Timothy Leary
Bluelighter
- Joined
- Dec 5, 2009
- Messages
- 61
I have found some interesting info on amphetamine metabolism and potentioattion not based on MAO inhibition. A lot of this basic info is taken from various websites, a lot of the time I just checked wikipedia, found some useful concept and fact checked the sources in a logical manner, university labs = good, dirty dave's speed page = bad. Some of it is theory an is identified as such.
MAOI's do not effect amphetamine metabolism directly very much as amphetamines' alpha carbon is hard for MAO's to break down, it does happen but so slowly that other hepatic mechanisms predominate. But what MAOI's can do is increase the half life of dopamine, the most common suspect for amphetamines mode of action. It is broken down by MAO isoform B as well as A. Other examples of related dopamine chemicals include norepinephrine and epinephrine, these are metabolized by MAO isoform A only. These chemicals have much more of a cardiac stimulant effect related to fight or flight response and much less effect on motivation and reward mechanisms than dopamine
Using MAOI's with stimulants can be very dangerous if you don't an MAO-B selective one, and if you use selegiline (the most common B selective drug) in 10+ mg dosages, as it crosses over to inhibit both isoforms of the enzyme and not just MAO-B. Since it is so long lasting because of its irreversible inhibition even if you keep on using a fairly low 5-7 mg dose or less daily you will run out of MAO-B eventually and it will attack A as well, you have to consider it takes a while for the body to make more MAO so if you use up 75% the first day then what happens after 3 days at that dose even if the drug is very selective.either way you get a crap load of epinephrine, nor-epinephrine and the like.
So you must be extremely careful if you use an MAOI of isoform B,especially seligiline. Selective and A inhibitors will kill you as with the higher doses of B selective ones. Some B inhibitors are less dangerous than selegiline as they are much more preferential to he B isoform than selegiline's still respectable selectivity. Even so I would not like to be the first to experimentally discover where the tipping point lies for the "safer" ones
I think the amphetamine would still last as long as normal in your body, it may just be stronger over the same time period as MAO is not involved in its disposal. This is just theory though, as far as the duration, amphetamine may have a longer half life in this case. The increased dopamine may compete for liver enzymes with amphetamine if there is to little MAO to do the job, but this is likely not the case. After the amphetamine was gone dopamine levels would drop to normal fairly quickly.
I think that there is a much better way to potential without too much danger, let me explain. I have been on Lisdexamphetamine (vyvance) for a while now and was taking 200 mg sertraline (paxil) concurrently. I started at 30 and then my psychiatrist recommended 60 mg so I went on that, and was amazed with the ability I gained, of course I knew dependence and neurotoxicity concerns and was not going to go on a binge. I was much more happy and able to cope with my fear of social interaction. I had to get off of it for a bit and during that time. During this time I took some crystaline harmala extract with a few other things, I made sure I had 5 half lives on both sides. But I decided that I would not get back on the sertraline as It had never seemed to do much and only held my fun with seratonin potentiation back. When I was put back on the vyvance a few weeks after I noticed that It didn't last half as long, I always dropped to an undetectable effect after 6 hours, I would do fine at the beginning of the day and but by 1:00 or so I could still do a bit better than normal but almost all effects were gone by then, in addition I noticed that there was a crash now (before it it was a slow disappearance of effects over the course of 12 hours, but there was no crash at all)
I looked up amphetamine metabolism on a whim and found out that it is broken down primarily by CYP2D6 which is inhibited by..... sertraline. I looked this found this-
www.springerlink.com/index/JWJHKGL15K87A3K6.pdf
Basically it was found that an increase in amphetamine levels and time it took for the effects to disappear in mice with 5 mg/kg, although in other studies not half as much as fluvoxetine and paroxetine. Some studies say that the effect from sertraline is not significantly significant, although dosages were 50- 100 mg in that case, almost 5 to 10 times smaller than the doses in the original study cited.
on sertralines wikipedia page it can apparently it caused a 70% increase in haloperidol levels at 150 mg
After all that, Does anyone have any experience with this kind of thing?
MAOI's do not effect amphetamine metabolism directly very much as amphetamines' alpha carbon is hard for MAO's to break down, it does happen but so slowly that other hepatic mechanisms predominate. But what MAOI's can do is increase the half life of dopamine, the most common suspect for amphetamines mode of action. It is broken down by MAO isoform B as well as A. Other examples of related dopamine chemicals include norepinephrine and epinephrine, these are metabolized by MAO isoform A only. These chemicals have much more of a cardiac stimulant effect related to fight or flight response and much less effect on motivation and reward mechanisms than dopamine
Using MAOI's with stimulants can be very dangerous if you don't an MAO-B selective one, and if you use selegiline (the most common B selective drug) in 10+ mg dosages, as it crosses over to inhibit both isoforms of the enzyme and not just MAO-B. Since it is so long lasting because of its irreversible inhibition even if you keep on using a fairly low 5-7 mg dose or less daily you will run out of MAO-B eventually and it will attack A as well, you have to consider it takes a while for the body to make more MAO so if you use up 75% the first day then what happens after 3 days at that dose even if the drug is very selective.either way you get a crap load of epinephrine, nor-epinephrine and the like.
So you must be extremely careful if you use an MAOI of isoform B,especially seligiline. Selective and A inhibitors will kill you as with the higher doses of B selective ones. Some B inhibitors are less dangerous than selegiline as they are much more preferential to he B isoform than selegiline's still respectable selectivity. Even so I would not like to be the first to experimentally discover where the tipping point lies for the "safer" ones
I think the amphetamine would still last as long as normal in your body, it may just be stronger over the same time period as MAO is not involved in its disposal. This is just theory though, as far as the duration, amphetamine may have a longer half life in this case. The increased dopamine may compete for liver enzymes with amphetamine if there is to little MAO to do the job, but this is likely not the case. After the amphetamine was gone dopamine levels would drop to normal fairly quickly.
I think that there is a much better way to potential without too much danger, let me explain. I have been on Lisdexamphetamine (vyvance) for a while now and was taking 200 mg sertraline (paxil) concurrently. I started at 30 and then my psychiatrist recommended 60 mg so I went on that, and was amazed with the ability I gained, of course I knew dependence and neurotoxicity concerns and was not going to go on a binge. I was much more happy and able to cope with my fear of social interaction. I had to get off of it for a bit and during that time. During this time I took some crystaline harmala extract with a few other things, I made sure I had 5 half lives on both sides. But I decided that I would not get back on the sertraline as It had never seemed to do much and only held my fun with seratonin potentiation back. When I was put back on the vyvance a few weeks after I noticed that It didn't last half as long, I always dropped to an undetectable effect after 6 hours, I would do fine at the beginning of the day and but by 1:00 or so I could still do a bit better than normal but almost all effects were gone by then, in addition I noticed that there was a crash now (before it it was a slow disappearance of effects over the course of 12 hours, but there was no crash at all)
I looked up amphetamine metabolism on a whim and found out that it is broken down primarily by CYP2D6 which is inhibited by..... sertraline. I looked this found this-
www.springerlink.com/index/JWJHKGL15K87A3K6.pdf
Basically it was found that an increase in amphetamine levels and time it took for the effects to disappear in mice with 5 mg/kg, although in other studies not half as much as fluvoxetine and paroxetine. Some studies say that the effect from sertraline is not significantly significant, although dosages were 50- 100 mg in that case, almost 5 to 10 times smaller than the doses in the original study cited.
on sertralines wikipedia page it can apparently it caused a 70% increase in haloperidol levels at 150 mg
After all that, Does anyone have any experience with this kind of thing?
Last edited:
