MDA stole my soul from me PLEASE HELP

[Jabberwocky]

I see you are horribly unfamiliar with the antidepressant literature. SSRIs sensitize and upregulate 5-HT1A heteroreceptors which have been shown to be critical for antidepressant response while they downregulate and desensitize 5-HT1A autoreceptors.

https://www.ncbi.nlm.nih.gov/pubmed/2532423/
https://www.ncbi.nlm.nih.gov/pubmed/12128004
https://www.ncbi.nlm.nih.gov/pubmed/19016488
https://www.ncbi.nlm.nih.gov/pubmed/17313964/
https://www.ncbi.nlm.nih.gov/pubmed/9822768
https://www.ncbi.nlm.nih.gov/pubmed/9564441

But if you can even be bothered to actually look at the in vivo literature on tryptophan depletion before you recommended it to the OP who is in a time of crisis that would be great, rather than assume that receptor upregulation is going to be good and ignore the effects that vulnerable populations could endure with tryptophan depletion. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585285/ -

"The technique of acute tryptophan depletion (ATD) has been employed in a variety of studies in order to understand the role of serotonin (5-HT) in various cognitive functions and neuropsychiatric disorders. ATD has been shown to induce a transient return of symptoms in patients recovered from depression, both in unmedicated patients and those stabilised on selective serotonin reuptake inhibitors (e.g. Delgado et al. 1990; Leyton et al. 1997; Neumeister et al. 2004)."

"Tasks with an emotional or reward-related component are also affected by ATD; previous studies have reported reduced sensitivity to reward and a negative emotional bias in healthy volunteers following ATD (Klaassen et al. 2002; Murphy et al. 2002; Rogers et al. 2003; Rubinsztein et al. 2001)."

"It is clear that there is large individual variation in response to ATD (Booij et al. 2003), which may be related to genetic factors (Crean et al. 2002; LeMarquand et al. 1999; Neumeister et al. 2002; Quintin et al. 2001). For example, one study to date has reported that women homozygous for the s allele at the 5-HT transporter linked polymorphic region (5-HTTLPR) were vulnerable to mood change following ATD, while those homozygous for the l allele did not show mood change (Neumeister et al. 2002)."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631647/ - "Ecstasy users carrying the s allele, but not comparison subjects carrying the s allele, showed abnormal emotional processing. On the basis of a comparison with acute tryptophan depletion, the authors hypothesize that chronic Ecstasy use may cause long-term changes to the serotonin system, and that Ecstasy users carrying the s allele may be at particular risk for emotional dysfunction."

Familiarize yourself with the literature before recommending nonsense like tryptophan depletion to someone in OP's position. If you were a doctor I would wish to see you banned from practicing medicine.

1. Nothing in the OPs post would preclude a tryptophan deficient diet -- NOTHING --

You should take your own advice -

your citations refer to 5HT1a

MDMA is a 5HT1a -- non-competitive antagonist https://www.mdma.net/5-ht1a/hippocampus.html and MDMA itself have been shown to upregulate 5HT1a


I was clearly referring to 5HT2A and C -- where MDMA acts as an agonist and causes downregulation

There are many 5TH2A and a few 5HT2C antagonists -- but they have not been shown to conclusively cause upregulation -- and carry significant side effects as they are all anti-psychotic drugs

Tryptophan deficient diets have however, been shown in an invivo rat model to cause upregulation

The curative effect of fasting on depression is likely attributed upregulation of 5HT receptors during the depleted state

 

[Cotcha Yankinov]

Apologies to HelloMe for clogging up the thread.

1. You have to prove a root biological cause that did not preceed the substance use - [snicker] fat chance of that

This ignores the possibility that one had vulnerable genetics but still displayed a normal phenotype prior to the environmental stress. One gene that has been found to increase the risk of adverse effects after MDMA and increase the risk of mental illness after stress is having a short form at 5-HTTLPR. The short form is associated with MDD only after stress, a gene - environment interaction. People with the short form who have not been through a stressful life incident etc. typically display a fairly average phenotype. Thus its certainly possible that the biology prior to the stressful incident was different and not actively producing depressive etc. symptoms, but was still vulnerable biology.

2. 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.

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.

I don't want to get into the human studies here though out of respect for the OP, if you do wish to do so then go make a post in neuroscience and pharmacology.

3. Cortisol is known to induce HPA dysregulation, and other endocrine dysregulation

Cortisol is known to produce neuroplastic effects... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946089/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038707/

See the neurogenic hypothesis of depression even.

What is more likely? Any one of a number of endocrine based hormonal/corticosteroid dysregulation known to be caused by acute stress - like that experienced during stimulant use/abuse all of which are known to cause marked mood disorders ?
Psychosomatically Induced mood disorders - also known to be caused by acute stress
Yes - you can THINK yourself into depression - depersonalization -derealization - anhedonia
OR-
Some magical UNPROVEN neuroplastic adaptation?
OCCAM SAYS WHAT?

How are you proposing that thinking or stress hormones produce a persistent change without neuroplastic changes?

The only way you can reconcile your #3 and these latest assertions with reality is by proposing that there is a persistent loop of cortisol and/or neural activity, as in, an acute increase in cortisol would reverberate throughout the brain/body persistently. Cortisol would act on neurons, neurons would release cortisol, etc. It is fundamentally neuroplasticity that would facilitate that possible loop, or help put a stop to the loop (or fail to stop it). Yes, it is possible for neural activity to echo throughout the brain, I imagine reverberating for quite a long time is possible, but that change in neural activity is going to lead to neuroplastic changes that could be contributing to the syndrome, including adaptations to stress hormones (which are known to induce depression).

It is probably not the elevated stress hormones themselves that directly cause effects on neurotransmission that cause depression (see glucocorticoid mediated euphoria for example) but rather the resulting neuroplastic changes that lead to depression.

 

[Cotcha Yankinov]

1. Nothing in the OPs post would preclude a tryptophan deficient diet -- NOTHING --

...Except for that she is having adverse effects from MDMA and there is an association between genetic vulnerability to these adverse effects and increased risk of depression after acute tryptophan depletion in females... I wouldn't go around recommending someone deprive themselves of a vital amino acid lightly..

You should take your own advice -
your citations refer to 5HT1a
MDMA is a 5HT1a -- non-competitive antagonist https://www.mdma.net/5-ht1a/hippocampus.html and MDMA itself have been shown to upregulate 5HT1a

I said 5-HT1A receptors were critical to anti-depressant response, not that we should block them... But I don't really see what point you're trying to make, we're talking about adverse effects of MDMA, not its therapeutic potential (which I fully acknowledge).

I was clearly referring to 5HT2A and C -- where MDMA acts as an agonist and causes downregulation

There are many 5TH2A and a few 5HT2C antagonists -- but they have not been shown to conclusively cause upregulation -- and carry significant side effects as they are all anti-psychotic drugs

5-HT2A/5-HT2C are regulated atypically. Blockade causes desensitization (https://www.ncbi.nlm.nih.gov/pubmed/12650852). Also 5-HT2 antagonists are not all AAPs, there is Mirtazapine for example, and Pimavanserin is now approved for Parkinson's disease psychosis.

Desensitization of 5-HT2 has been associated with anti-depressant response, and over expression of 5-HT2 has been associated with suicide victims.

(note to readers - mCPP is a metabolite of MDMA)
https://www.ncbi.nlm.nih.gov/pubmed/16360124 - "The mCPP-induced increase in the serum concentration of corticosterone was not blocked by the 5-HT2C antagonist SB242084, but was blocked by the 5-HT2A antagonist ketanserin. Chronic treatment with fluvoxamine and paroxetine attenuated the response to mCPP, while these SSRIs had no effects in control rats. These results suggest that the desensitization of 5-HT2A receptor function occurs in the same way as that of 5-HT2C receptor function through chronic treatment with either fluvoxamine or paroxetine as a consequence of prolonged exposure to elevated levels of serotonin. The hypersensitivity of 5-HT2A receptors is observed in depressed patients, and chronic treatment with many antidepressants such as tricyclic antidepressants have been reported to reduce 5-HT2A receptor density and/or efficacy. The desensitization of 5-HT2A receptor function might contribute to the therapeutic mechanism of action of these SSRIs, as seen with other classes of antidepressants."

Tryptophan deficient diets have however, been shown in an invivo rat model to cause upregulation

The focus should not be solely on upregulation of receptors, but rather the behavioral outcomes. The only reason the upregulation would matter to us is if it led to beneficial behavioral outcomes in MDD patients. But historically clinicans have used tryptophan depletion to induce depression in vulnerable patients as a probe...

The curative effect of fasting on depression is likely attributed upregulation of 5HT receptors during the depleted state

Not that non 5-HT2 subtypes or BDNF and so forth should be forgotten but...

https://www.ncbi.nlm.nih.gov/pubmed/24036107 - "Co-administration of 9h of fasting and imipramine (30mg/kg, i.p) produced the additive antidepressant-like effects in the FST and increased the ratio of p-CREB/CREB. Meanwhile, the additive effects were partially reversed by treatment with a 5-HT2A/2C receptor agonist, (±)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) (5mg/kg, s.c). Furthermore, the antidepressant-like effects of 9h fasting was also blocked by DOI compared to the non-fasting control group."

So its not 5-HT2 receptors mediating the beneficial effects of fasting, rather 5-HT2 activation leads to decreased benefits of fasting, so why not talk of SSRIs that are shown to enhance 5-HT1A signaling and sensitivity while downregulating "bad" serotonin receptors like 5-HT2?

Unfortunately fasting and acute tryptophan depletion might be mutually inclusive (unless there are studies on fasting with solely tryptophan/amino acid supplementation?), thus I still can't recommend fasting for the OP in good conscience...

 

[socrilus]

I mean I am sorta with Cotcha here. In the hormonal endocrine issues isn't it the effect of various hormones on neuroplasticity that mediates mood?

I am interested in the endocrine regulation theories bc I did get technically normal but somewhat low for age Testosterone in my LTC. If we go by the whole cortisol theory then maybe high cortisol from the stimulant actions of MDMA eventually downregulated my Test levels which creates symptoms that create stress then further affecting the system. Is this what you mean Shugenja?

It was all "subclinical" though and not caused by any true disease process. Its just my HPTA is suppressed

I kind of understand what Cotcha means though with reconciling the theories. Both the hormonal/biological stuff and the "psychological" side perpetuate each other. Its hard for the brain to regulate hormones under stress but its hard to be unstressed when the brain isn't regulating hormones?

 

[Itsgoneundertheboa]

Is there some sort of media campaign in the US about mdma causing long term comedowns. I know nobody in the UK who has suffered this, and nor have I ever read about it except on this board. Seems like bullshit to me, I cannot see one MDA pill causing this

Not seen one specifically but if you refer to the prevalence of reports on this site and the fact the majority is US centric - it is not representative of the reality IE amount of people taking MDxx to those that report these effects.

US population is 10 x that of somewhere like U.K. A site such as this will attract those that seek answers or need to discuss how they feel. I guess the point of having BL; but agree the prevalence is high in reality to the amount of users with no or positive.

It's like the 3 month rule- no proof whatsoever of validity but it appears this becomes accepted by power of suggestion. So it becomes the rule.

The problem is that everyone tries to catergorise themselves in order to get some explanation from the effect they feel. Power of suggestion and human nature of looking for answers.

Ultimately people everyday report many of the effects listed as LTC without ANY drug intake. We are all genetically different in some way.

I can drink 8 litres of strong beer, remain in control and never had any experience of losing all self control. My friend drinks just 3 litres loses control, is violently ill and suffers for 2 days after. Both our health is fine and checked.

If I take MD of course I get a change in feelings over the few days after taking. What goes up must come down. But I'm fully aware and make plans to compensate. In fact I celebrate the down as much as the up because it's the reason to use. I want to experience. A lot of older users plan for the event and make sure we do have space and time to reintegrate back.

We are all different and likely there is a potential for a drug to induce a change in mind state, as by there nature that's what they do.

Some can take large amounts frequently others not. Unfortunately reports of great times no issues and positive life effects simply don't happen on here anymore. You get flamed for speaking out. So a lot of us don't bother.

For example suggesting adrenaline based, low cardio exercise - flamed when ALL and every psyche doc will tell you it's proven. Studies for example of shock exercise - cold water swimming. Instant adrenaline caused by shock of cold water (fight or flight) then exercise in the water reduced all symptoms of those medically diagnosed with depression and not just whilst in the water but for days after.

Interestingly when you suggest it the inevitable answer is I feel too weak, I can't afford the time, it won't work for me, I'm too anxious / depressed to go do it, you have no understanding of how I feel. To a psyche that says a hell of a lot about how a person views their ability, will and keenness to get past the condition they are in.

Even in here you can see those that try to help give some science and offer some help to be told no you are totally wrong. Wtf?

Either you want the help and another view to increase your understanding or you already concluded your condition? If so what you still doing here? Sympathy? To show how great you are with knowledge of your condition? To persuade others there is simply no hope?

There are some really supportive guys and girls in here but everyone should perhaps consider carefully that those that give advice, evidence or personal experience don't have to. They do care? And I've said it before to label anyone who appears to have an issue via an online forum is downright wrong and dangerous.

Question for the OP - did any of the information you were given on BL have any positive impact or provide a positive answer? Have you now self diagnosed / been assisted to think, without any trained medical advice IRL, you have an LTC? Have you actually been and sort medical assistance and undergone any professional diagnosis?

Personally I know a lot of people who will match the symptoms listed who have never taken any substance. It's an undiagnosed condition even after many years of them searching for answer through research and reports. It's called chronic fatigue syndrome (CFS) or M.E. Who knows possibly MD compound can trigger it.

 

[Patsfan12]

Hellome I'm really sorry to hear what your going through as I can somewhat relate. I took half an ectasy pill about 3 months ago and a lot of what you said in the video I also feel but not as bad but I have other symptoms that for me are worse like visual disturbances. I also just had that wierd feeling like something is wrong and it also terrified me. I'm also in college and I have never been an anxious person put I know exactly what you mean when you said you felt anxious going to classes. I'm fighting through it and still going but it's not easy. Im not out of this myself yet so I can't really help you to much but all I can say is try your hardest to do things like going out and eventually it will get better it has to. I know it's so much easier said than done but you have to fight through it. There is no way there's brain damage from just 1 pill so it has to be some sort of disorder you triggered from the drug but it will get better in time as long as you take care of yourself and do all the right things like exercise, eat healthy, and stay away from all drugs and alcohol. I'm wishing you luck cause I wouldn't wish this on anyone.

 

[burn out]

I highly suggest you pick up some New Mood by Onnit. It's a blend of 5HTP, Tryptophan and other relaxing herbs, and has helped me out immensely.

this might be a good idea. have you tried any herbs to help you hellome? kava, valerian, mulungu and akuama seeds are all relaxing herbs which can help a person heal from traumatic experiences. you would be amazed at how much healing can take place when you just relax and stop obsessing over your condition. in my opinion, obsessing over your condition actually prevents healing and starts developing unhealthy brain patterns.

 

[Cotcha Yankinov]

obsessing over your condition actually prevents healing and starts developing unhealthy brain patterns.

This. I highly recommend mindfulness for this purpose.

 

[Nambo]

.


Slightly off topic but may be of interest. About 15 years ago I was desperately ill with 'CFS'. Very long story but basically you get diagnosed with CFS or ME when doctors have no fucking clue what is wrong with you and you experience various symptoms but primarily fatigue. Also my blood work religiously came back negative. The reason being is that you can actually have active Lyme / rickettsial / mycoplasma infections but blood test aren't sensitive enough or give false negatives. In any event I was treated with tetracycline antibiotics despite of negative blood results and I literally improved over night. The trick is finding a doctor to prescribe despite negative blood tests. Anyway you would have thought that haveing dealt with CFS for 3 years that the last thing I deserve is a LTC. There are a couple of overlaps between my CFS and LTC symptoms but the majority are very very different. I do however totally believe that because of my historic CFS I was far more vulnerable and subseptible because of my previous illness. Anyway maybe of interest...

 

[Jabberwocky]

Is there some sort of media campaign in the US about mdma causing long term comedowns. I know nobody in the UK who has suffered this, and nor have I ever read about it except on this board. Seems like bullshit to me, I cannot see one MDA pill causing this

Because there is no such animal.

There is hypersensitivity due to a change in the set point of the HPA axis -- and consistent fight or flight response -- ususally due to the dopamine and nor-adrenaline action of a non-MDMA substance

 

[Dresden]

To the OP,

You are whining. MDA did not steal your soul. It's not like it's the Devil or something. Just be glad you were blessed enough to have the opportunity to take it. I know I would be ecstatic to try MDA tomorrow. You're giving the drug more power over you than it deserves, when in reality YOU should be the one to have power ovet IT. By noy taking it next time if MDA is not your cup of tea, for example.

 

[LordOfTabs]

I literally had like a 3000 page novel written on neuropharmacology of pleasure, reward drive and love and the ability to bond with others. But I accidently deleted it.

But basically what I wrote was,
Because both i, and my mother have seriously abused stimulants for years (mainly MDA) eventually I started having visual distortions, and word for word the feelings your having. Today, both me and my mom are cured (well, being treated very well)
Assuming you didn't get a toxic batch and did damage to all 3 basic cognitive neurotransmitters, and enough to stop the circle, you can be cured.

Feeling "out of touch" is psychosis. Not like a swinging pocket watch, but more like you have adapted your mindset (just like you'd adapt to a missing finger being normal) to this state of consciousness. Here's how we solved it.

Both of us, separate doctor's, biologic mother/son
Always consumed the same substances and lived together
...and my god we knew how to do some drugs.
The diagnosis for us both was drug induced psychosis.
If you lie to your doctor about illegal drugs, he can't help.
If you feel like he is viewing you like your either a drug addict or crazy, LISTEN TO HIM.

Basically if you can't get one single feeling of pleasure, you will do nothing. And loose all your friends.
In other words, dopamine stopped saying "hey that was a good thing I did, I wanna do it again "
And serotonin is not there to say "hey that makes me feel happy! I'm going to continue to drive further, because after all, I kick ass!"
And europronorphrine is what lets you feel for others. Your out of balence man. There are ways to ease it without substances too

 

[Dresden]

I've gotten to the point that I feel hopeless just enough to matter anfd unmotivated and not in a good mood when I'm not on methamphetamine. It's a bad situation to be in and is likely to cause me more problens with my family soon. I don't ever want to quit using methamphetamine in my lifetime at this point. I started it 21 years ago. I'm probably gonna get some good beans (we used to call them "rolls" but that term seems to have slipped into oblivion circa 2016 after the age of methcathinone derived "molly"; anyway, I'm referring to pressed, stamped MDMA pills in casr you didn't know) soon, so maybe that'll help me. I just got out of 5 months of rehab.

 

[LordOfTabs]

UPDATE MY FRIENDS!
My psychosis been 99.9999% (slight visual dyslexia) after using a small amount of the worst drug for you.
Crystal meth.
Why did it help? Not because I did a shit Load of it. But because I believe now I had MAJOR DEPRESSION. Brought on by whatever, it seems we all have one thing in common.
Anxiety and desire for normality.
Your worrying so hard and never finding answers, so much your journeymanning
NEUROCHEMESTRY.

Reward yourselves. I think it is about a chain of these reactions. Desire->reward->happiness->reward from happiness->desire from reward from happiness (never ending)

We all know the basics right? You can't get all the reward without the happiness.

Your in balanced. Find what caused you to WANT to use psychoactive substances. And then use a small dose of the drug for that emotion and stop using drugs.

I have been psychosis free for about 9 hours so we will see if that sticks. Mine was lack of acknowledgement in my life during my initial use. Marijuana. Lol.
And it SPIRIALED. Ps. I'm not tweaking.

 

[LordOfTabs]

Sorry only 2 hits of meth. Stimulated dopamine in my brain but for some reason I still have cravings but no psychosis or emotional worries. Even starting to feel better and more normal as I waited to do any activity until I came all down.