MDMA Recovery (Stories & Support - 4)

[Jabberwocky]

Personally my tinnitus is 90% better after 6-7 years, and many people with tinnitus from various drugs (cocaine is a common one) report improvement over time. People with noise induced hearing loss related tinnitus typically take about 10-15 years to improve on the other hand.

But to this day, if I focus on the ringing it gets louder and louder, until it is quite loud.

That's because all this LTC crap is nothing more than an increased set point for the HPA axis and persistent hyperadrenalization leading to

hyperacusis and tinnitis
distortion of the sensorium due to removal of the filters


ITS NOT SEROTONIN

Its dopamine and adrenaline

If you really want to help people -- get off the neuroplasticity BS- wagon and get on the endocrine (hormonally induced catecholamine imbalance)

The brain is constantly being forced into a fight or flight response because the pituitary and adrenals are out of whack -- and teh HPA set point can never get back to normal


There is significant evidence to support this theory -- namely that substances that are primarily Serotonin Releasers like MDAI have a much lower (almost negligible) record of inducing "LTC" -- but that the substituted cathinones and other "dirty" MD drugs that are more dopamine and nor-epinephrine releasing are frequently and overwhelmingly implicaqted in "LTC", as are incidents where LARGE doses of MDMA are consumed -- more dopaminergic and nor-epinephrine

 

[Jabberwocky]

How long did it take you to get used to it?

when I had it from alcohol withdrawal it took over a year of tapered benzodiazepines

several people in this board have stated they found relief from multiple grams of vitamin C in ascorbate form daily

On the few occaisions I have had a non-afterglow event (from RC experimentation using doses no normal person should) -- it took less than a week to return to baseline using 8-12 grams of ascorbate daily

 

[socrilus]

That's because all this LTC crap is nothing more than an increased set point for the HPA axis and persistent hyperadrenalization leading to

hyperacusis and tinnitis
distortion of the sensorium due to removal of the filters


ITS NOT SEROTONIN

Its dopamine and adrenaline

If you really want to help people -- get off the neuroplasticity BS- wagon and get on the endocrine (hormonally induced catecholamine imbalance)

The brain is constantly being forced into a fight or flight response because the pituitary and adrenals are out of whack -- and teh HPA set point can never get back to normal


There is significant evidence to support this theory -- namely that substances that are primarily Serotonin Releasers like MDAI have a much lower (almost negligible) record of inducing "LTC" -- but that the substituted cathinones and other "dirty" MD drugs that are more dopamine and nor-epinephrine releasing are frequently and overwhelmingly implicaqted in "LTC", as are incidents where LARGE doses of MDMA are consumed -- more dopaminergic and nor-epinephrine

But the issue is aren't the hormonal and endocrine things also linked to neuroplasticity in both directions? Don't ALL the neurotransmitters in some way mediate endocrine function and the HPA axis? Aren't hormones exerting effects through neuroplasticity?

Could you both just be referring to similar things with different terminologies?

 

[Jabberwocky]

But the issue is aren't the hormonal and endocrine things also linked to neuroplasticity in both directions? Don't ALL the neurotransmitters in some way mediate endocrine function and the HPA axis? Aren't hormones exerting effects through neuroplasticity?

Could you both just be referring to similar things with different terminologies?

1. No

2. Not in the context of lower serotonin putatively caused by MDMA use, and really NOT EVER -- no neuroplastic change occurs when vasopressin acts

3. No, otherwise hormones would not work like they do. There is nothing in the literature regarding Addison's disease (chronically low cortisol) and neuroplasticity; nor is there anything regarding hypercortisol and neuroplastic changes -- except in regard to CHRONICALLY (YEARS) ELEVATED CORTISOL

Simply feeling scared will kick off a fight or flight response, yet there is no neuroplastic change from a single or even multiple events. Admittedly, chronically elevated levels of neurotransmitters can result in persistent neuroplastic changes, however, notwithstanding a few studies linking persistent elevated cortisol after MDMA use (flawed due to used of 90 day hair sample which cannot evaluate anything other than cumulative rather than persistent cortisol), there is no evidence of a persistent chronic change in endocrine levels from a single or few uses of MDMA.


Once in a f-or-f cycle -- it is a perpetuating cycle -- but driven BY THE HORMONES

 

[socrilus]

1. No

2. Not in the context of lower serotonin putatively caused by MDMA use, and really NOT EVER -- no neuroplastic change occurs when vasopressin acts

3. No, otherwise hormones would not work like they do. There is nothing in the literature regarding Addison's disease (chronically low cortisol) and neuroplasticity; nor is there anything regarding hypercortisol and neuroplastic changes -- except in regard to CHRONICALLY (YEARS) ELEVATED CORTISOL

Simply feeling scared will kick off a fight or flight response, yet there is no neuroplastic change from a single or even multiple events. Admittedly, chronically elevated levels of neurotransmitters can result in persistent neuroplastic changes, however, notwithstanding a few studies linking persistent elevated cortisol after MDMA use (flawed due to used of 90 day hair sample which cannot evaluate anything other than cumulative rather than persistent cortisol), there is no evidence of a persistent chronic change in endocrine levels from a single or few uses of MDMA.


Once in a f-or-f cycle -- it is a perpetuating cycle -- but driven BY THE HORMONES

Since when did addisons have anything to do with MDMA?

The stuff ive seen regarding cortisol seems to be all related to neural things like low cortisol in PTSD, CFS or the sympathetic nervous system "burning out". And stuff relating to the hypothalamus in general. The hypothalamus is controlled via neurotransmitters.

Also idk about neuroplasticity taking years (unless you are referring to childhood abuse etc?)

Otherwise how would things like SSRIs in those who respond (in general not necessarily LTC related) cause improvement? Isn't that theorized to be neuroplasticity at work?

Im just confused by your post cause you say no persistant endocrine changes but then contradict it by mentioning hormones as playing a role? And earlier you mentioned the pituitary which itself gets input from serotonin and other neurotransmitters doesn't it?

 

[Jabberwocky]

Since when did addisons have anything to do with MDMA?

The stuff ive seen regarding cortisol seems to be all related to neural things like low cortisol in PTSD. And stuff relating to the hypothalamus in general. The hypothalamus is controlled via neurotransmitters.

Also idk about neuroplasticity taking years (unless you are referring to childhood abuse etc?)

Otherwise how would things like SSRIs in those who respond (in general not necessarily LTC related) cause improvement? Isn't that theorized to be neuroplasticity at work?

Im just confused by your post cause you say no persistant endocrine changes but then contradict it by mentioning hormones as playing a role? And earlier you mentioned the pituitary which itself gets input from serotonin and other neurotransmitters doesn't it?

1. You asked a question about hormones and neuroplasticity -- the hyper-absence of the hormone cortisol is not associated with neuroplastic changes nor is the hyper-presence of cortisol -- except potentially with respect to long term chronic hyper-cortisol

2. Persistent neuroplastic change takes months to years

3. SSRI's cause an elevated level of extracellular Serotonin -- this leads to more serotonin being available at the synapse - like MDMA but to a lesser degree, chronic administration of SSRIs does lead to neuro plastic changes; but to answer your question in a very pointed manner

one or two or three days or even a week of lexapro doesn't really work -- and doesn't induce neuroplastic changes -- several weeks are usually needed to see an effect -- if neuroplastic changes occurred one SHOULD be able to quit the SSRI and be "BETTER" -- however, the obvers is the case -- google SSRI discontinuation syndrome

4. I said no persistent neuroplastic changes caused by a single dose or few day binge of MDMA or MDXX -- the hormonal release is emotionally driven -- not continually persistent -- intermittent

 

[Cotcha Yankinov]

There is significant evidence to support this theory -- namely that substances that are primarily Serotonin Releasers like MDAI have a much lower (almost negligible) record of inducing "LTC" -- but that the substituted cathinones and other "dirty" MD drugs that are more dopamine and nor-epinephrine releasing are frequently and overwhelmingly implicaqted in "LTC", as are incidents where LARGE doses of MDMA are consumed -- more dopaminergic and nor-epinephrine

I've always thought the higher incidence of adverse effects with more stimulating entactogens or MDMA + amphetamine combos could just have to do with more stress hormones --> more neuroplasticity, consistent with a higher likelihood of LTC-like symptoms from a bad trip rather than a pleasant one (LTC-like symptoms are reported from classical psychedelics as well)

no neuroplastic change occurs when vasopressin acts

there is no neuroplastic change from a single or even multiple events

no persistent neuroplastic changes caused by a single dose or few day binge of MDMA or MDXX

......Ignoring that vasopressin regulates ACTH, which of course causes downstream neuroplastic changes that are known to manifest with haste, the neurons that release vasopressin are in the paraventricular nucleus of the hypothalamus that contain the oxytocin releasing neurons.

https://www.ncbi.nlm.nih.gov/pubmed/11906204 - "Oxytocin-secreting neurons: A physiological model of morphological neuronal and glial plasticity in the adult hypothalamus."

"Oxytocin-secreting neurons of the hypothalamoneurohypophysial system undergo reversible morphological changes whenever they are strongly stimulated. In the hypothalamus, such structural plasticity is represented by modifications in the size and shape of their somata and dendrites, in the extent to which their surfaces are covered by glia, and in the density of their synapses. In the neurohypophysis, there is a parallel reduction in glial (pituicyte) coverage of their axons together, with retraction of pituicyte processes from the perivascular basal lamina and an increase in the number and size of their terminals. These changes occur rapidly, within a few hours. On the other hand, the system returns to its prestimulated condition on arrest of stimulation at a rate that depends on the length of time it has remained activated.

Such neuronal-glial changes have several functional consequences. In the hypothalamic nuclei, reduction in astrocytic coverage of oxytocinergic neurons and their synapses modifies extracellular ionic homeostasis and glutamate clearance and, therefore, their overall excitability. Since it results in extensive dendritic bundling, it may also lead to ephaptic interactions and may facilitate dendritic electrotonic coupling. A most important indirect effect may be to permit synaptic remodeling that occurs concomitantly and that results in significant increases in the number of excitatory and inhibitory synapses driving their activity. In the stimulated neurohypophysis, glial retraction results in increased levels of extracellular K+ which can enhance neurohormone release while an enlarged neurovascular contact zone may facilitate diffusion of neurohormone into the circulation. Ongoing work aims to unravel the cell mechanisms and factors underlying such plasticity and has revealed that neurons and glia of the hypothalamoneurohypophysial system continue to express juvenile molecular features associated with similar neuronglial interactions and synaptic events during development and regeneration."


The supraoptic nucleus containing the vasopressin and oxytocin releasing neurons has been well studied for its adaptive capabilities.. Considering MDMA works largely via oxytocin via 5-HT1A activation, I'd say this could be relevant...

 

[mf140]

http://www.drjoecarver.com/clients/49355/File/Chemical Imbalance.html

 

[socrilus]

http://www.drjoecarver.com/clients/49355/File/Chemical Imbalance.html

That is a highly simplified article so that the average person can understand it. In reality things are not that simple and serotonin isn't good or bad it does both depending on the receptors involved. Its not really as simple a filling a gas tank as he says it. Otherwise wouldn't filling our serotonin tanks up with 5-HTP or something be a cure really quickly yet some people here even got worse through 5-HTP?

But why would the average person with depression care to know about the complicated aspects.

Also all those "low serotonin" symptoms can be caused by other neurochemical or hormonal issues too and aren't restricted to serotonin alone.

 

[fnono33]

http://www.drjoecarver.com/clients/49355/File/Chemical Imbalance.html

heh, I have all these symptoms of low serotonin. All of them.

 

[Cotcha Yankinov]

I think the "low serotonin = depression" thing is widespread because the old view was that because serotonin boosters helped depression, depression must be caused by low serotonin. Some psychologists may have never moved beyond stating that simplistic explanation, I guess maybe because it works for the psychologist's purposes. At least depression isn't then viewed as a moral failure or that MDD patients families insist they should just will themselves out of severe depression. You may not be able to will yourself out of some mental illness any more than you can will yourself to grow 6 more inches. Not that cognitive behavioral therapy and attempting to consciously avoid rumination isn't helpful.

The new view is more along the lines of serotonergic signaling, and everything downstream of that (including functional, morphological and genetic changes) may oppose depressive pathology.

 

[socrilus]

I think the "low serotonin = depression" thing is widespread because the old view was that because serotonin boosters helped depression, depression must be caused by low serotonin. Some psychologists may have never moved beyond stating that simplistic explanation.

The new view is more along the lines of serotonergic signaling, and everything downstream of that (including functional, morphological and genetic changes) may oppose depressive pathology.

Yea I mean what about all the other stuff like cortisol, genetics, testosterone, etc? Surely these things play a role in clinical depression in some way? That article was written in 2002 it seems though so we have come a long way since in the research although the treatments haven't.

I'm sure as the treatments get better it will be easier to get out of the LTC faster.

The simple explanation I think is meant so the average person doesn't feel guilty about being depressed itself. There are a lot of people who just take the meds and get better and don't know anything about how they actually act other than they increase serotonin (all the ads on TVs push that at least). Even researchers don't really know.

I mean if serotonin was that good then why would SSRIs have so many side effects like low sexual desire in some people?

And then what about the people who don't do well on SSRIs....theres a ton of people out there (in general not LTC related) who do poorly on SSRIs. What is the explanation for that?

 

[Cotcha Yankinov]

You're right, there should be a multidisciplinary approach to depression as well as not tunnel visioning on any particular aspect of the biology - the SSRIs were only made fairly recently, with LSD being the cause of the discover of serotonin really not too long ago all things considered.

That boosting serotonin helped depression was a bit misunderstood, same with drugs that block dopamine helping schizophrenia (the degree of D2 receptor blockade with a drug correlates with the degree of efficacy for schizophrenia). People thought that excess dopamine was driving schizophrenia because of that discover but there are other root biological causes.

But the mechanism of increasing serotonin matters. For example, a serotonin releasing agent is going to act irrespective of pre-synaptic autoreceptors because there is guaranteed serotonin being dumped into the synapse that can bind post synaptically, while disabling the reuptake transporters on the other hand only increases serotonin concentrations in the context of natural presynaptic release of serotonin. If there was no presynaptic release of serotonin SSRIs wouldn't do jack, whereas serotonin releasing agents force serotonin into the synapse.

SERTs could be playing a more functional role as well, to quote someone much smarter than me "SERT is there to reduce the signal to noise ratio by terminating transmission. Some serotonergic signaling occurs by volume transmission, where serotonin is released from varicosities and then stimulates extrasynaptic receptors. In that situation, SERT helps to terminate transmission by keeping the extrasynaptic 5-HT level below the level where all the 5-HT receptors in the brain are saturated. Obviously there is also classical 5-HT synaptic transmission, where SERT acts to terminate signaling and to recycle some of the transmitter.

By contrast, the autoreceptors allow 5-HT neurons to monitor transmitter release, thereby fine-tuning transmission."

So disabling any of these homeostatic mechanisms is not just going to linearly increasing serotonin signaling, but could have different functional consequences. I've wondering how LTC sufferers would do with MAOIs for example, or Buspar, a direct agonist.

As far as some people reacting especially bad to SSRIs, there are probably various explanations, a simple one would be some suicide victims display up regulated 5-HT2 receptors, 5-HT2C receptors can inhibit dopamine and norepinephrine release for example.

 

[fnono33]

My condition seems to worsen by the day. The main symptoms giving me trouble now are fatigue, tinnitus and anxiety. I don't even care about the visuals. It seems like when my sleep starts to get better I then hit a period where it gets worse again. And then everything gets worse. Tinnitus is blaring now. 5 months in and I am totally broken.

 

[ADubbs]

FNOno I experience the same, my tinnitus is the loudest its been. The last week my sleep has suffered and my tinnitus has gotten louder. When my sleep is better for a week or so things start to seem a bit better.....but it's probably me just thinking its better. Mine is like a very high pitch hiss that ebbs and flows.

 

[fnono33]

It's a really rough stage. Feels like my body is destroying itself. One thing that happened was the tinnitus moved to just the left ear. But gained intensity.

 

[Amml]

It's a really rough stage. Feels like my body is destroying itself. One thing that happened was the tinnitus moved to just the left ear. But gained intensity.

Hey, have you already tried St. John's wort? Could be an alternative to SSRI's and may calm your symptoms

 

[Jabberwocky]

My condition seems to worsen by the day. The main symptoms giving me trouble now are fatigue, tinnitus and anxiety. I don't even care about the visuals. It seems like when my sleep starts to get better I then hit a period where it gets worse again. And then everything gets worse. Tinnitus is blaring now. 5 months in and I am totally broken.

The anxiety (caused by the HPA axis dysregulation ) is the cause of the fatigue and the tinnitus.

Hyperacusis and tinnitis are CAUSED by anxiety. The auditory processing in the brain has the gain turned way up due to the action of the stress hormones.

Of interest -- extremely high functioning Aspergers/ASD commonly suffer from hyper-capable sensorium -- hyperacusis being one. The incidence of tinnitus in ASD person with hyperacusis is very high.

 

[Jabberwocky]

I've always thought the higher incidence of adverse effects with more stimulating entactogens or MDMA + amphetamine combos could just have to do with more stress hormones --> more neuroplasticity, consistent with a higher likelihood of LTC-like symptoms from a bad trip rather than a pleasant one (LTC-like symptoms are reported from classical psychedelics as well)



......Ignoring that vasopressin regulates ACTH, which of course causes downstream neuroplastic changes that are known to manifest with haste, the neurons that release vasopressin are in the paraventricular nucleus of the hypothalamus that contain the oxytocin releasing neurons.

https://www.ncbi.nlm.nih.gov/pubmed/11906204 - "Oxytocin-secreting neurons: A physiological model of morphological neuronal and glial plasticity in the adult hypothalamus."

"Oxytocin-secreting neurons of the hypothalamoneurohypophysial system undergo reversible morphological changes whenever they are strongly stimulated. In the hypothalamus, such structural plasticity is represented by modifications in the size and shape of their somata and dendrites, in the extent to which their surfaces are covered by glia, and in the density of their synapses. In the neurohypophysis, there is a parallel reduction in glial (pituicyte) coverage of their axons together, with retraction of pituicyte processes from the perivascular basal lamina and an increase in the number and size of their terminals. These changes occur rapidly, within a few hours. On the other hand, the system returns to its prestimulated condition on arrest of stimulation at a rate that depends on the length of time it has remained activated.

Such neuronal-glial changes have several functional consequences. In the hypothalamic nuclei, reduction in astrocytic coverage of oxytocinergic neurons and their synapses modifies extracellular ionic homeostasis and glutamate clearance and, therefore, their overall excitability. Since it results in extensive dendritic bundling, it may also lead to ephaptic interactions and may facilitate dendritic electrotonic coupling. A most important indirect effect may be to permit synaptic remodeling that occurs concomitantly and that results in significant increases in the number of excitatory and inhibitory synapses driving their activity. In the stimulated neurohypophysis, glial retraction results in increased levels of extracellular K+ which can enhance neurohormone release while an enlarged neurovascular contact zone may facilitate diffusion of neurohormone into the circulation. Ongoing work aims to unravel the cell mechanisms and factors underlying such plasticity and has revealed that neurons and glia of the hypothalamoneurohypophysial system continue to express juvenile molecular features associated with similar neuronglial interactions and synaptic events during development and regeneration."


The supraoptic nucleus containing the vasopressin and oxytocin releasing neurons has been well studied for its adaptive capabilities.. Considering MDMA works largely via oxytocin via 5-HT1A activation, I'd say this could be relevant...

There is no hormonally induced persistent plastic change -- the plastic change is caused by GLUTAMATE stimulation of the neurons and also osmotic based induction-- -- the oxytocin isn't CAUSING the change

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1353616/pdf/jphysiol00796-0272.pdf

1. reversible morphological changes -- not persistent, as in that is the way they work -- they swell, then shrink -- as a feedback loop

1a. There is no hormonal action causing the morphological change


2. CRF drives ACTH release - not vasopressin

" Corticotropin-releasing factor (CRF) is probably the major ACTH secretagogue, but since vasopressin acts synergistically with CRF to produce an augmented release of ACTH, we suggest that the ACTH response to administered vasopressin depends upon the ambient endogenous level of CRF. "

https://www.ncbi.nlm.nih.gov/pubmed/2830315


Again, please provide evidence of persistent morphological changes induced by a single dose of MDMA/MDXX. If your theory that LTC is caused by some action of MDMA that induces a persistent morphological change -- it must happen after 1 dose -- as many LTC sufferers state only one dose.

What is more likely is that it is nothing more than mild acute PTSD -- from the HPA stress of the event. Persistent HPA axis dysregulation caused by

corticosteroid challenge
sexual assault
acute panic attack
response to extreme exercise

are well known and documented in the literature.

That symptoms of LTC are commonly exacerbated by alcohol or caffeine consumption -- provides more corroboration that it is Acute Stress response /PTSD/ HPA axis dysregulation.

If you really want to help people recover from "LTC" -- you would ascribe to my theory and test it.

 

[fnono33]

I am willing to give you the fact that a lot of it is anxiety. The fact that coffee brought me into a whole new world of pain doesn't really wash with the brain damage theory. But initially I think there may have at least been some kind of down regulation or axon loss. My brain cooked when the LTC started.