Rapid metabolizers support group

[[sh...]]

I am not a rapid metabolizer, I tried a couple times having half a grapefruit , and have experienced decreased Valium metabolism  without fail. That doesn't mean it is going to be simple figuring out equivalent of the juice you need to correct your metabolism.

But I hope that it works out for you for the trip.

Hemp oil has a much stronger inhibition than bergapten - grapefruit's one.

https://en.wikipedia.org/wiki/Bergapten

So citrus essential oils have it too.

[[Ki...]]

Yeah I tried that bergamot stuff for cholesterol and the metabolism effects but it just gave me horrid reflux and gas. Nasty stuff! I will only be a few days with no reliable juice so worst thibg is having to resort back to taking a mg or so in the daytime. Its funny how metabolism can change up too!

[[Ki...]]

Went back to grapefruit. I went on a trip for a week- it really does seem to help with sleep to only dose once a day. I only had 2 rough nights. I really think evening out things so the drug metabolizes properly makes a big difference.

[[...]]

Hi kitty and everyone ...... Not sure if this group is still active , but I'm trying to find out about CBD oil and whether it slows or even blocks metabolism of Valium ? I can't find any real evidence of which CYP enzyme it uses , maybe the 3A4 , in which case it might effect Valium metabolism .

I have a normal cyp3a4 , it the 2C 19* 17 that makes me a rapid metabolizer.... I believe not an ultra fast , but fast .

 

Thanks if anyone knows ...

MiYu

[[Ki...]]

I could not find anything other than both are CNS depressants- not any real info about specific metabolism interactions so much as direct side effects.

Iguess the reason this thread is so slow is that  probably not a whole lot of us are rapid enough metabolizers to need help with the problems it causes us lol!

Hope you have lots of windows soon MiYu!

[[Le...]]

Hi Miyu, if you have a *17 allele, then you are an ultra rapid metabolizer of 2C19, like me. I too am an extensive (normal) metabolized of 3A4.

 

"Individuals who carry one or two *17 gain-of-function alleles (e.g., *1/*17, *17/*17) may be categorized as UMs." See Drug Metabolizer Categories in this publication: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349992/

 

Don't know anything about metabolism of CBD oil.. My guess would be it may vary depending on the different types of CBD oils available? I'm not really sure. Will try to research if I'm able and will get back to you.

 

Sometimes I wonder if the way we metabolize the drug impacts the tapering process. I had a very difficult time tapering off Celexa back in the 90's. Of course, I was much younger and healthier, but I still remember the unpleasantness of that particular taper. Well guess what? Celexa is primarily metabolized by 2C19. Oddly, I find stuff like that interesting.

 

Hugs, Left 

 

P.S: well, Kitty beat me to the punch while I was typing.....

 

 

[[Ki...]]

I may have beaten you in speed but not in quality of answer! I just get excited when anyone posts here- we are a small group but we have problems others wont have. I read being a rapid metabolizer makes you the most likely to have problems on the livewello guide. It did not go into detail other than rapids and ultras are the least likely to have a " successful" experience with valium treatment. However that has nothing to do with a taper - since we are a lot more diligent than people who simply " take valium" I would guess we might have more bumps in the road but we all have an equal chance of completing the journey. At least I hope so!

[[Ki...]]

Another note of interest is they called slow metabolizers the most likely to be treated successfully. I wonder if they mean they would get the most BENEFIT from it. I get that way when I drink too much grapefruit juice, its always guesswork but sometimes I know I have been filling my shot glass up a little more than my brain wants me too when I get a full 8 hours of sleep and walk around half loopy all day... I wonder if thats what slow metabolizers feel like? I read some posts where people miss whole doses and never notice. They must be REALLY slow... lucky dogs

[[Le...]]

I may have beaten you in speed but not in quality of answer! I just get excited when anyone posts here- we are a small group but we have problems others wont have. I read being a rapid metabolizer makes you the most likely to have problems on the livewello guide. It did not go into detail other than rapids and ultras are the least likely to have a " successful" experience with valium treatment. However that has nothing to do with a taper - since we are a lot more diligent than people who simply " take valium" I would guess we might have more bumps in the road but we all have an equal chance of completing the journey. At least I hope so!

Well, Left is late again, what a surprise . iPad died, big storms, and then I started doing 10 things at once...next thing I know it's 11:15 pm, go figure! Anyway...

 

The whole genetics aspect of WD fascinates me too! Family and friends used to tease me about my natural curiosity and interest in the "whys" of everything. Anything remotely medical related was delegated to me to research on their behalf, and I was happy to do so. Now it takes me 2 hours to compose a post. 

 

According to my genetic report UMs of 2C19 have a higher risk of therapeutic failure due to decreased serum levels and poor efficacy (makes sense). Also possible adverse events associated with toxic metabolites. Knowing I'm an UM has been validating. Those nasty IDWDs are now alleviated by dosing 4xs/day. To think I was living that way for years is sad. Yes, we might have a few bumps that others don't, but there is no reason why we can't successfully taper off the drug. I don't want to be on a medication that has the potential to kill me if it's discontinued...no thank you! And the doctors wonder why I want off...really!? 

[[Le...]]

Another note of interest is they called slow metabolizers the most likely to be treated successfully. I wonder if they mean they would get the most BENEFIT from it. I get that way when I drink too much grapefruit juice, its always guesswork but sometimes I know I have been filling my shot glass up a little more than my brain wants me too when I get a full 8 hours of sleep and walk around half loopy all day... I wonder if thats what slow metabolizers feel like? I read some posts where people miss whole doses and never notice. They must be REALLY slow... lucky dogs

I'm an intermediate metabolizer of 2D6 (opioid painkillers, among many other meds) Was given Vicodin after spinal surgery in 2008 and passed out before the nurse could get the medicine cup out of my hand! They didn't know why I had the problem then...just no more Vicodin for me. Now I know why I passed out. Loopy, out of it, weird, are descriptions of how I feel/felt when given any drug metabolized by 2D6...it is not a pleasant feeling.

 

As for the Valium, it would be wonderful to only dose once a day... I dare not try the grapefruit experiment since I'm a normal metabolizer of 3A4 so who knows what would happen. But I'm really glad it works for you.

[[Ki...]]

I think my Mom must have had some kind of opioid metabolism problem- even the smallest dose knocked her silly. It does that to a smaller extent to me and to think I have not even lookex up my results for that stuff. Once I found out about the benzos and saw all my heart disease red flags I guess that was enough info for my brain - until I get the rest of it back lol. I would normally be curious too but my curiosity is sometimes surpassed by a bad case of the duuuuuhhhhs

[[...]]

Thanks Kitty and Left ......

The thing that's been worrying me is the toxic metabolites thing ... So you don't think that because we metabolize the parent drug fast we would also metabolize the metabolites fast too? I haven't found info on this ....

It's confusing !

 

Left, you and I have some similarities.... I am also nromal with the 3A4 , and yes , I have the *17 -heterogynous...which is the first pass enzyme on the Valium , and I think that's why it comes on so fast and hard for me.

 

I also have the opoid metabolism thing  the 2D6 variant . And Nat2 which I think makes toxins slower to clear. Apparantly klonopin isn't good fro me because of this , it uses the Nat2 somewhere second phase ...

 

What I do now is , because the initial V hits me like a ton of bricks , I break up 2 mg my pills into quarters and take a quarter every 20 mins or so! I do that for each of my three doses .

I've also found that when I wake up in the morning, it's best if only take 1/2 mg of the 2 mgs until I have breakfast . That 1/2 will knock me right back to sleep ! Then the food slows down the absorption rate for the rest. Still knocks me out mostly tho . My liver burns too and that bothers me .

Kitty , I think the grapefruit effects the 3A4?  Do you have a variant on that enzyme?

 

Left .... I tried citalopram once, the doctor said , oh , it'll take a few weeks to kick in .... Within 1/2 hour of taking 20 mgs I was out of my head ! I had an acupuncture treatment scheduled and was on the table with all the needles in and my limbs started jerking around, I had to have her take all the needles out!  Also not a good drug for me! Can't remember which enzyme .....

Very grateful I didn't end up on that one....

 

Anyway .... I am wondering if I shouldn't switch to maybe Librium , or even Ativan , which doesn't have the metabolites ..... I know no benzo taper will be easy , but the side effects........

 

There's also the issue of kindling which I believe is related to unstable amounts of the drug in our systems constantly......or can be anyway.

 

Thoughts? 

Thanks!

MiYu

 

[[...]]

I think my Mom must have had some kind of opioid metabolism problem- even the smallest dose knocked her silly. It does that to a smaller extent to me and to think I have not even lookex up my results for that stuff. Once I found out about the benzos and saw all my heart disease red flags I guess that was enough info for my brain - until I get the rest of it back lol. I would normally be curious too but my curiosity is sometimes surpassed by a bad case of the duuuuuhhhhs

 

You seem to communicate fine

Has your mom had her genes tested ? 2D6 would be the one to look at I believe for opiates....

[[Ki...]]

My Mom passed away a few years ago- but her reactions to anything like lortabs were bad. I would bet she did have some weird variant!

Iworry about kindling too but the way I read it was its a problem more if you go off completely then reinstate and not so much switching. That would just be more nasty but normal withdrawal. I think?

[[...]]

Some things I'm confused about , don't know if you kitty , or anyone else can help.....

If we rapidly metabolize with phase 1 liver enzymes , do we have more chance of toxicity from phase 2 liver not being able to keep Up?

Should we be inhibiting phase one and inducing / supporting phase 2?

 

I have a NAT 2 snp which makes me a slow acetylator... In phase two liver detox , so I'm worried about build up of toxins from Valium .

 

When I took my lunch dose today of Valium , I don't know what happened but it went in so fast it literally took my breath away and I was panting fro about 5 minutes , horrible . It passed ....

That used to happen to me with the steroids too , steroids are phase 1 inducers big time.

 

Also , do you take your V with food ? Anyone? I always do ......usually with some fat of some kind , often olive oil , which I have since read is a potential inhibitor of cyp450 3A4

 

Oh it's so complicated ! Seriously wondering if I'd have better luck with Ativan! Simple glucoronidation, no CYP enzymes involved .

 

Anyway , worried about toxicity from metabolites , Not to mention. the shock to my system when the V goes in SO fast . It doesn't always do that which makes me wonder .....?

 

I'm taking iron and b2 to help support nAT2, also experimenting cautiously with B12 for methylation.

 

Apparantly CBD is also a potent inhibitor of cyp3A4 ......good or bad for us?

 

HELP!! 

MiYu

 

 

[[...]]

Actually now I'm wondering if the heavy breathing was an adrenaline rush , caused the Valium as I have all this uncomfortable energy now ..... 

[[Ki...]]

I wish I had more knowledge about that. It does seem to be a problem with it hitting you so hard- but I never dosed evenly. It did hot me hard the first few weeks but thats typical. I do only dose at night because it does sometimes help some with sleep but dont have the same reactions you do. I was wondering about the metabolite issue since I go the grapefruit juice route but thats a whole different thing, my goal is just to get close to a normal metabolism. But I get hit after just three days of going too fast and most folks take a week so I dont think the metabolite thing would be the same as what you have. I hope you find some answers. I couldnt find anything different doing a search- it must not be a common problem or its just not worded right for a search  :'(

[[...]]

I wish I had more knowledge about that. It does seem to be a problem with it hitting you so hard- but I never dosed evenly. It did hot me hard the first few weeks but thats typical. I do only dose at night because it does sometimes help some with sleep but dont have the same reactions you do. I was wondering about the metabolite issue since I go the grapefruit juice route but thats a whole different thing, my goal is just to get close to a normal metabolism. But I get hit after just three days of going too fast and most folks take a week so I dont think the metabolite thing would be the same as what you have. I hope you find some answers. I couldnt find anything different doing a search- it must not be a common problem or its just not worded right for a search  :'(

 

Yeah , I've done so many searches! I just don't think the research is out there.

Or not yet anyway.

So you get WDs after three days? For me , when  I say hit , I mean the V effect knocks me out really fast after I take it . Then I feel the peak plasma about an hour later if I take it with food.

Then things seem to even out a bit for a few hours. The frost dose in the morning is the worst for some reason, makes me feel horrible!

The WDs come on probably within a week , but then they build for weeks it seems. Maybe that's just my unstable nervous system , I don't know , but I think it's been like that since the beginning of my taper. I've never recovered since I first started tapering a year ago . Never had Windows ....maybe one!

[[...]]

Kitty , when do you drink your grapefruit juice? Any idea how long it inhibits the enzymes for ? I'm not sure it inhibits the 2C19 , just the 3A4, which you have , I don't .

CBD oil may inhibit both ... Not sure ....

[[Ki...]]

I drink the grapefruit juice about an hour before I take my meds. I read some research about using it for chemo to help patients take less chemo by helping it hang around in their systems longer- less dosing, less side effects. They seemed to think it didnt matter with the time- I think they had the subjects drink an 8 ounce glass every third day. Thats kinda how I came up with drinking approx 3 oz a night. Sometimes more, sometimes none if I feel sluggish. I do like being able to dose just once at bedtime most days. Some days I still need a nibble around dinnertime. I did read lots of people take it with a high fat meal but that never helped me enough...

[[...]]

I drink the grapefruit juice about an hour before I take my meds. I read some research about using it for chemo to help patients take less chemo by helping it hang around in their systems longer- less dosing, less side effects. They seemed to think it didnt matter with the time- I think they had the subjects drink an 8 ounce glass every third day. Thats kinda how I came up with drinking approx 3 oz a night. Sometimes more, sometimes none if I feel sluggish. I do like being able to dose just once at bedtime most days. Some days I still need a nibble around dinnertime. I did read lots of people take it with a high fat meal but that never helped me enough...

 

Maybe I'll give it a try , thanks kitty . I'd love to dose once a day , tho I think 8 mgs at night would totally knock me out !

Have you read anything about cyp2c19 variants and grapefruit juice? I can only find it in relation to the 3A4 enzyme

Thanks!

MiYu

[[Ki...]]

I see 3A4, 1A2, 2C9 and 2D6 as being grapefruit connected. And other citrus too, not sure which all- pummelos and some oranges for sure. These were listed here https://en.m.wikipedia.org/wiki/Grapefruit–drug_interactions

[[...]]

I see 3A4, 1A2, 2C9 and 2D6 as being grapefruit connected. And other citrus too, not sure which all- pummelos and some oranges for sure. These were listed here https://en.m.wikipedia.org/wiki/Grapefruit–drug_interactions

 

Hi kitty , in your research have you come across anything scientific about rapidly metabolizing the parent drug diazepam causing more build up of metabolites? I can't find anything on it .

I'm just puzzled as to why I'm suddenly so so sedated by 1/2 mg of V .

I was out for three hours cold after taking 1/2 mg at lunch .

Awful ..... If phase one liver enzymes metabolism fast , and phase two can't keep up , I wonder if we get toxic .... I know this is true fro other substances .....things just get backed up .

 

Trying to make sense of what's happening to me with this and why it's so hard for me to taper also !

Sorry if Ive asked this before !

 

Miyu

[[...]]

OH I see benzo brain has already a asked the above questions.... Oh well ... Maybe I'll catch another response from someone ! 

[[Ki...]]

The articles I saw never mentioned that. Honestly I never even looked into " toxic metabolites" since all I was trying to do was metabolize it somewhat normally. But I suppose it could happen- its really weird that it would suddenly start making you so tired! I only get that way if I drink way too much grapefruit juice and dont take any days off, which I normally do...

I hope you can find an answer. Our little group doesnt seem to be getting any new members! 😞