Friday, July 11, 2008

dimethyltryptamine

this is a drug synthesized by the pineal gland during REM stages of sleep. it's said to have something to do with the vivid and sometimes euphoric contents of dreams, which also occur during REM. due to its otherwise elusive function in the brain/body and association with the oddball region (pineal) it has, therefore, been postulated as the chemical substance of consciousness.


"Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and included a rapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completely replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness." (Strassman et al. 2003)


Strassman, a psychopharmacologist at U. New Mexico is one of the first to postulate that DMT is in fact synthesized in the pineal gland. although it seems to be produced in other regions of the body as well, as it has been found in urine, blood and cerebrospinal fluid (Jacob and Presti 2004), although thought to be an insignificant metabolic byproduct. i guess because DMT is synthesized from a serotonin intermediate it followed, for Strassman, that this particular tryptamine could be produced by and secreted from the pineal gland. but nobody really knows where endogenous DMT comes from, suffice if to say, the body uses a pretty wide array of tryptamines (these are primarily monoamine neurotransmitters and hallucinogens), including the melatonin and serotonin produced in the pineal.

serotonin is supposedly converted into DMT by the pineal during REM sleep, playing a role in dream activation (Callaway 1988). Strassman thinks that when these levels get too high persons experience "mystical/spiritual consciousness." he thinks - and as of yet he has no chromatographic/spectrophotometric data to suggest this - that DMT over-synthesis occurs during birth, before death, near-death experiences and deep meditation. in the 1970's, it was speculated that DMT levels might have something to do with Schizophrenia... but the results of these studies were inconclusive (Angrist et al. 1975, and others which escape me...). what i would like to see is a correlational study comparing systemic and cerebrospinal DMT in healthy control subjects to those exercising deep meditation.

in the Strassman study cited above (2003), it becomes suggested that endogenous DMT may function as did trace amounts of DMT; namely, the chemical would be a non-hallucinogenic. returning to the Calloway proposal that DMT participates in dream activation, it would seem like the job of endogenous DMT would be to do activate hallucination, not suppress it. but that's only if you're of the opinion that dreams are hallucinations...

okay, so we have an idea of how DMT acts in the brain... sort of. both DMT and it's precursor, tryptamine act through a recently identified trace amine receptor (TA, localization unidentified but interacting with the dopamine reward pathway). but since i'm mostly curious about it's production in the brain as relevant to the pineal gland and consciousness, we're going to move in that direction instead...

as noted in the Schizophrenic studies, DMT can also be found in the peripheral nervous system and systemically. this would imply that it can be synthesized outside of the brain, and this idea is supported by the systemic localization of indolethylamine-N-transferase (IMNT). IMNT is the enzyme that tryptophan to make methyltryptamine, which is methylated again to yield dimethyltryptamine. this implies two things:

1)
DMT can be synthesized in peripheral tissue, and subsequently cross the blood brain barrier... which is uncharacteristic of most neurotransmitters.
2) since during the stress response the body produces excessive amounts of tryptophan, DMT has implications as a non-hallucinogenic, as proposed by Calloway...

so why does Strassman insist that endogenous DMT is produced in the pineal gland, and is a propagator of the hallucinations that deem it worth of sustaining the weight of consciousness? let's explore...

well... so aside from IMNT being part of the peripheral system, the pineal gland is home to quite a few other methyltransferases.

...that's it.

there's also the theory that DMT must be produced in the pineal because it has something to do with calcification of the gland, but that is not Strassman's theory, and even if DMT does play a role in calcification, that isn't sufficient to conclude that the tryptamine is produced there.

so you've got your aging pathology studies that note pineal calcification in response to abnormal secretion of melatonin (Sandyk and Awerbuch 1992), and your pineal calcification in response to excessive calcium influx and significantly decreased metabolic activity that would otherwise regulate calcium levels - characteristic of aging and essentially all aging pathologies (Krstic 1986).

link between calcification and melatonin? fine, i'll take it. link to dimethyltryptamine.................... come on, really? there's nothing? there gots to be something...

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