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Offlinemorrowasted
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Pharmacokinetics and subjective effects of 1P‐LSD in humans after oral and intravenous administratio * 1
    #26685311 - 05/21/20 10:07 AM (1 month, 20 days ago)

https://onlinelibrary.wiley.com/doi/abs/10.1002/dta.2821

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Wiley Online Library

Drug Testing and AnalysisAccepted Articles
RESEARCH ARTICLE  Open Access
Pharmacokinetics and subjective effects of 1P‐LSD in humans after oral and intravenous administration
Christina Grumann  Kerstin Henkel  Simon D. Brandt … See all authors
First published:15 May 2020
https://doi.org/10.1002/dta.2821
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/dta.2821.
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Abstract
1‐Propanoyl‐lysergic acid diethylamide (1P‐LSD) appeared as a non‐controlled alternative to LSD a few years ago. Although evidence is beginning to emerge from in vitro and animal studies that 1P‐LSD might serve as a prodrug for LSD, an equivalent evaluation in humans is unavailable. Controlled oral and intravenous self‐administrations of 100 μg 1P‐LSD hemitartrate are reported in two human volunteers followed by analyses of urine and serum samples using a fully validated LC‐MS/MS method. Psychometric evaluations included assessment of selected subjective drug effects and administration of the Five‐Dimensions of Altered States of Consciousness rating scale (5D‐ASC). In serum and urine, oral administrations of 1P‐LSD only led to the detection of LSD reflecting biphasic elimination with a terminal elimination half‐life of approx. t1/2=6.4 h. 1P‐LSD could be detected for only up to 4.16 h in serum and 2.7 h in urine following intravenous administration whereas LSD was detected in all serum samples (last sampling after approx. 24 h) and up to 80 h in urine. LSD showed first order elimination kinetics with an approx. t1/2=5.7 h, whereas 1P‐LSD showed a rapid decrease in concentration within the first hour followed by a slower decrease, most probably due to hydrolysis. Bioavailability of LSD after oral ingestion of 1P‐LSD was close to 100%. The psychosensory effects of 1P‐LSD and their time course were comparable to those seen after uptake of LSD in other studies which further supports the prodrug hypothesis. The 5D‐ASC scores were higher after oral compared with intravenous administration of 1P‐LSD.





interesting that oral ingestion seems to be stronger than IV


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InvisibleopenmindS
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: morrowasted] * 1
    #26685683 - 05/21/20 01:14 PM (1 month, 19 days ago)

Quote:

morrowasted said:

.....interesting that oral ingestion seems to be stronger than IV






Could that be because 1P-LSD isn't active itself and requires first pass metabolism for the active component/LSD to be present?

And when ingested orally the 1P-LSD is exposed to enzymes/metabolized into LSD more rapidly/effectively versus when it is administered IV?


Would that be the case for most pro-drugs?...






-OM

.


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Offlinechibiabos
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: openmind] * 1
    #26685854 - 05/21/20 02:42 PM (1 month, 19 days ago)

It could also have something to do with the fact that your circulatory system evolved to use veinous blood as a means of disposing of things that might harm important organs like your brain.  If LSD can be absorbed so easily though your skin then it's probably not going to have a hard time migrating through thin-shit epithelial tissue and into big arteries even if it has to go through the interstitial spaces.


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OfflineHolybullshit
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: chibiabos] * 2
    #26686206 - 05/21/20 05:38 PM (1 month, 19 days ago)

LSD is not absorbed through the skin under normal conditions. The myth of tripping from touching a crystal or while making sheets from getting the solution on your skin is just that, a myth, at best one might touch their eye or mouth while handling large amounts of LSD and be exposed that way. Otherwise about the only way you are going to absorb active amounts of LSD through your skin is with the assistance of something like DMSO.

I'm not sure what you are trying to say with "migration", but once a substance, any substance, is injected into your bloodstream it is dispersed throughout your entire circulation system within seconds.

I think openmind hit the nail on the head. And that would be the case for most pro-drugs, any inactive(or weakly active) compound which undergoes hepatic metabolism into a stronger one is going to be more effective and faster acting orally than IV. Think vyvanse(Lisdexamfetamine) or phendimetrazine. In fact, psilocybin is a prodrug for psilocin.


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Offlinechibiabos
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: Holybullshit] * 1
    #26686343 - 05/21/20 06:54 PM (1 month, 19 days ago)

Migration is exactly what it sounds like.  You can split hairs over the terminology but it never seemed to bother any of the people who taught me p-chem or molecular biology.  I'm also not sure what your point is unless you have some specific data in mind that compares IV to oral administration of LSD in the same way.  I already know what his point is, and it's not like it's definitely wrong, but unless you have something like a specific acylase in mind or know that there's some sort of steric effect from the propanoyl then it's basically just spitballing.

And yeah, blood circulates pretty quickly but venous blood doesn't just get shoved up to your brain like arterial blood.  It's generally cleaned up a lot first before it even makes it back to the heart.  And blood doesn't really seem like an environment where things like 1-P-LSD and LSD are bound to be terribly stable anyway.  And on top of that the only study I could really find to get data about LSD that's even relative to this question allows me to do a back of the envelope calculation that shows that the plasma concentration of LSD that shows that the molality per mass of the drug administered can be higher than the same figure for an IV dose.  That being said I had to make so many assumptions that it's basically just an arithmetic problem (where I was only really able to compare the largest figures for either data set) and I could have just as easily chosen my criteria to come to the opposite conclusion, so it's not like either idea is really looking more likely than the other as this discussion stands.


Edited by chibiabos (05/21/20 07:09 PM)


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InvisibleInvisible_Woe
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: chibiabos]
    #26686683 - 05/21/20 09:20 PM (1 month, 19 days ago)

:popcorn:


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OfflineHolybullshit
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: chibiabos]
    #26686798 - 05/21/20 10:25 PM (1 month, 19 days ago)

Drugs aren't getting magically metabolized out of your system in your veins before reaching your brain after being IVed.

Blood circulates around your body extremely quickly, and for the most part metabolisation happens in the liver and over time, you aren't breathing out LSD like carbon dioxide, and even what gets removed unchanged(very little) by your kidneys or intestines happens very slowly and it will circulate through your body literally thousands of times before any meaningful amount is removed. LSD isn't moving from your veins to your arteries in any substantial way besides within your circulatory system...and even if it was, how would it do it faster than the heart pumps it to them? After "migrating" out of your veins does the LSD just swim, at olympian speeds, to the arteries?

I'm sorry but a lot of the stuff you are saying just doesn't make any sense at all, I don't think you have nearly the grasp on the human body that you think you do, and I'm not going to waste my time trying to make sense of it any more.


Edited by Holybullshit (05/21/20 10:38 PM)


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Offlinechibiabos
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: Holybullshit]
    #26686890 - 05/21/20 11:40 PM (1 month, 19 days ago)

Oh, I'm sure that I don't know nearly as much about the human body as I think I do but I've never heard that response from somebody who wasn't just bugging out on account of the fact that they considered themselves to be smarter than average and were upset about the discussion moving outside of their comfort zone on account of somebody they considered their inferior.  It's sort of like when a solar physicist told me that I was talking nonsensical bullshit because I started to explain where antibodies come from and what T cells do in response to his bullshit rant about how AIDS isn't real.  I believe that his followup (more or less verbatim, but there was alcohol involved) was "I'm a scientist and you're not, therefore you can't argue with me."

But hey, I'm not going to stop you if you just want to quit and feel that self-satisfaction from telling yourself that anything you don't immediately have a context for is ridiculous and beneath your consideration.  :justdontknow:

edit:  You got me, I should have said "molarity" instead of "molality."  :whatever:


Edited by chibiabos (05/22/20 12:00 AM)


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InvisiblebadchadS
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: openmind] * 2
    #26687191 - 05/22/20 04:02 AM (1 month, 19 days ago)

Quote:

openmind said:
Quote:

morrowasted said:

.....interesting that oral ingestion seems to be stronger than IV






Could that be because 1P-LSD isn't active itself and requires first pass metabolism for the active component/LSD to be present?

And when ingested orally the 1P-LSD is exposed to enzymes/metabolized into LSD more rapidly/effectively versus when it is administered IV?


Would that be the case for most pro-drugs?...






-OM

.




Probably, the LSD Cmax levels were higher following the oral route, which supports this.

The VAS scores were really close though, so not super clear its all that stronger with an n=2.


--------------------
...the whole experience is (and is as) a profound piece of knowledge.  It is an indellible experience; it is forever known.  I have known myself in a way I doubt I would have ever occurred except as it did.

Smith, P.  Bull. Menninger Clinic (1959) 23:20-27; p. 27.

...most subjects find the experience valuable, some find it frightening, and many say that is it uniquely lovely.

Osmond, H.  Annals, NY Acad Science (1957) 66:418-434; p.436


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OfflineFractal420
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: badchad]
    #26687225 - 05/22/20 04:34 AM (1 month, 19 days ago)

injecting lsd I have always heard is very powerful. Never tried it, or would try it.

As for pro drugs, think about 4aco, there are many experience reports of IV and it’s a strong trip resembling dmt apparently, but quite a bit longer

So if thats a prodrug (which I believe it is), it is certainly active IV

Even converts to 4ho-Dmt in the baggie


--------------------
Dreaming of That face again.
It's bright and blue and shimmering.
Grinning wide
And comforting me with it's three warm and wild eyes.

Prying open MY third eye



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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: Fractal420]
    #26687324 - 05/22/20 06:04 AM (1 month, 19 days ago)

1P has to interact in your mouth/stomach to remove the nitrogen that's added to it which then leave 100% LSD... through IV it wouldn't have the same effect due to lacking the mechanism to remove the nitrogen.

P.S. i wish they would kind of leave the studying of 1P upto me:) papers like this will end up in a ban which would really make my life much worse.


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Offlinechibiabos
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: icetech] * 1
    #26688168 - 05/22/20 01:07 PM (1 month, 18 days ago)

The nitrogen you're probably thinking about is part of the indole.  The fact that it's 1P-LSD instead of LSD is because that nitrogen has a propanoyl substitution.  If you want to turn it into LSD then you need to deacylate it.  There are such things as acylases, and they do exist in your body, but in and of itself that doesn't necessarily mean that they'll be able to deacylate this molecule.  That being said the way that the propanoyl is actually bound to the nitrogen looks pretty much like a peptide bond so it's also possible that it could be attacked in a similar way.


Edited by chibiabos (05/22/20 02:03 PM)


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OfflinetacodudeS
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: chibiabos]
    #26690792 - 05/23/20 04:40 PM (1 month, 17 days ago)

So I'll share my experiences having had access to oxymorphone and oxycodone ir st seperate occasions having IV both. What I will say is I found oxycodone USELESS IV where it was like nearly injecting water. I believe because most of its activity fingers from its conversion to its morphine counterpart (oxymorphone) where when I would do what I'd consider small nasal doses of oxycodone I'd be nodding, which would be very strange as IV oxymorphone doses only caused me to nod even I stayed up too late.

Anyways my point being that it is likely skipping metabolism required to convert it to its active counterpart when using IV with prodrug based activity like 1p-lsd and oxycodone (while oxycodone I wouldn't say completely relies on the prodrug effect, but it converting to oxymorphone would explain a lot to me).


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Offlinechibiabos
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: tacodude]
    #26697104 - 05/26/20 01:36 PM (1 month, 14 days ago)

It's not really an invalid hypothesis but it's not really a scientific argument as it stands either.  A really cursory (emphasis on really cursory) look at the structure they managed to resolve for LSD binding to a 5-HT2B receptor (PDB: 5tvn) doesn't even make it that clear that the propanoyl would prevent it from binding to the receptor.  It could be plenty active on its own and more or less just be a stickier ligand than LSD.


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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: chibiabos]
    #26699229 - 05/27/20 11:00 AM (1 month, 14 days ago)

I love that we have people that actually look at how things work and not just scream that it's not the same effects and all that like usual :smile:


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OfflineFractal420
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Re: Pharmacokinetics and subjective effects of 1P‐LSD in humans [Re: icetech]
    #26700898 - 05/28/20 04:40 AM (1 month, 13 days ago)

As I was saying, some/many people believe 4aco isn’t fully active on its own, that acetylpsilo needs to turn to 4hydroxy, but if you IV the powder it sure as hell works

Oxycodone is 90% active orally and prolly less so via other methods, people who sniff it end up getting less bioavailability, no point in shooting it, it’s like sniffing a benzo

Also oxycodone is so much better than morphone IMO (same with hydro), though I’ve had some good times with dilaudid and opana, still no match for real oc. But I also realize I can’t use these opioids, I get way too into them. So it’s been like a decade, and I don’t plan to go back

I’m surprised at the Opi RC scene, all those people using iso and other powerful new analogs. It used to be the RC scene would not get into opioids, just tryps, phens, maybe some methylone and mxe. Now that mxe is harder to find people are using potent pcp analogs with opioid activity. Take care with that stuff! I imagine it might be nice tho


--------------------
Dreaming of That face again.
It's bright and blue and shimmering.
Grinning wide
And comforting me with it's three warm and wild eyes.

Prying open MY third eye



Edited by Fractal420 (05/28/20 04:49 AM)


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