E + 5 HTP - Should I be worried about serotonin syndrome?

[JWills20]

Nice one Futura - good read. However, Its not to do with Serotonin being 'stuck' in the synpatic cleft, because that would cause the opposite to the reported 'dulling' effect of SSRI's on MDMA. Indeed, serotonin situated within the synapse is 'psychoactive' and that's where it causes the subjective feelings. Pre-synpatic & post-synaptic serotonin does not, at least to my knowledge, affect consciousness. From what I understood, this was the key reason as to why SSRI's block MDMA: 'SSRI's occupy the same site on the 5-HT transporter that MDMA uses'. Thus, MDMA has an extremely diminished affinity for SERT and can't get into the pre-synaptic neuron to release serotonin into the synapse.

To me, this is quite solid evidence that SSRI's & MDMA should not cause SS, in fact, quite the opposite. Providing I haven't missed something of course!

 

[futura2012]

However, Its not to do with Serotonin being 'stuck' in the synpatic cleft, because that would cause the opposite to the reported 'dulling' effect of SSRI's on MDMA.

Yeah that was theory 1. Assuming that the MDMA had already started to cause release and the SSRI was blocking the recycling. However it seems that the recycling causes a limit on serotonin transmission not an increase.

From what I understood, this was the key reason as to why SSRI's block MDMA: 'SSRI's occupy the same site on the 5-HT transporter that MDMA uses'. Thus, MDMA has an extremely diminished affinity for SERT and can't get into the pre-synaptic neuron to release serotonin into the synapse.

Yes that was theory two and I now know this is the correct one. The MDMA simply cant get into the Neuron to have any effect. This is why for MDMA to do anything whilst on SSRI needs mega dose and even then all it will achieve is a rather subdued roll if anything at all.

To me, this is quite solid evidence that SSRI's & MDMA should not cause SS, in fact, quite the opposite. Providing I haven't missed something of course!

Yes spot on the SSRI protects you from the serotonin release properties of MDMA. The next theory to figure out is why does taking an SSRI 2 hours into a roll protect you from neurotoxicity?

It must prevent something unwanted getting into the presynaptic neuron or possibley getting into the reuptake transporter.

As to the exact mechanisms of this I have yet to discover.

 

[JWills20]

Yeah that was theory 1. Assuming that the MDMA had already started to cause release and the SSRI was blocking the recycling. However it seems that the recycling causes a limit on serotonin transmission not an increase.



Yes that was theory two and I now know this is the correct one. The MDMA simply cant get into the Neuron to have any effect. This is why for MDMA to do anything whilst on SSRI needs mega dose and even then all it will achieve is a rather subdued roll if anything at all.



Yes spot on the SSRI protects you from the serotonin release properties of MDMA. The next theory to figure out is why does taking an SSRI 2 hours into a roll protect you from neurotoxicity?

It must prevent something unwanted getting into the presynaptic neuron or possibley getting into the reuptake transporter.

As to the exact mechanisms of this I have yet to discover.

Apologies for hijacking this thread but I'm gunna reply anyways . The answer to that question is exactly the same as why SSRI's nullify MDMA. Taking the SSRI during the roll will then bind to 5-HT transporter as mentioned. Ofc, this will take as long as the peripheral metabolism and subsequent transport across the blood-brain barrier takes (1-2 hours i'd guess). Thus, while MDMA metabolizes and diffuses from the body, serotonin is gradually decreasing too. The SSRI will then bind to the 5-HT transporter blocking any dopaminergic free radicals from binding to the neuron thus acting in a neuroprotective mannor.

It appears like a fantastic means of protecting the serotonergic system from damage. Instead of using the usual techniques of minimizing the oxidative radicals caused or increasing binding sites for them (anti-oxidants), you can just destroy their damaging capabilities by blocking the transports with high-affinity, powerful SSRI's.

 

[futura2012]

The SSRI will then bind to the 5-HT transporter blocking any dopaminergic free radicals from binding to the neuron thus acting in a neuroprotective mannor.

Yeah I agree with your explanation upto this point. Im not so sure about there being any dopamine related free radicals in the mix. I also need to read up more about what exactly a free radical is, how it is produced and what harm it causes. also are there any other harmful things either in the synaptic gap or sucked into the presynaptic neuron.

It appears like a fantastic means of protecting the serotonergic system from damage. Instead of using the usual techniques of minimizing the oxidative radicals caused or increasing binding sites for them (anti-oxidants), you can just destroy their damaging capabilities by blocking the transports with high-affinity, powerful SSRI's.

The theory does sound great but would you be willing to do this every time you took MDMA? personally knowing what I know not if I were taking MDMA again then I would probably just opt for a limit of 150mG no redose and a 5HTP regime a few days after with the usual exercise etc.

After having experienced SSRIs first hand although theoretically they perform a single function a whole load of other "goodies" also comes with them. A major issue with limp dick for a start scary stuff! i doubt a single tablet would do that but it just seems taking more psychoactive drugs to combat other psychoactive drugs might be a little far. What are your personal thoughts?

 

[ebola?]

you can just destroy their damaging capabilities by blocking the transports with high-affinity, powerful SSRI's.

Animal studies show that this is only effective insofar as SSRIs block the effects of MDMA, so while they can be used to block a small proportion of damage as the effects of the MDMA trail off, SSRIs are quite limited in what the size of this proportion can be.

ebola

 

[JWills20]

Animal studies show that this is only effective insofar as SSRIs block the effects of MDMA, so while they can be used to block a small proportion of damage as the effects of the MDMA trail off, SSRIs are quite limited in what the size of this proportion can be.

ebola

I wonder why that is? I assume that the animal studies are administering brain-frying dosages? They usually do so. From my knowledge (and i'm by no means knowledgable), the mechanism of neurotoxicity is through dopamine binding to 5-HT because of the depletion caused by MDMA. They're then oxidized by the enzyme that usually metabolizes serotonin which instead creates a powerful, oxidative free radical that destroys the cell. Thus, if you took an SSRI 3-4 hours into the roll, while you're tailing off, it should bind to the 5-HT sites that are depleted thereby blocking DA access? Ofc, assuming that the dosages are, indeed, neurotoxic.

The theory does sound great but would you be willing to do this every time you took MDMA? personally knowing what I know not if I were taking MDMA again then I would probably just opt for a limit of 150mG no redose and a 5HTP regime a few days after with the usual exercise etc.

After having experienced SSRIs first hand although theoretically they perform a single function a whole load of other "goodies" also comes with them. A major issue with limp dick for a start scary stuff! i doubt a single tablet would do that but it just seems taking more psychoactive drugs to combat other psychoactive drugs might be a little far. What are your personal thoughts?

@Futura, if you re-read about MDMA-induced neurotoxicity one theory involves the aforementioned mechanism. Personally, I have no interest in consuming SSRI's at the tail end of a roll. In fact, often I'll bring 5-HTP, multivitamins & anti-oxidants to a rave and not actually take them. I'm pretty sure that your usual recreational dose (100-200mg) is not neurotoxic so it's futile anyway. I'd rather just relax and enjoy myself with a more laissez-faire attitude. I'd rather enjoy myself than spend time needlessly worrying about my serotonergic function... Haha!

I was more talking from a clinical perspective. Hypothetically, if you could block the damaging effects of high dose MDMA it would be far safer, chronically, and reduce the comedown, acutely.

 

[larson]

Guys this might be a little off topic but i was wondering can u drink alcohol a few hours after taking 5htp.Il be in Ibiza myself soon enough and after doing some research ive decided im going to take 5htp on the comedown to hopefully help with anxiety the day after rolling but as il be on holiday il want to keep drinking the next night.there will be 10 or 12 hours between taking 5htp and drinking alcohol again.Is this safe or has anyone on here done this? Thanks

 

[JWills20]

Guys this might be a little off topic but i was wondering can u drink alcohol a few hours after taking 5htp.Il be in Ibiza myself soon enough and after doing some research ive decided im going to take 5htp on the comedown to hopefully help with anxiety the day after rolling but as il be on holiday il want to keep drinking the next night.there will be 10 or 12 hours between taking 5htp and drinking alcohol again.Is this safe or has anyone on here done this? Thanks

Yeah you'll be fine. I've done it numerous times because the first time I tried it I experienced quite a lot of empathy while drunk. Needless to say, it was just because I ended up speaking to my ex-girlfriend and we got talking, and not because I took 5-HTP before.

But yes, 5-HTP will not interact with alcohol.

 

[larson]

Thanks for the reply JWills20 i really dont want to be sacrificing a few days of me holiday for 1 epic night but this seems like the best policy all round.Xanax and 5htp on the comedown and then nothing but drink drink and more drink for the next few days.

 

[zooloo]

so if you stop taking an SSRI or SSNRI a couple days before rolling itll be okay and the roll will not be nulled as much? or will it not make a difference if its already in your system?

 

[JWills20]

so if you stop taking an SSRI or SSNRI a couple days before rolling itll be okay and the roll will not be nulled as much? or will it not make a difference if its already in your system?

That will depend on many things. Most notably, how long you have been consuming the SS/N/RI and what anti-depressant you have been taking. They do tend to stay psychoactive even after cessation of consumption and would still nullify the MDMA.

 

[zooloo]

i have only been consuming venlafaxine at a very low dose for two weeks now and i have a huge concert coming up that i am going to take thizz at but if it hasnt been long and the dose is so low then would it help to stop taking it for like 3 days beforehand and then the day after i start up again? would that help at all lessen the nullness?
i tried sass like a week after being on this medication and i got pretty high.. not as hihgh as everyone else but i was satisfied so i know i can get high on it..

 

[ebola?]

so if you stop taking an SSRI or SSNRI a couple days before rolling itll be okay and the roll will not be nulled as much? or will it not make a difference if its already in your system?

It doesn't work this way for most people, as chronic administration of SSRIs downregulates 5ht receptors in a broad-spectrum way, attenuating response to MDMA for a good couple to several months after cessation. YMMV though.

ebola

 

[Dunno]

Doing a bit of reading, could Cyproheptadine be an interesting antidote to seorotonin syndrome? More harm reduction?
Maybe a new thread? Maybe add it to the everything you wanted to know about Ecstasy?