is it common for LSD to have no effect on someone?

[Goddess Mode]

Also, I have a good friend who experiences a diminished response to morphine. The phenomenon has been characterized.

I actually experience a fairly diminished response to most opiates/oids that apparently runs in my family, but I was not aware of anyone who is completely immune to morphine's effects. Do you know what the highest dose they used to test out peoples' responses was?

Thanks for that. That's very interesting - I had heard of endorphins but I didn't know that human cells actually produced morphine.

You say that LSD binds differently to 5HT receptors than tryptamines... what about phenethylamines (since it has the phenethylamine skeleton as well)?
I did a bit of research on unresponsiveness to LSD. Nearly everybody who reports that LSD doesn't do anything to them claims to have tripped on some other serotonergic psychedelic.

I do know a few people who are hyporesponsive to psychedelics (including LSD). Complete unresponsiveness seems unlikely though.
From what I've seen, 60-80mg of nasal DPT will blow most people's heads off. One guy snorted 120mg on his first go and he was still functional. He reported some strong mindfuck and visuals but he definitely wasn't overwhelmed (like anybody else would be). I don't think he would have felt 60-80mg. He is hyporesponsive to LSD as well.
Another guy can barely feel 25mg 2C-E... he thought it was a weak drug until he took 35mg.

No problem, I think it's quite intriguing myself.

As far as I know, they all bind differently to one another. This study that I just found seems to have tested the binding mescaline, DOB, DON, MDMA, psilocybin, DMT, LSD, 25I-NBOMe, and 25N-NBOMe, and the abstract claims that "The Val-156 residue appears to be common to all flexible docking results and all molecules interact with the transmembrane 3 helix. The other interactions are particular to each molecule." This would seem to suggest that there is quite a bit of variance between different molecules even within the same class of drugs, so any small molecular change could feasibly interfere with or enhance the binding of some drugs but not others. The pictures on that PDF look a little chaotic at first glance, but you can see in them that there differences in how they interact with it....

I tend to be pretty hyporesponsive to a lot of psychedelics compared to my friends at least actually. After years of not tripping I once with a close friend who had been off them for just as long took an equal amount of LSD at the same time, and I had a great refreshing trip like insightful and euphoric and everything but with not much visual or anything strong aside from just some colorful tracers on things, while he was curled up on the ground in the fetal position watching the universe continuously recreate itself uncontrollably. The same friend once took 15 mg of 4-HO-MiPT and was moving in and out of total delirium for a good amount of it, whereas 30 mg for is provides almost no visual or mental changes whatsoever, just a really nice empathogenic buzz with some feelings of light dissociation. I haven't tried it yet, but I have to guess that 60-80 mg of DPT will not be an overly strong dose for me. I've actually been realizing lately that most tryptamines and lysergamides that I've tried in general for me take place almost completely in the mind's eye, visuals and psychological distortions are almost always present at the right dose but comparatively much more minor in importance. Like, I can get to the point where I actually feel like I'm interacting with entities through my imagination and I can see them in the darkness when I close my eyes like a dream world, but there typically won't be any like fractal forms in them or anything and with eyes open it still won't be much more than mild patterns on surfaces and some light warping, even with DMT. It often feels like my trips wouldn't even have happened if I wasn't paying attention to them, unless the dose is just huge.

Strangely, the phenethylamines actually tend to feel like much heavier experiences to me, but that's just with the limited experience I've had with them compared to tryptamines so far.... That's not to say that I like them better necessarily, but they just hit me pretty hard. 25 mg oral doses of 2C-I for me are massively visual and actually feel quite dissociating. Meditating on that gave me my first ever experience of natural like totem pole and alligator forms and those kinds of things as concrete visuals.... I pushed it up to a couple of recklessly high oral doses, still under 100 mg though, and the visuals became oddly simpler in a lot of ways, but the dissociation became so intense that I went briefly out-of-body after smoking cannabis and came to in the most intense hallucinogenic hedonistic experience of my life, an extremely sexual encounter involving several entities that took place completely in-body and was so overwhelmingly euphoric that I completely lost the ability to move even an inch. Ever since then I've also found lower, more normal doses to touch upon that sort of spirit realm feeling as well.... 2C-B I've only tried a couple times a long time ago at low doses but even then it also gave me incredible color changing effects that I have yet to match since then. The only other things I have ever taken that come even close are MDMA (also hugely visual and delirious for me after a few hours) and 4-HO-MET (and 4-AcO-MET), which I should say is probably the exception to the tryptamine rule, it gives me crazy visuals even at normal doses.... I'm honestly a little nervous to try 2C-E some day just because of everything I've heard about it lol. Body stuff can mess with me quite a lot when I'm tripping and I've heard that it can be heavy in that way before, but everything about the trip sounds fascinating to me, and I'd love to see what it can do because even through the strength I get what people mean when they say that 2C-I can be hollow. I'd like to see what a really strong phenethylamine is like....

 

[Squatter Jones]

I'd like to say that I don't trip from lsd. I've had 13 hits in a go with no effect. I'm hoping I get to try dmt but until then I have had no hallucinogenic effects from psychedelics.

 

[Xorkoth]

Sometimes the reason for not tripping on LSD is that you have bunk LSD... it's the easiest drug in the world to pass off as someything else or to pass off plain blotter without any LSD on it as LSD, since you can't see it and it's tasteless. That aside though, I was unable to trip on LSD beyond faint threshold effects for many years, I tried it probably 15 times. My friends would be tripping hard and loving it off less than me from the same batch. I got ahold of those legendary Hofmann blotters circa 2006 or thereabouts, took 3 of them, barely felt anything, whereas my friend was saying one of them was a nice trip, and 2 blasted him out of this world. Then, 13 years after first trying it, I took 5 hits that were lab tested to be 115ug each (which is much higher than even the vast majority of the hits advertised on the DNM at 150-250ug - by the way if you ever get hits someone told you are that high they almost certainly are not. Someone on here sent a bunch of different DNM blotters advertised as high dosed to a lab to get the dosage tested and I think 1 out of the entire bunch came back as advertised, the rest were way lower, 60-80 at most, even when advertised as 250. FYI). Anyway I took those 5 hits, so 575ug, and I did finally trip, not super hard but I finally got LSD effects. After that, every time I took LSD I would be able to get that same level of effect, with less than 575ug. I could take like 3 street hits and get the same, or like 3 hits of 1p-LSD. I had several more trips where I seemed to "push through" to the next level of effects, and each time I did, I could get the same level of effect with even less. Nowadays I can take a half a hit of ALD-52 (so about 62ug) and get a solid light trip, or a whole hit and be fully tripping. 2 is almost too intense for me usually now. Seems that over time, I was able to totally reverse my natural tolerance. I don't know why but it seems like some people have an extremely high natural tolerance to it despite not having such for other psychedelics. A variety of people have reported such, as I experienced it firsthand.

I have never had any problems tripping on anything else. Just LSD. Actually the first times I tried AL-LAD I was still in my period of slow reduction in natural tolerance and I would need 450ug for a satisfying trip, but I bet nowadays I would need less.

Also if you're having trouble tripping on psychedelics, and you're taking SSRIs or some other meds, that's probably why, as for most, SSRIs drastically reduce the effectiveness of psychedelics.

 

[Solipsis]

Yes you'd have to have an independent party like a friend with no reason to lie who has taken hits from the same batch and consistently found them potent (preferably homogenous like liquid acid cause blotter hits could vary), while you tried even considerably higher doses and got nothing.

I disagree with what atara said earlier that it's not likely neurological, LSD acts on a lot of other things than 5HT2A but much less significantly and less dramatically - plus for example the threadstarter said he did feel weird in some way but did not trip. Could very well be consistent with a mutation in the 5HT2A receptor but that has to be pretty rare indeed. So plenty of people who think they are immune to tripping probably have not verified the other possible reasons like medication or bunk product.

A mutation wouldn't even have to make you unable to trip on any psychedelic, it could just prevent the proper binding of only some of them. I imagine complete dysfunction of the 5HT2A receptor would look like a very serious medical / cognitive condition, though I could be wrong. (no, turns out that is true: it is implicated as one possible etiology for depression and epilepsy. I guess there are a lot of ways a brain could cope if it develops entirely lacking one type of receptor - different pathways and relations could form).
Even if LSD could act on busted 5HT2A receptors but serotonin cannot, in those patients, it would likely have very different effects if any at all since the receptors would basically be rudimentary.

I wonder if it could have anything to do with LSD's potent effects apparently relying on the drug getting caught on the 5HT2A receptor and activating it for a very long time (thanks kaleida, interesting). If a mutation would prevent that snag of the diethylamide, it would not be nearly as potent for those people. There could even be an off chance that such people (there would be many possible mutations though so we can't pigeonhole them) may get a potent effect from analogues like the dipropylamide etc that normal (neurotypical) people would not trip on. But that's sci-fi ;p
The getting snagged is another reason why LSD's promiscuous binding wouldn't necessarily give you considerable effects: no reason to think that it gets snagged on all those other types of receptors too - just 5HT2A and 2B.

 

[KingsJewel]

I think there are definitely people with a natural tolerance. I just found this post because I am currently on 4 x tabs plus 10 x liquid drops it's been 10 hours and I hardly felt anything... it was my first time and my friend who's very experienced with lsd and has been wanting me to try took 2 x tabs and was WAAAAASTED.

Also just a side note, I can get high from smoking weed, but not edibles? I could eat 10 of the strongest cookies you can imagine, and still ask for more with no effects...

I've had mushrooms once before and they worked... but was like 10 years ago..

I feel kinda ripped off by it all to be honest. like I just have to miss out and it sucks major Wang.

 

[FuckinAcidMan]

I think there are definitely people with a natural tolerance. I just found this post because I am currently on 4 x tabs plus 10 x liquid drops it's been 10 hours and I hardly felt anything... it was my first time and my friend who's very experienced with lsd and has been wanting me to try took 2 x tabs and was WAAAAASTED.

Also just a side note, I can get high from smoking weed, but not edibles? I could eat 10 of the strongest cookies you can imagine, and still ask for more with no effects...

I've had mushrooms once before and they worked... but was like 10 years ago..

I feel kinda ripped off by it all to be honest. like I just have to miss out and it sucks major Wang.

That majorly sucks. LSD kicks so much ass when it works.

 

[TripSitterNZ]

I think there are definitely people with a natural tolerance. I just found this post because I am currently on 4 x tabs plus 10 x liquid drops it's been 10 hours and I hardly felt anything... it was my first time and my friend who's very experienced with lsd and has been wanting me to try took 2 x tabs and was WAAAAASTED.

Also just a side note, I can get high from smoking weed, but not edibles? I could eat 10 of the strongest cookies you can imagine, and still ask for more with no effects...

I've had mushrooms once before and they worked... but was like 10 years ago..

I feel kinda ripped off by it all to be honest. like I just have to miss out and it sucks major Wang.

are you on ssris or antipsychotics?

 

[Survivor69]

I'm 36 and just tried LSD for the first time about a year ago. I've tried it about a dozen times now, maybe more, and it seems to have virtually no effect on me. One time I did 20 hits of acid that was verified as potent by other people, and then was able to casually walk around in public, go out to eat at a restaurant, etc. I mean, it has some slight effects like making me a bit jittery and making my skin feel just slightly numb, but almost no psychedelic effects.

I have used shrooms extensively and they DO give me psychedelic effects (although it seems I have to take 3-4 times as much as most people to get a similar effect). But LSD has only given me the slightest hint of psychedelic effects -- and sometimes not even that. The dosage seems to be irrelevant because the most psychedelic effects I ever had was after 2 hits of acid, but they faded after a couple hours and did not return even when I took 4 more hits.

I'm just curious: how common is it for someone to have virtually no reaction to LSD? I keep waiting to hear someone say, "yeah, I knew a guy once who was the same way", but I haven't yet found anyone who's heard of such a thing.

Yeah, I knew a guy once who was the same way!
This was in the sixties, and acid was new. The guy in question had become frustrated at taking a trip and while others were clearly away with their fairies, he felt nothing. We discussed whether he was resistant to it and thus couldn't allow himself to 'let go'. It was clearly hanging him up, so I decided to assist by spiking him [dropping some acid in a coffee wityhout telling him], which would avoid any mental resistance and perhaps allow him to trip. It worked. He tripped after that, but not every time, sometimes nothing happened.

 

[KingsJewel]

are you on ssris or antipsychotics?

No. I have been on heavy pain killers in the past. I've never let my self take them for more than a couple of months before having a few months off. I haven't taken any for a few months now.

I've tried again and managed to get a bit more from it. Just dropped 5 straight away and I definitely felt it, but still not the level of mates who take 2. I'm at least happy I have managed to get a bit more out of it on another try. I'm sure if I took 10 at once I'd probably get some psychedelic stuff happening because this time I started just to notice geometric patterns, didn't last for ages though.

Also 30 min went by and I thought it was 2 hours...