MDMA Recovery (Stories & Support - 4)

[Cotcha Yankinov]

Ok interesting. MDMA itself is a stimulant so (And raises cortisol levels up to 800% when dancing at a rave and 150% without according to that one study) isn't it logical that it could disrupt the stress response regulatation by the HPA axis?

Either way the main issue is how exactly to address and repair the HPA axis so that it gets the proper signals to execute a normal stress response. Doesn't serotonin also control hormones so would hormones be an indirect way to see if the serotonin system or other stuff has recovered?

It's certainly possible that HPA axis dysfunction is playing a role in LTCs but whether or not it's truly causal is still up in the air - I haven't heard of people getting LTC like syndromes (especially with HPPD) from corticosteroids for example. Its possible that people are experiencing near normal HPA axis function now but during their MDMA experience they had a neuroplastic reaction to the stress hormones combined with the MDMA's effects on neurotransmission, could be why LTCs are more common with bad trips (also true with psychedelics).

Abstient methamphetamine users on the other hand show low levels of cortisol (although higher ACTH) and that is associated with depressive symptoms, while glucocorticoids can acutely cause euphoria.

But anyways, I wouldn't view it as in an LTC someone's system is just pumping out cortisol. It's more likely that the HPA itself is fine but that there could be have effects from the acute increase in cortisol. It's known to induce anxiety-like behavior in animals and alter neuroplasticity that can cause depression. But like I said, this is probably something that is not happening at present.

Considering the neurogenic hypothesis of depression, it does make sense that SSRIs can be effective for LTCs if LTCs are at least in part from stress hormone induced neuroplasticity (SSRIs can help reverse that neuroplasticity).

 

[Patsfan12]

I think I have heard of LTCs from very low doses, and I can tell you that girls especially can get bad hangovers from half a pill as well.

Yeah I'm a male but it's messed up it was my first time doing ectasy but I was really drunk and just did it without even knowing about LTC. The really messed up thing is like 6 of my buddies took all different amounts as well and none of them had any bad effects after a couple days. One of my friends took 9 pills that night and he was sweating and freaking out he turned out fine, one of my friends took 1 pill and all the girls at the party were freaking out saying they can tell he's so messed up, and me on the other hand was fine that night and nobody could even tell I was that messed up just drunk. I guess life just isn't fair sometimes

 

[socrilus]

It's certainly possible that HPA axis dysfunction is playing a role in LTCs but whether or not it's truly causal is still up in the air - I haven't heard of people getting LTC like syndromes (especially with HPPD) from corticosteroids for example. Its possible that people are experiencing near normal HPA axis function now but during their MDMA experience they had a neuroplastic reaction to the stress hormones combined with the MDMA's effects on neurotransmission, could be why LTCs are more common with bad trips (also true with psychedelics).

Abstient methamphetamine users on the other hand show low levels of cortisol (although higher ACTH) and that is associated with depressive symptoms, while glucocorticoids can acutely cause euphoria.

But anyways, I wouldn't view it as in an LTC someone's system is just pumping out cortisol. It's more likely that the HPA itself is fine but that there could be have effects from the acute increase in cortisol. It's known to induce anxiety-like behavior in animals and alter neuroplasticity that can cause depression. But like I said, this is probably something that is not happening at present.

Considering the neurogenic hypothesis of depression, it does make sense that SSRIs can be effective for LTCs if LTCs are at least in part from stress hormone induced neuroplasticity (SSRIs can help reverse that neuroplasticity).

What you said about meth users is what I am talking about basically. Also Ignoring HPPD, which doesn't seem to happen to everyone with an LTC. I only have visual snow which I don't consider HPPD since there are people who don't take drugs that also end up with this phenomenon. And I think you meant the opposite of neuroplasticity lol in the last statement.

LTCs also do occur with good trips so idk if the comparison to LSD bad trips is necessarily right.

Causality is interesting since it could be both the result and cause due to the perpetuation right lol. And LTC causes stress which in itself affects the stress hormones. So basically I guess I am saying is a combination of what you are saying with stress hormones inducing changes and then these changes perpetuating the stress hormones which induce changes (....)

But lets just take the non-HPPD symptoms. Also, didn't you say that the HPPD stuff can recover differently than the other stuff so they can be related to different pathways? Aren't some of these seen in corticosteroid w/d? And also SSRI w/d which may itself be related to corticosteroids?

Also what about people who are fine for some time after MDMA and then get the LTC later on randomly or from a different substance?

 

[Cotcha Yankinov]

Curcumin is safe and has nearly no side effects, this is one of the reasons why I hold it up so high.

I could be wrong, but didn't someone earlier in this version of MDMA recovery have a somewhat bad reaction to curcumin?

I think it's fairly safe as well but I would be cautious with mega dosing/p-glycoprotein inhibitors and taking a lot of a liposomal formulation like Longvida. I've found too much Longvida caused me some insomnia and restlessness, could be due to MAOI or effects on IDO metabolism. If one has the weird shifts in tryptophan metabolism seen with kynurenine dysfunction (indoleamine-2,3-dioxygenase related issues) then they could be more vulnerable to curcumin related adverse effects.

Of course correction of those tryptophan metabolism shifts would probably be therapeutic and necessary but I guess what I'm saying is if there's one thing we've learned from people's reactions to various supplements and things, it's take it slow and easy at first.

 

[Amml]

its a little worse than feeling a bit down, but I get your point haha.

Was i addicted? Who knows. Although the magic was wearing off, I could say no to nights out if I needed a bit more of a break, and I knew after my last couple of rolls that it really wasn't agreeing with me anymore (the comedowns would get a little longer), it would reach a point in time where I couldn't say no to my friends.

Its also probably important to note that before this kicked off I was incredibly stressed at my old job and dealing with the after effects of a bad relationship I.e I wasn't very content with life anyway and although I didn't feel depressed, it would be a well educated guess that my stress levels were already high and my serotonin levels a little low.

On reflection, Mandy of all the recreational drugs was one of the poorer choices to accompany the weekends and probably massively exasperated an already delicate mental state.

Sorry then, it only sounded in your previous like you were just a bit down. Do you have any other symptoms or in other words how would you describe your status?

 

[Cotcha Yankinov]

@Socrilus

So re: "neuroplastic reaction to the stress hormones combined with the MDMA's effects on neurotransmission" scenario, the thing to understand is that whatever cortisol related neuroplastic changes are doing in various scenarios, be it after an acute PTSD-inducing trauma or a classic 5-HT2A agonist (psychedelic like mushrooms or LSD), the cortisol related changes are in the context of the neurotransmission at that time. MDMA modifies transmission pretty darn uniquely although there are similar drugs that some people could have taken as well, but I do see some commonality between psychedelic related adverse effects and LTCs in the majority of LTC sufferers, which gives me the impression that's it's not solely related to cortisol, as in cortisol without the effects of MDMA wouldn't produce a truly LTC like syndrome, even if it was vaguely similar.

So the reaction to cortisol is modulated by whatever drug you're on (I'm sure not everybody here took MDMA) and what your neurotransmission is like during that period, and I'm sure that genetics play a role in vulnerability to stress related adverse effects, thus all the differing flavors of LTCs.

If a population size of one matters, I have a short form of the 5-HTTLPR that is associated with higher incidence of MDD after stressful life events and (by some measures) increased adverse effects after MDMA abuse.

 

[Amml]

I could be wrong, but didn't someone earlier in this version of MDMA recovery have a somewhat bad reaction to curcumin?

I think it's fairly safe as well but I would be cautious with mega dosing/p-glycoprotein inhibitors and taking a lot of a liposomal formulation like Longvida. I've found too much Longvida caused me some insomnia and restlessness, could be due to MAOI or effects on IDO metabolism. If one has the weird shifts in tryptophan metabolism seen with kynurenine dysfunction (indoleamine-2,3-dioxygenase related issues) then they could be more vulnerable to curcumin related adverse effects.

Of course correction of those tryptophan metabolism shifts would probably be therapeutic and necessary but I guess what I'm saying is if there's one thing we've learned from people's reactions to various supplements and things, it's take it slow and easy at first.

I mentioned that with the bad reaction, but it sounded to me like a single case that wouldn't be so relevant for the majority.
So if I understood right there are some people that would react bad to curcumin.
This is difficult, because some people get thrown of their path if they get a bad reaction again, but still with this risks I think it's worth a try, like with SSRI.
I mean I think I am right if I say that curcumin may be helpful, especially in long term direction and with the psychiologial protection of the brain from stress factors. And even small doses, when taken life long, like it is usual to use turmeric in India nearly every day, have beneficial effects. I read a study some time ago where they showed that elder people who regularly consumed foods with curry (about 2-3x/week) had significant better results in cognitive tests. And these are really extreme small doses of curcumin.

And could you explain this thing about the p-glycoprotein? I read an article on Wikipedia on it and if I understood right it is a protein that could transport lipophilic substances out of cells. Does curcumin has an effect on this transporter, and what are the effects then?

 

[Amml]

@Socrilus

So re: "neuroplastic reaction to the stress hormones combined with the MDMA's effects on neurotransmission" scenario, the thing to understand is that whatever cortisol related neuroplastic changes are doing in various scenarios, be it after an acute PTSD-inducing trauma or a classic 5-HT2A agonist (psychedelic like mushrooms or LSD), the cortisol related changes are in the context of the neurotransmission at that time. MDMA modifies transmission pretty darn uniquely although there are similar drugs that some people could have taken as well, but I do see some commonality between psychedelic related adverse effects and LTCs in the majority of LTC sufferers, which gives me the impression that's it's not solely related to cortisol, as in cortisol without the effects of MDMA wouldn't produce a truly LTC like syndrome, even if it was vaguely similar.

So the reaction to cortisol is modulated by whatever drug you're on (I'm sure not everybody here took MDMA) and what your neurotransmission is like during that period, and I'm sure that genetics play a role in vulnerability to stress related adverse effects, thus all the differing flavors of LTCs.

If a population size of one matters, I have a short form of the 5-HTTLPR that is associated with higher incidence of MDD after stressful life events and (by some measures) increased adverse effects after MDMA abuse.

AFAIK stress hormones like cortisol have an IMMENSE effects on neuroplasticity and neuronal death. Your theory sounds very good, drugs also cause changes in this factors and we still don't know them good enough to tell what they can do to an individual. So the combination of high stress levels, that are itself toxic to brain cells and the effect of MDMA (or other strong psychoactive substances) could eventually lead to those strong changes in our brains, that lead to a LTC.

 

[Amml]

Wait, I still have something interresting in mind. I read a study that showed that the neuroprotective effects of curcumin against cortisol induced neurotoxicity was completely reversed by 5-HT2A Agonists. I think this could be helpful, because it actually means that brain cells get more sensitive to the damaging effects of cortisol in combination with 5-HT2A agonists, like psilocybin, or MDA, which is a metabolit of MDMA and also binds to this receptor.
I'm sorry, not being sure if this information is right, it could also be another 5-HT receptor that was responsible, sadly I couldn't find the paper either, maybe you could find it?

 

[Cotcha Yankinov]

So if I understood right there are some people that would react bad to curcumin.

And could you explain this thing about the p-glycoprotein? I read an article on Wikipedia on it and if I understood right it is a protein that could transport lipophilic substances out of cells. Does curcumin has an effect on this transporter, and what are the effects then?

I think it could be people that have possible tryptophan metabolism shifts that have weird reactions, but I suspect this is small minority, and its not necessarily a bad thing but it could be a shock to the system if you will. But even the MAOI effects could cause some adverse effects if the dose were high enough.

P-glycoprotein you can think about conceptually as a transporter that transports molecules out of the CNS - disable it and you can achieve higher concentrations of compounds in the brain. I haven't heard anything about curcumin itself having an effect on P-glycoprotein but it is often paired with piperine. https://www.ncbi.nlm.nih.gov/pubmed/9619120 - As you can see we are talking +2000% with curcumin + piperine compared to curcumin alone, so definitely something to approach with caution. But by all means do try the various methods of ingestion if you wish, just know that I hope everybody is approaching it with care. I think we should try to learn from the other people who are having adverse reactions off of supplements and such. It might be a minority of people that would have a bad reaction to curcumin, but after all we are the minority that has had a bad reaction to MDMA-like substances when the vast majority of people are fine.

AFAIK stress hormones like cortisol have an IMMENSE effects on neuroplasticity and neuronal death

I would prefer to focus on the neuroplasticity aspect

 

[Cotcha Yankinov]

Also what about people who are fine for some time after MDMA and then get the LTC later on randomly or from a different substance?

Sorry it took me some time to find this reference again - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038707/

"Acute CORT (cortisol) treatment produced delayed onset of dendritic remodeling in the opposite direction in the BLA and mPFC with different time courses. Acute CORT induced dendritic hypertrophy of BLA spiny neurons, which was paralleled by heightened anxiety, both peaked 12 days after the treatment. Meanwhile, CORT-induced dendritic atrophy of mPFC pyramidal neurons peaked on day 6, concomitantly with impaired working memory. Both changed dendritic morphologies and altered behavioral outcomes were fully recovered."

 

[socrilus]

Sorry it took me some time to find this reference again - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038707/

"Acute CORT (cortisol) treatment produced delayed onset of dendritic remodeling in the opposite direction in the BLA and mPFC with different time courses. Acute CORT induced dendritic hypertrophy of BLA spiny neurons, which was paralleled by heightened anxiety, both peaked 12 days after the treatment. Meanwhile, CORT-induced dendritic atrophy of mPFC pyramidal neurons peaked on day 6, concomitantly with impaired working memory. Both changed dendritic morphologies and altered behavioral outcomes were fully recovered."

Wow interesting. Well the other side of things is in PTSD aren't cortisol levels often lower than controls? And aren't glucocorticoids also being investigated as potential treatments for PTSD like as a prevention measure even?

So it seems like both high and low have problems.

Interestingly I found a paper that said the opposite.

https://www.ncbi.nlm.nih.gov/m/pubmed/10910802/

 

[Cotcha Yankinov]

Wait, I still have something interresting in mind. I read a study that showed that the neuroprotective effects of curcumin against cortisol induced neurotoxicity was completely reversed by 5-HT2A Agonists. I think this could be helpful, because it actually means that brain cells get more sensitive to the damaging effects of cortisol in combination with 5-HT2A agonists, like psilocybin, or MDA, which is a metabolit of MDMA and also binds to this receptor.
I'm sorry, not being sure if this information is right, it could also be another 5-HT receptor that was responsible, sadly I couldn't find the paper either, maybe you could find it?

In cancer cell lines, 5-HT2A antagonism actually amplifies the pro-apoptotic (programmed cell death) effects of curcumin. But that's cancer cells. Typically 5-HT2A agonists are very anti-inflammatory (anti TNF-alpha, long known in the case of DOI for example).

I wasn't able to find that 5-HT2A agonists reverse the protective effects of curcumin in cortisol exposed cells, but 5-HT1A + 5-HT4 blockade does negate the protective effect of curcumin. Typically 5-HT2A receptors are downregulated with cortisol exposure anywho.

Also, just throwing it out there, you wouldn't need a metabolite like MDA to stimulate 5-HT2A, the serotonin releasing agents release enough serotonin to bind there.

 

[Cotcha Yankinov]

Wow interesting. Well the other side of things is in PTSD aren't cortisol levels often lower than controls? And aren't glucocorticoids also being investigated as potential treatments for PTSD like as a prevention measure even?
So it seems like both high and low have problems.

Cortisol levels are sometimes found to be lower in PTSD patients, but then again with dissociative PTSD patients, their heart rates can even drop while they tell of their trauma (Where as the opposite is typically true) - but in that portion of people whose heart rates drop, we wouldn't necessarily say that the heart rate drop is causing all of their symptoms. The low cortisol levels are probably adaptive changes from a repeatedly activated sympathetic nervous system. And CRF antagonists are being investigated for various conditions, see for example https://en.wikipedia.org/wiki/Antalarmin - I don't think any real clinician would use a sympathetic nervous system activator beyond reducing immediate suicide risk, but I have never even heard of that.

Interestingly I found a paper that said the opposite.
https://www.ncbi.nlm.nih.gov/m/pubmed/10910802/

Its very, very important to discern acute effects from chronic effects. Glucocorticoids are well known to cause euphoria in the short run but depression in the long run.

 

[mf140]

13844437[/URL]]Sorry then, it only sounded in your previous like you were just a bit down. Do you have any other symptoms or in other words how would you describe your status?

That's okay. My main symptoms are: lack of interest in things I normally enjoy, obsessional thinking about the situation I'm in, suicidal thoughts (although I'd never act on them), poor concentration, mild anxiety in situations I normally wouldn't have it, random muscle aches and pins and needles (different body parts at different times) and sometimes I feel a bit dizzy and get mild tinnitus.

All of the above are elevated by extra stress E.g. It's worse after a long day at work.

The depressive symptoms set in at the start of July. Before that, I just thought I had all sorts of things wrong with me (anxiety was sky high)

 

[Amml]

That's okay. My main symptoms are: lack of interest in things I normally enjoy, obsessional thinking about the situation I'm in, suicidal thoughts (although I'd never act on them), poor concentration, mild anxiety in situations I normally wouldn't have it, random muscle aches and pins and needles (different body parts at different times) and sometimes I feel a bit dizzy and get mild tinnitus.

All of the above are elevated by extra stress E.g. It's worse after a long day at work.

The depressive symptoms set in at the start of July. Before that, I just thought I had all sorts of things wrong with me (anxiety was sky high)

Have you tried some sort of medication?

 

[mf140]

Not yet. I've tried to fight it, but funnily enough trying to fight it has probably made it worse. It's like if someone tells you not to think of a pink elephant, you think of a pink elephant. Think I'm going to give the SSRIs a go.

 

[Amml]

It's not just something you can beat, because it affects your whole thinking. That's the mean part of the LTC.
If you tell a schizophrenic person that their voices aren't real, they still would hear them. The same with LTC, or any other stronger case of a mental illness.

 

[socrilus]

What are meds to try if SSRIs have failed at curing the symptoms? Surely they can't be the only ones?

I heard Mirtazapine mentioned. I just became so fatigued/groggy on it though at the lowest dose and couldn't really function the next day had to stay in bed. Only lasted a day thankfully.

Do TCAs have sexual side effects?

 

[Cotcha Yankinov]

Hey Socrilus, mirtazapine is a pretty strong antihistamine but that effect is known to wear off after a couple weeks, and also at the higher doses the more anti-depressant type effects will kick in (around 45mg), so you could try to stick with it for a little and maybe titrate up a bit faster than usual. It can be activating for most once the dose is up there.

TCAs can have sexual side effects but as I understand it, with some of them (especially the ones with 5-HT2A antagonism) it's better than SSRIs.