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Offlinepsillyboy
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Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD * 2
    #26539237 - 03/16/20 09:09 PM (2 months, 11 days ago)

https://psychedelicreview.com/study-finds-ald-52-1p-lsd-and-1b-lsd-are-prodrugs-of-lsd/

In a November 2019 study published in Neuropharmacology, researchers tested whether the LSD (lysergic acid diethylamide) derivatives ALD-52 (1-acetyl-LSD), 1P-LSD (1-propanoyl-LSD), and 1B-LSD (1-butanoyl-LSD)  are active compounds or prodrugs of LSD.1 The scope of the study included learning about the pharmacological effects and mechanism of action of these 1-acyl-substituted LSD derivatives.



Study Design
The study used a three-pronged approach for testing the LSD derivatives: competitive binding studies and calcium mobilization to examine the interaction with serotonin receptors, head twitch response (HTR) studies in mice to assess in vivo activation of serotonin 5-HT2A receptor, and LC/MS (liquid chromatography/ion trap mass spectrometry) to quantify the amount of LSD in the blood of rats treated with two of the three derivatives.

Serotonin Receptor Interaction and Activation
The binding affinity data indicated that the 1-acyl substitution on the LSD derivatives reduced their affinity for 5-HT1A compared to LSD (9.5 nM). The magnitude of the effect depended on the length of the acyl group (note that the higher the Ki, the less affinity the compound has for the receptor):

1B-LSD: Ki = 345 nM = 36-fold lower affinity than LSD.
1P-LSD: Ki = 637 nM = 67-fold lower affinity than LSD.
ALD-52: Ki = 1,054 nM = 111-fold lower affinity than LSD.
For 5-HT2A, an acetyl or propanoyl group on LSD’s indole nitrogen reduced receptor affinity by more than 10-fold compared to LSD (14.7 nM). Substitution with a butanoyl group reduced affinity around 5-fold:

ALD-52: Ki = 174 nM
1P-LSD: Ki = 196 nM
1B-LSD: Ki = 87.7 nM
Interestingly, the 1-acetyl substitutions increased the affinity of the derivatives at 5-HT2C by about 2-4-fold compared to LSD (45.3 nM):

ALD-52: Ki = 10.2 nM
1P-LSD: Ki = 13.0 nM
1B-LSD: Ki = 20.8 nM
After determining the receptor binding affinity for the three LSD derivatives, tests using Gq-mediated Ca2+ flux in HEK cells (calcium mobilization) examined whether the derivatives activated the serotonin receptors.

The data showed that ALD-52, 1P-LSD, and 1B-LSD were very weak partial agonists at the human 5-HT2A compared to LSD. Interestingly, despite showing comparatively high affinity for 5-HT2B and 5-HT2C, the compounds showed no agonist activity at those receptors. This behavior is in contrast to LSD, which is an agonist at recombinant human 5-HT2B and 5-HT2C receptors.

The study also assessed the binding affinity of 1B-LSD for 24 other monoamine receptors. Overall, the data indicated that 1-butanoyl substitution had a detrimental effect on binding to most of the receptors, compared to previously reported data for LSD. The binding affinity at these receptors was 10-100-fold lower than for LSD. The two main exceptions were 1B-LSD binding at the 5-HT2C receptor, as discussed earlier and 5-HT2B.

HTR Testing
Although the data indicated the 1-acyl substitution on the derivatives reduced their affinity and efficacy at 5-HT2A, ALD-52, 1P-LSD, and 1B-LSD still induced head twitches in mice and showed a relatively high potency compared to other hallucinogens. The authors noted that “…the rank order of potency of the four lysergamides is inversely proportional to the length of the substituent present on the indole nitrogen.” ALD-52 had about half the potency of LSD and 1P-LSD about one-third. The potency of 1B-LSD was only 14% of LSD.

LC/MS Analysis
The authors reported that the LC/MS analysis indicated, “High levels of LSD were detected in the plasma of rats after subcutaneous administration of ALD-52 and 1P-LSD, demonstrating these compounds are rapidly and efficiently deacylated in vivo.” The authors noted that ALD-52 and 1P-LSD appeared to undergo deacetylation at roughly the same rate. This theory was evidenced by the rats have almost identical plasma levels of LSD after being treated with either compound.

In addition to LSD, the analysis also detected ALD-52 and 1P-LSD in the plasma along with several of their metabolites. The data correlated with previously published results for rats and humans.

The Importance of Identifying and Understanding Prodrugs
Prodrugs expand drug formulation options by having different solubilities and other physical properties. A prodrug can take the place of a drug that doesn’t have adequate pharmacokinetic or biopharmaceutical activity in the body. They can also provide solutions for compounds that are toxic or have undesirable side effects. Prodrugs may also present an array of options when it comes to harnessing the entourage effect for developing targeted formulations.

The principal finding of this study is that ALD-52, 1P-LSD, and 1B-LSD are prodrugs of LSD. Additional aspects of this work indicate that 1-acyl substituted LSD derivatives are potent hallucinogens despite having less efficacy at the 5-HT2A receptor. Scientists will apply these findings and design new experiments that will answer (and, as is the nature of science, create) additional questions about how psychedelic drugs work


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: psillyboy] * 1
    #26539462 - 03/16/20 11:05 PM (2 months, 10 days ago)

Well that puts the nail in the coffin of that debate :smile:


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: Psicomvb]
    #26539637 - 03/17/20 12:57 AM (2 months, 10 days ago)

So cool to finally see this. But I'm sure people will continue to talk about how they can distinguish ALD-52 from LSD. WHo needs a LC-MS/MS when you have a burn out who's tried LSD and ALD-52 a few times?

It's also interesting that the acylated compounds appear to be antagonists at 5HT2B and 5HT2C.


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OfflineHolybullshit
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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: breeg89] * 1
    #26540158 - 03/17/20 09:44 AM (2 months, 10 days ago)

Quote:

breeg89 said:
So cool to finally see this. But I'm sure people will continue to talk about how they can distinguish ALD-52 from LSD. WHo needs a LC-MS/MS when you have a burn out who's tried LSD and ALD-52 a few times?

It's also interesting that the acylated compounds appear to be antagonists at 5HT2B and 5HT2C.




Well, the come up could be different, and differences in ratios/rates of metabolism means it would be quite difficult to figure out truly equipotent dosages...and taking into account how different the affects can be at different dosages...I'm sure they do "feel" slightly different. But yeah, overall they should be pretty much exactly the same(which has been my experience).

I mean, if I gave you 100 mcg of LSD one time and 150 mcg of LSD another time and told you they were equipotent doses of the different substances you'd probably believe me.

Same deal with conversion rates, if I gave you a time release version of one drug and an instant release version of the same drug, you could probably tell them apart pretty reliably after enough experiences. Although the type of experience you get from psychedelics, and what I am guessing a pretty short half lives from these analogs, makes this hypothetical less relevant.

Don't mistake me though, I'm an obsessive contrarian but I absolutely agree with what you are saying. Especially qualitatively, which is what the people you are referring to are talking about, they are pretty much indistinguishable.

The information about 5-HT2B activity is quite comforting, that has been my main concern regarding LSD analogs...not that I really take them often enough to worry about valve damage, but still.

What I would like to see is, first half life, and then some data regarding dopaminergic activity. I don't think it would really change the recreational experience, but it could have some impact on micro-dosing IF(big if) the half lives of any of the parent compounds are long enough to matter(which I am doubtful of or you'd think people would trip for longer on these compounds than straight LSD).


Edited by Holybullshit (03/17/20 10:03 AM)


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: Holybullshit]
    #26540872 - 03/17/20 04:07 PM (2 months, 10 days ago)

^ All good points. More quantitative pharmacokinetic data would be cool.


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: breeg89]
    #26541206 - 03/17/20 07:21 PM (2 months, 10 days ago)

Welp, that's that.  Thanks for posting this.  Very informative.


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: psillyboy] * 1
    #26542323 - 03/18/20 11:22 AM (2 months, 9 days ago)

Quote:

psillyboy said:
https://psychedelicreview.com/study-finds-ald-52-1p-lsd-and-1b-lsd-are-prodrugs-of-lsd/
The authors noted that ALD-52 and 1P-LSD appeared to undergo deacetylation at roughly the same rate. This theory was evidenced by the rats have almost identical plasma levels of LSD after being treated with either compound.





Quote:

psillyboy said:
https://psychedelicreview.com/study-finds-ald-52-1p-lsd-and-1b-lsd-are-prodrugs-of-lsd/

The data showed that ALD-52, 1P-LSD, and 1B-LSD were very weak partial agonists at the human 5-HT2A compared to LSD



Quote:

psillyboy said:
https://psychedelicreview.com/study-finds-ald-52-1p-lsd-and-1b-lsd-are-prodrugs-of-lsd/

Although the data indicated the 1-acyl substitution on the derivatives reduced their affinity and efficacy at 5-HT2A, ALD-52, 1P-LSD, and 1B-LSD still induced head twitches in mice and showed a relatively high potency compared to other hallucinogens...ALD-52 had about half the potency of LSD and 1P-LSD about one-third.




Can anyone explain this to me? How is it that blood plasma levels of LSD are identical in mice after being treated with both ald52 and 1p, and that deacetylation happens at the same rate with great efficiency and speed, yet the potency of 1p is only 2/3 that of ald52 despite the fact that both compounds have very weak 5HT2A affinity relative to LSD?


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: psillyboy]
    #26542406 - 03/18/20 12:15 PM (2 months, 9 days ago)

This study shows that these drugs are active and do bind to some receptors. Yes, it shows that they're also prodrugs (which we already knew), but it also shows that they do in fact bind to stuff, and that they have a different binding profile than LSD.


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: nooneman]
    #26542455 - 03/18/20 12:41 PM (2 months, 9 days ago)

Yes, that's clear. However, I wouldn't have thought the effects would be so strong? You'd think given the characterization from the study that the differences between actual 1p effects vs ald52 effects would be more negligible relative to the effects of the LSD they both convert into than to warrant ip being only 2/3 the potency of ald52.

At any rate, this suggests that we should actually expect a not insignificant qualitative difference between these analogs and LSD itself, these differences owing to the effects of these acetyl-lysergamides prior to deacetylation and conversion to LSD in the body.


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: ReynardTheFox] * 2
    #26542479 - 03/18/20 01:00 PM (2 months, 9 days ago)

LSD's potency is partially because it gets trapped in receptors and binds continuously. If you just looked at its binding profile, you wouldn't expect it to be as active as it is. I wouldn't be surprised if these do as well, which might make their effects much more apparent despite the relatively low affinity.

Take LSD's affinity for dopamine receptors. According to its binding affinity, LSD shouldn't have any dopamine activity at recreational levels, yet it clearly does, possibly because it seems to get trapped in receptors on the rare occasions when it does bind. If these lysergamides work the same it might amplify their effects relative to their binding affinities.


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OfflineReynardTheFox
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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: nooneman]
    #26542582 - 03/18/20 02:01 PM (2 months, 9 days ago)

The study says that the analogs had reduced binding affinity and also less efficacy at the 5HT2A receptor. They were shown to have not only weaker binding affinity than LSD, but also much weaker agonism.

I appreciate your input, I'm just still not convinced that your explanation explains the difference. Weak agonism plus the fact that these lysergamides are rapidly and efficiently metabolized into LSD should still render almost the entire experience to be caused by the LSD rather than the prodrugs themselves, and if 1p and ald52 metabolize into equal amounts LSD then I don't see where this huge discrepancy in potency between 1p and ald52 can be coming from.


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: nooneman]
    #26543018 - 03/18/20 06:34 PM (2 months, 9 days ago)

Quote:

nooneman said:
This study shows that these drugs are active and do bind to some receptors. Yes, it shows that they're also prodrugs (which we already knew), but it also shows that they do in fact bind to stuff, and that they have a different binding profile than LSD.




But their affinities/activity are so low(and probably short half lives as well) that they won't have much activity at the doses usually taken.

Quote:

If you just looked at its binding profile, you wouldn't expect it to be as active as it is.




Really? its affinity for 5-ht2a is 2.3 nanomolars.

It is its extremely low dissociation rate(how tightly it binds to the receptor) which explains its unusually long duration of action, that you wouldn't necessarily expect given its half life...I think this is probably what you are trying to describe.

Quote:

I wouldn't be surprised if these do as well, which might make their effects much more apparent despite the relatively low affinity.




Even if what you were saying was true(which I am not sure it is, I mean yes LSD "sticks" to the receptor or in other words has a low dissociation constant, but thats what affinity is)...their affinity is still relative to LSD, so unless this "special" action at the receptors happened to a MUCH higher degree for the analogs than  for LSD then it doesn't matter.

-------------

We all know how much a persons headspace can affect the trip, and the "come up" could have the effect of altering ones headspace heading into the trip. Differences in come up can be explained by the data seen here, and differences in come up can affect the rest of the trip. But that doesn't nean the pharmacological action is any different from LSD a few hours in.


Edited by Holybullshit (03/18/20 10:28 PM)


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: Holybullshit]
    #26543172 - 03/18/20 07:53 PM (2 months, 9 days ago)

I wonder if this means that the analogues can induce more nausea than regular LSD. Im not sure if thats exactly how it works, but im pretty sure Zofran helps with nausea because of its 5-ht2c antagonism.


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: psillyboy]
    #26543464 - 03/18/20 10:28 PM (2 months, 8 days ago)

noice


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: trvptamine]
    #26543475 - 03/18/20 10:34 PM (2 months, 8 days ago)

Generally its 5-ht3 antagonism that helps nausea...there are some selective 5-ht2c agonists(think Locaserin) which can have nausea as a side effect, but their action at the receptor is much more selective than what you see here. LSDs affinity 5-10x higher at 5-ht2a then these analogs are at 5-ht2c...I would think you are correct and their increased affinity might mean a higher likelihood to induce nausea in some people, but overall they are still quite a bit more selective for 5-ht2a in practice(as prodrugs), but that would depend on their efficacy at said receptor and what kind of doses we are talking about.

I imagine its more likely that other targets and downstream effects are a more primary cause of nausea at lower dosages but their increased 5-ht2c affinity could play a larger role at higher dosages, depending on their IA at the receptor.


Edited by Holybullshit (03/19/20 09:36 AM)


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: Holybullshit]
    #26545789 - 03/20/20 04:01 AM (2 months, 7 days ago)

LOL.
How stupid... so like, you're saying, if we turn a crystalline structure over on its side, or re-arrange the composition of microscopic crystals... it modulates the frequency of the piezoelectric fields induced by our bio-electric fields... and is still coming from the ergamine precursor. Wow. Good job, science team, bravo, wow, really nice work, oh me oh my. Now, Pro-Drug is a term I disagree with. It is overly simplistic and is often used as white collar slang, which is not something we should ethically be advising.

Your (scientific community) inferiority complex is justified by your countless endeavors to make something very simple seem very complicated. Ergo, Ergot with different body load. *Slow hand clap* You got me laughing at the title. Thank GOD we burned most of our medical documents, to keep them away from you disgusting Americans.

I think people nerd out too much, thinking they'll understand the human brain if they JUST DO ENOUGH MATH!!!! Lol, don't you think our computers fuck with people? Do you not understand that to truly understand this, you would have to be reliant completely on analog? Not Anal logs, for you monkeys out there.


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: 999]
    #26545890 - 03/20/20 07:25 AM (2 months, 7 days ago)

Quote:

999 said:
LOL.
How stupid... so like, you're saying, if we turn a crystalline structure over on its side, or re-arrange the composition of microscopic crystals... it modulates the frequency of the piezoelectric fields induced by our bio-electric fields... and is still coming from the ergamine precursor. Wow.




I'm sorry, what?

Pro-drug isn't slang, it is when a parent compound is metabolized into another active drug...usually one that is responsible, or mostly responsible, for the effects resulting from ingestion of the original compound.

So even if the analogs discussed here are more active at 5-ht2c than 5-ht5a because they are quickly metabolized into LSD, the majority of activation after consumption will be found at 5-ht2a, not 5-ht2c...thats what I meant by "in practice". In fact, depending on how quickly they are metabolized very little of the effects may be coming from the parent compound.

And I'm not quite sure what you mean by "ergot/ergot with different body load"...as most of LSD's psychedelic activity is from activation of the 5-ht2a receptor, as you can see the analogs are many orders of magnitude less potent at said receptor...so at the doses consumed they probably aren't producing much psychedelic effect at all, at least not the effects we associate with 5-ht2a.

And by "we" do you mean the Nazi's? Is that someone you regularly use the royal we with? Though it wouldn't be surprising that is a group you would readily associate yourself with considering your anti-intellectual leanings.


Edited by Holybullshit (03/20/20 07:36 AM)


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: 999] * 1
    #26546064 - 03/20/20 10:08 AM (2 months, 7 days ago)

Quote:

999 said:

Thank GOD we burned most of our medical documents, to keep them away from you disgusting Americans.






WTF is this? What country are you in? You seem like a pseudo intellectual asshole. I've been doing LSD and various chems of the like (people would say it was LSD, I have no lab to confirm, never did) since 1979 by the way. Why take a jab at "disgusting americans"?


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: psillyboy]
    #26548155 - 03/21/20 08:05 AM (2 months, 6 days ago)

ive always wondered...how can it be a prodrug yet have a shorter duration than LSD?


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: Holybullshit]
    #26548248 - 03/21/20 09:24 AM (2 months, 6 days ago)

Quote:

hTx said:
ive always wondered...how can it be a prodrug yet have a shorter duration than LSD?



As far as i understand only al-lad has a shorter duration and that was not part of the study.



Quote:

Holybullshit said:
Quote:

999 said:
LOL.
How stupid... so like, you're saying, if we turn a crystalline structure over on its side, or re-arrange the composition of microscopic crystals... it modulates the frequency of the piezoelectric fields induced by our bio-electric fields... and is still coming from the ergamine precursor. Wow.




I'm sorry, what?

Pro-drug isn't slang, it is when a parent compound is metabolized into another active drug...usually one that is responsible, or mostly responsible, for the effects resulting from ingestion of the original compound.

So even if the analogs discussed here are more active at 5-ht2c than 5-ht5a because they are quickly metabolized into LSD, the majority of activation after consumption will be found at 5-ht2a, not 5-ht2c...thats what I meant by "in practice". In fact, depending on how quickly they are metabolized very little of the effects may be coming from the parent compound.

And I'm not quite sure what you mean by "ergot/ergot with different body load"...as most of LSD's psychedelic activity is from activation of the 5-ht2a receptor, as you can see the analogs are many orders of magnitude less potent at said receptor...so at the doses consumed they probably aren't producing much psychedelic effect at all, at least not the effects we associate with 5-ht2a.

And by "we" do you mean the Nazi's? Is that someone you regularly use the royal we with? Though it wouldn't be surprising that is a group you would readily associate yourself with considering your anti-intellectual leanings.




:whathesaid: or :whatshesaid:


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: hTx]
    #26548418 - 03/21/20 11:04 AM (2 months, 6 days ago)

I've never found ald52 to be shorter duration. That's assuming it was actually ald52. Who knows? Definitely at least LSD. Perhaps your blotters were something different? Definitely shouldn't be shorter duration. How many times have you done it? Was it your dose maybe?


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: Holybullshit]
    #26548482 - 03/21/20 11:35 AM (2 months, 6 days ago)

Quote:

Holybullshit said:
Generally its 5-ht3 antagonism that helps nausea...there are some selective 5-ht2c agonists(think Locaserin) which can have nausea as a side effect, but their action at the receptor is much more selective than what you see here. LSDs affinity 5-10x higher at 5-ht2a then these analogs are at 5-ht2c...I would think you are correct and their increased affinity might mean a higher likelihood to induce nausea in some people, but overall they are still quite a bit more selective for 5-ht2a in practice(as prodrugs), but that would depend on their efficacy at said receptor and what kind of doses we are talking about.

I imagine its more likely that other targets and downstream effects are a more primary cause of nausea at lower dosages but their increased 5-ht2c affinity could play a larger role at higher dosages, depending on their IA at the receptor.





Lol, you want some crackers with that salt??


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Offlinesk8fast
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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: illustrain]
    #26548631 - 03/21/20 12:50 PM (2 months, 6 days ago)

I've only tried the analogue AL-LAD of LSD and it had shorter effects and seemed to have a euphoric push to it like it couldn't ever get a dark tone to it like some of my LSD trips. Maybe it was the dosage. I'm not saying LSD is dark AL-LAD was just lighter and more cartoonish than LSD to me


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: ReynardTheFox]
    #26548794 - 03/21/20 02:13 PM (2 months, 6 days ago)

I had legit 1p-lsd, lasts about 9 hours versus lsd which is 12 hours.


...
I thought this was common knowledge.


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OfflineReynardTheFox
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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: sk8fast]
    #26551192 - 03/22/20 05:15 PM (2 months, 5 days ago)

How many acid trips do you have under your belt? In my experience, LSD can be many things and have quite different qualities from trip to trip. It's not always as easy to distinguish between these drugs as one might assume. That's been my experience at least. Dose too might be an issue.


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OfflineHolybullshit
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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: sk8fast]
    #26551635 - 03/22/20 09:29 PM (2 months, 4 days ago)

Quote:

sk8fast said:
I've only tried the analogue AL-LAD of LSD and it had shorter effects and seemed to have a euphoric push to it like it couldn't ever get a dark tone to it like some of my LSD trips. Maybe it was the dosage. I'm not saying LSD is dark AL-LAD was just lighter and more cartoonish than LSD to me




AL-LAD was not part of this study.

But I absolutely agree with your assessment of AL-LAD, I especially enjoy it for day tripping.

Quote:

ReynardTheFox said:
...In my experience, LSD can be many things and have quite different qualities from trip to trip. It's not always as easy to distinguish between these drugs as one might assume...




^THIS, a million times this.

LSD itself can feel like a different drug from one experience to the next, especially at different dosage levels...so OF COURSE if you give someone a different compound(which turns out to be a prodrug) they are going to say it feels "different" from LSD. Even moreso when they have only used true LSD a handful of times.


Edited by Holybullshit (03/22/20 09:55 PM)


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OfflineHolybullshit
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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: hTx]
    #26551646 - 03/22/20 09:35 PM (2 months, 4 days ago)

Quote:

hTx said:
I had legit 1p-lsd, lasts about 9 hours versus lsd which is 12 hours.


...
I thought this was common knowledge.




It's not...what is common knwoledge is that EITHER LSD or 1p can last 9-12 hours during any given experience depending on a plethora of factors...such as tolerance, how much sleep you had that week, what you ate that day, time of ingestion, how well it was absorbed, personal biology at any given time and especially dosage, and a layman without data which isn't even known yet can't possibly calculate equipotent dosages of each drug(except ballpark figures from anecdotal reports). So its like taking 75mcg of LSD one time and it lasting x amount, 100mcg of LSD another time and it lasting y amount and declaring that tye MUST be different drugs.

Even though LSD's trip length and intensity can vary from trip to trip even at the exact same dosage.

Also, the thing about prodrugs is that even though you would assume they would last longer because of the conversion happening over time...it also means that peak plasma levels may/will be lower than if you had taken M1 from the start..., for most drugs this doesn't mean much BUT LSD's long duration of action is not explained by its half-life, which is only 3.6 hours, its explained by its extremely low dissociation rate, so lower peak plasma levels could in fact affect the length of the experience.

To put it simply, even IF you could calculate a dosage that would lead to the same area under the curve if peak plasma levels differed it wouldn't be unimaginable that DoA would be affected.

-------------

The fact of the matter is, any differences between LSD and the analogs listed here are probably mostly due to pharmacokinetics and not pharmacodynamics.

The come up may be somewhat affected by pharamacodynamics, and ones headspace being shifted by the come up could affect how one feels through the rest of the trip...but for the remaining 90% of the experience any differences felt can be chalked up to pharamcokinetics and ones own expectations.

Don't underestimate how much ones own expectations could color the experience...people read about the "differences" in these compounds before taking them and it becomes a self-fulfilling prophecy.


Edited by Holybullshit (03/24/20 09:40 AM)


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OfflineHolybullshit
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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: illustrain]
    #26555492 - 03/24/20 06:57 PM (2 months, 3 days ago)

Quote:

illustrain said:
Quote:

Holybullshit said:
Generally its 5-ht3 antagonism that helps nausea...there are some selective 5-ht2c agonists(think Locaserin) which can have nausea as a side effect, but their action at the receptor is much more selective than what you see here. LSDs affinity 5-10x higher at 5-ht2a then these analogs are at 5-ht2c...I would think you are correct and their increased affinity might mean a higher likelihood to induce nausea in some people, but overall they are still quite a bit more selective for 5-ht2a in practice(as prodrugs), but that would depend on their efficacy at said receptor and what kind of doses we are talking about.

I imagine its more likely that other targets and downstream effects are a more primary cause of nausea at lower dosages but their increased 5-ht2c affinity could play a larger role at higher dosages, depending on their IA at the receptor.





Lol, you want some crackers with that salt??




Excuse me? What's that supposed to mean?


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: lifeiswhatyoumake]
    #26611380 - 04/18/20 09:45 PM (1 month, 8 days ago)

Love this


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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: Holybullshit]
    #26614102 - 04/20/20 01:42 AM (1 month, 7 days ago)

Well i did do a shit load of reading on 1p before i took it.

Thanks for the info about LSD length of trip not wholly related to half-life i did not know that.
I remember reading reddit for a while and everyone seemed to agree that 1p was shorter in duration, had a different feel to it and could be a prodrug of 25.

I dosed 200ug and it was pretty tame, didnt last but maybe 8 hours total...girlfriend took 300ug and liked it.
The main difference i noticed was the headspace was a lot less trippy than L..i guess it WAS actually L but with the pro-drug conversion only what are you saying..1/3 the potency? Maybe even less. 100ug of real L was/is trippier/more profound than 300ug of 1p...been years though so tough to say from memory i remember being a bit unimpressed by it though.
I took 200ug of real L maybe a few months after 1p thinking i had a good idea of how it would affect me...
and MY GOD it was nothing like 200ug of 1p. It was WAY more intense. WAY trippier headspace and thoughts...even experienced ego-death and a feeling of being reborn..it was fucking amazing!


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OfflineHolybullshit
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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: hTx] * 1
    #26614728 - 04/20/20 11:12 AM (1 month, 7 days ago)

I wouldn't be surprised if in HUMANS more than 1/3(of what actually reaches the bloodstream) gets converted to LSD...but it gets introduced to the bloodstream more slowly, meaning peak plasma levels won't get as high, and if peak levels never get as high it won't occupy as great a number of receptors and even if similar levels of occupancy are achieved it would be hard to predict how the trip would be affected by how quickly those occupancy levels are achieved. It's kind of like IV cocaine vs snorted...it's a totally different experience, you'd never think they are even the same drug, snorting more cocaine won't change that. I'm sure it has something to do with your bodies innate allostasis mechanisms, which allows it to temper the experience depending on how quickly occupancy is achieved.

Bottom line is the pharmacokinetics obviously change the experience, even if similar occupancy levels are achieved(which is far form guaranteed even at a higher dose) the shape of the curve will be different and this changes the effects. And as I previously stated, LSDs long duration is as much(or likely more) due to its extremely high affinity than its half life...so even at an "equipotent" dosage one shouldn't expect the duration to mirror LSD, even LSDs duration can vary pretty greatly at the same dosages from trip to trip, for a plethora of reasons...not to mention sublingual administration is not a very reliable delivery method, as far as consistency goes.

I'm not arguing, and I don't think many(if any) are, that LSD and all these analogs will provide the exact same experience...too many variables and its obviously very nuanced. Although I think they are a LOT closer than what many people would have you believe. But there is no arguing with the science...these are pro drugs for LSD and their actions, for almost all intents and purposes, for the majority of the experience, are caused by LSD.

I put that in bold because at the beginning, during the come up and shortly after, these substances are probably exerting effects of their own and coloring the experience...there is no predicting how what head-space this puts one in affects the rest of the trip nor what affect it has on allostasis nor future occupancy levels of LSD.

Also, this whole thing becomes much cloudier and confusing because very often when people think they are taking "real" LSD, they aren't...they are taking an RC which isn't even a lysergamide...it could be that they are getting an experience closer to LSD from these analogs than from the supposed "real" LSD they took on some other occasion. Not that these substances aren't extremely powerful and capable of providing great experiences in and of themselves, they are just different from LSD...in my experience LSD provides a much clearer headspace than most of the super potent RCs which are capable of being delivered on blotter/gel.


Edited by Holybullshit (04/20/20 11:26 AM)


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OfflineAz88
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Re: Study Finds ALD-52, 1P-LSD, and 1B-LSD Are Prodrugs of LSD [Re: Holybullshit]
    #26648800 - 05/04/20 08:01 PM (24 days, 1 hour ago)

Thank you for sharing this. ...now to find 1B-LSD in America...


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