How Does MDMA Make One High Through Serotonin?

[CoolTweetPete]

post 69447

The whole empathetic thing, I hate to say it (but don't), is actually a bad thing.

I can testify to this personally. MDMA makes it easy for you to develop inappropriate emotional bonds. Think falling in "love" with someone who's completely wrong for you.

I would argue that falling in love is a form is psychosis. The empathy

post 69438

I don't think MDMA increases serotonin initially. I think it increases dopamine, and then once you've come down, perhaps the stress of the high increases serotonin (or perhaps it temporarily "depletes dopamine").

Either way, I did not feel helpless or subordinate on MDMA. I felt profoundly empathetic, energised yet calm. I don't consider it a stimulant, even though it's technically an amphetamine. I disagree with Such Saturations comment that you can easily tell when someone's on MDMA; poor quality stuff is often cut with amphetamines and can jack people up, but pure MDMA is a VERY calm/clean high.

agreed. I'm very calm on MDMA - almost blissful. I get good s*** though.

Agreed -- My friends though, often have trouble not showing it (jaw movement, sloppy walking, etc). I also think this has to do with how clean the MDMA is of adulterants. Even so, I don't typically experience any of these symptoms even at doses up to 500mg.

I also don't experience the next day symptoms a lot of people report (depression, anxiety). If I don't drink or do anything dumb (other drugs that rhyme with Spokane), I will usually wake up with a distinct feeling of calm and optimism the day after using MDMA. I suspect this may have something to do with a genetic polymorphism I identified on my 23andMe results. Nutrigenomics can be very difficult and confusing to read about, but I have a methylation defect that makes breaking down serotonin difficult if I recall reading it correctly. I've always wondered about this but most people talking about nutrigenomics online don't have much experience with MDMA, lol.

 

[CoolTweetPete]

post 69447

The whole empathetic thing, I hate to say it (but don't), is actually a bad thing.

I can testify to this personally. MDMA makes it easy for you to develop inappropriate emotional bonds. Think falling in "love" with someone who's completely wrong for you.

I would argue that making inappropriate emotional bonds is the purpose of using MDMA. This is a transcendent experience, which highlights the intrinsic nature of 'love'.

It does not mean you have to follow this experience up with bad decisions (e.g. having a long-term relationship with someone, or even seeing them again lol)

 

[Such_Saturation]

Just don't wake up with weird rashes

 

[lexis]

post 103975

post 69447

The whole empathetic thing, I hate to say it (but don't), is actually a bad thing.

I would argue that making inappropriate emotional bonds is the purpose of using MDMA. This is a transcendent experience, which highlights the intrinsic nature of 'love'.

---------------------------

How is 'inappropriate' understood in the context of biochemistry and physiology?

 

[Sheik]

http://i.imgur.com/jG8GeH9.jpg
This thread.

 

[DaveFoster]

post 69442 ive never taken MDMA but have had lot of experience with other similar things, and just a lot of herbal stuff...and have had high serotonin at points and know what its like...and the illusion of why many might think it feels good. Its not a true good feeling, im sure with MDMA the amphetamine portion masks and overcomes some of serotonin's effects, which is why people are still active and awake on MDMA, tho I have seen a friend at a party pass out on the concrete right in the middle of the action after having taken MDMA ..I guess it started wearing out. Seretonin seems to enhance tactile sensation, but it kind of dumbs you down and makes you weak and susceptible to infections and BS. Its not a true feeling of happiness that comes with sharp mind, wakefulness, and most importantly capability and strength of resolve. Its more the...massage me, tickle me, serenade me, but basically I can only sit here and not really do anything...and when serotonin is high, information isn't assimilated properly..its like you'll be watching a video or listening to something and rather than actually listening to the concepts, thinking about it, assimilating it...its more just hearing the sounds and having them massage you...but nothing valuable happens and you'll forget it all or basically have not even heard it.

Most people and society, because of the diet and lifestyle since they were young, and the fact just about everyone is perpetually constipated and has irritating foods in their intestine...they think 'feeling good' is like when you eat a large meal and get lazy and can laze around on the couch...its more a sedation escape feeling. Almost no one actually knows what its like to feel good in a doped, healhy, clean intestine, fully nourished, capable way. Once you've tasted that, anything that provokes serotonin and makes you wanna lay down and receive massage or whatever is offensive, because you realize its just weakening.

The whole empathetic thing, I hate to say it (but don't), is actually a bad thing. Not that empathy is bad...but theres a reason you have the desire to avoid certain people or things and not leak energy towards them...over time such interactions not only drain you but fill your mind and life with non optimal, dragging down, weakening things. I know exactly what its like to have high serotonin...it is very hard to get mad or judgemental at first, but its not in a healthy way. It leaves you open to being taken advantage of, and being propagandized, and leaking your time and energy to parasitical or unworthy people and things...and over time youll never get anywhere, do anything, accomplish anything, or grow in a true meaningful way.

A true feeling of doped happiness, strength, wakefulness, acuity of senses, capability, just allows you to avoid negative influences, and actually promote the good things without being tempted or lulled by BS or propaganda, or lazy negative people, and doesn't allow you to accept sub par sad depressed average toxic things as 'ok'. The 'empathy' is really just a weakness that allows complacency in and for things that are totally not ok at all, and that you should be immune to, and have the intelligence, awareness, and capability to avoid and change

Fantastic. This dichotomy of judgement and acceptance may be extended to include the collectivist versus individualist forces in society. There are those who embrace this kind of opinion that everyone should be integrated, accepted, unchallenged, unoffended, and not judged against any standard. These same people say that the ends sometimes justifies the means, that we should just accept "balance and moderation," tolerate what is, as we can never hope to change it, live within the context of the system, and try not to rock the boat. Refraining from "leaking energy" is just that, conservation. Conservation manifests in a political scene of economic conservatism, where an individual resists the urge to allocate resources where it will not bring personal benefit. This altruistic, self-sacrificing, dogmatic, politically-correct acceptance of mediocrity and just "going with the flow" is simply distasteful and off-putting in all regards.

Excellence is possible, and perfection is asymptotically approachable, so let's not settle for the lesser of two evils, or what makes the greatest number content at that moment in time, a la the neo-progressive, relativist, post-modernist dialogue. Rather, focus on that which will bring you happiness, efficiency, and success, and associate with those who will challenge you, help you grow, and assist you in your journey. Don't just exist; live.

 

[Parsifal]

Fantastic. This dichotomy of judgement and acceptance may be extended to include the collectivist versus individualist forces in society. There are those who embrace this kind of opinion that everyone should be integrated, accepted, unchallenged, unoffended, and not judged against any standard. These same people say that the ends sometimes justifies the means, that we should just accept "balance and moderation," tolerate what is, as we can never hope to change it, live within the context of the system, and try not to rock the boat. Refraining from "leaking energy" is just that, conservation. Conservation manifests in a political scene of economic conservatism, where an individual resists the urge to allocate resources where it will not bring personal benefit. This altruistic, self-sacrificing, dogmatic, politically-correct acceptance of mediocrity and just "going with the flow" is simply distasteful and off-putting in all regards.

Excellence is possible, and perfection is asymptotically approachable, so let's not settle for the lesser of two evils, or what makes the greatest number content at that moment in time, a la the neo-progressive, relativist, post-modernist dialogue. Rather, focus on that which will bring you happiness, efficiency, and success, and associate with those who will challenge you, help you grow, and assist you in your journey. Don't just exist; live.

There is a lot of truth in your statement but this is a bit narrow, dualism is not a good way of looking at things.
We are in a fake society in every aspects and with a lot of lies (what you are calling the altruistic self-sacrificing thing is totally fake, this gives the illusion of a society with justice while behind the scenes our economical and political systems are big lies and a huge amount of manipulation), problems and suffering could be avoided just by letting people understand what their true physiology is and growing children with good foods and the less oestrogens and serotonin as possible.

There would be a lot less violence (agression), depression, stress, blindness/unconsciousness, sociopaths to rule others or excessively gushy and fake people, the extremes would be more balanced in every way .

PS: Sorry, my english is far from being perfect .

 

[DaveFoster]

We are in a fake society in every aspects and with a lot of lies (what you are calling the altruistic self-sacrificing thing is totally fake, this gives the illusion of a society with justice while behind the scenes our economical and political systems are big lies and a huge amount of manipulation), problems and suffering could be avoided just by letting people understand what their true physiology is and growing children with good foods and the less oestrogens and serotonin as possible.

There would be a lot less violence (agression), depression, stress, blindness/unconsciousness, sociopaths to rule others or excessively gushy and fake people, the extremes would be more balanced in every way .

I completely agree. I believe the sense of entitlement and way people strive for equality, rather than personal greatness, is caused by an excessive feminine, serotonergic, and "R" reproductive strategy mindset. The sociopathic mindset is not one of an individual who seeks to improve himself and share his gifts in the world, but rather one who fears rejection and thus chooses to forego interaction with others, and would rather play a zero-sum game where he builds walls and selective, biased filters around his or her own worldview. (Ray Peats reference to serotonin as a filter comes to mind.)

Essentially, this shuts down the emotional and psychological growth process, which breeds a cycle of fear (like that perpetuated by promises of politicians).

 

[Makrosky]

When considering MDMA effects, nothing about RP's view on serotonin makes sense to me. MDMA main effect is releasing serotonin to the synaptic space. Indeed it has other described (and probably some undiscovered yet) effects on dopamine, oxytocin, etc. but the main one is on serotonin as far as I know.

I had MDMA this weeked and I have used it many times before, so I subjectively know the substance besides what it does biochemically speaking. This time I'm observing it through serotonin perspective and, sincerely, it doesn't fit RP's theories. I had an increase of temperature. Increase of intensity of orgasms. Increase on love and expansiveness feelings. Of love to life, to beauty things. To friends. More clarity of mind... Not the analytical mind. No the mind to read papers or go to work but to the sensual mind. Creative mind. Oh and by the way, my bowel movements improved drastically the day of mdma and the day after. Another sign of good metabolism. And of course this is not only me all these effects are shared among most of the people who uses MDMA. Look at an RP excerpt by the way :

Even in brief
social encounters (of a few seconds), these body feelings may
take on a conformation of openness and love, of sexual feeling,
or of a closed anxious coldness. In the pleasant experience, the
visceral feeling resembles channels which open and extend
outward toward the other person; at times, these channels
seem to make powerful contact with the other person's.
Occasionally, when I feel very energetic, especially on sunny
days, I have an intense sensation of sweetness that seems to
travel up from behind and below my navel, to a spot behind my
sternum. I call this my body's smile energy, because it feels the
same as the pleasure which goes with a smile.
When I described these perceptions to an older person, she
reported having lost those feelings in middle age, and she said it
seemed that they had been "insulated" by the extra fat she had
put on. (People who don't notice those sensations may wonder
how a person could feel insulated from something which is
inside oneself. The point is that they are sensations of openness
of the body to the world.) Her comments caused me to associate
the feelings with thyroid function and metabolic rate. I have
noticed that when I feel sluggish from bad weather or diet, those
feelings seem muffled, or barely perceptible.
Recently, I described these body feelings to a friend (in her
early twenties) who wasn't sure what I meant. For several weeks,
she didn't experience anything that seemed like my descriptions.
She began taking thyroid a few weeks ago. Within a few days of
the time that she had increased her dosage (from 1/2 to 1 grain),
she told me that she had begun to feel things she had never felt
before, feelings of openness and intensity in her body. Another
friend, the same age, said she had orgasms easily when she was
18 and 19, but in the last 2 or 3 years had been unable to.

This is what RP considers is a good metabolism, aided by thyroid in the example. Yet this happens when you take MDMA and it is mostly because it floods you with serotonin. How the hell is this possible then ?

Btw, no matter what it does biochemically speaking, I think it heals you in a deep level, at least temporarly. It kinda reboots you, or reminds you how you can be. Or who you are in the first place.

 

[Such_Saturation]

It depletes serotonin

 

[CoolTweetPete]

post 108674 When considering MDMA effects, nothing about RP's view on serotonin makes sense to me. MDMA main effect is releasing serotonin to the synaptic space. Indeed it has other described (and probably some undiscovered yet) effects on dopamine, oxytocin, etc. but the main one is on serotonin as far as I know.

I had MDMA this weeked and I have used it many times before, so I subjectively know the substance besides what it does biochemically speaking. This time I'm observing it through serotonin perspective and, sincerely, it doesn't fit RP's theories. I had an increase of temperature. Increase of intensity of orgasms. Increase on love and expansiveness feelings. Of love to life, to beauty things. To friends. More clarity of mind... Not the analytical mind. No the mind to read papers or go to work but to the sensual mind. Creative mind. Look at an RP excerpt :

Even in brief
social encounters (of a few seconds), these body feelings may
take on a conformation of openness and love, of sexual feeling,
or of a closed anxious coldness. In the pleasant experience, the
visceral feeling resembles channels which open and extend
outward toward the other person; at times, these channels
seem to make powerful contact with the other person's.
Occasionally, when I feel very energetic, especially on sunny
days, I have an intense sensation of sweetness that seems to
travel up from behind and below my navel, to a spot behind my
sternum. I call this my body's smile energy, because it feels the
same as the pleasure which goes with a smile.
When I described these perceptions to an older person, she
reported having lost those feelings in middle age, and she said it
seemed that they had been "insulated" by the extra fat she had
put on. (People who don't notice those sensations may wonder
how a person could feel insulated from something which is
inside oneself. The point is that they are sensations of openness
of the body to the world.) Her comments caused me to associate
the feelings with thyroid function and metabolic rate. I have
noticed that when I feel sluggish from bad weather or diet, those
feelings seem muffled, or barely perceptible.
Recently, I described these body feelings to a friend (in her
early twenties) who wasn't sure what I meant. For several weeks,
she didn't experience anything that seemed like my descriptions.
She began taking thyroid a few weeks ago. Within a few days of
the time that she had increased her dosage (from 1/2 to 1 grain),
she told me that she had begun to feel things she had never felt
before, feelings of openness and intensity in her body. Another
friend, the same age, said she had orgasms easily when she was
18 and 19, but in the last 2 or 3 years had been unable to.

This is what RP considers is a good metabolism, aided by thyroid in the example. Yet this happens when you take MDMA and it is mostly because it floods you with serotonin. How the hell is this possible then ?

Btw, no matter what it does biochemically speaking, I think it heals you in a deep level, at least temporarly. It kinda reboots you, or reminds you how you can be. Or who you are in the first place.

100% ^

 

[Makrosky]

It depletes serotonin

Such, what do you understand by deplete ? It releases it so it can activate the receptors to an unusual degree. It is the days after when you are out of serotonin because there's none in the presynaptic vesicles, it has been used. And then it is precisely when you start to feel the very well known blue mood phase that lasts a few days.

Edit : I try to make myself clear : It is not that it releases the serotonin and it magically goes to the trash bin. It releases the serotonin and the serotonin is there in the synaptic space activating the receptors.

 

[Makrosky]

And also, I've taken cypro and it's not remotely near what happens with MDMA.

Maybe Ray, or what we think Ray thinks, is abusing the dichotomy of serotonin bad/dopamine good.

 

[Such_Saturation]

Look at page 792 and you will see the 60% lowering of serotonin in the blended brain after just 3 hours: http://www.maps.org/images/pdf/1996_chu_1.pdf

Also look at how much similar the metabolites of MDMA are to dopamine. They could easily be having that action seeing as MDMA itself doesn't really seem to do much. Its metabolism and breakdown are compatible with the time to feel the effects.

A report that intracerebroventricular injection of MDMA failed to cause neurotoxicity in rats led to speculation that a metabolite, rather than the parent compound, is responsible for the neurotoxic effects of MDMA.

(MDMA, Ecstasy) is excreted in human urine mainly as conjugates of its metabolites 3,4-dihydroxymethamphetamine (DHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA).
----------
Furthermore, both, DHMA and HMMA, were identified as inhibitors of dopamine sulfation.

sulfation is a major inactivation pathway for catecholamines such as the
neurotransmitter dopamine

From the first article:

Schmidt and Taylor have shown that uptake blockers, such as fluoxetine and citalopram [SSRI], can block or reverse the acute depletion of [tryptophan hydroxylase activity by] MDMA, indicating the involvement of the 5-HT transporter in such depletion.

In fact,

The coadministration of potent and selective uptake inhibitors (6-nitroquipazine and paroxetine) of 5-hydroxytryptamine (5-HT) completely antagonized the reduction of 5-HT levels in the cerebral cortex 3 hr after a single administration of MDMA (10 mg/kg).

Subjective experience:

I find i need at least 3/4 of a gram of pure Mandy to get anywhere and even then the effects are not as brilliant as I am told they should be (having never tried Mandy off prozac)

------------

you probably wont feel a thing. I know from experience. If you feel anything, it'll be the shittier side effects if its speedier M. I couldn't roll for over 2 months after I quit taking an SSRI and I was only on it briefly.

 

[PhilParma]

Just read this and it made me think of Ray Peat.

"[MDMA] alters an enzyme that synthesizes serotonin in your brain—tryptophan hydroxylase—so it doesn't work as well. Your serotonin levels disappear, and the other neurotransmitters in your brain take over. Over time a person's brain chemistry shifts from a serotonin-based system to more of a dopamine or norepinephrine-based system."

Sounds like a rocket ship to Peat optimal brain chemistry.

 

[Pointless]

I thought people got permanent depression from abusing MDMA.

 

[Fractality]

It's probable that the depression and other deleterious effects are due to its effects on cortisol. It's virtually guaranteed to give me a cold sore if I use it.

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.

MDMA, cortisol, and heightened stress in recreational ecstasy users. - PubMed - NCBI

 

[Area-1255]

People sometimes argue that MDMA increases serotonin, so how can a serotonin antagonist act like an antidepressant. I have never tried it nor do I have any desire to, but how does MDMA make one feel good, high, emphatic, etc, if serotonin makes one feel apathetic, depressed, dull, etc? It seems to confuse people and fuel the theory that low serotonin causes depression.

Because it reverses the transporters and it releases dopamine as well as serotonin. Serotonin is numbing when it activates the receptors that are negatively coupled to G-Proteins, but with serotonin 2A receptor activation, that is where dopamine is released and certain polymers/heteromers are activated which ultimately triggers glutamate activation in neural circuits where they overlap with visual-cortical-networks. Therefore hallucinations (in some cases, but stronger with Acid) and euphoria occur through that pathway, antagonism has a beneficial effect as well, because blocking the receptor tends to decrease cortisol/prolactin which results in one better effect over time. Therefore in regards to Depression, it's mostly long-term blockade of 2A which has benefits, whereas short-term activation seems to have empathogenic and euphoric effects.

 

[Parsifal]

It's probable that the depression and other deleterious effects are due to its effects on cortisol. It's virtually guaranteed to give me a cold sore if I use it.

This is the only way to free your mind from authoritarism though and experience true love

 

[Luann]

It doesn't make sense that "serotonin depletion" is what causes the after-effect of serotonin. The serotonin was stored first, then activated when the drug user took mdma. So, how does your body miss something that was in storage, not activated, in the first place? It doesn't, in fact I wonder if the activity of serotonin in an ecstasy user is responsible for the depression afterward.