How Does MDMA Make One High Through Serotonin?

Dayman

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That's not what its showing for me.
Attachment.

why are you linking to some weird product called phytoserm? this thread is about MDMA and serotonin.

Asked Ray about MDMA. Answer :
In pure form and moderate dose (e.g., 1 to 1.5 mg per kg body weight), I think it’s likely to be helpful for changing the pattern of chronic stress/learned helplessness, and maybe the chronic degenerative diseases produced by inescapable stress. The production of nitric oxide is likely to be a problem with large doses or chronic use.

More info : Ray Peat Email Advice Depository

@Such_Saturation @Area-1255 @Parsifal @Fractality @PhilParma @Liubo @Pointless

this is interesting, I thought he would suggest much lower dosages.
So in the interest of escaping learned helplessness a moderate dose on the rare occasion might be okay
 

Fractality

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why are you linking to some weird product called phytoserm? this thread is about MDMA and serotonin.



this is interesting, I thought he would suggest much lower dosages.
So in the interest of escaping learned helplessness a moderate dose on the rare occasion might be okay

I am mildly surprised at his response as well. MDMA raises cortisol several hundred times. This can likely be mitigated by avoiding the stressful physical activity associated with its use.

Even still, I get a cold sore nearly every time I take it.
 
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CoolTweetPete

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Hi @Area-1255

You seem very knowledgeable on this subject and I'm curious of your opinion on the possibilities of my subjective case.

When I take MDMA I experience the same (presumably) euphoric high everyone else reports but most everyone else I know seems to have trouble the next day. I typically feel great the morning after even if I ingested a lot of alcohol. I'm able to get up and do my chores without much effort while others are comatose.

I took a 23&Me test once and checked myself for genetic mutations, and the site said I had a few including one called a CBS (cystiathone beta synthase) mutation. According to the very confusing Nutrigenomics diagram I drooled at for several hours someone with this mutation would be less able to effectively breakdown serotonin.

I've theorized that this might explain my affinity for MDMA with little short term repercussion. Do you think this could account for my lack of strong side affect? Is MDMA safe (in your opinion of course) for someone to take weekly if that were the case? I also saw you mention that dopamine receptors become resistant at some point.

Thanks for your insight. I always look forward to your posts.
 

CoolTweetPete

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I am mildly surprised at his response as well. MDMA raises cortisol several hundred times. This can likely be mitigated by avoiding the stressful physical activity associated with its use.

Even still, I get a cold sore nearly every time I take it.

Do you have a source for the cortisol raising effect? I've thought of maybe taking Lapodin with it in the past.
 

Fractality

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Do you have a source for the cortisol raising effect? I've thought of maybe taking Lapodin with it in the past.

Stress develops when an organism requires additional metabolic resources to cope with demanding situations. This review will debate how recreational 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) can increase some aspects of acute and chronic stress in humans. Laboratory studies on the acute effects of MDMA on cortisol release and neurohormone levels in drug-free regular ecstasy/MDMA users have been reviewed, and the role of the hypothalamic–pituitary–adrenal (HPA) axis in chronic changes in anxiety, stress, and cognitive coping is debated. In the laboratory, acute ecstasy/MDMA use can increase cortisol levels by 100–200%, whereas ecstasy/MDMA-using dance clubbers experience an 800% increase in cortisol levels, because of the combined effects of the stimulant drug and dancing. Three-month hair samples of abstinent users revealed cortisol levels 400% higher than those in controls. Chronic users show heightened cortisol release in stressful environments and deficits in complex neurocognitive tasks. Event-related evoked response potential studies show altered patterns of brain activation, suggestive of increased mental effort, during basic information processing. Chronic mood deficits include more daily stress and higher depression in susceptible individuals. We conclude that ecstasy/MDMA increases cortisol levels acutely and subchronically and that changes in the HPA axis may explain why recreational ecstasy/MDMA users show various aspects of neuropsychobiological stress.

MDMA, cortisol, and heightened stress in recreational ecstas... : Behavioural Pharmacology
 

CoolTweetPete

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Wow. Thanks for that. I have definitely felt cold hands and feet after prolonged use and 20+ hours without any food.
 

frant26

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MDMA lower serotonin though

Last night I took ~180mg MDMA with some friends (we do this once per year), we had sushi for dinner, one Red Bull and very little alcohol.

Interesting observations:
- That's 2mg/kg body weight; Peat said it should be fine in a range of 1-1.5mg/kg
- Perfect high, not too intense, felt nicely oxytogenic/dopaminergic
- Went to bed late (after a glass of milk and some cheese), and slept about 6 hours
- Woke up refreshed, WITHOUT any nasal congestion or sneezing which had been happening for the past 7+ days even taking Benadryl
- I felt "light", calmly happy, muscles very relaxed, and wanting to move/dance all day
- Ate the usual, temperatures throughout the day very good, sustained 36.7-36.9ºC -- not something I can easily achieve

I'm pretty sure it lowered serotonin/histamine and was a totally positive experience. Not something I can easily replicate with haiduts supplements. I'm kinda puzzled but happy.
 

PhilParma

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I took 75mg of MDMA. I felt nice for a couple of hours. In some way it reminded me a lot of alcohol drunkenness, but without the grogginess or loss in sharpness. Two nights later I was crying for no reason, or for extremely trivial ones. The depression lasted a few days and then gradually dissipated. Meanwhile my blood sugar dysregulation problems resurfaced just as I was beginning to conquer them. So, without the blood tests to confirm it, my subjective experience affirms the idea that this drug powerfully increases cortisol. Actually, in the week after taking the drug, there were times that I felt a dull pain in my kidney/adrenal area. I will not be taking MDMA again.
 

sladerunner69

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I took 75mg of MDMA. I felt nice for a couple of hours. In some way it reminded me a lot of alcohol drunkenness, but without the grogginess or loss in sharpness. Two nights later I was crying for no reason, or for extremely trivial ones. The depression lasted a few days and then gradually dissipated. Meanwhile my blood sugar dysregulation problems resurfaced just as I was beginning to conquer them. So, without the blood tests to confirm it, my subjective experience affirms the idea that this drug powerfully increases cortisol. Actually, in the week after taking the drug, there were times that I felt a dull pain in my kidney/adrenal area. I will not be taking MDMA again.

I understand that if you take mdma more than once per lifetime you run the very legitimate risk of yransforming into a poofball.
 

sladerunner69

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Anyone I know who uses MDMA regularly is thoroughly strange, has a taste for "oddities", has noticableble difficulty understanding higher dimensions of intellectual thought (even moderately so), and will exhibit behaviors and mannerisms of extreme stress (high tension, speaks kurtly and bluntly, etc)
 

Douglas Ek

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Why would serotonin always mean something bad?
Neurotransmitters helps your nerves and neurons to communicate with each other. Probably serotonin release in some parts of your brain makes you feel good. Like someone mentioned earlier that serotonin release in some parts of the brain triggers the release of dopamine and oxytocin. These hormones and transmitters in turn trigger another cascade of events resulting in what you feel everyday. It's all just cascades of transmission happening resulting in changes of electrical waves and in blood flow through out your brain and nervous system. It's way to complex for scientists to study and understand it. Only thing they can measure is that if you take an SSRI your serotonin metabolites increases which would conclude that it affects your serotonin levels. How it affects them and what that means for your mood or brain specifically no one has a clue. Serotonin in your gut probably has a whole different function than serotonin in your brain. People need to stop saying that this and that is bad. If it's there it's there for a reason to function for something. Then of course these system can go haywire and out of balance like any hormone or cell in your body and it will cause an effect on you. Keeping serotonin at bay might help with energy through increased dopamine but removing it completely would **** you up bad.
 

bionicheart

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SSRI's affect dopamine and noradrenaline because they enhance serotonin. Some effects may be related to sigma-1/sigma-2 modulation.

What about the mechanism of Trintillex (vortioxetine?) it's not considered an SSRI but an atypical antidepressant (according to my doctor) but upon further investigation it's a serotonin modulater/ stimulator, specifically agonizing 5HT1a and partially agonizing 5HT1b. This makes me think it acts on similar receptors as MDMA, (minus the amphetamine) so could it be helpful in major depression?
 

oriana

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I see this is an old thread but in case anyone listening...

A non-peaty friend just told me that he got 5-HTP to take to prevent MDMA comedown. I gave him a lecture (unsolicited) on serotonin and how ***t it is. He replied that 5-HTP is the consensus on the internet for best comedown prevention.

I think the ultimate solution is either not using mdma at all or in the context of doing it so rarely that you leave time for the comedown. BUT:

Assuming the comedown is actually a cortisol crash, what might actually be less harmful ways of preventing that than 5-HTP?

If the cortisol crash is the mechanism, then is 5-HTP maybe provoking a stress response and marshaling stress hormones that make you feel better or is there another mechanism in addition?
 
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Douglas Ek

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I see this is an old thread but in case anyone listening...

A non-peaty friend just told me that he got 5-HTP to take to prevent MDMA comedown. I gave him a lecture (unsolicited) on serotonin and how ***t it is. He replied that 5-HTP is the consensus on the internet for best comedown prevention.

I think the ultimate solution is either not using mdma at all or in the context of doing it so rarely that you leave time for the comedown. BUT:

Assuming the comedown is actually a cortisol crash, what might actually be less harmful ways of preventing that than 5-HTP?

If the cortisol crash is the mechanism, then is 5-HTP maybe provoking a stress response and marshaling stress hormones that make you feel better or is there another mechanism in addition?

MDMA probably have mechanisms of action we dont really know how they work. Different parts of the brain release different chemicals, blood flows to different areas etc. saying that a drugs effect is only because of serotonin is probably unlikely. MDMA does release tones of dopamine aswell as oxytocin. It might be that serotonin itsnt the cause of pleasure at all just like lsd blocks som ht receptors and activates some and same for the dopamine receptors. It couls also be the case that ray peat is wrong about serotonin being harmful but i believe it is. Ive done **** loads of mdma and it brought me to a dark place. I had all the symptoms of excess serotonin for 2-3 years. And all symptoms or low dopamine. Staying away from drugs forever helped reverse the damage that i had done on myself and finally after 4 years im glad to say i feel normal today. But when i railed 1 gram mdma by myself in one evening jesus christ. That ***t is so toxic to the brain. Pure poison
 

Vinero

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I see this is an old thread but in case anyone listening...

A non-peaty friend just told me that he got 5-HTP to take to prevent MDMA comedown. I gave him a lecture (unsolicited) on serotonin and how ***t it is. He replied that 5-HTP is the consensus on the internet for best comedown prevention.

I think the ultimate solution is either not using mdma at all or in the context of doing it so rarely that you leave time for the comedown. BUT:

Assuming the comedown is actually a cortisol crash, what might actually be less harmful ways of preventing that than 5-HTP?

If the cortisol crash is the mechanism, then is 5-HTP maybe provoking a stress response and marshaling stress hormones that make you feel better or is there another mechanism in addition?
Back when I used to do MDMA, I always took some phenibut or other sedative like a benzo to help me get through the comedown.
 

Peatogenic

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So interesting about pboy's comments on empathy being a less than ideal thing. I've been experiencing that shift away from a kind of lovey dovey ...enraptured quality...the state of being too emotionally swayed by others in even non-romantic ways...and I thought it might be a bad thing, but part of me knew it was just a New thing, and it actually is more Sharp and autonomous....like a clarity of things, more rapid fire synthesis of information and being kind of "above" the emotional state, while still able to access it. I've been in a kind of ecstasy through my life, but I know now that this ecstasy can be misleading.

But I came here to write that I was confused....the studies actually show that MDMA depletes serotonin in the brain, I thought.
 

magnesiumania

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To me its obvious that the chemisty that MDMA induce is very complex. But a simple theory is that it throws your system totally off balance while at the same time provide you with the chemistry to efficiently deal with that. Possibly this can apply to all drugs.
 

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