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

[morefun2compute]

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.

 

[sean107]

I do know a guy who can take just about any psychedelic and doesn't trip. He doesn't take anything else either so I know there isn't something blocking him from tripping. Do you take any meds like SSRI's or antipsychotics?

 

[AA357]

Are you on any meds? It seems very hard to believe that anyone can have such an immunity to LSD.
Most antipsychotics will make tripping impossible. Certain MAOIs are known to drastically diminish the effects of LSD. SSRIs do this to a lesser degree. I imagine lisuride and other prescription drugs that bind to 5HT2a receptors would also blunt the effects of LSD quite considerably due to competition.

 

[Flickering]

It's actually not unheard of. Now and then on this board someone comes along claiming to have never felt a thing from any psychedelic. One of my friends just naturally has major tolerance to everything he's tried which has included LSD, ayahuasca and DMT. 60mg of DMT wasn't enough for him to break through.

It sounds like your ~1.5mg trip had you experiencing the physical symptons of that much acid, namely agitation and vasoconstriction, with none of the psychedelic effects. Bugger. Maybe try mescaline? It's has a different chemical base, so maybe that'll make a difference. I don't know enough about psychopharmacology to say for sure though. Best of luck.

 

[4meSM]

Are you on any meds? It seems very hard to believe that anyone can have such an immunity to LSD.
Most antipsychotics will make tripping impossible. Certain MAOIs are known to drastically diminish the effects of LSD. SSRIs do this to a lesser degree. I imagine lisuride and other prescription drugs that bind to 5HT2a receptors would also blunt the effects of LSD quite considerably due to competition.

^this

Are you sure you're really getting LSD? 20 hits of quality LSD is A LOT, you would definitely feel it if you felt the shrooms.
Have you taken other psychedelics before?

 

[CrypticArc]

It's possible you have a high resistance but even then I doubt you would be able to take 20 hits and be able to function just fine. Maybe your friends are pussies and your shit's bunk? Maybe it's your storage method, or maybe the batch you got your acid from was just laid weirdly. The way acid absorbs into blotter, it's definitely possible that one half of a sheet was super super strong and the other half was much weaker if the person laying it was inexperienced or made a mistake. just a thought but it doesn't seem likely that you're just immune to psychedelics or your brain function would be radically different than most people's.

 

[PriestTheyCalledHim]

It's not unheard of. I know people who took LSD in the late 60s and they did not trip or have a psychedelic experience; but everyone else who they were with who did take the same LSD did trip and have a psychedelic experience. Are you on medications at all? I suspect when you took 20 hits some of those were not really LSD or any drug at all but the ones that were, were just very weak LSD.

 

[morefun2compute]

No, I was on no meds whatsoever in most instances I tried it. I have indeed have very deep experiences with mushrooms, and with them my body has a predictable response curve with respect to dosage. And like I said, numerous other people were happily tripping off one or two hits from the sheet from which I took 20. Since I did have some psychedelic effects in one case -- but only for a relatively short time -- I think that my body simply develops an extremely high short-term tolerance, in some cases so quickly that I don't perceive any effects at all.

It's not really a problem I'm trying to solve. I'm quite happy with mushrooms. I was curious about the folklore on that sort of thing.

 

[CrypticArc]

I would try finding some nice liquid LSD if I were you, and testing that out with a couple drops. Then you'd know for sure if it's your body just not reacting to the acid for some reason. also try smoking a bunch of weed or eating edibles with it.

 

[Flickering]

I'm curious to know what people find so hard to believe about the idea that LSD might have no effect on a certain type of brain.

 

[AA357]

I'm curious to know what people find so hard to believe about the idea that LSD might have no effect on a certain type of brain.

Have you ever heard of a person who doesn't respond to amphetamine or morphine? The effects vary from one person to another but nobody is immune to them. Why would LSD be any different?

 

[Flickering]

A fair and interesting point. However, the neurochemistry behind LSD is very peculiar. It is such a tiny thing, potent to the microgram. The LSD molecule itself has no direct interaction with the brain's receptors. Rather, it seems to trigger a signal that causes the brain to induce its own, 12-hour trip. In essence, LSD is merely the catalyst that sparks a chain reaction. It's the finger that flicks the long line of dominos. Stimulants and opiates, on the other hand, work by blocking dopamine receptors and causing the brain to flood with pleasure chemicals. There's no getting around that, unless your brain is sufficiently innured to the effects (which is to say, you've taken heroin so often that the neurotransmitters themselves have essentially frayed from overuse.)

 

[casual1]

A fair and interesting point. However, the neurochemistry behind LSD is very peculiar. It is such a tiny thing, potent to the microgram. The LSD molecule itself has no direct interaction with the brain's receptors. Rather, it seems to trigger a signal that causes the brain to induce its own, 12-hour trip. In essence, LSD is merely the catalyst that sparks a chain reaction. It's the finger that flicks the long line of dominos. Stimulants and opiates, on the other hand, work by blocking dopamine receptors and causing the brain to flood with pleasure chemicals. There's no getting around that, unless your brain is sufficiently innured to the effects (which is to say, you've taken heroin so often that the neurotransmitters themselves have essentially frayed from overuse.)

Rubbish. Here is some info on LSD and the brain: https://en.wikipedia.org/wiki/Lysergic_acid_diethylamide#Pharmacology

 

[Flickering]

Yeah, I suck at neuroscience.

 

[Goddess Mode]

Flickering, while you may have gotten the neuroscience wrong, I think you actually had a valid point.

AA357, you point out that there aren't people who are completely immune to morphine or amphetamine, but this really isn't that fair of a comparison with LSD. The fact of the matter is, morphine actually exists in your body endogenously (I could link to a paper about this but there are so many fascinating ones out there I recommend you just do a search yourself), and amphetamine is only a single carbon difference from phenethylamine, another significant endogenous molecule we have in us. These things make it seem exceedingly unlikely that there would ever be at least developmentally healthy people who weren't able to get a response from them.

LSD, on the other hand, is pretty far removed from what our brains are wired to get at 5-HT2A. The fact that it contains a tryptamine skeleton in it is little more than a fun coincidence because lysergamides and tryptamines don't bind to the 5-HT2A receptor the same way. On top of that, it's well known in the scientific world that almost any small modification to the structure of LSD, basically any aside from the couple leading to the RCs that exist now, results in molecules with either massive drops in potency or a complete loss of activity. And that's important to consider I think because of the 5-HT2A receptor itself.... Though we call this receptor one thing, it is not the same in each of us. Literally hundreds of mutations to the gene encoding the 5-HT2A receptor are known, and some of them (His452Tyr is a popularly researched one) actually have functional consequences, meaning that the same drug can bind with different affinity and efficacy to the "same" receptor in different people. Some of the mutations, like the aforementioned one, seem to be very common in the population, but some are known to be incredibly rare. Knowing this, is it not conceivable that in a world of seven billion people just every once in a while there will be someone with a receptor with just the wrong functional change to prevent an already very abstract molecule from binding properly, or at least potently?

 

[Nexus_Tripper]

Try snorting 10mg of crystal LSD. If that doesn't work, I'd say you are immune to LSD.

 

[4meSM]

^ yeah do it for science.
I wonder if you're immune to all lysergamides or somehow your body didn't absorb the LSD.

 

[sekio]

LSD is very bioavailiable orally, I thought.

I'd suspect personal genetic variance in this case. Sometimes it happens with some classes of psychedelics, to some people. I have heard of people who don't respond to PEAs, people who respond poorly to tryptamines, people who seemingly get less effect from LSD etc. so it's not like these kind of things are totally unknown.

 

[atara]

Not likely neurological. LSD interacts with too many different kinds of receptors for a person to lack all of them.

Any strange diseases in your history, OP? You may have an antibody to ergolines.

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

 

[AA357]

Flickering, while you may have gotten the neuroscience wrong, I think you actually had a valid point.

AA357, you point out that there aren't people who are completely immune to morphine or amphetamine, but this really isn't that fair of a comparison with LSD. The fact of the matter is, morphine actually exists in your body endogenously (I could link to a paper about this but there are so many fascinating ones out there I recommend you just do a search yourself), and amphetamine is only a single carbon difference from phenethylamine, another significant endogenous molecule we have in us. These things make it seem exceedingly unlikely that there would ever be at least developmentally healthy people who weren't able to get a response from them.

LSD, on the other hand, is pretty far removed from what our brains are wired to get at 5-HT2A. The fact that it contains a tryptamine skeleton in it is little more than a fun coincidence because lysergamides and tryptamines don't bind to the 5-HT2A receptor the same way. On top of that, it's well known in the scientific world that almost any small modification to the structure of LSD, basically any aside from the couple leading to the RCs that exist now, results in molecules with either massive drops in potency or a complete loss of activity. And that's important to consider I think because of the 5-HT2A receptor itself.... Though we call this receptor one thing, it is not the same in each of us. Literally hundreds of mutations to the gene encoding the 5-HT2A receptor are known, and some of them (His452Tyr is a popularly researched one) actually have functional consequences, meaning that the same drug can bind with different affinity and efficacy to the "same" receptor in different people. Some of the mutations, like the aforementioned one, seem to be very common in the population, but some are known to be incredibly rare. Knowing this, is it not conceivable that in a world of seven billion people just every once in a while there will be someone with a receptor with just the wrong functional change to prevent an already very abstract molecule from binding properly, or at least potently?

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.