MDMA Recovery (Stories & Support - 4)

[socrilus]

@shugenja

The thing is though what *exactly* causes the anxiety and all other symptoms to appear in people who were normal prior to the ingestion of whatever the MDXX was.

Like what purely psychological process can be pinpointed as causing the anxiety. I understand you mention the HPA axis stuff which is biological but then you said its emotionally mediated.


Also---not everybody even has a bad trip on MDXX and yet still ends up with an LTC. What exactly is responsible for the process which causes the LTC when there has been no bad trip and it occurs a few days later.

But interesting that you mentioned extreme exercise cause some types of excersise do leave me feeling unwell for the day during this LTC....

 

[Cotcha Yankinov]

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 .

I never said neuroplastic effects were being mediated by oxytocin (although they may certainly be mediated by other hormones). Anyways see for example https://www.ncbi.nlm.nih.gov/pubmed/15841107 "Administration of SCH 23390 into the medial prefrontal cortex blocks the expression of MDMA-induced behavioral sensitization in rats: an effect mediated by 5-HT2C receptor stimulation and not by D1 receptor blockade."

So 5-HT2C hypofunction can mediate neuroplastic effects, and before you have said "I was clearly referring to 5HT2A and C -- where MDMA acts as an agonist and causes downregulation", taken from this rather messy thread http://www.bluelight.org/vb/threads/807227-MDA-stole-my-soul-from-me-PLEASE-HELP/page2

Anyways
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641577/ - "chronic stress plasticity in the hypothalamic paraventricular nucleus"

"Stress responses are controlled in large part by the paraventricular nucleus of the hypothalamus, which contains three functionally distinct neural populations that modulate multiple stress effectors: 1) hypophysiotrophic PVN neurons that directly control the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis; 2) magnocellular neurons and their secreted neurohypophysial peptides; and 3) brainstem and spinal cord projecting neurons that regulate autonomic function.

Evidence for activation of PVN neurons during acute stress exposure demonstrates extensive involvement of all three effector systems. In addition, all PVN regions appear to participate in chronic stress responses. Within the hypophysiotrophic neurons, chronic stress leads to enhanced expression of secreted products, reduced expression of glucocorticoid receptor and GABA receptor subunits, and enhanced glutamate receptor expression. In addition, there is evidence for chronic stress-induced morphological plasticity in these neurons, with chronic drive causing changes in cell size and altered GABAergic and glutamatergic innervation."

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.

Behavioral sensitization is known to stick around for a while, one study in particular showed behavioral sensitization persisted 1 year after a single dose of amphetamine for example.

https://www.ncbi.nlm.nih.gov/pubmed/19236907/ "Sensitizing regimens of (+/-)3, 4-methylenedioxymethamphetamine (ecstasy) elicit enduring and differential structural alterations in the brain motive circuit of the rat."

But you never replied to my previous response when you said "You argue neuroplastic adaptations -- and I call BULLSHIT on a BULLHORN You have failed to provide 1 shred of scientific evidence that any neuroplastic adaptation occurs after a single recreational dose of MDMA. If you have such a study == please provide it. I would love to see how they show PROOF of neuroplastic adaptation after 1 use." (from the aforementioned messy thread)

To which my reply was:
"I think you're fundamentally misunderstanding how learning and the brain works. Even reading a book changes the brain persistently via neuroplasticity if you remember any bit of it, this applies to experiences as well (including drug experiences). Take for example the studies showing MDMA assisted therapy is vastly more effective for PTSD than regular therapy, with the patients showing much high rates of remission at long term follow ups after only a few sessions. How else do you propose this would be accomplished if not by virtue of modulation of neuroplasticity?

How else would animals show conditioned place preference with MDMA and cross sensitization with other drugs of abuse if it weren't for biological changes? It is known that MDMA induces DeltaFosB just like other drugs of abuse."

Acute cortisol is known to induce fast acting neuroplastic changes as well, but my key point is that these neuroplastic changes are occurring in the context of xyz drug influenced neurophysiology and acute neurotransmission.

https://www.ncbi.nlm.nih.gov/pubmed/24603007 just for example, "Corticosterone-induced enhancement of memory and synaptic Arc protein in the medial prefrontal cortex"

To ask me for proof of MDMA producing a neuroplastic change is absolutely ridiculous - its a complete misunderstanding of learning. Of course you're going to learn from an experience, how else would you change from any experiences if they didn't produce neuroplastic changes? How else do you propose one learns?

You can try to argue that hormones form a feedback loop and that no neuroplastic adaptations are needed but that argument doesn't pan out with learning (or behavioral sensitization), which is dependent on processes such as LTP and LTD.

 

[ADubbs]

Well...whatever it is, I fried my brain....whether it's serotonin or dopamine, probably both...doing MDMA two nights in a row dosing multiple times, and using with Adderall and pot and beers for my first time cooked me......and then totally relapsing even worse smoking weed and drinking a few weeks later....something is screwed up with serotonin. Everyone is different.

What do you think about HPPD Shugenja? Seems to coincide with a lot with LTCs.

Any theories on why Benzo's work so good for HPPD and LTCs?

My hyperacusis is terrible as well. Any loud noises are piercing. Mostly at night and in the morning. My tinnitus isn't horrible....could be at worse, but at night it keeps me from sleeping.

 

[Cotcha Yankinov]

Everyone is indeed different, and benzos even made fnono worse although they have worked for others.

LTCs and HPPD might have to do with hyper-excitability in some ways, hence benzos usefulness by boosting inhibitory neurotransmission.

The anti-epileptics are serious drugs, but Gabapentin/Lyrica are two to talk about with your doctor. They should be less habit forming than benzos.

 

[socrilus]

Yea something is likely the cause but I don't think hyper focusing on serotonin like cotcha said above is the way to go when there are so many other things that regulate mood.

Low serotonin is a simplistic explanation for the general population. I don't think doctors or psychologists have time to explain much of the real theories of mood disorders when giving the SSRI meds and don't know it completely either. So its become a popular phrase just to say low serotonin.

 

[Jabberwocky]

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.

No, your brain did not cook.

You most assuredly had no axonal loss or pruning -- unless you injected 400-800 mg directly into your brain or body cavity two to four times.

 

[Jabberwocky]

@shugenja

The thing is though what *exactly* causes the anxiety and all other symptoms to appear in people who were normal prior to the ingestion of whatever the MDXX was.

Like what purely psychological process can be pinpointed as causing the anxiety. I understand you mention the HPA axis stuff which is biological but then you said its emotionally mediated.


Also---not everybody even has a bad trip on MDXX and yet still ends up with an LTC. What exactly is responsible for the process which causes the LTC when there has been no bad trip and it occurs a few days later.

But interesting that you mentioned extreme exercise cause some types of excersise do leave me feeling unwell for the day during this LTC....

It is simply that your HPA axis cannot handle the hormonal stress caused by substance use.

In the same way that some soldiers can handle multiple tours of duty and drag dead and dying comrades to safety with little ill effect; some soldiers suffer PTSD from one limited engagement with the enemy.


The overwhelming majority of MDMA users can handle the hormonal challenge of taking some scooby snacks and going for a roller coaster ride -- apparently YOUR HPA axis cant.

 

[Jabberwocky]

To ask me for proof of MDMA producing a neuroplastic change is absolutely ridiculous - its a complete misunderstanding of learning. Of course you're going to learn from an experience, how else would you change from any experiences if they didn't produce neuroplastic changes? How else do you propose one learns?

You can try to argue that hormones form a feedback loop and that no neuroplastic adaptations are needed but that argument doesn't pan out with learning (or behavioral sensitization), which is dependent on processes such as LTP and LTD.

Nope - you propose a persistent neuroplastic change -- I called BULLSHIT then and I call BULLSHIT now.

All of the examples you provided refer to CHRONIC stress and neuroplastic change.

The bottom line is that their HPA axis could not handle the stress challenge. It got knocked silly, and they are basically suffering from PTSD because of it.

The STRESS of the experience on their HPA axis is the CAUSITIVE FACTOR - period -- not any action of MDMA itself


ROLLING BALLS or GETTING YOUR BALLS almost SHOT OFF overseas -- result in the same sequelae


and as far as benzos NO\T WORKING -- a small but non-trivial percentage of people have paradoxical reactions to SOME benzos - personally temazepam actually makes me hyper and UNABLE to SLEEP -- alprazolam (xanax), valium, lorazepam (ativan) -- they all work fine

 

[Brain_fog88]

Hey everyone,

Long time lurker and first time poster. I wanted to reach out to everyone and let them know that it does get better and time is the biggest solution to our problems. I also wanted to tell my story that it may help others and my myself because I'm hitting a roadblock in my recovery.

Since April of 2016 I've been struggling with an LTC. It was subtle at first and built into your typical obsessive intrusive thoughts and constant search for examples of people with a similar situation. It got to the point where I felt detached from any concept of who I used to be before the LTC. The person I am now couldn't fathom being the outgoing, uplifting, charismatic person I was before the LTC.

The first few months were a mix of worsening anxiety, detachment, recognizing I was depressed, feelings of emptiness, and complete lack of emotions. I often felt that the person I used to be was dead and that I should just end my life to stop the suffering and self loathing.

Thankfully, I stumbled across this site and you guys gave me hope. I knew that something resembling a recovery was possible and that with enough time I could regain a level of normalcy that I thought was lost. So thank you everyone!

It took me until month 6 till I really started to feel again. Honestly, it would get almost unbearable for a day or two and then the following days or weeks would be amazing! I found there was a pattern of dread and depression followed by something close to the happiness I once felt. I figured it was my brain recalibrating and relearning what happiness was by showing me what the exact opposite is which was pure depression. Each jump I made it over followed with longer periods of normalcy.

Now I'm at the 7 and a half month mark and I am feeling a little lost. Up until this point I wanted to avoid SSRIs because I wanted to see how far I could get with pure willpower and I was afraid that it would change my natural reprogramming. I wanted to give the old me a chance to fight his way to the surface before I tried them. Now I'm realizing that the old me may be gone forever. That old me was effortless and everything came easy to him. Now I struggle to remember situational things day to day. It feels like nothing is getting stores in my long term memory. I get moments of clarity, though, where everything just flows like it used to and those moments give me hope that I'm still me!

I want to know where I go from here. How do I get my old working memory back? How do I remember faces like I used too? Those things that we take for granted and are so innate to what it means to be human and develop connection are actually very difficult to consciously cultivate. I wonder if I should try and SSRI or some kind of endocrine therapy that shugenja mentioned. I will keep giving it time cause I'm 80% better and I desperately want that last 20%!

Any help or input would be great! Thanks again for listening and everyone's stories and advice over these long months!

 

[socrilus]

It is simply that your HPA axis cannot handle the hormonal stress caused by substance use.

In the same way that some soldiers can handle multiple tours of duty and drag dead and dying comrades to safety with little ill effect; some soldiers suffer PTSD from one limited engagement with the enemy.


The overwhelming majority of MDMA users can handle the hormonal challenge of taking some scooby snacks and going for a roller coaster ride -- apparently YOUR HPA axis cant.

Well here you make more sense but in your reply to Cotcha you then say the stress of the experience is the causal factor and not the MDMA itself. Here you imply the MDMA itself threw the HPA axis off.

Because if its simply the psychological stress of the experience then it doesn't make sense cause people can have a good experience and still end up with the LTC. After all LTC stands for long term comedown so its a prolonged comedown. So if you are saying that the hormonal challenge of MDMA is too much and then it can't seem to recover quickly then I sort of finally understand what you are getting at.

So then theoretically wouldn't the LTC be solved once the hormones and HPA recover to what they were prior to the disturbance? Isn't that a bit simple?

 

[Cotcha Yankinov]

Nope - you propose a persistent neuroplastic change -- I called BULLSHIT then and I call BULLSHIT now.

All of the examples you provided refer to CHRONIC stress and neuroplastic change.

https://www.ncbi.nlm.nih.gov/pubmed/18524625 - "Acute stress regulation of neuroplasticity genes in mouse hippocampus CA3 area--possible novel signalling pathways" "

Stress exposure can lead to the precipitation of psychiatric disorders in susceptible individuals, but the molecular underpinnings are incompletely understood. We used forced swimming in mice to reveal stress-regulated genes in the CA3 area of the hippocampus. To determine changes in the transcriptional profile 4 h and 8 h after stress exposure microarrays were used in the two mouse strains C57BL/6J and DBA/2J, which are known for their differential stress response. We discovered a surprisingly distinct set of regulated genes for each strain and followed selected ones by in situ hybridisation. Our results support the concept of a phased transcriptional reaction to stress. Moreover, we suggest novel stress-elicited pathways, which comprise a number of genes involved in the regulation of neuronal plasticity. Furthermore, we focused in particular on dihydropyrimidinase like 2, to which we provide evidence for its regulation by NeuroD, an important factor for neuronal activity-dependent dendritic morphogenesis."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091695/ "The pivotal role of stress in the precipitation of psychiatric diseases such as depression is generally accepted. This study aims at the identification of genes that are directly or indirectly responding to stress. Inbred mouse strains that had been evidenced to differ in their stress response as well as in their response to antidepressant treatment were chosen for RNA profiling after stress exposure.

Forced swimming as acute stressor was applied to C57BL/6J and DBA/2J mice and resulted in sets of regulated genes in the paraventricular nucleus of the hypothalamus (PVN), 4 h or 8 h after stress. Although the expression changes between the mouse strains were quite different, they unfolded in phases over time in both strains.

This search for stress-regulated genes in the PVN revealed its impact on interesting genes (GNAi2 and APP) and a novel gene network. In particular the expression of APP in the PVN that is governing stress hormone balance, is of great interest. The reported neuroprotective role of this molecule in the CNS supports the idea that a short acute stress can elicit positive adaptational effects in the brain."

Of course acute stress elicits neuroplastic changes if chronic stress does as well, and they may certainly be different than chronic stress related adaptations but its not like it isn't incremental. Its similar to someone believing that evolution goes - Homo Erectus, Homo Erectus, Homo Erectus, bam Homo Sapien - its really much more gradual and subtle. It would be very hard to truly draw the distinction between an evolutionary ancestor and our present day selves occurring at any given being, but there are incremental changes. There is no means to change tomorrow if we can't change today.

The STRESS of the experience on their HPA axis is the CAUSITIVE FACTOR - period -- not any action of MDMA itself

Furthermore I will argue that acute and chronic stress related neuroplastic changes are subject to modulation by neurotransmission, or rather that the activity-dependent neuroplasticity is modulated by stress hormones. See activity-dependent neuroplasticity. Neurotransmission is well known to alter plasticity... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728073/ - "Signaling Mechanisms Linking Neuronal Activity to Gene Expression and Plasticity of the Nervous System"

"Sensory experience and the resulting synaptic activity within the brain are critical for the proper development of neural circuits. Experience-driven synaptic activity causes membrane depolarization and calcium influx into select neurons within a neural circuit, which in turn trigger a wide variety of cellular changes that alter the synaptic connectivity within the neural circuit. One way in which calcium influx leads to the remodeling of synapses made by neurons is through the activation of new gene transcription. Recent studies have identified many of the signaling pathways that link neuronal activity to transcription, revealing both the transcription factors that mediate this process and the neuronal activity–regulated genes.

These studies indicate that neuronal activity regulates a complex program of gene expression involved in many aspects of neuronal development, including dendritic branching, synapse maturation, and synapse elimination."

I still think you're really misunderstanding memory and learning.

I don't think that stress hormone related adaptations are the entire picture, I see some differences in PTSD and LTCs that could be due to the state of neurotransmission induced by drugs at the time. For example HPPD, yes visual snow can very likely occur with sleep deprivation and anxiety in PTSD but I'm not aware of full on HPPD being present in PTSD a short time after the inciting event, and certainly not at the rate that it is present in LTCs and classical psychedelic related depersonalization syndromes. Depersonalization is also frequently co-morbid with HPPD, which makes one wonder if HPPD is more primary to these syndromes and deserves more attention.

 

[Cotcha Yankinov]

Hey everyone,
I want to know where I go from here. How do I get my old working memory back? How do I remember faces like I used too? Those things that we take for granted and are so innate to what it means to be human and develop connection are actually very difficult to consciously cultivate. I wonder if I should try and SSRI or some kind of endocrine therapy that shugenja mentioned. I will keep giving it time cause I'm 80% better and I desperately want that last 20%!

Any help or input would be great! Thanks again for listening and everyone's stories and advice over these long months!

Welcome Brain Fog

The mainstays that some people swear by are cardio and mindfulness, and medications like SSRIs are also something to talk to your doctor about if you feel like you're not making enough progress unmedicated. Sleep is really important and is definitely something to consider practicing mindfulness for if your sleep is not up to snuff. An app called Headspace is pretty good to learn the basics with.

Sorry for the recent drama in the thread 8)

 

[Cotcha Yankinov]

Well here you make more sense but in your reply to Cotcha you then say the stress of the experience is the causal factor and not the MDMA itself. Here you imply the MDMA itself threw the HPA axis off.

Because if its simply the psychological stress of the experience then it doesn't make sense cause people can have a good experience and still end up with the LTC. After all LTC stands for long term comedown so its a prolonged comedown. So if you are saying that the hormonal challenge of MDMA is too much and then it can't seem to recover quickly then I sort of finally understand what you are getting at.

So then theoretically wouldn't the LTC be solved once the hormones and HPA recover to what they were prior to the disturbance? Isn't that a bit simple?

I think there are enough differences between LTCs and purely stress and aversive memory related disorders (PTSD) that stress hormones and sensitized stress response are not the complete picture, HPPD for example, which involves semi-persistent psychedelic-like visuals after a drug experience, probably won't occur from stress alone (modulation of neurotransmission by a substance is needed), and it does reportedly happen after pleasant psychedelic trips. So it can occur without extreme stress, and to my knowledge doesn't occur solely with stress, hinting that the drug itself played a central role in causing the HPPD syndrome.

 

[fnono33]

Concerning our symptoms there are people who get them just from living life. HPPD in normal people is called visual snow syndrome. They seem to have all the symptoms. The difference betweeen the normal people and hppd'ers is that they don't seem too hopeful of improvement. They seem to think that it's permanant. Hppd people seem to think that time will heal them. I'm interested to know why this would be.

 

[Cotcha Yankinov]

Just to clarify what I meant, I meant that people don't usually get the HPPD visuals other than visual snow without a psychedelic substance. It certainly happens but why it happens at such a high frequency with LTCs etc. is my question. Depersonalization also occurs at a high rate with HPPD. But if it's the HPPD contributing to the depersonalization, the depersonalization contributing to the HPPD, or something else causing both at once (or a combination of all three) is up in the air I suppose.

Visual snow on the other hand is pretty common, especially with sleep deprivation, as well as visuals before falling asleep. But the other HPPD visuals aren't nearly as common in non drug users.

 

[socrilus]

Or it could be 4) different things causing DP and HPPD entirely right.

And how many people here have full blown HPPD besides just the VS/tinnitus? Not too many right if you exclude only VS?

 

[Cotcha Yankinov]

I suppose there could be two different mechanisms with DP and HPPD downstream of different causes, and the other LTC symptoms could be another effect entirely.

I certainly don't think it's all explainable (both LTCs and pure HPPD from classic psychedelics) by solely an up regulated stress response. And if there is a chronically up regulated stress response, there are going to be adaptations downstream of that.

I personally had what I would call moderate HPPD, and it's down to mild now (6 years sobriety from E, but still use of various other substances and long term sleep deprivation), but had some visual snow since I was younger.

 

[Cotcha Yankinov]

The difference betweeen the normal people and hppd'ers is that they don't seem too hopeful of improvement. They seem to think that it's permanant. Hppd people seem to think that time will heal them. I'm interested to know why this would be.

Part of it may be an "I got this way without a drug in my system so I can get out of it naturally too" kind of mentality. It might also bother them less if they don't have negative associations with all the stuff. If you have emotional symptoms and insomnia to boot with the visuals, well that's a lot different than having solely visuals. LTC sufferers on the other hand probably get reminded of all the emotional stuff every time they think about the visuals too much, and then they start regretting, and everything goes further downhill with regret.

 

[socrilus]

Part of it may be an "I got this way without a drug in my system so I can get out of it naturally too" kind of mentality. It might also bother them less if they don't have negative associations with all the stuff. If you have emotional symptoms and insomnia to boot with the visuals, well that's a lot different than having solely visuals. LTC sufferers on the other hand probably get reminded of all the emotional stuff every time they think about the visuals too much, and then they start regretting, and everything goes further downhill with regret.

I think fnono just meant the opposite lol in that the people who haven't taken drugs are *less* hopeful.

 

[Cotcha Yankinov]

Oh, hmmm, sorry must've read too fast.

If it is the case that drug naive people that have visual snow are less hopeful, I could understand them thinking it's never going to change if they've had it all their life.

While on the other hand people who are used to bad trips, comedowns and hangovers that pass with time might think HPPD will pass as well, even if it does take a lot more time.