The Big and Dandy Endogenous Psychedelics Thread (mega-merged)!

[mad_chemist]

I agree with the latter statement, but not the former; they don't call it the "DMT flash" for nothing.

i'd definitely call a flash an NDE, more significantly so than a "k-hole"


methylation of n-acetyl-serotonin would give DMT; there are a few psychoactive compounds (including 5-MeO-DMT) that are derived (metabolized) from 5-HT, melatonin, and 5-HIAA

 

[crOOk]

@BilZ0r
Darkness is NOT equals to no sensory input.
Psychosis still alive? Like, the guy who was exposed to the lack of sensory input went bonkers? Or the guy who got the wicked idea to write that shit? It might be psychosis, yes.
BUT, sometimes, meaning always, "WE" have to do a reality check, too, you know. All that shit how geniusses were always taken for mad fools in the past.
Examples are Christopher Columbus, Mihir Bose, Adolf Hitler, no wait... Hitler was the other way around actually. Anyway, Hittler's not the point, you get the idea... Blahblahblah...

crOOk

 

[BilZ0r]

Yes, but the arguement was crook, that because of the complete darkness that the subject was in, he produced more melotonin, and more 5-meo-dmt.

"Beginning 6 years ago, I locked myself up, in absolute darkness for 14 days. This floods the brain with Melatonin, and forces the pineal gland to produce and be active."

 

[Neo1]

Pineal metabolism

There's an interesting article HERE on manipulating your own pineal metabolism.

A unique biochemical mechanism exists within the human pineal gland. A pair of naturally occuring pineal enzymes, hydroxy-indole-O-methyl transferase (HIOMT) and indole-N-methyl transferase (INMT), are capable of converting serotonin into a number of potent hallucinogens. Regulated by a variety of neuroendocrine mechanisms, these enzymes normally act on specific substrates and function as catalysts in the formation of biogenic amines. However, if they get out of phase with their normal substrates and act on pineal serotonin, they form potent psychoactive compounds within the human brain.

Interestingly enough, pineal catabolism can be intentionally shifted toward the production of these endogenous hallucinogens by a simple manipulation of amine metabolism. If you increase the concentration of pineal serotonin and block its normal enzymatic inactivation, it becomes a substrate for other pineal enzymes, like HIOMT and INMT. As their names imply, HIOMT and INMT are methyl transferase enzymes. They catalyze the transfer of a methyl group from one compound to another. As these enzymes add methyl groups to the indole-oxygen and amino-nitrogen positions, serotonin is converted into 5-methoxy-N,N-dimethyltryptamine, a relatively unknown but extremely potent hallucinogen.

So eat a twinkie bar, take some l-tryptophan and a short-term mao, and perhaps load up with something that donates methyl groups (SAMe / s-adenosyl-methionine)..... sit in a darkened room for a week or two..... and Bob's your uncle

 

[fastandbulbous]

indole-N-methyl transferase (INMT),

That name implies that the N-methylation takes place on the nitrogen atom of the indole nucleus, not the side chain nitrogen present in tryptamine. The fact that he uses that name more than once discounts the idea that it is a typo.

Call me picky, but when people don't use the correct enzyme name (it should be called tryptamine N-methyl transferase or serotonin N-methyl transferase), I'm instantly filled with the feeling that it's new age psychobabble by people full of wishful thinking and only a slight understanding of biochemistry, as enzymes with a name that specific are generally very picky about their substrates

 

[Neo1]

Wow.. it's good to see that psychosis is still alive and well...

Now, yes, there is evidence that 5-MeO-DMT is produced in the brain, likewise DMT... but I don't see the connection. 5-MeO-DMT is a product of serotonin, which is produced during the day and for the first hour of darkness, then it's productions rapidly decreases... And even if you disagree with that, melatonin doesn't keep being produced in higher and higher levels in darkness... in an animal exposed to constant darkness (or blind people), melatonin production continues to cycle in a psuedo-circadian fashion, though not perfectly.

Melatonin is produced from serotonin, which is produced from tryptophan, and there are many factors which influence its production.... enzyme substrates, light/dark, and also electromagnetic fields. I think the guy isn't psychotic, he's onto something. Science is still learning about pineal metabolism.

The biosynthesis of melatonin was discovered to be dependent on a number of substrates and co-factors, and on the activity of a number of enzymes including the light-sensitive: hydroxy-indole-O-methyl transferase (HIOMT). (Lerner et al, 1958; 1959).
As Brownstein and Heller (1968 ) demonstrated, this enzyme – which catalyses the conversion of serotonin to melatonin – is modulated by nerves that impinge directly onto the pineal gland, the activity of which, in turn, depend upon input from the optic nerves. Thus a small proportion of the impulses set up in the optic nerves bypasses the main visual pathway and, instead, takes a circuitous route to the pineal. Stimulation of these nerves increases the activity of HIOMT and, hence, stimulates the synthesis of melatonin.
Bright light inhibits melatonin production by inhibiting nerve tone to the pineal, whereas darkness has the opposite effect and, by increasing neural activity to the gland, stimulates the production of melatonin. This effect of light is dependent both upon its wavelength and its intensity.
In 1973, Cardinali et al showed that red light produced minimal inhibition of melatonin synthesis, whereas green light caused maximal stimulation. In addition, illumination with a light intensity of 0.5 microwatt/cm2 for forty-eight hours produced a fifty per cent decrease in melatonin synthesis in the rat pineal gland.
By way of comparison, sunlight, which strongly inhibits melatonin production, has an intensity of around 50,000 microwatt/cm2, whereas full moonlight has an intensity of around 0.3 microwatt/cm2. (Altschule, 1975).
Because of its low light intensity, the moon was originally thought to have no effect on the production of melatonin by the pineal gland. However, as we discuss below, more recent studies have produced results that suggest there may be some link between lunar phase and the secretion of melatonin (Law, 1986).

In addition to light, other electromagnetic (EM) radiations influence melatonin production, and EM fields of varying strengths and types – including earth strength magnetic fields – have been shown to influence melatonin production to the same degree as the exposure to light does: both in vivo, and in vitro and in a number of species including humans (Reiter & Richardson, 1992; Reiter, 1993a,b; Schneider et al, 1994; Yaga et al, 1993). Further, magnetic fields of this general type have been found to be effective in directly stimulating pineal tissue (Richardson et al, 1992).

(from: The Pineal Gland And The Ancient Art Of Iatromathematica )

 

[fastandbulbous]

Thing is, he's using the name of an enzyme that will not carry out the biochemical process he further relies on. If he can't get that right, it doesn't look good for everything else he's written

Also, organisms have all sorts of feedback mechanisms to keep the levels of biologically active chemicals within certain bounds (such as the alpha-2 autoreceptor which responds to high levels of nor-adrenaline to prevent further release, or that dopamine/nor-adrenaline inhibit the activity of tyrosine hydroxylase, which converts tyrosine to DOPA), and the only way that you get levels above those normally seen is when pathological processes intervene, such as carcinomas.

As a last point (which BilZ0r has also mentioned), the starting material for 5-methoxy DMT would be serotonin, not melatonin. The N-acetyl group would prevent the second methyl group from becoming attached, so by going from serotonin to melatonin, it's actually a step backwards in the process

 

[Neo1]

^^^ Do serotonin and melatonin levels influence each other?

There is more than one biochemical pathway in the pineal (you know more about the details of the biochem, Fastandbulbous, so please correct me if I am wrong). The pathway the the psychedelic tryptamines does not go through the tryptophan ---> 5-hydroxytryptophan etc patyhway, but rather through a different route.

Also, just because science might not have sussed how it all works in the pineal, it doesn't mean that such things as darkroom meditations are a load of hooey.... it just means that we don't quite understand HOW it all works yet.

Pineal metabolism may be altered not just through circadian rhythm and electromagentic fields. Ananda ( the guy who does the darkroom retreats) is also messing about with faraday cages in darkrooms even though his biochemical knowledge may be a bit sketchy.

Perhaps certain normal pineal processes may reach saturation point and then other tryptamines are synthesised along different pathways.

This also leads me to think (as a layperson!) that if one were to dose on both 5-hydroxytryptophan (to saturate the normal pathway AND l-tryptophan, then under the right conditions (mao inhibition etc), the l-tryptophan would get shunted to the other pathway, the one that synthesises the psychedelic tryptamines.

Please feel free to shoot holes in these conjectures..... this is a fascinating subject

 

[Neo1]

Darkroom enlightenment

Dark Room Enlightenment
All spiritual traditions have used Dark Room techniques in the pursuit of enlightenment. In Europe,
the dark room often appeared in underground form as a network of tunnels, in Egypt as the Pyramids, in
Rome as the catacombs, and by the Essenes, near the Dead Sea in Israel, as caves. In the Taoist
tradition caves have been used throughout the ages for higher level practices. In the Tao, the cave, the
Immortal Mountain, the Wu San, represents the Perfect Inner Alchemy Chamber. Meditating and fasting
in the cave is the final journey of spiritual work. The caves are the Earth Mother and its energy lines. Like
the hollowing bones, caves contain the earliest information of life stored inside the Earth. Caves contain
the vital essence of the Earth Power. The Tao says: ‘When you go into the dark and this becomes total,
the darkness soon turns into light.’
In the Dark Room, our mind and soul begin to wander freely in the vast realms of psychic and spiritual
experience. When you enter this primordial state or force you are reunited with the true self and divinity
within. You literally ‘conduct’ the universal energy. You may see into the past and future, understand the
true meaning of existence, and begin to understand the order of things. You return to the womb, the
cocoon of our material structure and Nature’s original Dark Room.
Complete darkness profoundly changes the sensory sensibilities of the body/brain. We are deprived
of all visual reference. Sounds begin to fall away as we lose contact with the external world and turn the
senses inward. The effect of darkness is to shut down major cortical centers in the brain, depressing
mental and cognitive functions in the higher brain centers. Emotional and feeling states are enhanced,
especially the sense of smell and the finer senses of psychic perception. Dreams become more lucid,
and the dream state manifests in our conscious awareness. Eventually, we awaken within ourselves the
awareness of the Source, the spirit, the soul. We descend into the void, into the darkness of deep, inner
space.
Darkness activates the deepest centers within the brain, the glands of the Crystal Palace, establishing
a connection with the Original Source, the Wu Chi (Fig. 1). The pineal gland connects us to the
Universal Energy. From the hypothalamus gland, we project our soul or spirit upwards, and receive the
descending Universal Energy. The pituitary gland receives the Cosmic Force, used to launch the spirit
bodies into the earthly or human plane for traveling.

From: Dark Room Enlightenment

 

[kaoskid]

chris columbus was not a genius, he just got lucky.

 

[mad_chemist]

As a last point (which BilZ0r has also mentioned), the starting material for 5-methoxy DMT would be serotonin, not melatonin. The N-acetyl group would prevent the second methyl group from becoming attached, so by going from serotonin to melatonin, it's actually a step backwards in the process

wrong.

an actual starting point, technically (if you want to be anal about it) is l-tryptophan....because l-tryptophan eventually metabolizes into 5-HTP, which metabolizes into serotonin, serotonin eventually metabolizes into melatonin (or other tryptamines, depending on the chemical balance in the process of enzymatic actions on the respective substrates)

 

[fastandbulbous]

OK, all of the tryptamines (plant alkaloids included) start with tryptophan; the point I was trying to get across is that once you've committed to melatonin, you can't get to 5-methoxy DMT without removing the N-acetyl group, and without the N-acetyl group, you don't have melatonin. The point where metabolism of tryptamines goes down different paths is once N-acetylation takes place.

The furthest you're going to get with an acetyl group attached to the sidechain nitrogen is 5-methoxy-N-acetyl-N-methyltryptamine, and the monomethylated tryptamines seem to be devoid of any activity; even the route of formation via the quaternary amine isn't possible because of the presence of the acetyl group.

So I don't know which part you're saying is 'wrong'

Neo 1

Any excess of an amino acid is generally dealt with by transaminase enzymes in the liver (they convert the amine group to a keto group, with ammonia - which is converted to urea - as the other product, the ketone derivative being utilized in the citric acid cycle as far as possible. After that, anything unusable tends to be excreted - for indole derivatives, some end up as skatole (3-methylindole), which is what gives shit it's distinctive odour - also why some tryptamine RC's smell like shit - skatole is a minor impurity),. I'll have a look and find out which metabolite in the formation of tryptamine neurochemicals acts as the negative feedback in the pathway (like dopamine/noradrenaline inhibiting tyrosine hydroxylase).

Any alterations in conciousness achieved by dark retreats etc., had chance to also utilize a proceedure for screening out external stimuli (like medatation), so would be comparable in effects to ketamine and other dissociatives, rather than 5-methoxy DMT ( the bit about returning to womb, possibilities of future and past etc., could be describing a K-hole)

 

[mad_chemist]

amt is one monomethylated tryptamine (though not endogenous)
that has activity

n-acetyl serotonin/melatonin would be the precursors for 5-meo-dmt, because they're the precursors for DMT

what I was trying to get at was, if one were to take l-tryptophan with an MAOI, and a methylator like l-methionine, one would theoretically get raised levels of said tryptamines.

 

[fastandbulbous]

amt is one monomethylated tryptamine (though not endogenous)

By monomethylated, I was referring to methylation of the nitrogen atom (hence all the stuff about the N-acetyl group preventing the process from going any further). AMT is methylated at the alpha carbon, which is a different creature alltogether (it's generally referred to as sidechain methylation as opposed to N-methylation).

n-acetyl serotonin/melatonin would be the precursors for 5-meo-dmt, because they're the precursors for DMT

I very much doubt it. DMT doesn't have any ring substitution, whereas serotonin and melatonin are compounds substituted at the 5 position. The substrate for endogenous DMT will be tryptamine, which is also found in tissue, but at much lower levels than serotonin or melatonin.

Again, this is one further step back along the biosynthetic chain. Why hydroxylate the 5 position, only to later remove it again.

Have you got a reference for N-acetyl serotonin/melatonin being the precursor for 5-methoxy DMT, as I've never seen anything about it, and to be honest, it doesn't look like a feasable biosynthetic route, purely because of prior N-acetylation.

And taking more doesn't mean higher final levels of end product. As I mentioned earlier, the products of the biosynthesis generally act as an inhibitor of one of the proceeding biosynthetic enzymes. Taking more tryptophan will only result in more being deaminated in the liver once levels of serotonin reach a certain point (MAOI have no effect on the transaminase enzymes in the liver, or the synthetic enzymes, only the enzyme that destroys the tryptamines)

 

[mad_chemist]

Have you got a reference for N-acetyl serotonin/melatonin being the precursor for 5-methoxy DMT, as I've never seen anything about it, and to be honest, it doesn't look like a feasable biosynthetic route, purely because of prior N-acetylation.

two, actually..TIHKAL and DMT the Spirit Molecule, but maybe I'm thinking of DMT as the end product

And taking more doesn't mean higher final levels of end product. As I mentioned earlier, the products of the biosynthesis generally act as an inhibitor of one of the proceeding biosynthetic enzymes. Taking more tryptophan will only result in more being deaminated in the liver once levels of serotonin reach a certain point (MAOI have no effect on the transaminase enzymes in the liver, or the synthetic enzymes, only the enzyme that destroys the tryptamines)

not necessarily; I also mentioned taking a methylating compound, hence l-methionine, in conjunction with an MAOI; the transaminase enzymes would really have negligible effect

and regarding the melatonin theory...is it really that hard to believe that by-products of n-acetyl-serotonin are in fact psychedelic compounds, namely DMT and 5-MeO?? 5-MeO is in fact endogenous, as is DMT, though their roles are as poorly understood as melatonin. There still is no "proof" (as you purely left-brained hard-nosed linear thinkers strive for) for melatonin's role in circadian clock rhythms, and other regulatory biological functions.

and by the way...the starting point of said tryptamines in plants isn't tryptophan, it's gramine.

 

[fastandbulbous]

the transaminase enzymes would really have negligible effect

Where did you get that from. Transaminases are the main enzymes that come into play whenever there is a excess of amino acids, so saying that they'd have negligable effect seems like a flippant dismissal of an important metabolic route for the amino acids

and regarding the melatonin theory...is it really that hard to believe that by-products of n-acetyl-serotonin are in fact psychedelic compounds, namely DMT and 5-MeO??

Yes, for the reasons I've mentioned in previous posts.

There still is no "proof" (as you purely left-brained hard-nosed linear thinkers strive for) for melatonin's role in circadian clock rhythms

I've got an old text book (Ganongs textbook of physiology) that refers to melatonins role in circadian rhythms, and it's from when I was at university 20 years ago, and as far as the bit about left brained etc., I think that it has nothing to do with elucidating biosynthetic pathways. It either does or it doesn't, everything else is just supposition and guesswork, however educated a guess.

 

[mad_chemist]

Where did you get that from. Transaminases are the main enzymes that come into play whenever there is a excess of amino acids, so saying that they'd have negligable effect seems like a flippant dismissal of an important metabolic route for the amino acids

so why/how does a compound like DMT make its way through the digestive tract and into the 5HT pathways, after those compounds are ingested? the psychoactive effects are quite noticeable

I've got an old text book (Ganongs textbook of physiology) that refers to melatonins role in circadian rhythms, and it's from when I was at university 20 years ago, and as far as the bit about left brained etc., I think that it has nothing to do with elucidating biosynthetic pathways. It either does or it doesn't, everything else is just supposition and guesswork, however educated a guess.

well, I've apparently come across a 2002 abstract from the Journal of Neuroscience Nursing ( June issue) which says the contrary; in depth study of melatonin, 7-page article; studies on rats, rabbits, and other furry non-primates don't constitute proof. According to the studies, there was no conclusive evidence that melatonin has any specific biological role in humans (because results were inconsistent).

 

[crOOk]

According to the studies, there was no conclusive evidence that melatonin has any specific biological role in humans (because results were inconsistent).

I second that. Hehe, I worked at a German institute that conducted those studies... "Institute for Hormone and Reproduction Research" in Hamburg, Germany. Too bad they shut down recently because of financial issues...

crOOk

 

[fastandbulbous]

so why/how does a compound like DMT make its way through the digestive tract and into the 5HT pathways, after those compounds are ingested? the psychoactive effects are quite noticeable

I gather you mean combined with a MAOI, so it doesn't get metabolized in the gut?

Because it's not an amino acid. Transaminases have amino acids as their substrates, not amines.


The question of melatonins function in humans:-

It's inconclusive because you can't sacrifice humans at the end of an experiment, whip their brain out, slice it then measure levels of melatonin, like they do with rats, rabbits etc.; and although the role of serotonin etc in things like cognition, awareness etc is still well beyond an exact understanding, the circadian rhythm is a pretty basic function that all mammals possess, so although it's not always applicable to humans, I don't think it'll be that different for all mammals (us included).

This isn't conclusive either, but there is a definite link between light exposure and levels of melatonin, so it must have some role that is linked to the day night cycle (and possibly why it is used so much in recovering from jetlag - it resets the internal circadian clock), nothing to do with any sort of psychedelic activity though

 

[mad_chemist]

This isn't conclusive either, but there is a definite link between light exposure and levels of melatonin, so it must have some role that is linked to the day night cycle (and possibly why it is used so much in recovering from jetlag - it resets the internal circadian clock), nothing to do with any sort of psychedelic activity though

yes, that much has been established, since the pathway to the pineal begins at the optic nerve; there's just no definite assigned role to melatonin, it seems to have a variety of functions, yet its metabolites (DMT has been already been established as one of them) have interesting properties; problem is, they metabolize quickly, probably another reason studying them would prove difficult