That’s not necessarily so. They may not be active because they can't cross the blood brain barrier on their own. But could be very active if injected directly into the brain. I don't believe any of them were ever injected directly into the human brain to test for activity within the human brain. Any breakdown or byproducts that cannot pass the blood brain barrier that form within the brain may be active in the brain because they don't need to pass the blood brain barrier.

Very little tests have been done on what forms within in the human brain. Most of these tests are based on urine analysis, not by examining alkaloids that have formed in the human brain that have bound to neurotransmitter sites in the brain.

True but also maybe not many studies have been done looking for LSD specifically in brain tissue either. Maybe it has I dunno?

Receptor binding studies could also at least give an idea of what is more potent etc. But yea to answer that question may require extensive literature review to see if its been done. SAR relationships etc.

If LSD forms a compound in the brain that is water soluble, it would not likely be effective if ingested orally or injected (unless injected into the brain), because it wouldn't pass the blood brain barrier. Researchers would think it’s inactive because they don’t normally inject drugs into human brain tissue to test for activity. If it formed inside the brain, it doesn’t need to enter the brain. LSD could simply serve as a way of passing it through to the brain, where it then forms and becomes active.

The effect of LSD peak after LSD is already nearly gone from your body. I don’t think LSD causes the experience. It doesn’t sound right to me. With psychedelics like DMT, it’s the DMT that is obviously causing the effects because it peaks when brain levels are at their peak and diminishes as the brain levels of DMT diminish. There’s a direct correlation. I believe the same is true for most psychedelics, but NOT LSD. That’s why I don’t think LSD is active, and that it must be a byproduct or break down product of LSD that’s doing all the magic.

Or it could be rapid withdrawal effects of LSD that are doing the magic. Hmmm.

In other words, LSD could simply be a prodrug of an unknown metabolite that forms in the brain after LSD enters it. There are many prodrugs that work on this very same idea. It is reasonable that LSD could be a type of prodrug.

LSD does bind to receptors in our brain that's been proven. Seriously check out what structure activity relationships have been done on LSD it could help answer this question. I simply don't feel like looking through the literature but I do agree with you in theory what you are saying is possible and it does happen with certain compounds. Heroin turns into morphine in the brain and thus becomes activated in a sense.

Most studies look at urine or blood like we said and thats not a good way to say whether or not LSD is hanging out in the brain or not or whether or not one of its metabolites are binding to receptors in our brain. Those studies are doable and may have been done.

All of this is absolute gold. Its amazing keep up the good posting.

I'm really, really interested to learn more on this.

Keep going!

Even Hoffman thinks that LSD is a prodrug of some sort because it is eliminated from the body so fast. He talked about it in; LSD: My Problem Chilc

bump

Everything points in the direction of it being a prodrug.

When i take LSD, it always takes 1 hour before the psychedelic effects start. It doesn´t matter whether i have an empty stomach or not, it doesn´t matter whether i swallow it or put it under my tongue, it´s always 1 hour, give or take a few minutes.

If it would affect the brain directly you would expect it to hit faster, and you would expect different methods of ingesting under different circumstances to lead to a greater variation.

I think that it enters the bloodstream pretty fast, but that metabolising it into the real active compound(s) always takes exactly X minutes.

come up can start in less than 20 minutes, different metabolism rate?

In all the hundred's of times i took acid, it always took around one hour. I never had it working within even 45 minutes.
Physical sensations start almost immediately, but for me the psychedelic effects always take no more and no less than an hour to start.
I think this is true for the majority of people.

Yeah, I was lumping physical effects in with 'come up' but I see what you're getting at.

Wich makes it all the more plausible that it indeed IS a prodrug. How can something have physical effects, almost from the moment that you take it, while it takes a full hour for the colours and lightshow to begin?

My employer has been threatening the workforce with random drug testing for a couple of years now. So far nothing has come of it except sending round a document detailing what they would test for. One of the categories they list is "popular" hallucinogens although they aren't specific on what the popular hallucinogens are.

Its claimed in the document that they can use gas chromotography to detect hallucinogens. I'm not sure how effective this is.

W

I experience a very pleasurable warming sensation and pooling of energy about 25 minutes in. Full psychadelia by 45. Always a faster peaker than anyone else I ever voyage with. I have a reasonably fast metabolism and am unfortunately hardheaded with almost every other psychadelic.

This theory of lsd being a prodrug has a lot of credibility, imo.

Whenever LSD is consumed, SWIM notices the effects immediately. Pretty much, as soon as it touches his tongue he knows that he ate something that's gonna make him feel a little funny. Visuals start at about the 45 min to 60 min mark. The idea of LSD as a prodrug really excites me and I wish that more research was being done to verify this.
Does anyone have any thoughts on as to why the trip itself is 'wavy'? With upswings and downswings?

For Swim usually it took 30-40 min to even start feeling any changes, but the last 2-3 experiences were unusually fast, deep and powerful.

She was peaking in less than 20 min. The peak lasted at least 2 hours. Judging by the trip content, undoubtedly it was the acid. Could it be some kind of sensitization to the drug?

Speaking from personal experience I am of the opinion that LSD is a pro-drug.Many moons ago when I aspired to the DMT experience but had absolutely no way of obtaining the said item, I injected LSD intravenously in an attempt to reproduce an experience akin to a psychedelic blast-off.My guestimate of the dose would be 80-100mcg.

There was absolutely NO discernible rush at all.However, I did begin to feel it after about 10 minutes and the time to the peak took approximately 90 minutes as opposed to almost 180 minutes and the peak experience was not noticeably more impressive than taking the same dose orally.Once the peak was reached the tempo of the trip was identical to the oral route.

This suggests excellent oral bioavailability for LSD.

SPINAL FLUID!!????? Are you suggesting that they sometimes take spinal fluid to test for substances?

Yeah, i also notice the effects immediately. But those are the physical effects. The psychedelic effects always take an hour to kick in.

I think that almost every psychedelic has this wavy character you describe (besdides vaped DMT maybe). LSD has it much more than other drugs though.

Why this is is indeed an intruiging question. As far as i know, you hardly see ever see this effect in other than psychedelic substances. You clearly don't have it with alcohol.
The case of LSD also makes it clear that this effect can't have anything to do with the speed at wich it's entering the bloodstream.

It could ofcourse have something to do with the metabolism of LSD into the substance that realy affects the brain, if LSD is indeed a prodrug.
But it's probably much more complex than that.