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Serotonin Syndrome : Combining SSRIs with serotonin releasers vs other SSRI drugs.

mydrugbuddy

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Do any of the good people here educated in pharmacolgy/bio-chemistry (or the self-taught with a good understanding) know what's more risky it terms of serotonin syndrome if combining anti depressants with either serotonin releasing recreational drugs: either releasers or other re-uptake inhibitors ?

On a practical, logical, common sense level it seems that combining SSRIs would complement each other without too much risk, whereas I can easily understand that combining releasers with re-uptake inhibitors could have the potential to cause some dangerous chaos in the brain chemistry. I would like to know if this is actually correct thoug before i make myself a guinea pig in an experiment.

I am on low dose SSRI antidepressants (50mg Sertraline) but I have on many occasions combined serotonin releasing substances with them without coming to any noticeable harm (Methylone, MDAI, MDMA, 4FA etc). Initially this was due to ignorance of the risk of serotonin syndrome, although it became obvious immediately that the SSRIs block all the good effects of MDMA and Methylone in particular. Over the last couple of years before i knew about serotonin syndrome I had stopped taking the SSRIs for a couple of days before any planned dosing of serotonin releasers chiefly so as i could get better effects from the recreational drugs. I know SSRIs can take weeks to leave the brain entirely, but I believe that most, or at least a lot of the 'active metabolites' (if thats the correct trem) should be eliminated in a couple of days. By sticking to this method I have been able to take and enjoy MDAI occasionally with no problems whatsoever.

TBH though i have run into pretty severe problems on a couple of occasions though, but both times were due to taking stupidly large doses of drugs i beileve. I had an extremely bad headache recently by being reckless with my dosing of 4A. Not sure if that was serotonin related but it was unlike any headache I'd ever had before. On one other occassion I'd had another bad reaction by going on a binge involving a stupid mix of substances; I think it was MDPV, MDAI, MXE, and synthetic canniboids. Basically i was fucked. Again not sure if that was serotonin related.

I was recently offered a very good deal on some Tramadol so i snapped them up, totally forgetting about the serotonin thing. Only done a little research so far, but the fact that Tramadol is a re-uptake inhibitor rather than a releaser must be significant ?

I would be very grateful if anyone could contribute to this thread and increase the knowledge and undesrstanding of this condition and its risk factors. Thanks in advance !
 
Combing SSRI's and serotonin releasers - in particular research chemicals whose exact pharmacology/pharmacokinetics are unknown is indeed not advisable. Serotonin syndrone is a serious issue.

Do any of the good people here educated in pharmacolgy/bio-chemistry (or the self-taught with a good understanding) know what's more risky it terms of serotonin syndrome if combining anti depressants with either serotonin releasing recreational drugs: either releasers or other re-uptake inhibitors ?

On a practical, logical, common sense level it seems that combining SSRIs would complement each other without too much risk, whereas I can easily understand that combining releasers with re-uptake inhibitors could have the potential to cause some dangerous chaos in the brain chemistry. I would like to know if this is actually correct thoug before i make myself a guinea pig in an experiment.

Combining SSRI's is seen as pointless due to shared mechanism of action

I was recently offered a very good deal on some Tramadol so i snapped them up, totally forgetting about the serotonin thing. Only done a little research so far, but the fact that Tramadol is a re-uptake inhibitor rather than a releaser must be significant ?

Tramadol is actually thought to have serotonin releasing properties as well
 
Combining releasers with reuptake inhibitors can vary in consequences. In general, when one agent has a much greater binding affinity than the other, the former will 'block' the activity of the latter. This is the case with MDMA and the vast majority of SSRIs in clinical use. When the binding affinities are similar, the effect is synergistic instead. With atypical serotonergic drugs, for example DXM (a non-specific serotonin reuptake inhibitor) or tramadol (a low grade, atypical serotonin releaser), the effect is often synergistic.

You want to avoid synergistic promotion of serotonergic action.

ebola
 
Thanks for the replies. I've also been doing a lot of googling on the subject this afternoon but I havent really learnt much of any use that I didnt already know from Bluelight.

Its repeated everywhere that there is a risk of serotonin syndrome or seizures when combining Tramadol with SSRIs. I couldnt find information anywhere on how high the risk is though, from what i can gather it is relatively rare. Doctors guidelines for prescribing SSRIs and Tramadol at the same time seem to be carefully consider, but it doesnt seem to be ruled out alltogether if there are no other viable alternatives. I've seen accounts of people taking high doses of both with no problems.

I dont think Im going to do that though; what I'm considering now is to stop the Sertraline for at least 2 or 3 days before trying a low dose of Tramadol. That way the Sertraline should have mostly been eliminated, which should significantly lower any risks.
 
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