"MDMA Drug−Drug Interactions
MDMA, once taken, is not selective to CYP2D6 and interacts with several isozymes of P450. In fact, the contribution of CYP2D6 to MDMA metabolism has been reported to be less than 30% (Segura et al., 2005). Thus, several other P450 isoenzymes such as CYP1A2 and, to a lesser extent, CYP2B6 and CYP3A4 have the capacity to contribute to the microsomal oxidative metabolism of MDMA and MDA. A recent study showed that while CYP2D6 was inhibited by MDMA, CYP1A2 increased its activity (Yubero-Lahoz et al., 2012). Another clinical trial showed there was a conversion from MDMA to HHMA in vivo, despite the CYP2D6 inhibition by paroxetine, suggesting alternative metabolic pathways (Segura et al., 2005). Other enzymes may, therefore, become more predominant once CYP2D6 is inhibited which could further contribute to MDMA metabolic disposition.
The administration of inhibitors of CYP2D6 activity can influence 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% of MDMA concentrations, but decrease concentrations of its metabolite HMMA by 40–50% (Segura et al., 2005; Farré et al., 2007; Hysek et al., 2011, 2012). Moreover, the pharmacological effects of MDMA are decreased, probably due to competition for the uptake transporter decreasing MDMA entry in neurons.
CYP2D6 is also the source of a number of drug–amphetamine interactions because it regulates the biotransformation of many therapeutic drugs. Antiretroviral drugs (ritonavir, a known CYP2D6 inhibitor) and MAO inhibitors have been reported to be the main cause of life threatening interactions with MDMA (Henry and Hill, 1998; de la Torre et al., 1999; Papaseit et al., 2012)."
http://journal.frontiersin.org/Journal/10.3389/fgene.2012.00235/full
If somebody takes another drug working over the P450 enzymes the interactions can be the following:
Enzymatic inhibition
If drug A is metabolized by a cytochrome P450 enzyme and drug B inhibits or decreases the enzyme's activity, then drug A will remain with high levels in the plasma for longer as its inactivation is slower. As a result, enzymatic inhibition will cause an increase in the drug's effect. This can cause a wide range of adverse reactions.
It is possible that this can occasionally lead to a paradoxical situation, where the enzymatic inhibition causes a decrease in the drug's effect: if the metabolism of drug A gives rise to product A2, which actually produces the effect of the drug. If the metabolism of drug A is inhibited by drug B the concentration of A2 that is present in the blood will decrease, as will the final effect of the drug.
Enzymatic induction
If drug A is metabolized by a cytochrome P450 enzyme and drug B induces or increases the enzyme's activity, then blood plasma concentrations of drug A will quickly fall as its inactivation will take place more rapidly. As a result, enzymatic induction will cause a decrease in the drug's effect.
As in the previous case it is possible to find paradoxical situations where an active metabolite causes the drug's effect. In this case the increase in active metabolite A2 (following the previous example) produces an increase in the drug's effect.
It can often occur that a patient is taking two drugs that are enzymatic inductors, one inductor and the other inhibitor or both inhibitors, which greatly complicates the control of an individual's medication and the avoidance of possible adverse reactions.
This means that you can harm yourself even if you don't feel the interactions... Don't mix drugs working on P450 enzymes (antidepressant, neuroleptics, grapefruit and so on).
I try to figuere out if Abilify inhibits or induces the P450 enzymes... This happens if you don't inform yourself right. Makes me crazy if I think about taking MDMA while on a low low dose of around 0,5 mg Abilify 8(. Well I don't have to mention that it didn't work. It was probably the reason why I couldn't sleep, in case of enzymatic inhibition, because it increased the amount of Abilify in the plasma greatly.
Probably increased the amount of MDMA in the boodstream, too.
MDMA, once taken, is not selective to CYP2D6 and interacts with several isozymes of P450. In fact, the contribution of CYP2D6 to MDMA metabolism has been reported to be less than 30% (Segura et al., 2005). Thus, several other P450 isoenzymes such as CYP1A2 and, to a lesser extent, CYP2B6 and CYP3A4 have the capacity to contribute to the microsomal oxidative metabolism of MDMA and MDA. A recent study showed that while CYP2D6 was inhibited by MDMA, CYP1A2 increased its activity (Yubero-Lahoz et al., 2012). Another clinical trial showed there was a conversion from MDMA to HHMA in vivo, despite the CYP2D6 inhibition by paroxetine, suggesting alternative metabolic pathways (Segura et al., 2005). Other enzymes may, therefore, become more predominant once CYP2D6 is inhibited which could further contribute to MDMA metabolic disposition.
The administration of inhibitors of CYP2D6 activity can influence 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% of MDMA concentrations, but decrease concentrations of its metabolite HMMA by 40–50% (Segura et al., 2005; Farré et al., 2007; Hysek et al., 2011, 2012). Moreover, the pharmacological effects of MDMA are decreased, probably due to competition for the uptake transporter decreasing MDMA entry in neurons.
CYP2D6 is also the source of a number of drug–amphetamine interactions because it regulates the biotransformation of many therapeutic drugs. Antiretroviral drugs (ritonavir, a known CYP2D6 inhibitor) and MAO inhibitors have been reported to be the main cause of life threatening interactions with MDMA (Henry and Hill, 1998; de la Torre et al., 1999; Papaseit et al., 2012)."
http://journal.frontiersin.org/Journal/10.3389/fgene.2012.00235/full
If somebody takes another drug working over the P450 enzymes the interactions can be the following:
Enzymatic inhibition
If drug A is metabolized by a cytochrome P450 enzyme and drug B inhibits or decreases the enzyme's activity, then drug A will remain with high levels in the plasma for longer as its inactivation is slower. As a result, enzymatic inhibition will cause an increase in the drug's effect. This can cause a wide range of adverse reactions.
It is possible that this can occasionally lead to a paradoxical situation, where the enzymatic inhibition causes a decrease in the drug's effect: if the metabolism of drug A gives rise to product A2, which actually produces the effect of the drug. If the metabolism of drug A is inhibited by drug B the concentration of A2 that is present in the blood will decrease, as will the final effect of the drug.
Enzymatic induction
If drug A is metabolized by a cytochrome P450 enzyme and drug B induces or increases the enzyme's activity, then blood plasma concentrations of drug A will quickly fall as its inactivation will take place more rapidly. As a result, enzymatic induction will cause a decrease in the drug's effect.
As in the previous case it is possible to find paradoxical situations where an active metabolite causes the drug's effect. In this case the increase in active metabolite A2 (following the previous example) produces an increase in the drug's effect.
It can often occur that a patient is taking two drugs that are enzymatic inductors, one inductor and the other inhibitor or both inhibitors, which greatly complicates the control of an individual's medication and the avoidance of possible adverse reactions.
This means that you can harm yourself even if you don't feel the interactions... Don't mix drugs working on P450 enzymes (antidepressant, neuroleptics, grapefruit and so on).
I try to figuere out if Abilify inhibits or induces the P450 enzymes... This happens if you don't inform yourself right. Makes me crazy if I think about taking MDMA while on a low low dose of around 0,5 mg Abilify 8(. Well I don't have to mention that it didn't work. It was probably the reason why I couldn't sleep, in case of enzymatic inhibition, because it increased the amount of Abilify in the plasma greatly.
Probably increased the amount of MDMA in the boodstream, too.
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