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Substances for different metabolic types
I'm a rather strong believer in utilizing pharmacology (and especially psychopharmacology) to not only cure ailments but enhance or improve bodily function (legally, of course). However - and I was wondering if anybody else on this board deals with this and couldn't find an older post about it - my body's metabolism makes this difficult as an ultra-rapid metabolizer.
(As you all are intensely familiar with your own bodies and anatomy in general I'm sure I don't need to post this but just in case: chemicals are broken down by different metabolites in your liver, and very many pharmaceuticals use a small handful, especially CYP2D6. You can get expensive tests done to establish the type of metabolizer you are [poor, intermediate, rapid, and ultra-rapid, with rapid being the most common] which depends on how many copies of certain genetic enzymes you have, though I found out after some research, an... interesting experiencing taking [legally prescribed] Rx codeine-based cough medicine during a particular bad cold, and then examination of my own DNA data.)
Even caffeine and other simple things have no effect on me - I tried, in my trial and error phase, taking two NoDoz and one of those "SUPER" energy drinks for probably a total of ~440mg of caffeine at once and still found myself sleepy on my morning commute. Many pharmaceuticals have a similar negligible effect. My saving grace is in prodrugs (again, probably not necessary to clarify but: most drugs function after intake and the liver metabolizes them out of function - prodrugs function after being metabolized by liver, causing longer duration and decreased intensity in most people but increased and faster administration of the active metabolite in people like me - e.g. I (again, legally) take Vyvanse/lisdexamfetamine, which is a prodrug of dextroamphetamine and at my current dose of 70mg PRN it turns me into an entirely different person almost, increasing my function, drive, sociability, creativity, physical energy, and of course wakefulness, etc.).
So - as you can imagine, many supplements and nootropics don't function in me the way people claim they should (I never tried modafinil because after being prescribed I realized it would potentially decrease the bioavailability and thus the function of my birth control which I very much do not want, ha).
I was wondering if anyone else here deals with similar problems and if so, if there are (AGAIN, legal) supplements/nootropics/OTC products, etc. that might have a better chance of working on ultra-rapid/ultra-extensive metabolizers (without extensive contraindications/negative reactions with birth control, haha). So far I'm happy with how Vyvanse enhances my entire self, but it would be interesting to experiment with different options, especially since Vyvanse isn't particularly cheap as a brand name pharmaceutical.
Thank you in advance and I hope this prompts some interesting and helpful discussions for others as well!
Comments
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If I were you, my first step would be to investigate the safety and mechanisms behind CYP2D6 inhibition in a methodical, calculatable way. Instead of trying to find prodrugs of useful chemicals, it might be easier to instead alter your general metabolism of said chemicals.
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You could look into choline precursors like CDP-choline and alpha-GPC. They both increase acetylcholine and CDP-choline also increases uridine. If you are an ultra-rapid metabolizer you might benefit from CDP-choline in particular since it has a half-life of 70 hours. Just remember to start out with a low dose and work your way up. I started with the recommended dose of 500 mg CDP-choline and was unable to sleep for three days straight. Nowadays I mostly use alpha-GPC because of its more sensible half-life of 5 hours.
Other supplements you could look into include N-Acetyl L-Tyrosine and Acetyl-L-Carnitine. Also, I don't think efficacy of peptides is affected by metabolization rate, but I wouldn't dabble in that without a firm understanding of their mechanisms of action and possible interactions.
Last but not least, you could check if bypassing the gut would help with bioavailability. The gut can account for many of the differences in how people respond to drugs perorally (through the mouth). So it might be best to eliminate this factor. For instance, if peroral caffeine does not produce expected effects you could try intranasal administration. But proceed with caution, many drugs are not well studied when it comes to alternative administration routes.
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@malinoise Thanks for sharing, and for explaining the small details. We came from different fields same elements are not obvious to everybody. You mention expensive test to establish the type of metabolizer. What are this test?
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@trroyyc said:
If I were you, my first step would be to investigate the safety and mechanisms behind CYP2D6 inhibition in a methodical, calculatable way. Instead of trying to find prodrugs of useful chemicals, it might be easier to instead alter your general metabolism of said chemicals.That does sound like a good idea and I believe there are substances I've read about that limit the function of CYP2D6-controlled enzymes. I think I'd have to do more poking around my strands to see what the state of other liver enzyme altering genetic markers I have are - there are about six or eight I believe that define most metabolisms.
Thanks for the advice!
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@nullduggery said:
You could look into choline precursors like CDP-choline and alpha-GPC. They both increase acetylcholine and CDP-choline also increases uridine. If you are an ultra-rapid metabolizer you might benefit from CDP-choline in particular since it has a half-life of 70 hours. Just remember to start out with a low dose and work your way up. I started with the recommended dose of 500 mg CDP-choline and was unable to sleep for three days straight. Nowadays I mostly use alpha-GPC because of its more sensible half-life of 5 hours.Other supplements you could look into include N-Acetyl L-Tyrosine and Acetyl-L-Carnitine. Also, I don't think efficacy of peptides is affected by metabolization rate, but I wouldn't dabble in that without a firm understanding of their mechanisms of action and possible interactions.
Last but not least, you could check if bypassing the gut would help with bioavailability. The gut can account for many of the differences in how people respond to drugs perorally (through the mouth). So it might be best to eliminate this factor. For instance, if peroral caffeine does not produce expected effects you could try intranasal administration. But proceed with caution, many drugs are not well studied when it comes to alternative administration routes.
I will definitely do some research into these, thank you very much for the suggestions!
I've noticed that ROA helps with some substances and does nothing for others. I was prescribed Adderall before Vyvanse and it worked (not for very long, but better than normal) better when taken the intranasal route rather than orally. Some substances (like alprazolam) it seems to make no difference in how it functions.
(Again, a disclaimer that all of these substances were legally prescribed by an MD and acquired from a pharmacy - my medical professional knows of my metabolic problems and ways I have tried to enhance the utility of normal doses rather than trying to simply get higher doses.)
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@kuroro86 said:
@malinoise Thanks for sharing, and for explaining the small details. We came from different fields same elements are not obvious to everybody. You mention expensive test to establish the type of metabolizer. What are this test?Of course, I'm glad you found it useful to read!
There are a variety of tests on the market that test how many alleles you have of things like CYP2D6 (the most common, but many tests also test for others), which shows what kind of metabolizer you are (e.g. I have more than two copies of the CYP2D6 allele, which makes me an extensive metabolizer).
Fair warning that these tests haven't been heavily studied as they're fairly new to the general market (as far as I know?) so take the results with a grain of salt if you get one. Also keep in mind that most tests on the market are designed to see how you might metabolize one specific drug (this is particularly popular with modern antidepressants SSRIs/SNRIs).
There are plenty to choose from but they all require a prescription to receive one and there's a good chance your insurance won't cover it, it's not like 23andMe or something where you can just buy a box at CVS and send it back in the mail (again, as far as I know). I believe Quest Diagnostics offers the test (and will test for more than just 2D6), and the company GeneSight.
I found it more helpful just to get my genetic information and look up my counts for myself, though I understand why someone would want the oversight and analysis of a doctor! If you're interested I recommend talking to one (your primary care doctor if necessary, but if you see someone for specialized medicine like a psychiatrist they might be more knowledgable) and asking for a rundown of how genetics affects the metabolism of your medication, let them know if you feel a certain medication you take isn't working, and see if a test is something they recommend.
Best of luck to you and if you want to talk more feel free to come back or message me :)
