

This characterization is a bit misleading. Recognition of faces is not impaired at all, recognition is also not impaired of some of your most terrifying inner thoughts. Instead, you recognize them fine and are simply not bothered because you perceive them in an unbiased, rational context.

>>exhibits some ‘empathogenic’ effects (such as increased openness and trust)

Some? I know, good medical science has to be conservative. However empathy, emotional connection and understanding, can become almost savant like. I won't give an example - too hard to offer an anecdote and not sound hyperbolic or like an exaggerated account. How's this: I believe it to be significantly understated.

>>positive long-term effects outlast acute pharmacological effects

Let that sink in. Who would believe taking an anti-depressant once could change your life years later? They would not believe it, because like every other mental health drug, anti-depressants can easily stop working (to the degree they work at all) as soon as you stop taking them. This is not like that. It's some kind of unusual mechanism that for reasons not yet entirely clear, is just very different from other drugs.

I would ask that no one act on my opinion by using illegal drugs. I'm not worried about liability, or even legality. The problem is simply that self-administering street drugs comes with quite a bit of risk that for some reason, a lot of people don't mind ignoring. Worst case you could be intentionally poisoned as part of a scam and die. You could get the wrong substance, for example fentanyl is unknowingly taken all the time, and again easily die. You might somehow get the real thing, but precise dosing is difficult enough that overdosing LSD is very common. Having the wrong dose will not kill you, but the results can be bad enough many people feel like death would have been an easier option. Some people believe that impurities and imprecise dosing are responsible for a lot of what people describe as "bad trips".

I don't have a dog in this hunt, I will simply point out that people who have used LSD have been claiming that it's pretty much magic, that everyone should try it, etc... for decades. The very guarded initial ventures into real research seem to be entirely secondary to the evangelical zeal of some people who have taken the drug in question, and feel it's "essential".

Edit: I should point out that obviously, they could have reached this conclusion because it is that amazing, but a lot of people have ironclad convictions about everything from drugs to religion after all. The research should hopefully offer an answer that can be, frankly, believed.

The research is secondary because it is something they read about long ago compared to an actual experience they had that may have impacted their life. Most of it's proponents are in favor of more research, but with that being almost impossible still felt the available information was impressive enough.

The research is only secondary for people that don't want to turn on critical thinking or set aside biases.

I would say this is not relevant, because it true for all debates.

Just like climate science, some are open minded, some people could not be dissuaded with any amount of evidence.

When there is an absence of new evidence for such a long period of time, the research can become secondary out of laziness and forgetfulness rather than a refusal to think critically.

You suggest folly as a possible explanation, but there are a few problems with the cogency of that.

1) You point to nothing in this paper, other research, my comment, or contemporary comments of others to support that hypothesis.

2) The behavior you describe skeptically could match equally well a society where most people live unaware of a great truth hidden to them, in part because the government has made even acquiring information illegal.

In North Korea, a small minority whisper fantastical ideas that are difficult to comprehend, let alone believe. Most of the world is not starving. Places exist with untold self-determination. Our leader is not God. These people often speak with an almost "evangelical zeal".

3) Do you see me doing thrill-seeker liquor store holdups with a "Born to Lose" tattoo on my chest? Ok that was De Niro, but the point is how do you explain people who do not fit the profile? I am not new age, spiritual, or culturally connected to these ideas. I resent mysticism, super natural forces, and magic.

Of course I accept the possibility of being wrong. But the little recent research governments have allowed hasn't yet pointed to that. And until it does how can I deny things that, while anecdotal, are based on first hand observations?

Maybe we'll have solid data some day, if I'm wrong I'll buy you a beer.

I'm pointing to a basic desire for evidence when presented with claims, especially extraordinary ones, especially when presented with religious fervor. That is all.

"Oh Amygdala, Oh Amygdala... Have mercy on the poor bastard!"

In other words, the cure for fear is acid.

Possibly. but don't just go down a tab hoping to get rid of a phobia.

LSD is a key, not a door.

That would never occur to me - I'm more interested on what would change in political views if more people used LSD. Fear-driven politics have been central to many changes in the past years. Maybe LSD could have spared us.

I'm guessing people might perceive that politics is simply a manifestation of ego games not dissimilar to hierarchical rituals of chimpanzees and this is unlikely to change ever until human nature itself changes. Along with the astonishingly unlikely glimmer of hope that human nature can in fact change.

Or maybe the conscious decisions not to behave like chimps with alopecia ;-)

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