Hi,
Today, I took 20mg of lexapro (escitalopram) that was prescribed to me. It is my first time using it so my brain hasn't 'adjusted' (not that I intend to let it). After nearly 12 hours of taking it I have definitely experienced effects. Dilated pupils, muscular tension, twitchiness, lack of appetite, some confusion, and a strange mental state that is neither anxious nor 'calm'. Just neutral.
I have read that these effects are accomplished because ssri's block the reuptake of serotonin, therefore leaving more of it in the synapse.
mdma does the same thing, but additionally reverses the 'reuptake pump' and fills the synapse with serotonin.
My question is: judging by my symptoms above, I imagine that I have a lot of excess serotonin floating around in my synapses (like one would with mdma), yet I haven't experienced any euphoria, insight, or pleasure whatsoever... I haven't tried mdma (due to unknown purity of what's out there), but I can't imagine that the serotonin level would be much higher or people would be experiencing very strong side effects.
So - what's the difference? If judging by mdma, a high amount of serotonin causes the 'blissful' effects, why wouldn't doing so by another means accomplish the same thing?
Cheers,
Cris

MDMA does a lot more than just acting as a SSRI. Where do you get that idea from?


I get sick just thinking about fucking up my system with pharmaceutical SSRI's
Watch out. They can do more damage than many or most illegal drugs. Especially if mixed with other drugs.

Neither MDMA nor SSRIs has any significant impact on serotonin production, they only affect the serotonin levels in the synapses. And no, MDMA does not act as a SSRI. MDMA reverses the direction of the serotonin transporter to release serotonin directly into the synapse, instead of pumping it out of the synapse.

SSRIs on the other hand block the serotonin transporter, so serotonin can neither be pumped in nor out of the synapse. In addition it reduces the amount of serotonin that gets released by vesicle trafficking. This makes synaptic serotonin levels build up slowly over time.

MDMA does therefore cause a rapid high concentration of serotonin, while SSRIs flatten the serotonin levels. That is exactly why you don't feel bad, but also not good, on SSRIs. They inhibit any real change in synaptic serotonin levels, a change that is a major cornerstone in the fundaments of a human life.

I would strongly discourage use of any SSRIs. They are no real solution to depression, they only treat the symptoms of an underlying cause. It is extremely rare to have real flaws in the serotonin system that cause depression. The cause is to be found in your way of life and/or way of thinking. Eat healthy and varied foods, meditate, exercise out in the nature, think positive and reduce the amount of negativity from media, and you will feel much better.

With love

Hi Crisp,

Speaking as someone who is (bio)chemistry ignorant but experienced with BOTH Lexapro & MDMA:

These drugs are worlds apart.

Honestly, even at that hefty dose level (20 mg) I would say do not expect any euphoria per se. After 2-6 weeks you may notice a lessening of depression symptoms, with concommitant improvement in corollary symptoms such as better appetite, more energy, better sleep etc. Another things that the medical professionals underplay, but that seems fairly consistent for new users of Lexapro - expect very bizarre, vivid and memorable dreams. Lexapro takes about 2-6 weeks to build up levels in the body. Immediate effects from a single dose are probably not placebo - it is a powerful drug - but are not indicative of what to expect from the drug with daily use over weeks/months/years. I would respectfully recommend extended use only for very severe and long-standing depressive symptoms.

MDMA is completely different. One single dose and most users achieve the full effects. No need to build up. Effects are profound, unmistakeable and generally very positive with energy, tingliness, euphoria, insight, feelings of strong love/attachments, including at times inappropriate feelings/behaviors towards strangers.

Peace & Love,
Pandora

Thanks for the replies everyone, it's good advice, I don't want to get hooked on these things. Call this experience academic interest.
According to wikipedia, mdma both reverses the action of the reuptake pump, and acts as a ssri. quote: 'MDMA is classified as a combination serotonin reuptake inhibitor (SRI) and serotonin-releasing agent (SRA)'.

Therefore MDMA's empathogenic effects are caused by having large amounts of serotonin in the synapses, correct? The amount of lexapro that I took caused definite effects / side effects which seemed concurrent with what I've read about having high levels of serotonin in the brain. Any more and I could probably have had some degree of serotonin syndrome. So assuming that 'high levels' of serotonin cause empathogenic effects, or at least happiness, why would I have not got even a hint of that? How could it cause a 'flattening' effect? I could have boosted the amount of serotonin even more by taking a small dose of 5htp, but I was feeling it so strongly that I was afraid to.

Pandora - thanks for your response. The whole idea of downregulating my serotonin receptors in such a way that it prevents psychedelics from functioning sounds very distasteful to me. I understand the whole 'building up' principle, in so far as it changes your brain chemistry, but I can still feel the (single) 20mg dose I took 24 hours ago. They don't write that on the packaging

Cheers,
Crisp

Here's an excellent and somewhat relevant tangent for anyone interested!

http://www.pbs.org/wgbh/...rontline/medicatedchild/

Correct, MDMA is a SRI, but not a SSRI - because it is not selective.


Well, first of all the heightened amount of serotonin caused by SSRIs is in no way even comparable to the vast amount of serotonin you have in your synapses during a MDMA trip. Secondly, MDMA does not only cause heightened serotonin levels, it also increases the level of norepinephrine and dopamine, by the same route (reversal of the transporter's way of action).

Third, SSRIs do normally not increase your serotonin content over the normal. When you are depressed, you often have small amounts of serotonin in your synapses. SSRI increases this amount, but normally not over the regular amount of regular people (as MDMA does).

Finally, MDMA causes a rapid peak in synaptic serotonin, while SSRIs build up the serotonin over the course of several weeks. Serotonin levels is one thing, a thing just as important is the time frame for the increase or decrease of serotonin levels. A rapid increase (as with MDMA) will result in extreme happiness and empathogenic effects, while a short increase (as with SSRI) will not give effects even near this.

As serotonin is forced to stay in the synapses, you do not experience the increase and decrease in synaptic serotonin that unmedicated people do. You are therefore essentially inhibiting yourself from feeling what you really feel. That is obviously not a good idea.

(Edited to be more easy to undestand)

Thanks for the reply evening glory. I haven't been using it for weeks, I experienced quite a significant serotonin buildup from the ssri after taking a single 20mg dose, peaking at about 10 hours (it was definitely increased over the 'normal'. The difference between the serotonin buildup from the ssri and say, a low dose of mdma would have been the time that it took (i.e. over 1-2 hours vs 10 hours, aside from the different mechanisms). Considering the side effects that I had (i.e. dilated pupils, muscle tension, etc.) there must have been a fair bit of serotonin there. I imagine that this would have produced at least mild euphoric effects. The serotonin level was obviously boosted, as it was effecting me in many ways, but no euphoria/empathy or anything. Is it simply the extended hours that it took to build up that prevented the pleasant effects? This is very interesting to me.

I also find it very interesting! No, it is not only the time frame of the build-up. It is a combination of all the points I explained. I believe the increase in synaptic norepinephrine and dopamine in addition to serotonin is likely to be the most prominent factor. It is a common misconception that MDMA only boosts serotonin levels.

Even though you did indeed experience a higher synaptic serotonin level (which I have no doubt about), this level is nowhere close to what even a mild dose MDMA would cause. Combine that with the extended time frame and the lack of norepinephrine and dopamine action, and you have your answer.

To get a better understanding of the difference in action of serotonergic effects from MDMA and SSRI, imagine you have a one-way road. Normally, all the cars move from A to B. With SSRIs, the road is closed. With MDMA, the direction is changed to be from B to A. No matter how long you keep the road closed, you will not get more cars to A than if you change the direction the cars are travelling. Of course, this is oversimplified, but hopefully you get the idea.

I see where your coming from, but I just read several accounts of people combining ssri's with other serotonin boosting substances, and they all mentioned serious adverse side effects due to the excess serotonin (which couldnt' be more intense with mdma, or I imagine people would find it WAY too toxic) but none of these reports mentioned any positive feelings at all (mostly just sickness).

That is indeed interesting, but not unexpected. SSRIs only affect serotonin. MDMA affect serotonin, norepinephrine and dopamine. Dopamine is known as "the reward drug", which would account for euphoria. Norepinephrine action could account for some stimulant effect. A combination of this with the serotonin action, and the intense speed of the build-up, is likely to be the reason behind MDMAs effects.

It is also likely that some of the effects from MDMA is because it binds to some serotonin receptors. I am not up to date on the research of this, but seeing how the sister compound mescaline binds to several 5HT-receptors, this is not unlikely. The effects of MDMA can therefore be because of much more than increased levels of serotonin, noreinephrine and dopamine.

You should take a look at this slideshow: http://www.dancesafe.org/slideshow/

I don't see why it's not expected though... the unique 'empathetic' quality of mdma is thought to be due to it primarily causing a dramatic increase in serotonin levels (not due to it's effects on dopamine or norepinephrine, otherwise speed would cause empathy) - so I don't see why you can overload your brain with serotonin to the point of illness by means other than mdma, and totally skip any of the empathetic effects.
Thanks for the slideshow, I'm looking at it now.
I haven't read anything about it binding to receptors, but that sounds more likely.

Here is some numbers on the activity of MDMA on our receptors. The numbers are taken from this article.

MDMA: 4.00 Imidazoline1, 3.64 5ht2b, 3.26 Ca+Channel, 3.21 Alpha2C, 3.09 Alpha2B, 3.07 M3, 2.94 Alpha2A, 2.54 M5, 2.43 M4; 0.00: 5ht2c, 5ht1d, D2, 5ht1e, 5ht1a, 5ht2a, Alpha1A, Alpha1B, 5ht5a, 5ht6, 5ht7, D1, Beta2, SERT, DAT, NET, 5ht1b, H1, H2, D3, KOR, Beta1, M1, M2, D5, D4, CB1, NMDA, MOR; ND: DOR, Sigma2, CB2, Sigma1

If now serotonergic receptor activity accounts for some of the effects, 5HT-2B is where you will find the reason.

Also note that while speed does not give empathogenic effects, it does also not increase serotonin. I am merely suggesting that MDMA's effects is from a combination of increased serotonin, dopamine and norepinephrine - not from one single of them. That could, however, easy be tested by taking drugs that increase dopamine and norepinephrine while taking SSRIs. This leads me to believe receptor activity also has a key role.

quote: MDMA's effects is from a combination of increased serotonin, dopamine and norepinephrine
-Yes, I'm sure it is. However, serotonin is the dominant one. Check the table at the bottom of this page (the lower numbers represent more releasing potential for a certain neurotransmitter): http://en.wikipedia.org/wiki/Releasing_agent

On a side note, a good 24 hours after the lexapro, I consumed 50mg 5htp and I feel pretty good. (not recommending this to anyone).

After taking the 50mg 5htp yesterday (over 24hrs after the ssri), I felt a definite mood lift (nothing pushy though), and colours seemed somewhat enhanced - pupils were still moderately dilated. Went out drinking for st paddys, noticed no real interaction. Came home and attempted to hit the machine several times, and barely got anything. It was a very frustrating feeling. What could have caused this? (wasn't the alcohol, btw)
Cheers

It is common for people on SSRI to get next to no effects from psychedelics acting at the 5HT-system. Even though it was a long time since you consumed escitalopram, it's half-life is around 30 hours. In a week or so, you should be able to use psychedelics with full effect again.

I have, however, heard cases where people taking SSRI for extended periods of time have problems achieving effects even months or years later. The mechanism of this is not known to me. What is known to me, is that SSRIs are some really nasty substances I wouldn't touch with a ten foot pole.

Since my receptors shouldn't have 'downregulated' yet, that couldn't be the cause... Could the excessive level of serotonin have somehow taken precidence in the synapse and not allowed much room for other molecules to bind? If this is true, then I imagine that people on MDMA would experience slowed down/muted effect from spice... any info on this?

Also, that experience made me feel as though SSRI's have a nasty side. The slight lift I managed to achieve was (eventually) pleasant though. I am considering trying a very low dose of SSRI with 5htp next week.

Eat vitamine B6 with that 5htp.

SSRI´s are nasty indeed, but firstly citalopram and escitalopram are the friendliest of the SSRI´s and secondly, you should never quit using medication without consilting the doctor proscribing it.

Combining substances that affect levels of serotonin with SSRI´s is also risky and can have unpredictable effects, some of wich could be fatal.

I like to add that i have once taken tryptophan with a very light dose of syrian rue (less than half a gram) and most definately felt slight XTClike effects then. So indeed there are ways to experience with serotonin kick´s. But NOT when combined with any of the SSRI´s.

Caapi is the best and probably one of the safest ways to experience such a serotoninrush, although it affects dopamin levels as well and has other effects. Caapi, combined with small amounts of peyote is better than MDMA. it´s extremely euphoric and gives a rush that lasts for hours.

MDTripper - Apparently, B6 combined with 5 htp converts the 5 htp into serotonin BEFORE it reaches the brain, rendering it much less effective. 5 htp crosses the blood brain barrier on it's own and is supposed to work a lot better... At least what I've read.

Polytrip - What specifically is nasty about SSRI's provided you don't take them everyday? I haven't been on it before, I'm just trying to figure out if this unique chemical (prescribed) can do anything useful for me.
What about low doses of SSRI's combinged with 5htp? The fact that ssri's are long lasting seems to be the major downside. I have read about cases of Serotonin Sydrome (nasty probem) occuring from combining SSRI's with 5 htp, because people thought - oh, a pill or two of 5htp can't hurt, on top of my DAILY prescription... Whereas I cut my pill in half and took it over 24 hours after the ssri and the effects were pleasant. There may be a way to experience (at the perfect dosage) a pure serotonin boost at a pleasurable level with these two. What I'm really interested in is why they would block the effects of spice in an ssri naive person. Oh, and:
>>>DONT TRY THIS AT HOME, LADIES AND GENTLEMAN, IT COULD GO VERY WRONG. <<