I'm confused about this compound. Is it psychedelic? I see reports that it's a pure 5ht antagonist, but I also see a few sources that say it's an agonist aswell and that it's psychoactive but I see nothing definative. Can anyone shed some light on this for me?
lysergol?
- Thread starter toxide
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fastandbulbous
Bluelight Crew
It's not a psychedelic. There are a few compounds that are 5HT2a agonists, but are not psychedelics as it seems there also needs to be some action regarding secondary messengers that's needed for full psychedelic activity
^^^yes, it is the major receptor mediating the psychedelic effects of serotonergic hallucinogens. However, a single type of G-protein coupled receptor can couple to multiple downstream effectors, and the effectors to which it couples are dependent on how it is activated by an agonist. Different agonists will cause distinct conformational changes in the receptor, and thereby traffic the receptor stimulus selectively to certain signaling pathways. Is that clear or should I break it down a little more? I believe Bilz0r wrote a more extended treatment of this topic in the Erowid/Bluelight guide to neuropharmacology.
dimensiontripping
Bluelighter
5-HT2 said:
so for a psychedelic substance to be activated visually, mentally and physically different agonists have to affect the g-protein differently down the line? and what if the psychedelic does not affect serotonin directly? are there any psychedelics that do not affect serotonin or its levels in the brain minimally or not at all? Ive understood in my own experience the visual constants of psychedelic substances so ive concluded that many different substances are effecting the same parts of the visual cortex. but would there need to be different agonists to create different types of visuals? like fractals of lsd and 2c-e to the more quirky non mathematical ones shrooms sometimes produce?
Beenhead
Bluelight Crew
no, a molecule that is an agonist at the seratonin site causes the receptor (protein) to change shape. Different Molecules will casue the receptor to make different shapes, and thereby mediate the downstream effect that the receptor will signal too.
So for a drug to be psychedelic it must activate the 5ht2a receptor in a way to change its conformation so that the receptor signals downstream to the correct places that create the effects
Others may activate the 5ht2a in a way that does something completely different because it did not change the receptors conformation in the same way.
So for a drug to be psychedelic it must activate the 5ht2a receptor in a way to change its conformation so that the receptor signals downstream to the correct places that create the effects
Others may activate the 5ht2a in a way that does something completely different because it did not change the receptors conformation in the same way.
swilow
Bluelight Crew
^Could it be said then, that while 5HT2a activity is essential, it doesn't appear to be what actually ultimately causes the experience? That would have to be true for LSD in particualr, seeing as how it is expelled from the brain quickly and not much actually gets there. Are these drugs somehow activating endogenous psychedeli release 'downstream'?
Beenhead
Bluelight Crew
Did you make that assumption on your own or did you read it before in literature. Because it really shows intelligence or an understanding of a subject when you predict theory in your study. 
Yes that is what many people speculate! And the case you stated with LSD is why people started to think that.
Yes that is what many people speculate! And the case you stated with LSD is why people started to think that.
swilow
Bluelight Crew
^Both read and speculated.
psychedelicious
Bluelighter
Man, why do you guys need to make it so complicated? Acid fucks you up - that's all there is to it!
feelgoodhit
Bluelighter
^ pfffft n00b.
8)
8)
MattPsy
Bluelighter
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swilow said:
This was thought to be the case but it was actually not the case - the testing equipment used just wasn't sensitive enough.
What is for certain though is that LSD is one extraordinarily potent molecule! The second part of your statement is true.
No, I believe it is just the 5-HT2A receptor that causes the effects, but there is definitely a distinct conformation it must take to cause psychedelic effects - there are potent 5-HT2A agonists that aren't at all psychedelic (and it's not just because they can't get past the BBB or whatever).
LSD's effects at DA receptors seem to amplify it's effect, which is probably why strong dopaminergic stimulants seem to boost the effects of other psychedelics too
. (imo, they change the nature of them too... more electric, neon, geometrical and mathematical... but maybe that's just me, hehe)If the "cascade' theory were true it wouldn't be possible to stop trips with 5-HT2A antagonists. Having experienced a full blown psychosis trip reduced to soberity over the course of 20 mins from Risperidone, and seeing the same happen to friends given the same (Seroquel works good too), I can confidently say this isn't the case
.
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dorothyperkins
Bluelighter
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Are there any indications of the likely effects of these non-psychedelic 5HT2A agonists?
I speculate that the effects of the signalling cascade are short lived, and stop fairly quickly if no agonist binds to the receptor. The effects only continue as long as agonist molecules repeatedly bind to, trigger and dissociate from the receptor. Putting sufficient antagonist in there too reduces the frequency that agonist molecules bind and downstream signalling returns to normal.
I speculate that the effects of the signalling cascade are short lived, and stop fairly quickly if no agonist binds to the receptor. The effects only continue as long as agonist molecules repeatedly bind to, trigger and dissociate from the receptor. Putting sufficient antagonist in there too reduces the frequency that agonist molecules bind and downstream signalling returns to normal.
Morninggloryseed
Bluelight Crew
fastandbulbous said:
How do we know for sure? I've seen animal behavioral tests that seem to indicate LSD-like activity for lysergol...according to Hoffman himself.
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swilow
Bluelight Crew
Possibly because the 5-HT2A antagonists are also causing a inverted cascade effect? I don't see how its possible to say that 5HT2a agonism is purely reponsible for the effects, when there are 5=HT2a agonists with as much affinitey as LSD, that are not psychedelic. BOL-148 is described in TiHKAL as being "as potent a seratonin agonist as LSD". Shulging also noted that IV use of this compound did have some activity at 1 mg, and a 'short intoxication following 20 milligrams administered over a 20 minute period'...though he does mention that unreacted LSD may be present in the solution.
Jabberwocky
Frumious Bandersnatch
5HT2a agonism is certainly not essential in any logical sense.
Yet another reminder about how little we know about psychedelics. I'm strapped in for the next 50 years of psychedelic research, its going to be great!
Yet another reminder about how little we know about psychedelics. I'm strapped in for the next 50 years of psychedelic research, its going to be great!
swilow
Bluelight Crew
^There with you Mister S_S!
Hah
Bluelighter
- Joined
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some food for thoughts
The Adrenochrome Hypothesis and Psychiatry
A. Hoffer, M.D. Ph.D. and H. Osmond, M.D.
http://orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml
"Between 1954 and 1962 we treated several thousand alcoholics with psychedelic therapy using LSD, usually 200 to 400 mcg. In the usual reaction the first changes would occur in about one hour. Increased anxiety was usually the first reaction. Within two hours they would experience the usual reaction. Anxiety would fluctuate but was seldom high or a problem. However, many alcoholics did not have the usual reaction even with 400 mcg. They remained very tense and uncomfortable all the time. This group did not profit from their experience. In a few patients an injection of adrenochrome after two hours would, within a few minutes, bring on the typical LSD reaction. We concluded that LSD did not act as an hallucinogen per se but that it induced an increase in the production of adrenochrome which was the hallucinogen. An individual who could not make enough adrenochrome would not be able to have the typical LSD reaction. This conclusion was supported by our earlier finding that vitamin B3 markedly reduced the intensity of LSD reactions whether given before or during the LSD reaction. By blocking the adrenochrome effect it would also block the effect of LSD. It would also explain why bromo-LSD, a very potent antiserotonin, would not be an hallucinogen. bromo-LSD probably has no effect on adrenalin oxidation and would not increase the formation of adrenochrome. These are interesting speculations. Perhaps now with increasing interest in free radical hypotheses and in oxidized derivatives of the catecholamines, scientists will direct their interest back into these areas."
The Adrenochrome Hypothesis and Psychiatry
A. Hoffer, M.D. Ph.D. and H. Osmond, M.D.
http://orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml
"Between 1954 and 1962 we treated several thousand alcoholics with psychedelic therapy using LSD, usually 200 to 400 mcg. In the usual reaction the first changes would occur in about one hour. Increased anxiety was usually the first reaction. Within two hours they would experience the usual reaction. Anxiety would fluctuate but was seldom high or a problem. However, many alcoholics did not have the usual reaction even with 400 mcg. They remained very tense and uncomfortable all the time. This group did not profit from their experience. In a few patients an injection of adrenochrome after two hours would, within a few minutes, bring on the typical LSD reaction. We concluded that LSD did not act as an hallucinogen per se but that it induced an increase in the production of adrenochrome which was the hallucinogen. An individual who could not make enough adrenochrome would not be able to have the typical LSD reaction. This conclusion was supported by our earlier finding that vitamin B3 markedly reduced the intensity of LSD reactions whether given before or during the LSD reaction. By blocking the adrenochrome effect it would also block the effect of LSD. It would also explain why bromo-LSD, a very potent antiserotonin, would not be an hallucinogen. bromo-LSD probably has no effect on adrenalin oxidation and would not increase the formation of adrenochrome. These are interesting speculations. Perhaps now with increasing interest in free radical hypotheses and in oxidized derivatives of the catecholamines, scientists will direct their interest back into these areas."
swilow
Bluelight Crew
^Most peoplemdon't find adrenochrome to be psychedelic though.