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MDMA Recovery (Stories & Support - 5)

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@Cotcha

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033019/

Look what I found. Earlier in the thread you said that things would just downregulate with excess 5-HT right?

But this paper claims:

"Although description of the functional attributes of the serotonin polymorphism have been contradictory (Karg et al., 2011), clinical data would prompt us to suspect that the short allele is associated with an inability of the serotonin transporter to cope with excess synaptic 5-HT in the somatodendritic raphe area but this statement remains speculative."

So the *short* serotonin transporter supposedly has trouble with high 5-HT (though they admit its contradictory)

"The expected compensation of autoreceptor down-modulation to enhanced peri-raphe 5-HT is overwhelmed by the magnitude of agonism during “flooding” and putatively exceeds the capacity of the autoreceptor to sufficiently “down-modulate” (Blier et al., 1998) (Figure ​(Figure3),3), a contention supported by 5-HT1A irreversible KO rodent studies described below (see Bipolar Versus Unipolar Depression: Data from Animal Models)."

This paper is in reference to SSRI non response. But if MDMA releases tons of serotonin, could a similar thing happen with the short serotonin allele?

..And then of course presumably excess 'bad' serotonin can impact HPTA-neuroendocrine function?

Btw, in Figure 4 of this same paper they interestingly recommend consdering Lamictal as one of the things for people with TRD/SSRI non-response.
 
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The thing about MDMA and other releasing agents is that they bypass autoreceptor function. Autoreceptors like presynaptic 5-HT1A can normally inhibit 5-HT cell firing, and presynaptic 5-HT1B/5-HT1D autoreceptors can inhibit the ability of vesicles to dock to the cellular membrane and release their (5-HT) content into the synapse.

But because MDMA doesn't work based off of enhancement of endogenous cell firing or natural vesicle docking related neurotransmitter release, autoreceptors have no say on MDMA's neurotransmitter releasing effects. This is what fundamentally makes MDMA a serotonin releasing agent (SRA) vs. e.g. prozac which is an SSRI. Both increase serotonin but have vastly different effects partly because MDMA isn't constrained by autoreceptors.

Normally a lot of serotonin is released from various parts of the cell and it can then travel to a distant point (so called non-synaptic volume transmission) and the job of SERT would be to normally terminate serotonin transmission by modulating the extracellular level of 5-HT. So one theory would be that decreased SERT expression with the short allele at 5-HTTLPR means decreased ability to modulate extrasynaptic 5-HT binding/volume transmission.

Some SERT knockout studies attempting to mimic the short allele (hypoexpressing SERT state) have shown that there are compensatory effects that occur if SERT is hypoexpressed during a development phase but the findings and implications aren't clear cut.

What could be happening is that during the excess 5-HT period, postsynaptic 5-HT1A (good) receptors are desensitized, and during a later period (MDMA use) if the postsynaptic 5-HT1A are desensitized again, there could be a lack of 5-HT1A mediated inhibitory control over the stress response. If the 5-HT1A autoreceptors are continually stimulated with the SERT hypoexpression then this could mean that post-synaptic 5-HT1A may be continually stimulated (by virtue of decreased autoreceptor tone over 5-HT cell firing) and hence the postsynaptic 5-HT1A could be more vulnerable to desensitization with MDMA.

After the e.g. hippocampus cells cease receiving the neurotrophic benefits of postsynaptic 5-HT1A stimulation, the cell's inhibitory control over the stress response could start to weaken.
 
I still feel like, if anything, lowered dopamine levels or people with lower dopamine might be prone to LTC more. Vast oversimplification but I just don't think low serotonin is an explanation.

Majority of the LTC symptoms (excluding HPPD like stuff--I dont know too much about that) like apathy/low motivation/low sex drive/etc etc. Aren't these all related more to DA than 5-HT? Of course indirectly for example 5-HT 2A antagonism can raise DA I think but still.
 
socrilus said:
Of course indirectly for example 5-HT 2A antagonism can raise DA I think but still.
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At the same time, its thought that stimulation of 5-HT2A/5-HT2C receptors with MDMA use can result in inhibition of interneurons that results in downstream dopamine release. 5-HT2A receptors also provide a lot of excitatory input to dopamine rich areas like the basal ganglia.

One study examining dopamine levels in abstinent MDMA user's brains found that they had normal levels except for elevated levels in one region (Putamen), which were on average about 10% higher. However, that doesn't necessarily reflect the LTC population. Its common for increased dopamine to occur with continued amphetamine use as a type of sensitization.

But I personally think the role of dopamine in mood is overplayed. Dopamine is much more novelty/craving (wanting) related than related to the actual enjoyment (liking) of a drug.

It might not be helpful to conceptualize any of these problems as being due to a single receptor system
 
Cotcha Yankinov said:
At the same time, its thought that stimulation of 5-HT2A/5-HT2C receptors with MDMA use can result in inhibition of interneurons that results in downstream dopamine release. 5-HT2A receptors also provide a lot of excitatory input to dopamine rich areas like the basal ganglia.

One study examining dopamine levels in abstinent MDMA user's brains found that they had normal levels except for elevated levels in one region (Putamen), which were on average about 10% higher. However, that doesn't necessarily reflect the LTC population. Its common for increased dopamine to occur with continued amphetamine use as a type of sensitization.

But I personally think the role of dopamine in mood is overplayed. Dopamine is much more novelty/craving (wanting) related than related to the actual enjoyment (liking) of a drug.

It might not be helpful to conceptualize any of these problems as being due to a single receptor system
Click to expand...

That last point is definitely true. But if anything I think the role of serotonin in depression and anxiety is overplayed and also potentially backwards.

High serotonin in social anxiety: https://www.sciencedaily.com/releases/2015/06/150617115327.htm

For all we know its the SSRI effect on steroids like allopregnanolone and cortisol which leads to remission.
 
^However that would be too much serotonin in the amygdala, which is one of the areas in which the serotonin transmission isn't volume transmission. Meaning that it could be that the amygdala is hyperactive because of hypofunction of serotonin elsewhere, or a chronic deficit of neurotrophic serotonin signaling elsewhere

I'll also add that some parts of the amygdala are largely GABAergic, to make matters even less cut and dry
 
I wonder if Ihatenotfeeling offed herself...

Neuro appointment in 2 days so hopefully that will lead to some answers. I've lately been kind of at peace with the thought that I won't recover although it's of course sad. Writing this mainly for recording my journey for whoever stumbles upon it. My main symptoms now at 4 months:

-Constant confused state, difficult to think, concentrate, socialize / look people in the eye
-Sensitivity to all stimulation (light, sound, socializing). Causes worsening of symptoms,
confusion,agitation, tremors
-Severely dizzy, nauseous at times
-Anxiety/Agitation (has improved at least at home)
-Involuntary eye movements (improved some)
-Eyesight problems: difficulty focusing eyes,double image, cross eyed?, visual snow and blotches, after images (started noticing HPPD recently, very bad in dark)
-Weird sensations behind eyes (especially left one) - pressure/pulling sensation. Other head area sensations
-Body and neck especially twitching&tremors
-Electric feelings in spine, body jolting - called Lhermitte's sign apparently
-Tinnitus
-Fatigue
-Low mood, irritability (again improved, but not great still)
-Head aches, a bit feverish feeling
-(Lost weight - due to being sick/spending so much time in bed)

Word garbling and stuttering hasn't happened recently.

Closing eyes and laying down helps sometimes when things are really bad

My life resembles nothing of what it was before this. There's great variation in the daily intensity. On the worst days the symptoms get so severe I have to lay down eyes closed and I can't even speak at times, feels like almost a seizure/stroke, close to losing consciousness. On the better days I still feel bad but it's not unbearable to be at home, I can even be in a jokeful mood sometimes. I'm trying to identify triggers but I don't know. Last time it happened after I ate some chinese food (MSG?) but this could just be coincidence.

Can't go outside/to public much at all. At least I'm not that anhedonic. It's not much of a life but it's the only thing that makes me not acutely suicidal as I can enjoy things like eating, games, tv, reading and for that I'm grateful. I'm also appreciating the times now when I'm not in that seizure-level of suffering. I still think about suicide/euthanasia and feel that it would probably be my decision eventually if things were to stay like this. Things are still evolving but to what degree? Has anyone ever recovered from this kind of injury?

It would be nice to know what is behind my symptoms, but I'll leave the guesswork aside as I have no clue.
 
No, neurologist appt on wednesday

The clinic is along a shopping centre.. I have no idea what that kind of stimulation means but it does scare me.
I have 1 benzodiazepine left but ideally I would like to go in my unmedicated state.
 
I never had that kind of sensitivity to stimulation but I agree going in unmedicated state is better to give a better idea of your symptoms.

Why neurologist instead of a psychiatrist or neuroendocrinologist?

One thing you might consider asking about is the neuroendocrine stuff (for non HPPD related symptoms) but idk how much a neurologist deals with that.

My social abilities have improved since getting on TRT btw though not back to normal.

It felt like TRT improves anxiety+function more so than mood.

However, I did have a period of a few days where I felt amazing but that was short lived. Still better than pre TRT LTC though.

I also deal with that horrific nausea still though mostly after exercise.

Edit: oh wait I totally missed that you had those weird electric and eye symptoms. So thats why you are seeing the neuro?
 
rrandy said:
Every hour or 2. The longest i've slept without waking up was 3 or 4 hours since the beginning of this shit.
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I managed to finally get a good nights sleep after popping a 10mg benzo pill and hour before bed.

Other than that, try St. Johns Wort tea and Melatonin.

My sleep pattern is still quite choppy (7 weeks after 250 mg dose). I have drug related nightmares and wake up before my alarm.
But its a lot better than during the first two weeks.
 
Howl, I have a lot of the same symptoms as you, however yours sound more severe. I have the weird electrical head sensations, Tinnitus, sensitivity to light and sound, BFEP....also the muscle jerking. These things will come down in the coming months....mine have been about the same for 6 months now but I think we learn to get used to them. I also feel like a constant seizure state. I'm getting an EEG next week.... we'll see what it shows.

I think symptom acceptance has helped me somewhat....try and separate the symptoms that are "uncomfortable' versus unbearable. Things like VS and tinnitus and sound sensitivity may be uncomfortable versus nausea is probably unbearable? Depends on the severity I guess. Anything to help cope.
 
Also I had bad food sensitivity in the beginning.....things with lots of garlic set me off and spiked my symptoms....kava tea....decaf green tea.....
 
Citizen said:
I managed to finally get a good nights sleep after popping a 10mg benzo pill and hour before bed.

Other than that, try St. Johns Wort tea and Melatonin.

My sleep pattern is still quite choppy (7 weeks after 250 mg dose). I have drug related nightmares and wake up before my alarm.
But its a lot better than during the first two weeks.
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My sleep also improved a lot thankfully. I usually only wake up once or twice and get around 7 hours total. I still don´t feel rested afterwards but I hope this will improve too.
 
coolioduder said:
Hi everyone,

Long time lurker since new years of 2017, currently in about 8 months. I have linked my story below, I typed it up on reddit for better formatting.

https://www.reddit.com/r/Drugs/comments/6si2ql/mdma_long_term_comedown_need_help_and_advice/

I am going to my gp tomorrow to have him take me more seriously, what test should I have done? I am thinking blood work and hormones done? What else do you guys suggest?
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Ok so the people saying brain damage--ignore that as its not going to be helpful to focus on that.

However, you DO want to focus on working on the things that can be worked on. And yes, that does include proper hormone blood work as it is an avenue. Howevee, do note that this is a hurdle I had to get through and it was to find a good psychiatrist and HRT doc (who wasn't a typical endocrinologist--most of them brushed me off too) to work together and have all my steroid hormones starting from the very top of the chain at pregnenolone down to the bottom like Testosterone, DHT/E2 and cortisol.

Also complete thyroid testing but my thyroid was actually optimal.

Be aware that the connection between hormones and mental health is bidirectional though. Thats why its a vicious cycle.

Its also why some of the psych drugs can also help.

As a side note, also interesting that somebody on that reddit thread mentioned BPC-157. It seems to be getting quite popular lately to repair amphetamine abuse damage or benzo damage. But so few studies there and no studies on humans.

NMDA antagonists like ketamine I did try for this LTC but- for me- the ketamine did not work due to it being so anxiogenic/DP causing. My depression got "better" for a month only because I was so anxious about the mild DP that my brain had something else to worry about than the depression. And I did not even have DP prior to it. Thankfully that DP subsided in 4-6 weeks I went to baseline.

And I am now on a hormone protocol which has helped (TRT/HCG/Pregnenolone). But still hasnt completely helped so im looking into augmentation via psych drugs. But im actually currently trialing BPC-157 first.

HRT has helped mostly my anxiety and libido aspects of things. Im still struggling with low motivation and low mood (less than before) but I feel like the Testosterone has at least allowed me to be more productive in spite of it.
 
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Back from the neuro, which was a complete waste. He basicly read the symptom list I wrote, did some test like touch your nose, follow my finger... only odd thing was when he tapped the knee reflex my whole body twisted sideways at the same.

He thought I should see a psychiatrist and this is out of his expertise. Said he could get an mri or something but this likely won't help me. After I mentioned the mental stuff he thought the rest was psychosomatic.

I'm so tired of this.. it's so kafkaesque... it's the same when I went through a bad reaction to an ssri.

The "good" news is that it wasn't completely overwhelming. Yes it was bad and my hands and voice was shaky but I could do the checking in and talking on my own. I had earplugs on the taxi ride.

Not sure what next. I guess I'll be seeing a psych. The problem I have with psychiatry is the sort of "let's try everything and see what sticks" type of treatment. It's all very vague with no tangible tests. And any iatrogenic effects can always be explained with underlying this or that.



@socrilus
I could consider TRT if I ever reach a level with only some lingering weakness or such. Right now I'm such a complete mess I don't care if something makes me feel a bit less like a wreck. :D
I do feel extremely "meek". When I talk to people my voice just shrivels and my hands shake.
Are you planning to stay on it indefinitely? I'm wondering what the long term effects are. Have your symptoms been at the same level the whole time? Mood issues only, or did you have something else?

@Citizen
This resulted from a single binge abuse. I took 2 lines, 2 unknown pills + 1 adderall and small amount of alcohol in the space of 26 hours. Countless times I've ruminated back on that weekened, what was I thinking, it's a combination of many factors which I regret immensely. But wallowing in that only feels worse... this is the new reality. I've read that story and those are inspiring but it worries me that I have such different symptoms, so many weird physical things like the out of control eyes. I can even post my own recovery story from a serious ssri reaction if anyone is interested. It's odd to me that the symptoms I had then were more like most peoples "ltc"; ie. dp/dr, anhedonia, insomnia... I don't know how much this plays a role in this.

@Adubbs
I've noticed we have some similarities. Both of us also took the adderall in the mix. However my condition started right away I think yours came with a delay? It's hard to say which symptoms would be bearable. Maybe the tinnitus and HPPD. Those would be hard to accept and live with but I suppose maybe you could learn not to get distracted by them? But I can't pick and choose any symptoms they unfortunately come in a package and overall this is unbearable. I mean in the sense that I can not live any sort of normal life. I'm disabled and unable to function. Your right about he acceptance though... the more I resist this, the more I wish this wasn't so the harder it is. I guess one reason why I am just sitting at home is because I don't like people seeing me like this, anxious twitchy mess. But the more I'm just like oh well screw it the easier it is.
 
howlowhowlstheowl said:
Back from the neuro, which was a complete waste. He basicly read the symptom list I wrote, did some test like touch your nose, follow my finger... only odd thing was when he tapped the knee reflex my whole body twisted sideways at the same.

He thought I should see a psychiatrist and this is out of his expertise. Said he could get an mri or something but this likely won't help me. After I mentioned the mental stuff he thought the rest was psychosomatic.
Click to expand...

Keep pushing for a diagnosis for the physical stuff dude. You likely will have to see several professionals until you´ll find the one who can help.
 
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