Serotonin Syndrome MDMA + Tramadol Please Help

[hernandonez]

First Question, (which leads into my SS question): About a 6 weeks ago I sprained my ankle really bad and got a script for some norcos which I abused a few times a week. 2 weeks after I sprained my ankle, I went to a rave and took ecstasy (red YouTube=155-170mg MDMA). I took the pill in halves. After the first half hit me, I waited about an hour before I took the second and I rolled for a good 3 hours. I have a relatively low tolerance to MDMA having only done it 4 times prior. My friend who has rolled far more times than I have took the same pill in halves at the same times I did and rolled for 5-6 hours. It made zero sense to me that I didn't roll as hard or as long as he did given he's taken ecstasy three times as much as I have. I know some opiates affect serotonin but I read that hydrocodone does not. Was it the hydro that shortened and lessened my roll?
the only other drug I took was oxy and that was a full month before the rave.
The rave was on the 24th of May.

Around the first week of June I began taking tramadol for my ankle and so I can fall asleep. I only took it once or twice a week and when I did I took around 200mg over the course of an hour, I never exceeded that dose. I was doing that until <<event X>> which was from June 20-June 22. On the first day, my buddy and I started off with half a blue android (full=200mg MDMA) and it didn't hit me as hard as it hit my friend (same friend from the other rave). Off just half the pill he rolled hard for 3-4 hours, while I ended up taking the other half after about 2 hours because I felt the effects diminish. The second half hit me just like the first and had a mild roll for another 2 hours. I still had another red YouTube from before and took that in halves as well every 2 hours after my second dose. I ended up taking approximately 400 mgs that night and didn't roll too hard compared to my friend who's one blue android lasted him 10 hours by taking it in halves. We were sober for day 2. Then on day 3, I took approximately 450 mgs. This time I just took bigger doses and rolled pretty hard but for only a short time. The next night, Monday, at home I had trouble sleeping so I took 200 mg of tramadol before bed and right away felt really nauseous. I felt like shit and knew something was wrong. I remember waking up still feeling nauseous and could not eat breakfast. After taking a shower, I felt a little better to where I could eat something. About a couple hours after that I went to the mall with a friend and her driving made the nausea worse and right when I got out of the car I threw up. I thought that would make me feel better but the nausea crept up again but not as bad. I had dinner a few hours later and could not finish because I still felt like shit. Right when I get home about an hour after eating, I throw up again. That's when I knew something was up and did some research and found that I had mild symptoms of serotonin syndrome. I had been getting little muscle spasms throughout the day. Then when I went to bed the hallucinations started to occur and they were not pleasant at all and sometimes made me jump. I could not stop sweating either. I made it through that night and woke up still nauseous and my symptoms were still there but I was not throwing up anymore. After a couple days I began to feel normal again. Will my serotonin levels go back to normal if I stay away from everything for a couple months?
I know the tramadol really messed with my serotonin levels but is that the only reason why I didn't roll hard or for the length of time I wanted to?
And since I stopped the tramadol and any other opiate, will I be able to have better rolls or did I just permanently fuck things up?

Thanks to whoever takes the time to read all this and answer my questions.

 

[falsifiedhypothesi]

you didn't roll as hard because you are taking mdma way too often. MDMA tolerance isn't like tolerance to most drugs, it will deplete your serotonin so much that it may take months to get it back to normal. When you take mdma days in a row you are beating the shit out of your serotonin receptors, so to speak. Depleting your serotonin like that can lead to depression, memory loss and most likely other forms of cognitive impairment. I would suggest waiting a month or two in between doses, it will also help preserve the magic. This is just my very simplistic understanding.

The tramadol probably didn't do any permanent damage just be sure to research drug interactions before you take more than one drug in a day.

 

[Bob Loblaw]

~~> Med

 

[BlueBull]

TL;DR at bottom
If you really had serotonin syndrome (SS) you should have been rolling very very hard as SS is a rise of serotonin to toxic levels. MDMA has its effects because of heightened serotonin levels so logically whenever you get SS because of MDMA or a combination of MDMA and something else you should be rolling much harder than normal. As evidenced by the stories from people that combined MDMA and an MAOI, they first start to roll much harder than they have ever rolled before and that quickly spins out of control until usually hospitalization is required

Lowered serotonin levels = muted roll (like for instance with an SSRI + MDMA), heightened serotonin levels = rolling harder and possible serotonin syndrome when levels really get out of control (like for instance with an MAOI + MDMA). You almost certainly didn't experience SS as that happens during a roll, not a full day after

Tramadol can increase serotonin levels a bit, but not by much and I don't think enough to cause SS in moderate doses, more so because serotonin levels would be lower than baseline from your roll the day before. I am almost certain you are experiencing a comedown and some symptoms of excessive stimulant use, which is normal for the way you are (ab)using MDMA. There is a case known about someone that experienced SS (or so they think) from taking tramadol and other serotonergics (here) and there is one important sentence to take away: " reports of serotonin syndrome involving tramadol alone were absent". This means if it was SS it had to be the combination of MDMA and tramadol which caused it and if that was the case you would have experienced a very hard roll which seemed out of control and not start to show symptoms the day after, when your serotonin levels are lowered significantly compared to the day before. Furthermore excessive use of MDMA causes all the symptoms you describe: muscle twitches (as do most stimulants), nausea (MDMA is very hard on the stomach and nausea is very common, certainly with big doses and back to back days), anxiety and associated sweating, visual disturbances. This amplified by you reading about SS and getting a bit worried

Real SS is pretty rare while users of MDMA that think they have SS but don't really are much more common

Also about your roll being less intense, it could have numerous reasons, like your stomach being fuller than your mates (this has a big influence), your pill being on the lower end of the spread (the crew that makes the androids is known to have big spreads in their pills), amount of sleep, other substances involved, mindset (also big influence), general health and so on. Also, like falsifiedhypothesi said, you are rolling way too often, this creates tolerance which only goes away slowly, not like with other drugs. This will have had an influence too without a doubt. Not to mention the back to back days...

TL;DR
Almost certainly not serotonin syndrome. Could only happen from MDMA+tramadol (very unlikely) and would happen during a roll when serotonin levels are heightened, not the day after. Symptoms would be more severe and wouldn't appear the day after but during the roll. Roll would be insanely intense. You are experiencing a comedown I think, combined with signs of excessive stimulant use. You rolling less hard can have countless reasons, we won't know for sure. Also you are rolling way too often, slow down or you will ruin the substance for yourself very fast

 

[hernandonez]

thank you guys for your answers, I really appreciate you taking the time to help.
hopefully I can get a few more replies so I have a better idea of what happened.

 

[Fizzyhoow]

Have you ever used MDMA some time after Tramadol (days weeks whatever)? Reason I'm asking is because it seems like pretty cool recreational drug for occasional use, but I'm worried the SSRI effect might numb my serotonin receptors somewhat to make the MDMA less effective.

As for you question, BlueBull has it mostly covered. I'm pretty sure opioids don't affect serotonin or MDMA in any way except Tramadol, which acts as an SSRI. It's possible it down-regulated your receptors somewhat prior to your second roll, but general tolerance is probably more likely.

Stomach contents do really matter as far as the strength of your roll is concerned, as well as the acidity. The more acidic your stomach is the worse the MDMA will be absorbed. If you had been drinking juice all day and your friend hadn't, then that could be an explanation. As a tip, try consuming 1 or 2 tablespoons of baking soda, or just Tums if you can get those, to lower the acidity. I might add that as a reduction technique, try to drink grapefruit juice beforehand (during the day) to inhibit the CYP3A4 enzyme so less MDMA is converted to MDA (with neurotoxic metabolites), and continue drinking it or some other juice during your roll (to increase acidity again) so you pee out more of the MDMA unchanged.

 

[Black]

TL;DR at bottom
TL;DR
Almost certainly not serotonin syndrome. Could only happen from MDMA+tramadol (very unlikely) and would happen during a roll when serotonin levels are heightened, not the day after. Symptoms would be more severe and wouldn't appear the day after but during the roll. Roll would be insanely intense. You are experiencing a comedown I think, combined with signs of excessive stimulant use. You rolling less hard can have countless reasons, we won't know for sure. Also you are rolling way too often, slow down or you will ruin the substance for yourself very fast

actually, i think it sounds like serotonin syndrome in this case (at least more than usually ). muscle spasms, nausea and vomiting are typical symptoms (normally the people who falsely suspect serotonin syndrome always focus in the unspecific emotional effects), and he did take mdma first and tramadol afterwards, when most of the mdma was gone. mdma has a pretty long elimination half life (compared to the positive subjective effects) and with huge doses like that enzyme inhibition makes it even longer (potentially increasing the half life of mda (albeit that is only present in low concentrations) to over 20 hours), so complications like this are not impossible in this time frame. the question is if there are still relevant quantities of mdma/mda present after such a long time...
there is less serotonin avaiable after mdma (especially after these huge doses), but that doesn't mean that its all gone and that there there cannot be higher local concentrations of serotonin released causing symptoms. of course the op didn't go to hospital and without a proper diagnosis we cannot know.

@op
serotonin syndrome does normally clear up in 24h to a couple of days, just like you reported. even if it was serotonin syndrome, you did not do any permanent damage, but you should stay clear of serotonergic drugs for a while now to give your brain time to find its equilibrium again.

 

[Black]

I might add that as a reduction technique, try to drink grapefruit juice beforehand (during the day) to inhibit the CYP2D6 enzyme so less MDMA is converted to MDA (with neurotoxic metabolites), and continue drinking it or some other juice during your roll so you pee out more of the MDMA unchanged.

grapefruite juice inhibits CYP3A4, not CYP2D6. but it's CYP3A4 that turns mdma into mda. still this is a minor pathway accounting for less than 10% of mdma in humans, CYP2D6 is the more important enzyme, turning mdma into hhma.
besides, there is no good evidence that taking normal doses is mdma is neurotoxic, so fucking around with your enzymes is at best unnecessary and might at worst cause dangerous interactions with other drugs you might be taking.

 

[BlueBull]

actually, i think it sounds like serotonin syndrome in this case (at least more than usually ). muscle spasms, nausea and vomiting are typical symptoms (normally the people who falsely suspect serotonin syndrome always focus in the unspecific emotional effects), and he did take mdma first and tramadol afterwards, when most of the mdma was gone. mdma has a pretty long elimination half life (compared to the positive subjective effects) and with huge doses like that enzyme inhibition makes it even longer (potentially increasing the half life of mda (albeit that is only present in low concentrations) to over 20 hours), so complications like this are not impossible in this time frame. the question is if there are still relevant quantities of mdma/mda present after such a long time...
there is less serotonin avaiable after mdma (especially after these huge doses), but that doesn't mean that its all gone and that there there cannot be higher local concentrations of serotonin released causing symptoms. of course the op didn't go to hospital and without a proper diagnosis we cannot know.

I partly agree, or at least I don't know if I fully agree :D On the one hand every bad hangover I've had (after too high a dose and/or rolling multiple consecutive days) could then be classified as mild serotonin syndrome but on the other hand when looking at the symptoms needed for a diagnosis, mild to severe MDMA after-effects would indeed probably be diagnosed as mild serotonin syndrome by a doctor. I just have some doubts these symptoms could actually be caused by elevated serotonin levels, though they may be diagnosed as such judging solely from the symptoms. Tramadol does increase serotonin levels slightly and indeed even after rolling for multiple days on doses like that your serotonin stores are not depleted. I just don't know if, even locally, levels could reach high enough to cause symptoms like this, more so because it happened after using so much MDMA for multiple days, not during and because tramadol is 'only' a mild reuptake inhibitor. In any case the border between normal (after-)effects of serotonergic drugs and genuine serotonin syndrome is pretty vague indeed. More so because if I recall correctly you can't actually measure serotonin levels externally, or is there a way to measure brain serotonin levels without actually doing a biopsy of the brain?

By the way tramadol has or used to have recreational value to me, apparently some people get a very enjoyable high out of it while others feel absolutely nothing. So I've messed around with it a bit. And occasionally doses of 200mg (I've actually only once taken 50mg more than that. 200mg already produces pretty intense effects, taking more increases side-effects to unpleasant levels) would cause muscle spasms, light tremors and nausea, once or twice up to the point of vomiting. This was usually if I hadn't eaten in a while or if my body was not performing at 100% in some other way, like when seriously exhausted after a festival. Tramadol can be an unpredictable drug and in itself can cause things like this in my experience

 

[Black]

is tramadol really a reuptake inhibitor? i thought it had a yet unknown mechanism, but if it just blocks SERT like an ssri i don't see any way it could induce serotonin syndrome with mdma...

 

[BlueBull]

is tramadol really a reuptake inhibitor? i thought it had a yet unknown mechanism, but if it just blocks SERT like an ssri i don't see any way it could induce serotonin syndrome with mdma...

Well from the information I came across tramadol has SNRI properties. It is structurally similar to the SNRI venlafaxine (effexor), though of course that doesn't automatically mean they have similar pharmacodynamic properties. These SNRI (or SSRI at least) properties seem to be confirmed by the fact that if I take a significant dose of tramadol before a roll, the effects of MDMA are noticeably diminished. Still not 100% sure though

One article that seems to confirm this:

Much of the toxicity in tramadol overdose appears to be attributable to the monoamine uptake inhibition rather than its opioid effects. Agitation, tachycardia, confusion and hypertension suggest a possible mild serotonin syndrome. No arrhythmias beyond tachycardia were seen.

and one more

Tramadol is a racemic mixture of two enantiomers, (+)-tramadol and (-)-tramadol. Although the (+)-enantiomer is preferentially an inhibitor of serotonin reuptake, the (-)-enantiomer is a potent inhibitor of noradrenaline reuptake

 

[Fizzyhoow]

My bad, I mixed it up. Still though, MDA's metabolites have shown to be quite neurotoxic, so warning him for it isn't a bad thing right?

 

[Black]

@bluebull

thanks for looking it up, it seems unlikely then that the combination would cause serotonin syndrome. however tramadol is metabolised by CYP2D6 to the o-desmethyltramadol (which is no snri and a stronger opioid), so taking tramadol together with or shortly after mdma should enhance tramadol's own serotonergic effects (which aren't pleasant) and reduce the analgetic effects...

@fizzyhoow
do you have any reference to that? that actually fits nicely into the picture that we see with animals that metabolise mdma mainly into mda showing much greater toxicity, and i'd like to have a source for further discussions.
if there's toxicity induced by reactive oxygen species produced by some of mda's metabolites (we know that any serotonergic damage we see in some animal experiments is due to ros) it still means that the concentrations of these metabolites have to be above a certain threshold where the cells' limits of ros detoxification are reached, so it's not going to be relevant in humans at typical doses (at least to humans who metabolise mdma like humans and not like baboons ).