Is there any empathogen safe and EFFECTIVE to take on an SSRI??

[neurotic]

@InterestingFACT hmm you're saying then that 5HT1A agonism is not fully responsible for empathogenia? i always thought increased serotonin didn't contribute to empathogenia. if serotonin release caused empathogenia then amphetamine would be an empathogenic too, right?

 

[InterestingFACT]

@InterestingFACT hmm you're saying then that 5HT1A agonism is not fully responsible for empathogenia? i always thought increased serotonin didn't contribute to empathogenia. if serotonin release caused empathogenia then amphetamine would be an empathogenic too, right?

I think 5ht1a is responsible for empathogenia (nice word). But keep in mind that serotonin itself is a ligand at 5ht1a.

Regular dexamp doesn't have much serotonin affinity. Meth has some--which likely accounts for the subjective differences between the two. Still, much less than MDMA. Also other amphetamine analogues like 4-fa are significantly empathogenic.

EDIT: After looking into it a bit more, MDMA actually (remarkably) doesn't have significant affinity for SERT. Apparently it acts as a releasers primarily through disrupting VMAT-2, which then causes the concentration gradient to push SERT backwards--at least according to the opinions of the folks in this thread

If that is the case, it still makes sense that an SSRI would block its action, because MDMA is still causing SERT to run backwards--it's just doing it indirectly.

This being said, I'm pretty sure that it definitely does act as an agonist at 5ht1 and 5ht2, but it doesn't bind very strongly. I'm going to see if I can find its binding affinities.

EDIT2:
http://link.springer.com/article/10.1007/s00213-005-0174-5?LI=true#page-1
http://www.jneurosci.org/content/31/19/7190.full

These are useful. In particular, this:

Pharmacological profile of R- and S-MDMA
R-MDMA exhibited moderate affinity for 5-HT2A receptors (Ki = 4.7 ± 1.1 μM) and lower affinity for SERT (Ki = 24.5 ± 0.8 μM). R-MDMA exhibited no appreciable affinity for either 5-HT1A receptors, NET, or DAT (Ki > 50 μM) (Table 2). In contrast, S-MDMA exhibited no affinity at 5-HT1A and 5-HT2A receptors (Ki > 50 μM), but high affinity for SERT (Ki = 222 ± 62 nM) and moderate affinity at both DAT and NET (Ki = 2.3 ± 0.4 μM and 7.8 ± 2.1 μM, respectively) (Table 2).

Table 2.
MDMA enantiomers binding profiles

5-HT1A	5-HT2A	NET	SERT	DAT
R-MDMA	>50	4.7 ± 1.1	>50	24.5 ± 0.8	>50
S-MDMA	>50	31.80 ± 7.60	7.8 ± 2.1	0.22 ± 0.06	  2.3 ± 0.4

That table is hard to read in this format--for some reason it won't preserve the shape when pasting. But neither R-MDMA or S-MDMA have significant 5ht1a affinity. R-MDMA has moderate 5ht2a affinity, while S-MDMA has low 5ht2a affinity. And R-MDMA has some binding at SERT but little at NET or DAT, while S-MDMA has some binding at NET, SERT, and DAT. So basically the R isomer is mildly psychedelic, while the S isomer is a triple monoamine releaser. It also turns out that the S-isomer of MDMA is the one which shows the most activity. So direct release of serotonin is probably the main element in MDMA's effects, while activity at 5ht2a from the R isomer might subjectively contribute. (You can find the quote showing that in the thread I linked you.)

 

[neurotic]

Interesting stuff.

EDIT:

I still have some doubts/questions though. I remember reading about a study about administration of 8-OH-DPAT, a selective 5HT1A agonist (actually also 5HT7 agonist), in mice and it raised oxytocin and prolactin concentrations, aswell as some sort of behaviour that i don't remember the name, something like them mice spending more time together. And then another study (here) about administration of a 5HT1A antagonist blocking the 8-OH-DPAT effects.

That was what led me to believe that 5HT1A activation was what made MDMA and the likes different from regular stimulants (coke, amph), not the serotonin release. Because you see, amphetamine and meth are also serotonin releasers (i believe also by blocking/reversing the vesicular monoamine transporter, i don't know) and coke also increases serotonin levels via reuptake inhibition, and none of them are empathogens.

MDMA may have low affinity to 5HT1A but may be it has a big efficacy, making it more efficient to release oxytocin?

But if empathogenia comes from 5HT1A agonism and not MDMA's effects on SERT/VMAT whatever, then how SSRIs block its effects?

I'm just a layman, looking for some answers... May be i should start a thread at NPD though...

 

[LSDiesel]

+1 for the suggestion of taking LSD for empathy. LSD is my favorite drug simply for the reason that I could take a few grains of sugar, line it up on a surface and say to myself "this is e, or this is k, or this is dope, and I would feel the feelings I want to feel. LSD and even mushrooms have an amazing ability to make you experience sensations by sheer will! Granted it might be harder since you never experienced MDMA, so you don't have a point of reference stored in your memories to prime, but I have found LSD to have empathic qualities to it. I can definetly "will myself" into feeling "like I am rolling" if i surround myself with the right stimuli and environment.

 

[InterestingFACT]

Interesting stuff.

EDIT:

I still have some doubts/questions though. I remember reading about a study about administration of 8-OH-DPAT, a selective 5HT1A agonist (actually also 5HT7 agonist), in mice and it raised oxytocin and prolactin concentrations, aswell as some sort of behaviour that i don't remember the name, something like them mice spending more time together. And then another study (here) about administration of a 5HT1A antagonist blocking the 8-OH-DPAT effects.

That was what led me to believe that 5HT1A activation was what made MDMA and the likes different from regular stimulants (coke, amph), not the serotonin release. Because you see, amphetamine and meth are also serotonin releasers (i believe also by blocking/reversing the vesicular monoamine transporter, i don't know) and coke also increases serotonin levels via reuptake inhibition, and none of them are empathogens.

MDMA may have low affinity to 5HT1A but may be it has a big efficacy, making it more efficient to release oxytocin?

But if empathogenia comes from 5HT1A agonism and not MDMA's effects on SERT/VMAT whatever, then how SSRIs block its effects?

I'm just a layman, looking for some answers... May be i should start a thread at NPD though...

So the study you mentioned showed that stimulating the 5ht1a receptor could result in oxytocin and prolactin releases, "empathogenia," etc. but serotonin is the natural agonist at all 5ht receptors. By this I mean to say that MDMA is an empathogen because it causes a strong rapid serotonin release. This serotonin release will stimulate every serotonin synapse, including 5ht1a. Stimulus of the 5ht1a receptor by serotonin promotes "pair bonding" etc. the empathogenic experience, essentially.

The reason that d-amp isn't empathogenic would be simply that it doesn't cause as much serotonin to be released.

Does that make sense?

 

[neurotic]

Yeah it does thanks for clarifying, i never knew serotonin release from MDMA was so big, that could explain long term comedowns

 

[JWills20]

Yeah it does thanks for clarifying, i never knew serotonin release from MDMA was so big, that could explain long term comedowns

MDMA is the largest specific releaser of serotonin we know of. But if that was simply the case for LTC's, then everyone would be experiencing one because it's always releasing incredibly high amounts of 5-HT. LTC's go a lot deeper than simply 5-HT depletion.

 

[t-girl72]

Because I take Zoloft (for 8 years) and tried x before I knew about Serotonin Syndrome. I took SOOOO much of it, not realizing why I wasn't feeling anything. From what I can gather, I have given up any hope of an MDMA or x type experience. I have researched and can't find any conclusive information stating I could ever feel shit from either. I stick to coke and booze and just carry on lol.

 

[UK Warrior]

Not really, no. Like you say, the risks are there, so if you really want to try it, and have your heart set on rolling, stop taking your medication until the drugs are out of your system entirely and then take the MDMA. The implied harm is NOT worth the risks you pose to yourself. Of course, you'll know better than anyone whether not taking your meds is advisable, personally, I'm on Trazodone, and I stop taking it well beforehand if I plan on doing anything, except marijuana. You can take the Klonopin on the comedown though, if you feel the need to.

Unfoftunately, In my teens, I never knew about mixing drugs. I used to get an absolutely amazing roll off of half a E ( Tested of course), then stopped for a while.

I Was placed on Fluoxetine(Prozac) , and then Citalopram as they never seemed to help me Social phobia and anxiety. During this time, I took in total 4 Pills in a night (Ready for serious wrist slippage now, again I did not know about redosing MDMA back then) and only felt a slight lift, whereas friends were spangled off of 1-1/2 for the night.

Fast forward to now, I was removed from SSRI'S, and around 8 months after, I tried a pill for old times sake, and oh my, it was like a while body, walking orgasm! I was in the passenger seat of a car, and the streetlights seemed to be leaving amazing trails, and I genuinely felt real love for everyone I was with, an experience I wish to Try again soon.

The only problem is, I am now on mirtazapine 30MG at night, for around 2 months.
This drug is not an SSRI, it is a tetracyclic antidepressant.

Has anyone effectively rolled while on TCAS, and are there any dangers (apart from the usual dangers of using Ecstasy.

Thanks again, Uk Warrior

 

[BlueBull]

Here is some info for you UK Warrior: Click and here is some more

There is a part about mirtazapine and MDMA in both links. Keep in mind that this is not scientific research so thread very lightly There are indications that it can mute the roll a bit/a lot (depending on dosage of both martazapine and MDMA) but should not produce adverse effects. But as I said these are experience reports so take them with numerous grains of salt. Use your own discretion. My advice would be to not try the combo as there are a lot of unknown factors

 

[Marauder]

6-apb worked surprisingly well while I was on 200mg/day Zoloft for years along with wellbutrin.

6-apb and 6-adpb are known to work with almost no reduction in effects on people taking SSRIs. I don't think any other empathogen works actually. And 6-apb is one of the best drugs I've ever taken.

5-apb/5-mapb DO NOT work on SSRIs

 

[neurotic]

6-apb worked surprisingly well while I was on 200mg/day Zoloft for years along with wellbutrin.

6-apb and 6-adpb are known to work with almost no reduction in effects on people taking SSRIs. I don't think any other empathogen works actually. And 6-apb is one of the best drugs I've ever taken.

5-apb/5-mapb DO NOT work on SSRIs

any one with some advanced neurology knowledge could care to make a guess on why is that so? may be 6-APB is a strong 5HT1A agonist so the prevention from serotonin release from SSRIs isn't enough to prevent empathogen effects?

and Marauder do you care to explain more about your experience? was it a very speedy roll or did it have that loved-up feeling to it too?

i'm interested...

 

[vskeldon]

What are other names for meth?

 

[Cotcha Yankinov]

MDMA is the largest specific releaser of serotonin we know of. But if that was simply the case for LTC's, then everyone would be experiencing one because it's always releasing incredibly high amounts of 5-HT. LTC's go a lot deeper than simply 5-HT depletion.

Let us not forget MDAI.

 

[Innerpeace]

6-apb worked surprisingly well while I was on 200mg/day Zoloft for years along with wellbutrin.

6-apb and 6-adpb are known to work with almost no reduction in effects on people taking SSRIs. I don't think any other empathogen works actually. And 6-apb is one of the best drugs I've ever taken.

5-apb/5-mapb DO NOT work on SSRIs

any one with some advanced neurology knowledge could care to make a guess on why is that so? may be 6-APB is a strong 5HT1A agonist so the prevention from serotonin release from SSRIs isn't enough to prevent empathogen effects?

and Marauder do you care to explain more about your experience? was it a very speedy roll or did it have that loved-up feeling to it too?

i'm interested...

sure, 6-apb works stronger on ne and dopamine levels with some serotonin release. 5-apb works much stronger on serotonin release and less on dopamine and noradenadline that is why 6-apb is more speedy than 5. also why the mathylated versions, from what I understand are quite similar in that the 5 version, 5-mapb has lots of serotnin release with lessened dopamine and nor-adrenaline (or ne) , and 6-mapb has little serontin release and morestimmy (more dopamine and ne release)

Let us not forget MDAI.

mdai takes a higher dose . actually 5-mapb is as strong or almost twice as strong in serotonin release compared to the holy grail, mdma

 

[InterestingFACT]

sure, 6-apb works stronger on ne and dopamine levels with some serotonin release. 5-apb works much stronger on serotonin release and less on dopamine and noradenadline that is why 6-apb is more speedy than 5. also why the mathylated versions, from what I understand are quite similar in that the 5 version, 5-mapb has lots of serotnin release with lessened dopamine and nor-adrenaline (or ne) , and 6-mapb has little serontin release and morestimmy (more dopamine and ne release)



mdai takes a higher dose . actually 5-mapb is as strong or almost twice as strong in serotonin release compared to the holy grail, mdma

You're right that 6-apb has relatively negligible affinity for SERT (ki 2698 ), but significantly greater affinity for NET (ki 117) and DAT (ki 150).

However, those are not properties that we would consider to be characteristic of empathogens. 6-apb's main distinguishing property is that it a more significant affinity directly for several different serotonin receptors, including weakly at 5ht2a/c and fairly strongly at 5ht7, an extremely potent full agonist at 5ht2b (ki 3.6), and a fairly high affinity agonist at all three alpha2 adrenoceptor subtypes.... but fails to act significantly at SERT as a releasing agent. In other words it acts more like a classical psychedelic.

5-apb, on the other hand, has weaker, though non-negligible affinity for most serotonin receptors (with the exception of 5ht2b, for which it is a high affinity full agonist, ki 12.7), but is a (very) strong serotonin releasing agent.

This dichotomy of effects is consistent with their design. Both 5- and 6-apb are rigid analogues of MDA wherein the electronegative oxygen is constrained to one "side" of the molecule--either "below" or "above" the ring structure. They and their N-methylated cousins were synthesized in order to determine MDMA's orientation towards its binding sites.

This is perfectly analogous to the differences in activity between (+)-MDA (weak as a serotonin releaser due to its low affinity for SERT, but direct agonist at several serotonin receptor subtypes) and (-)-MDA (strong serotonin releaser, but poor affinity for serotonin receptors). 6-apb is just a slightly "better"-fitting key than 5-apb at 5ht receptors, but this comes at the cost of its ability to enter water wk

 

[Cotcha Yankinov]

Oxytocin is an option for someone on serotonergics.

 

[LucidSDreamr]

its sucks you can't experience mdma.....its like the heroin of psychs/stims

and if u did be dumb enough to take mdma on an ssri, it definitely wouldn't be as good as never hvaing taking ssris

 

[Innerpeace]

You're right that 6-apb has relatively negligible affinity for SERT (ki 2698 ), but significantly greater affinity for NET (ki 117) and DAT (ki 150).

However, those are not properties that we would consider to be characteristic of empathogens. 6-apb's main distinguishing property is that it a more significant affinity directly for several different serotonin receptors, including weakly at 5ht2a/c and fairly strongly at 5ht7, an extremely potent full agonist at 5ht2b (ki 3.6), and a fairly high affinity agonist at all three alpha2 adrenoceptor subtypes.... but fails to act significantly at SERT as a releasing agent. In other words it acts more like a classical psychedelic.

yes I was thinking mda the whole time while posting this and even scattered thoughts aftewards as i think about this stuff bc science interests me. Im glad we have some intelligent discussion going on and you seem like an intelligent guy in binding affinitys , chemistry and science areas

5-apb, on the other hand, has weaker, though non-negligible affinity for most serotonin receptors (with the exception of 5ht2b, for which it is a high affinity full agonist, ki 12.7), but is a (very) strong serotonin releasing agent.

Exactly, and this is why 5-mapb has stronger serontin release from a logically perspective, just an added methyl to the 5-apb, but I can tell you from my knowledge of chemistry an added methyl can change the potency and strength huge-time. I dont mean to come across as a smart ass k, I just want to learn and have a great discussion

my first batch of 5-mapb that tested good ihad psychedleic effects, that i severe negative side effects two days afterwardsthat lasted over a week. i threw that batch out it was tan. next batch was white and didnt get psychedlic effects if at all, just fear decrease, which emoethogeons do. do you think 5-mapb is an empathogeon?

This dichotomy of effects is consistent with their design. Both 5- and 6-apb are rigid analogues of MDA wherein the electronegative oxygen is constrained to one "side" of the molecule--either "below" or "above" the ring structure. They and their N-methylated cousins were synthesized in order to determine MDMA's orientation towards its binding sites.

This is perfectly analogous to the differences in activity between (+)-MDA (weak as a serotonin releaser due to its low affinity for SERT, but direct agonist at several serotonin receptor subtypes) and (-)-MDA (strong serotonin releaser, but poor affinity for serotonin receptors). 6-apb is just a slightly "better"-fitting key than 5-apb at 5ht receptors, but this comes at the cost of its ability to enter water wk

what do you mean comes out the ability to enter water week?

hopefully the bolded worked, this really could be in another seperate thread as what we are talking about i science, chemistry based . This works though I guess? Im just here to learn and share what I know and see if I can learn something i dont know

 

[InterestingFACT]

Oops. I guess I cut off the last part of my post.

I meant to say that it comes at the cost of its ability to enter serotonin neurons (via SERT) and thus weakens its activity as a serotonin releaser.

Also n-methylation largely kills 5ht receptor affinities and thus psychedelia (Shulgin helped prove this by demonstrating the inactivity of n-methyl-2c-X compounds.) This is why MDMA is so much less psychedelic than MDA, and likewise is why 5-mapb doesn't do much of anything besides release serotonin. I'm actually not aware of any studies specifically evaluating 5-mapb's binding affinity at sites other than transporters, but it seems to be taken as gospel around here that it remains a 5ht2b agonist like its n-desmethyl cousin. If this is the case, it's likely that it follows the same rules as (+/-)MDMA wherein one enantiomer is significantly more potent a receptor agonist than the other. Differences between the two batches might be due to a different mix of isomers, or you may have just received a different drug (like 5-mapdb... if memory serves attempted synths of 5 and 6 mapb often wind up unintentionally producing at least some quantity of 5 and 6 apdb, respectively.)

Long story short, in terms of the thread's goal, serotonin receptor agonists can still have a subjective effect on someone taking an ssri, but serotonin releasers will have a greatly blunted effect. So 6-apb > 5-apb for someone on SSRIs. Also consider other "MDMA-like" receptor agonists, like 5-meo-mipt.

Also FYI, the first batch of "6-apb" that went around in the UK years ago that everyone loved so much was actually probably 6-apdb. This is part of the reason why people are often disappointed at how little euphoria modern batches of 6-apb generates. Meanwhile, 6-apdb is still available, but for whatever strange reason people tend to just ignore it despite consistently positive experience reports.