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Lamotrigine cancelling LSD but no other psychedelic for a guy (??)

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psood0nym

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I took 400ugs of LSD and gave another 400ugs from the same blotter to a guy who takes lamotrigine. I had the expected responses, including massive pupil dilation, and he didn't. He said he was a "hard head" for psyches and his reaction convinced me, though he only had a handful of previous psychedelic experiences. Curious, I gave him some 5-MeO-DMT and that made him trip hard enough to puke. About 5 hours after we first dosed he nonchalantly said since he wasn't tripping he had some writing to do and calls to make and was going to drive home. I insisted that he should stay for safety reasons in case he was somehow misinterpreting his state. He was quite adamant he was essentially sober and took off and nothing more ever developed.

A few months later we each took 20 mg of 4-AcO-DMT. I expected he'd need a lot more after 400ug LSD gave him nothing, but 20 mg of 4-AcO-DMT resulted in him tripping so hard he was bordering on incoherency, and his pupils indicated it too (clearly his last "35mg" 4-AcO-DMT experience administered by dropperfuls of an ethanol solution was misinterpreted somewhere along the line or it had degraded in solution). He was not a hard head. In terms of subjective intensity for me, the 400ug LSD (this same blotter worked for other people same as it did for me) was far stronger than this 20mg of 4-AcO-DMT. I ended up taking 20mg more throughout the night, and after he leveled out he had a blast.

I'm very curious why he didn't trip off of the LSD. The only potentially relevant factors for consideration I can offer is that he takes lamotrigine (that's all he takes), he had just quit smoking a few days before the LSD dose and was in nicotine withdrawal and using a patch, and he indicated his aunt also "can't trip off of LSD," but there could be any number of reasons she might have stated that. He's not extremely bipolar but was clearly on the down side of a cycle during the time the LSD was in him (plus the nicotine cravings were making him irritable of course). None of these things seems to suggest a likely explanation to me, but perhaps someone knows something I don't?

If I had a gun to my head the best I could offer is that something about these factors influenced the functional selectivity of LSD's activity in neurons but not 4-AcO-DMT or 5-MeO-DMT, but due to the limits of my knowledge about that it's about as cogent an explanation for me as "because Jesus did it."
 
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There exist polymorphisms in nature of the 5-HT2a receptor that decrease its ability to trigger e.g. hallucinations from psychedelic drugs. Ostensibly one could exist that would destroy the ability for LSD to bind without causing excessive loss of function in the receptor. In the "worst case" it would be genetically conserved too. The fact that other family members don't seem to be effected by LSD supports this theory.

http://molpharm.aspetjournals.org/content/66/5/1293.full.pdf

There's an erowid report of someone who took LSD while on lamotrigine and it seems she got the hallucinations just fine. So I don't think that's to blame.

http://www.erowid.org/experiences/exp.php?ID=68733

If he's up for guinea-pigging, he should get his genome sequenced and do all the hallucinogens possible :P
 
So there's a genetically inherited difference in the structure of his 5-HT receptors that repels LSD's binding to the receptor but is not affected by other psychedelics that produce their pharmacological effects by docking at the just same receptor? Nine percent, huh? I had considered this, but wasn't aware of any reports of "LSD immunity," though I suppose that's not surprising, plenty of other ways to rationalize LSD not working, heh. Thanks, I think your explanation is plausible, but also that there is more to it (but your reply is more than I hoped for!).
 
very interesting.

besides this sort of receptor structure difference, and differences in metabolism, what other general categories of things commonly form the physical basis for the same drugs affecting different people differently?
 
endotropic said:
Uneven lay of the blotter?
Click to expand...
Good suggestion, but unlikely. At the time, the righteous efforts of myself and others had managed to eat through around 50 hits of a connected, 4 print, 5X5, 100 tab sheet, with consistent results every time -- that is until this suspected genetic freak went and put a pebble in the shoe of our faith.
 
I bet it has something to do with the different psychedelics certain selectivity of certain receptors over others, like I believe you stated. Who knows really though. Either way a bit to advanced for me. I mean it could come down to any number of factors, at least in my mind......
 
I take lamotrigine and can certainly feel the full effects of LSD. It is well documented that lamotrigine attenuates the effect of dissociative NMDA receptor antagonists, but psychedelics shouldn't be that impacted. Your friend is just an oddball it seems.
 
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