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Lysergamides [LSD Subthread] Extremely High Doses & Receptor Saturation

L

LSDreamer

Bluelighter
Joined
Mar 5, 2008
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Background reading:

LSD receptor saturation dose [archived scraps]
Thumbprinting LSD [archived]


So, a number of people who have taken ridiculously high dose LSD (20+mg) report subjective effects that are different from a lower dose, say 2mg. Theoretically, this shouldn't be the case due to receptor saturation. I know that LSD has a very sloppy binding profile, but I don't know all of the specifics. Theories?
 
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The sloppy binding profile is probably part of the story. LSD is active at many, many receptor sites. It's possible that an amount that saturates 5-HT2a receptors isn't enough to saturate others with notable effects, so higher doses could still increase the effect even if 5-HT2a would have been equally saturated with a much smaller amount.

Another theory of mine is based on the so-called cascade effect (the theory that LSD triggers a cascade of brain activity and that the subjective effects are due to this cascade and not the direct receptor agonism). The primary difference between higher and lower doses beyond the saturation point is how long the receptor stays saturated, from what I recall reading anyway... It could be that LSD's receptor activity at 5-HT2a acts somewhat like a gas pedal, so keeping it saturated longer leads to a more intense effect from the cascade, not just a longer time frame. With typical doses, LSD is active in the brain for only part of the subjective effects' duration, one of the primary warrants for the existence of the cascade effect. If LSD is triggering a longer-term cascade as it stimulates 5-HT2a receptors, it would make sense that higher doses = longer period of saturation = more intense overall cascade.
 
LSD is a partial agonist with a surprising affinity for a wide number of receptors. Beyond the 5-HT2a receptor, we have the dopamine D2/D3 receptors. Hence, with a super-huge dose, I'd bet the first noticeable effect would be a desire to puke. This nausea has occurred to me following large-ish doses of other ergoloids like ergometrine. After that, I suppose the trip would take off. I've never had that intense and long-lasting of a mindfuck on a psychedelic, so I don't even know where to begin ;).

My largest experience with LSD itself I would estimate at around 500-800 ug (but in all honesty, one can never be sure of the exact amount to the ug, but it was about 10-12 hits) and it was the most wondrous experience of my life. Considering that my 'wits' were still completely intact and I was still capable of acting in a relatively normal manner after that dose, I suppose I could venture a little higher. But taking anything more than 1.5-2mg just sounds reckless--no sense taking the risk simply for a greater intensity of side effects. I know that the LD50 is extraordinarily high (upwards of 350mg or 5000x the active dose--and even then, this is merely a theoretical number as I believe only one person has ever died as a result of LSD and he ingested at least a couple of grams), but why waste such a precious compound? If a person somehow had access to that amount (and I would never want to know if they did, things like this should be kept completely secret and never be discussed), it would be best to preserve it as a lifetime supply...for a rainy day.
 
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do you know if the person died from the lsd itself, or side effects, such as being scared to death?

a couple of grams, just wow............. would it just be like dreaming i wonder?
 
Wasn't the fellow who died from injecting LSD a meth addict who thought he was shooting a couple grams of meth?
 
Riemann Zeta said:
This nausea has occurred to me following large-ish doses of other ergoloids like ergometrine.
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sorry to get OT, but have you tired pure erogmetrine (ergonovine)? i have been very curious about this compound as it is one of the major alkaloids in morning glory seeds, and it has a very similar structure to LSD. also, under the LSD entry in pihkal, shulgin suggests ergonovine to have LSD like activity at ~10-20mg. anyone ever try this?
 
The Wizard said:
Wasn't the fellow who died from injecting LSD a meth addict who thought he was shooting a couple grams of meth?
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I believe it was 350mg or thereabouts, but yes. And you do have to wonder if there was also speed involved considering the circumstances.
 
Xorkoth said:
I believe it was 350mg or thereabouts, but yes. And you do have to wonder if there was also speed involved considering the circumstances.
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Quoting from the journal report:

Routine toxicogical examination of the liver was carried out elsewhere prior to the submission of the samples to this laboratory; no drugs were detected. RIA of the ante-mortem serum in this laboratory demonstrated the absense of amphetamine [1] and cannabinoids [1], thus LSD was the only drug detected in the case.
 
I would think that LSD's high affinity for DA receptors could've played a role in heart failure. Combined with meth still in his system his heart could've lost its beat and he would've died. I'm pretty sure people were charged in a similar case in which someone died due to "LSD overdose". The expert witnesses time and time again said that LSD played a role but without the other drug it would be impossible. LSD is seen as so safe by many people, but it is a drug. And I've heard 600mcg is the saturation point, but I've also heard 1.5mg. And the issue came up that 600mcg might be the point at which 5-ht or a subset is saturated.

And the OP... did you change your name and bring this up again? Who was the ignant d-bag who wouldn't let this argument die early this last winter? That poster didn't know anything about nuthin' and he/she would use buzzwords (sans information) that I fed him/her on Youtube to use in bluelight debates on the subject. It was really pathetic. Now what was his/her name?

Peace,
PL
 
The saturation point (>90% receptor occupancy) for 5HT2a receptors with LSD is around the 1500ug mark, but as mentioned, it also interacts with receptors for dopamine, noradrenaline & histamine. I would imagine that interacting wit those would only be a minor factor detrimental to the overall experience.

I honestly can't think of a reason other than bravado, stupidity or an unfortunate accident for consuming over say 5mg of LSD in one go - fucked if I would (my biggest dose is around the 600ug mark and that was enough1)
 
It's probably the placebomine. Leary said that he could give people incredible doses and as long as he told them "It's 200 mics" they never knew the difference.
 
^Leary was also insane and unscientific as hell. And no, LSD doesn't cause ergotism. LSD isn't toxic at doses any of us are likely to have access to.
 
i heard that after 1000 the receptors r saturated but at like a thumbprint(5000) other recpectors r used. This is a very intersting topic and hope it is discussed further, myabe sum1 who ahs treid a thumbprint tell how it differs from a low does
 
I don't know about receptor saturation but the most I've ever taken was 14 green gels, pretty good but nothing spectacular and I had a high tolerance at the time so it wasn't blow-the-top-of-your-skull-off intensity or anything like that, just very strong, lasted quite a long time, and left me fried for about a week. The hardest I ever tripped however, was 6 hits of very strong, super-clean liquid, one of the most joyous and ecstatic experiences of my existence; I traveled outside my body and into my mind, where it seemed like I was traversing the actual neural chasms of my very thoughts, as in I no longer existed but rather my non-existence was a product of some kind of abstract spiral/fractal of ideas, time, and energy, very CRAZY but yet beautiful and soul-cleansing at the same time. Sorry if that sounds strange but i don;'t know any other words to explain it. One point I would like to make though is that on many of my high-dose trips I would experience a recurring " theme " if you will, almost like a mental motif. It was visions of outer space, mainly stars and galaxies, and me (or my awareness if you wish to call it that) was traversing the cosmos while I moved higher and higher into eternity/oblivion/infinity or whatever you wish to call it.
 
i went to a drug progy at the hospital once. i heard of a kid they call 'orange juice"....he drink 2000 hits of liquid acid to avoid cops catching him [cuZ THAT WOULD be like life..]..anyway...hes far gone in a psychward...and all thats known about him is that he thought he was a cup of orange juice, and evry time he fell over, he needed his friends to pour oj on his head...some waked out shit like that...just thought id share...

ii also here, if u take too too much, u may never come out..
 
I don't know if Dextermeth is still on these forums, but for some reason I recall reading stuff on here about his experiences with thumbprints
 
nofxboyy said:
i went to a drug progy at the hospital once. i heard of a kid they call 'orange juice"....he drink 2000 hits of liquid acid to avoid cops catching him [cuZ THAT WOULD be like life..]..anyway...hes far gone in a psychward...and all thats known about him is that he thought he was a cup of orange juice, and evry time he fell over, he needed his friends to pour oj on his head...some waked out shit like that...just thought id share...
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Yeah that's a famous urban myth that's spread throughout the world - someone who lived down my street "knew" someone who thought he was glass of orange juice too. It's absolute bullshit.

The bit you missed out was the orange juice guy is too frightened to ever sit down because he thinks he will "spill".
 
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