MDMA vesicular 5-HT depletion and other topics

[socrilus]

It does sort of scare me that MDMA (even in pure form) can be so unpredictable. I mean you don't get drunk once or even take coke or opiates once and then end up with all these crazy symptoms weeks later.

I agree completely. There is definitely something strange about MDMA that makes this persist.

I realize some people have issues with weed but those seem even more rare than MDMA which seemingly can cause issues long after the drug is out of the system too. (As in the delayed LTC im talking about) You never hear about any delayed problems with weed.

I thought I was out of the hole after I recovered from the initial comedown but evidently I still develop symptoms weeks later.

I have a friend who also did mdma and he had social awkwardness symptoms (but no other symptoms) for around a month after. And he is a generally outgoing person. Thats absolutely ridiculous that it can cause that. It subsided for him on its own in a month but still. I didnt notice anything wrong in that month he had that problem but he definitely later admitted (after he got out that) that MDMA is a weird drug in terms of perception.

Perception changes are ridiculous.

I wouldnt be surprised if low Testosterone is responsible for some of these symptoms. Low Test can trigger social awkwardness in even extroverted people.

 

[Cotcha Yankinov]

^Weed is well known for causing some cognitive issues for a month that pretty much clear up with regularity, although people can also get depersonalization/depression/anxiety after weed too

Psychedelics are another drug that people can have problems with, including a while after taking them. Some of that persistent altered state of consciousness stuff is more psychosis though. Dissociatives when abused for months on end can cause some real issues too.

One thing to keep in mind is that all these symptoms that we talk about develop in people who are drug naive, so eventually these symptoms and drug use will coincide entirely, or the drugs will merely throw vulnerable people over the symptomatic threshold

 

[JK25]

^Weed is well known for causing some cognitive issues for a month that pretty much clear up with regularity, although people can also get depersonalization/depression/anxiety after weed too

Psychedelics are another drug that people can have problems with, including a while after taking them. Some of that persistent altered state of consciousness stuff is more psychosis though. Dissociatives when abused for months on end can cause some real issues too.

One thing to keep in mind is that all these symptoms that we talk about develop in people who are drug naive, so eventually these symptoms and drug use will coincide entirely, or the drugs will merely throw vulnerable people over the symptomatic threshold

Hey guys I'm back and also Cotcha I do have to apologize profusely for the lack of any recent posts on threlfs discussing the matter at hand but when we agreed to start this thread I was at the ass end of a 5 day methamphetamine binge obviously totally disillusioned and perplexed to a point of where anything I tried to read because butofof the sleep deprivation and nothing going down onto stomach it would be so far out of focus

 

[Cotcha Yankinov]

No worries JK try to get some sleep and eat something man, toodles

 

[JK25]

Hey guys I'm back and also Cotcha I do have to apologize profusely for the lack of any recent posts on threlfs discussing the matter at hand but when we agreed to start this thread I was at the ass end of a 5 day methamphetamine binge obviously totally disillusioned and perplexed to a point of where anything I tried to read because butofof the sleep deprivation and nothing going down onto stomach it would be so far out of focus

Within my documents folder I already have more than 1200 other dissertations? peerzreviewed journals or solid scientific research studies done and all of the main functions of all of the most important biological and physiological structures within the brain as well as but I also download numerous studies more than 25 studies regarding specifically the script we require. I will post them accordingly.

Also I read through the tread and there is some true ignorance floating around in here. Correct and accurate data and stats need to be put forth so more have access to it for their own wellbeing

Good people I am actually falling asleep as we speak. Took 450mg tramadol, 60mg Midazolam....and that me for today.

 

[Stringer_Bell]

Cothca and JK25, what dose do you think causes total depletion of serotonin? Do you think re-dosing has a significant effect on serotonin depletion? Does pre-loading help at all with the bad effects of MDMA do you think?

JK25 - hope you're feeling better man.

 

[Cotcha Yankinov]

It seems that high doses and repeated dosing are necessary for serotonin depletion in animals and I suspect it's the same with humans.

Administration of the serotonin precursor 5-HTP at the same time as MDMA administration can help attenuate some of the harmful effects of high dose MDMA in animals but I don't think 5-HTP will be helpful after more than a few days (especially after a few months, I maintain that at that point a vesicular shortage isn't the problem)

I'm sure antioxidants before rolls are a great idea, they certainly seem to be for animals. Some of the knockdown of tryptophan hydroxylase is due to oxidative stress. So antioxidants may help with the acute serotonin depletion as well. Oxidative stress can also have effects on serotonin receptor regulation.

 

[Stringer_Bell]

Thank you Cotcha, appreciate the answer and rationale behind it.

 

[ADubbs]

It's brain damage, I'm totally convinced of that

 

[Cotcha Yankinov]

It's brain damage, I'm totally convinced of that

"brain damage" is a misleading term though, for example if part of the brain (hippocampus) atrophies with depression, is this "damage"?

It is known that hippocampal volume can increase when depression is treated, and there is a case report of a young person whose hippocampus did indeed recover volume after MDMA abuse when they were rehabilitated, so I would watch out for using words like damage because they tend to freak people out depress them (damage is equated with permanent) and that becomes a self fulfilling prophecy - then their outlook is worse and they are actually less likely to recover because they're ruminating/anxious

 

[ADubbs]

"brain damage" is a misleading term though, for example if part of the brain (hippocampus) atrophies with depression, is this "damage"?

It is known that hippocampal volume can increase when depression is treated, and there is a case report of a young person whose hippocampus did indeed recover volume after MDMA abuse when they were rehabilitated, so I would watch out for using words like damage because they tend to freak people out depress them (damage is equated with permanent) and that becomes a self fulfilling prophecy - then their outlook is worse and they are actually less likely to recover because they're ruminating/anxious

I don't disagree with you, but it's a fundamental change that occurred during one night....to me that's damage, albeit it may not be permanent

 

[JK25]

"brain damage" is a misleading term though, for example if part of the brain (hippocampus) atrophies with depression, is this "damage"?

It is known that hippocampal volume can increase when depression is treated, and there is a case report of a young person whose hippocampus did indeed recover volume after MDMA abuse when they were rehabilitated, so I would watch out for using words like damage because they tend to freak people out depress them (damage is equated with permanent) and that becomes a self fulfilling prophecy - then their outlook is worse and they are actually less likely to recover because they're ruminating/anxious

Hey Cotcha

Okay now this has been in the back of my mind a lot and since we started I’ve looked at many, many studies from the basics like the psychopharmacology of MDMA in humans as well as the pharmacokinetics, studies done on humans, although I frown upon it also studies on primates and rats. Studies on SERT, the synthesis thereof in a normal brain and compared it to post-MDMA use, looked at the different biologies of the areas in the brain most affected, studies on MDMA neurotoxicity and also studies on pre-, and post poly-drug use, FMRI-, MRI-, PET-, and VMAT expression images etc.

I’ve sifted through it all and I came to one conclusion, what were we aiming for when starting this thread? Not only what occurs within the brain that includes tryptophan and its analogues, but I think the end-answer we are aiming at and the ultimate question would be is how the brain synthesizes SERT (5-HT mainly), but also 5-HT1A, 5-HT2A etc. post MDMA use. I have noticed such small changes in Dopamine and the other neurotransmitters that I will leave them out completely to save myself 1 or who knows 20 paragraphs (?), they are affected but not nearly as much as Serotonin and Serotonergic pathways, okay maybe a brief description about how MDMA affects the Dopamine within the Hippocambus and Nucleas Accumbens, maybe, I’ll see how lazy I am.

So this may be a lengthy post when I’m finished but I think I’ve come to a cohesive conclusion on how the brain synthesizes Serotonin post-MDMA. Whether it be after a once-off administration or after heavy use. The mechanisms in action will be involved in both scenarios either way.
I will reference (hopefully) all downloaded studies, journals, papers and dissertations I’ve used to come to my conclusion so you can go peruse for an interesting read. I will post it as soon as I have finished it.

 

[Cotcha Yankinov]

On your original post in that other thread you seemed to use SERT and serotonin interchangeably sometimes - I assumed by the context that you meant serotonin in most cases and that serotonin depletion was the topic, rather than SERT hypoexpression.

SERT expression may not return to 100% normal in some cases in humans, but this could be some sort of compensation rather than a reflection of nerve terminal loss or an issue with synthesizing new SERTs. The same can be said with DAT hypoexpression after amphetamines in humans.

Changes in receptor expression are a different animal as well, as people with mental illness can often show altered receptor expression. That being said, I will say that some former MDMA abusers have upregulation of 5-HT2A in cortex, which could indicate solely decreased pre-synaptic release or maybe loss of some feed-forward excitation that normally would result in increased pre-synaptic release.

In one case, MDMA abusers actually showed about 10% increased dopamine in the putamen with IIRC normal levels elsewhere, but that could just be a typical senstization-to-amphetamine type thing (similar to the persistent locomotor sensitization that animals can show after a single dose of amphetamine).


Just to be clear, I've never argued that former MDMA abusers don't have abnormalities visible with neuroimaging (especially the heavy chronic abusers) and neurocognitive abnormalities, but my main argument was that people aren't having issues 1 year post-MDMA because of a vesicular shortage of serotonin

I'd be happy to read your upcoming post, toodles
CY

 

[JK25]

On your original post in that other thread you seemed to use SERT and serotonin interchangeably sometimes - I assumed by the context that you meant serotonin in most cases and that serotonin depletion was the topic, rather than SERT hypoexpression.

SERT expression may not return to 100% normal in some cases in humans, but this could be some sort of compensation rather than a reflection of nerve terminal loss or an issue with synthesizing new SERTs. The same can be said with DAT hypoexpression after amphetamines in humans.

Changes in receptor expression are a different animal as well, as people with mental illness can often show altered receptor expression. That being said, I will say that some former MDMA abusers have upregulation of 5-HT2A in cortex, which could indicate solely decreased pre-synaptic release or maybe loss of some feed-forward excitation that normally would result in increased pre-synaptic release.

In one case, MDMA abusers actually showed about 10% increased dopamine in the putamen with IIRC normal levels elsewhere, but that could just be a typical senstization-to-amphetamine type thing (similar to the persistent locomotor sensitization that animals can show after a single dose of amphetamine).


Just to be clear, I've never argued that former MDMA abusers don't have abnormalities visible with neuroimaging (especially the heavy chronic abusers) and neurocognitive abnormalities, but my main argument was that people aren't having issues 1 year post-MDMA because of a vesicular shortage of serotonin

I'd be happy to read your upcoming post, toodles
CY

Okay before I start my in-depth, scientifically-accurate and pier-reviewable hypothetical thread response, kindly note all studies used will be mentioned as I go along or all referenced at the end and hopefully most will have URL-embedded links after my final post on the subject, this discussion is a very mentally stimulating activity and a very enjoyable one at that I might say. Scouting through hundreds upon hundreds of pages of raw, factual data throughout multiple and seemingly endless archives of all manner of doctrines across various fields of subjects and disciplines of academia. Hereafter a great deal of a “Methylphenidate-induced state” of intellectual focus is required.

Fuck knows where I'm going with this or if I’ll even finish this document at all, stimulant-induced manual override of typing will commence and I will try to finish. I'm doing my Masters in Neuro-Psychopharmacology atthis year after all, this is peasant literate shit compared to my end-of-year dissertation after all. I am on page 211 now and my area of study: “The physical experience that biologically and inorganically, artificially induced states of consciousness has on the perception of the mental ego and self-sensing demographic-specific lifestyle and geographically baised culturally induced perceptions by the initial first-experience response of non-addictive, non-substance abusing humans falling into all normal states/categories of an adult E.Q. at 90-110points, and an adult I.Q at 90-110points, an E.M.S.S. scale of 5points or less and a Rorchard-Wissheinz-Halbrun test at 4-6points per unit scale. Prerequisites applicable to and/or preference for all; pre-, mono-, and poly-substance use/abuse subjects. Screening and determination of subjects to be physically healthy, by intelligence, (must be within local populous’ average, with a 2.5%-5.0% degree of maximum variance permitted) and emotionally stable factors of neutrality established, (must be within local populous’ average, with a 2.5%-5.0% degree of maximum variance permitted). Final acknowledgements reached and closing conclusion via integrating individual experiences per subject’s post-study interview and also acknowledgements reached and closing conclusions whilst disregarding all nature and nurture induced-, pre-conceived biased”. .....basically the initial psychic and physical effects experience that people have whilst high or tripping on their first dose of first initial administration ever of various drugs. I don’t have access to a proper place or unlimited access to a USD 2million FMRI scanner to do a properly preformed, administrative, double-blind, control and non-control, pier-review for academically sound post publish editing....so my study comes from studying many, many, many previously performed human trials. No rats, no monkeys, actual willing human subjects taking their very first trip into altered consciousness Hahaha got to love it...my mentor said it is fine and to go with it as long as it will hold up to a panel of neuroscientists’ grading and final assessments.

Some will understand all information given fourth with immediate effect (ie. This thread’s initializer Cotcha for one, accept my friend request dude!) and others will have to take a second read-through but all will come to know. Now mentally take in and process these following paragraphs and try to come to accept this viewpoint. Personally except my theorem and fathom the state of understanding accompanying the competence of this visual external stimulus. Through Occam's Razor basically I will present and connect these various data sources of information for you, so you don't have to spend your valuable time of your drugged-upselves passing the time, it is easy just read. I will, at some time or another finally clearly conclude this thread, as you will come to accept it as well, by using all of the facts, perfectly ontological in post-processed form, unbiased in a nice black-on-white (blue-on-grey?) 2-dimensional, in a language that spells colour and flavour and flavour as it initially was when the words were invented with an Epidemiologic correct fucking “u”, I love ye old, U.K. Oxford’s Internationally Standardised linguistic spelling/grammar format of British English (established and grounded within about less than 50 years through widespread occurrence and practical installation of the N.K.J’s version of the Christian Bible, fuck me this book has been edited enough now leave it be, it was fine already with the one printed by Guttenburg oh my soul) I will make you also perceive it my conclusions as factual, personally some will know it to be structured right and ultimately a read worthy of a publishable dissertation of at least honourary Ph.D. quality...this is to say that If I actually finish it sometime this century hahahahaha.

 

[JK25]

Regarding the brains way of coping with complete SERT depletion (sorry Cocha if it seems that I sometimes use the former terms to an extent that they are perceived as different rather than synonyms for Serotonin) throughout all inter-cranial parts and neuralpathways including the very bottom of the brain stem before we hit the first vertebrae, creating normal stainable biosynthesis of SERT post-MDMA administration by the means of neuralplasticity is not a hypothetical situation, it is actual and applicable immediately after MDMA neuraltoxicity.

Looking at a "normal", post-adolencent, just-old-enough to fall into adult-age human pre-drug/trauma brain contains roughly 82,1-, to 110-billion neurons, this number (still argued over pfffft, I think we're ballpark-over it already here) was calculated by -Maxwell et. al. 2001- studying hundreds of FMRI's, PETS, normal X-Rays and advanced MRI's from inception circa 1970 to present and using countless mathematical formulae and synthetic models and many methods of calculation almost always naturally comes up with and leads us to this number that is averaged to the estimation of between 86-, and 110-billion neurons, give or take 11-billion.

Examples of formulae such as 1.) theorems of naturally-occurring, observational-dependent living unit dispersion, 2.) super-imposed and quantity-estimational result of pinpointed positional micro-, and macro-systems' impositions and also more basic biological calculations for estimations and results on organisms and natural area dispersion 3.) taking a sample size ie. 1cm(2) x 1cm(2) and using surface area x sporadic spread x possible occurrence x factor of time etc. etc.
Okay. Now each neurons' dendrites' nerve endings may have the ability to connect with 4,000 to 21,000 other neurons' dendrites' nerve endings through creating and sustaining synapses. These pathways connect relatively distant areas of the brain and the entirety of the nervous system throughout life and these specific connections ultimately makes up your consciousness as memories, experiences etc. Lets look also into the biological arena that is the ability of separately contained biological systems' ability (i.e. organs) for auto-restoratitive, self-repairing abilities and phenomenon, such as the obvious regenerative properties of the liver as one example.
Let us look into the biological arena that is the ability of separately contained biological systems' mono induced-expression for auto-restoratitive, self-repairing abilities and phenomenon with obvious regenerative properties such as those of the liver as one example thereof. Now looking at a “fresh” brain/cluster of neurons. The normally occurring biological and physiological prosess of Neurogenesis starts roughly between weeks 2 and 3 post-conception, pre-foetus, and continues until birth at the rate of 250,000 new neurons per minute.

Neurogenesis is coined as the brain's ability to create new neurons independently. After MDMA-induced neurotoxicity it is not just repairing the damage done through chemically-induced degeneration, oh fucking no, but it has the full capacity the ability to actually grow entirely new and fresh neuron-sites, formations also of completely and entirely new, independently located neuron-clustered areas, all with new cells with new dendrites with new axions and new nerve endings void of defects with perfect bio-synthetical synaptic electro-magnetically induced relay and absorption capabilities never used and ready for immediate training and rewiring-applicable assossioations of 10 to the 10^th degree squared ready for data packet handeling via and through its neighbouring neuron-cluster. Most people think this is it. Even orthodox amd new-school academics in the field still insist that we are born with x-amount of neurons for life, full-stop. This limits neurobiology in its entirety and is also an ignorant approach to the most complex accumulation of cells that forms this biological supercomputer that is used and/or abused for your personal pleasure. This ignorance is no longer acceptable in my eyes following a paper and study done at the -SALK Inst. in San Diego et. al 1999- when the neuroscientists there discovered neurogenesis happening in a 72-year-old's brain!

Dude, at 72 you can still take up and master the violin and become a master of it within 5-10 years (or 10,000 hours as Malcolm Gladwell asserted is the average amount of practice/input/involvement/man-hours necessary to master any field of study or any doctrine or any type of any physical activity) As professor of Neurology at Harvard Medical School, Dr. A. Pascual-Leone hypothesized: you only need to do a certain action/think a certain though/experience an event or new environments, and by regular practice/mindfulness/repetition neurogenesis can, does and will occur up until physical bodily death.
This ignorance is no longer acceptable in my eyes. One specific paper published about a study done at the -SALK Inst. in San Diego et. al 1999- when the neuroscientists there discovered neurogenesis happening spontaneously within the frontal and lateral brain tissues in a 72-year-old's brain!!! Dude, at 72 you can still take up and master the violin and come to master it within 5-10 years (or 10,000-hours as Malcolm Gladwell asserted as the average amount of practice/input/involvement/man-hours necessary to master any field of study or any doctrine or any type of any physical activity and master it completely)

As professor of Neurology at Harvard Medical School, Dr. A. Pascual-Leone hypothesized: you only need to do a certain action/think a certain though/experience an event or new environments in a constant manner, and by regular practice/mindfulness/repetition neurogenesis can, does and will occur up until physical bodily death.

Imagine the experience of physical-bodily death, your entire source energy matrix detached from the body, all personal experiences from all previous lifetimes are accessible and are experienced at once, no pain, nothing but pure source energy vibrations, 4-7th dimension existence throughout all time experienced simultaneously and also not so. Just a state of bliss...okay way off the path here let's get back to the point I was making. I think I was concluding the following, I think.......fuck knows where am I again? What day is it today....? Phuza Thursday! In South Africa there is such an overwhelming alcohol abuse situation that spreads country wide haha. Mieliemeel beer Mondays, Tequila Tuesdays, Wacky Wednesdays, Phuza Thursday (ethnic slang for “to drink alcohol profusely”), and then the obvious Hoza Hoza Weenend! Dude fuck Ireland, during the FIFA Football world cup in 2010 I saw first hand how 4 or 5 black ethnis grandfathers above the age of 60-70 drink the Irish spectators under the fucking table they could no longer grasp onto none the less actually sit at. Okay wayyyy off topic, will post as I compose later.

 

[JK25]

Just to be clear, I've never argued that former MDMA abusers don't have abnormalities visible with neuroimaging (especially the heavy chronic abusers) and neurocognitive abnormalities, but my main argument was that people aren't having issues 1 year post-MDMA because of a vesicular shortage of serotonin

Regarding this sentence, I'm shit-sifting through 11 downloaded pdf's ragarding post MDMA SERT and also varioous other neurotransmitter levels at various stages of use and also at varying ages on mono-once off use and also some studies done on veterans on the scene, I think the youngest obviously studied was 18 (to be legally viable and for tenure acquisition etc.) and the oldest person studied in once paper was 81, 82-ish. I will compile and revert appropriately later.

 

[JK25]

Let us break down some basics, I am admitting I was inaccurate regarding a previous post wherein I asserted it takes 3-4 months for VERT (apologies again *VMAT) structures to re-generate, and I do say I'm sorry for the naive impulsive, non-factually based response, no no no, they aren't completely targeted by either MDMA itself nor by it's main active post-first phase metabolic breakdown analogues, VERT levels remaining post-MDMA use ranges within still normally functional levels of 82-, to 98% within all SERT-dominant systems, varying according to dose and is subject dependent as well.

Apologies, I feel like a drol.

 

[JK25]

Now on another note, uuuurg, that fucking bright glowy thing in the sky emitting protons that makes your light-sensitive photoreceptor-retinal cells see is out in full force today, no such thing as Winter in Afrika oh my fucking soul. , Gucci Light Shades Aquired anddddddd...Approved for indoor use captain, pccccchhhhh. Fuckoff day lighters.

The sight of daylight equals death to me. You see the moon you see the stars, but the shit that I'm on will send you to Mars
hahaha.

I'm multitasking like 6 botched-abortions in a cabbage patch over Christmas no fuck no let me fix my weave and next we will break down various effects of chemically induced toxicity focusing on SERT, DOP, EPIN, NOREP and loosely 5-HT1a and 5-HT1b, and skipping 5-HT2a and 5-HT2b as MDMA's affinity for the latter is less than 0,5-, to 1,0-3,0% MAX. and not worthy of further exploration

 

[JK25]

"brain damage" is a misleading term though, for example if part of the brain (hippocampus) atrophies with depression, is this "damage"?

It is known that hippocampal volume can increase when depression is treated, and there is a case report of a young person whose hippocampus did indeed recover volume after MDMA abuse when they were rehabilitated, so I would watch out for using words like damage because they tend to freak people out depress them (damage is equated with permanent) and that becomes a self fulfilling prophecy - then their outlook is worse and they are actually less likely to recover because they're ruminating/anxious

brain damage enough of it to actually be called brain damage is only picked up after years and years of MDMA abuse and not only MDMA but years and years of poly-drug abuse. Resulting in tangible, visible reductions in brain matter volume, scarring, aneurysm-type vein structures and even actual Swiss-Cheese looking holes throughout the entire grey matter surface area within the cortex, this is resultant specifically from 10+ years of Methamphetamine abuse. Oh my fuck.

 

[JK25]

MDMA on the brain.