Hello there!
I have spent a few hours researching this subject (which have lead to the background information below). I have however not been able to find answers to the things that I was looking for so I’ll try my luck here (I have read the mega-thread about why MDMA does not work for me).
Anyways, I believe that I am one of the 1 % of the caucasians that are ultra-rapid metabolizer of the enzyme CYP2D6, which means that I experience less effect of MDMA compared to the general. I have taken it four times (with more than one month apart) and on all occasions I have experienced minor effects (a bit more sharp/awake, a bit happier but far from experiencing the euphoria that most people describe). This was also the case my first time (when my remaining friends were tripping quite hard).
I do not take any SSRIs, I’m in "full health”, both physically and mentally, BMI around 22, at least 4 weeks have passed since each intake. Nor I have ever experienced any negative side effects from it (I feel better the day after MDMA compared with a night of four beers)
Last weekend I took the same E batch as some of my friends, starting with the same dose as the others (2/3 of the tablet that showed ecstasy data 160mg MDMA), so around 100mg. After about 1h it had hit for all my friends but I felt no noticeable change, after another 45 minutes, I took another 1/3 but did not notice any difference then either. 3h after the first intake I took another full tablet (so a total of 320mg) but did not notice any difference. 3h after the second intake, I felt no effect at all. While all my friends were clearly very effected of it.
I do not know if it makes a difference to the case, but I ate about 4h before taking the first tablet and was sure to add water (~ 40cl / h), sodium every two hours and multivitamins/magnesium supplement every 3 hours to minimize the risk of hyperthermia, salt-imbalance and neurotoxicity. Did not drink alcohol, did not smoke nor took any other drugs during the night. Afterwards I could conclude that I did have a little effect since I experienced increased energy, a little more love for people around me, and that the music was a bit better - and that I had minimal jaw tension the following day (otherwise no AT at all)
I have promised myself that I should not take any drugs other than MDMA, so it feels like I am being a bit ”left out” when hearing all the stories of how amazing it should be, compared to what I have felt so far. So I have some questions based on my hypothesis that I am an ultra-rapid metabolizer of CYP2D6, I have very poor knowledge of chemistry and biology so I hope there are more experienced people here that can help me (and I am sorry if the questions are super basic for the average Joe chemist):
[COLOR=#212121 !important]1. A "simple" solution to my problem is to try to take more at the same time. But I do not really understand how it works with AT / neurotoxicity when it comes to being a ultra-rapid metabolizer. Assuming that I do have the enzyme defect; will the body ”take care” of all the MDMA immediately? Or is it like I am not experiencing that much positive effects but I am still getting all the negative stuff from taking more? Let’s say hypothetically that I take a 200mg dose, will I then ”experience” positive effects of lets say 80mg but my body still has to cope with the negative effects of taking 200mg? Or would it even out that I ”only” get the negative things from the amount that actually seems to be taken up by the body (~80mg).
2. There are so-called enzyme inhibitors that I understand will suppress the activity of CYP2D6 so that you go from ultra-rapid to normal. From an article:
"The administration of inhibitors of CYP2D6 activity can affect the metabolism of MDMA, and in turn MDMA can inhibit drugs metabolized by CYP2D6. Previous administration of antidepressants with CYP2D6 inhibitory actions, such as paroxetine, reboxetine, or duloxetine, produce 15 -30% or MDMA concentrations, but decrease concentrations of its metabolite HMMA at 40-50% (Segura et al., 2005; Farré et al., 2007; Hysek et al., 2011, 2012). Moreover, the pharmacological effects of MDMA is reduced, probably due to competition for the uptake transporter decreasing MDMA entry into neurons ".
But when I look at CYP2D6 inhibitors, it's mostly antidepressant drugs that I have understood that you should not mix with MDMA. Have also read other "immunity threads" where people always ask if the person in question take SSRIs and then have the hypothesis that this is why they don’t feel an effect. Which I think sounds very contradictory (it is an inhibitor but at the same time they are saying that it might be the reason to why one does not get an effect, which to me sounds like like an inducer). Or are there some antidepressants that are inhibitors and some that are inducers?
Assuming I would find a reasonable inhibitor (is there one?), how dangerous is it to combine those? Can you be fucked up even if you were going to experiment with a small dose, say 75 mg?
3. More in general terms: what would you have done if you were like me: 1) wants to get an effect but would like to stay away from extreme neurotoxicity and dangerous drug cocktails. Would not eating as much + grapefruit juice be reasonable for me for instance? Or any other suggestions? Would be greatly appreciated.
I think that was all, thank you very much in advance.
Best regards.
[/COLOR]
I have spent a few hours researching this subject (which have lead to the background information below). I have however not been able to find answers to the things that I was looking for so I’ll try my luck here (I have read the mega-thread about why MDMA does not work for me).
Anyways, I believe that I am one of the 1 % of the caucasians that are ultra-rapid metabolizer of the enzyme CYP2D6, which means that I experience less effect of MDMA compared to the general. I have taken it four times (with more than one month apart) and on all occasions I have experienced minor effects (a bit more sharp/awake, a bit happier but far from experiencing the euphoria that most people describe). This was also the case my first time (when my remaining friends were tripping quite hard).
I do not take any SSRIs, I’m in "full health”, both physically and mentally, BMI around 22, at least 4 weeks have passed since each intake. Nor I have ever experienced any negative side effects from it (I feel better the day after MDMA compared with a night of four beers)
Last weekend I took the same E batch as some of my friends, starting with the same dose as the others (2/3 of the tablet that showed ecstasy data 160mg MDMA), so around 100mg. After about 1h it had hit for all my friends but I felt no noticeable change, after another 45 minutes, I took another 1/3 but did not notice any difference then either. 3h after the first intake I took another full tablet (so a total of 320mg) but did not notice any difference. 3h after the second intake, I felt no effect at all. While all my friends were clearly very effected of it.
I do not know if it makes a difference to the case, but I ate about 4h before taking the first tablet and was sure to add water (~ 40cl / h), sodium every two hours and multivitamins/magnesium supplement every 3 hours to minimize the risk of hyperthermia, salt-imbalance and neurotoxicity. Did not drink alcohol, did not smoke nor took any other drugs during the night. Afterwards I could conclude that I did have a little effect since I experienced increased energy, a little more love for people around me, and that the music was a bit better - and that I had minimal jaw tension the following day (otherwise no AT at all)
I have promised myself that I should not take any drugs other than MDMA, so it feels like I am being a bit ”left out” when hearing all the stories of how amazing it should be, compared to what I have felt so far. So I have some questions based on my hypothesis that I am an ultra-rapid metabolizer of CYP2D6, I have very poor knowledge of chemistry and biology so I hope there are more experienced people here that can help me (and I am sorry if the questions are super basic for the average Joe chemist):
[COLOR=#212121 !important]1. A "simple" solution to my problem is to try to take more at the same time. But I do not really understand how it works with AT / neurotoxicity when it comes to being a ultra-rapid metabolizer. Assuming that I do have the enzyme defect; will the body ”take care” of all the MDMA immediately? Or is it like I am not experiencing that much positive effects but I am still getting all the negative stuff from taking more? Let’s say hypothetically that I take a 200mg dose, will I then ”experience” positive effects of lets say 80mg but my body still has to cope with the negative effects of taking 200mg? Or would it even out that I ”only” get the negative things from the amount that actually seems to be taken up by the body (~80mg).
2. There are so-called enzyme inhibitors that I understand will suppress the activity of CYP2D6 so that you go from ultra-rapid to normal. From an article:
"The administration of inhibitors of CYP2D6 activity can affect the metabolism of MDMA, and in turn MDMA can inhibit drugs metabolized by CYP2D6. Previous administration of antidepressants with CYP2D6 inhibitory actions, such as paroxetine, reboxetine, or duloxetine, produce 15 -30% or MDMA concentrations, but decrease concentrations of its metabolite HMMA at 40-50% (Segura et al., 2005; Farré et al., 2007; Hysek et al., 2011, 2012). Moreover, the pharmacological effects of MDMA is reduced, probably due to competition for the uptake transporter decreasing MDMA entry into neurons ".
But when I look at CYP2D6 inhibitors, it's mostly antidepressant drugs that I have understood that you should not mix with MDMA. Have also read other "immunity threads" where people always ask if the person in question take SSRIs and then have the hypothesis that this is why they don’t feel an effect. Which I think sounds very contradictory (it is an inhibitor but at the same time they are saying that it might be the reason to why one does not get an effect, which to me sounds like like an inducer). Or are there some antidepressants that are inhibitors and some that are inducers?
Assuming I would find a reasonable inhibitor (is there one?), how dangerous is it to combine those? Can you be fucked up even if you were going to experiment with a small dose, say 75 mg?
3. More in general terms: what would you have done if you were like me: 1) wants to get an effect but would like to stay away from extreme neurotoxicity and dangerous drug cocktails. Would not eating as much + grapefruit juice be reasonable for me for instance? Or any other suggestions? Would be greatly appreciated.
I think that was all, thank you very much in advance.
Best regards.
[/COLOR]
