P450 enzyme CYP2D6 is of importance in medicinal chemistry, pharmacology and medicine. It belongs to one of the major group of liver enzymes that metabolize drugs (and other crap) that float around your system. For several reasons, CYP2D6 is especially troublesome for scientists working with discovering new drugs.

To name one such reason, the individual variation of CYP2D6 expression among the human population is very high. In other words, a certain drug that is primarily eliminated by CYP26D may have a half-life of say 4 hours in one patient, but 0.5 hours in the other, at the same dose and route of administration. The pharmaceutical industry hates these things. So do doctors. They want complete control. In this case, I take their side.


One of the most classic CYP2D6 substrates is codeine, an opiate used in managing mild to moderate pain. Most often, it is used in combination with an NSAID or acetaminophen (paracetamol), because of their synergistic effects. Such combination medications are available in almost every country in the world.

Whether codeine is a drug or a prodrug is debated. Long story short: When you ingest codeine and it enters your blood stream, the first thing your liver tries to do is breaking it down via so called first-passage metabolism (if taken orally).

Now, here comes the funny part, where your body gets a little more action than it was aiming for. In trying to protect you from codeine, the evil intruder, your liver decides to chop the molecule in pieces. Armed and loaded with CYP2D6, the liver knocks off a methyl group (vide ninja). But the result is, as you know, morphine – an opiate 5-10 times stronger than codeine itself. Dang.

Presumably, the pain relief — and the not completely unpleasant buzz — that you get from codeine is due to the fact that your body partly (5-10 %) converts it into morphine, which enters your central nervous system, finds opiod μ-receptors and yada, yada…

10-15 % of the population, however, report no positive effect whatsoever from taking codeine. This is consistent with findings that roughly the same number of people have significantly diminished levels of active CYP2D6 enzymes. In other words, 1 in 8-10 people have little or no use of codeine. A major hassle for this patient group is that the typical physician is quite reluctant to prescribing anything stronger for everyday pain conditions. Hence, these poor souls risk suffering more pain in life than necessary.

I happen to be at the very other end of the spectrum. Hehe. We select 1-2 % go under the name ultrarapid CYP2D6 metabolizers. (And it sounds cool too!) I haven’t had my genes mapped, so I cannot be entiery sure, but still I feel fairly certain.

For reasons I will not go into, I have been prescribed both codeine and morphine, separately, at several occasions. I know what 10 milligrams of morphine feels like. I also know what 60 milligrams of codeine feels like. The latter is the standard dose used to treat for instance toothache, migraine and other half-decent pain conditions. You don’t get morphine for these. But I do. Sort of.

Because — believe it or not — 60 milligrams of codeine has in my experience and body much more oomph in it than 10 milligrams of morphine. I would even go so far as to say peroral codeine is stronger than intravenous morphine. In me. So yeah, I am pretty sure my liver is unusually loaded with CYP2D6, and that it is damn active too.

Finally, I hope my doctor never read this. “Hi. My name is Fredrik, and I am an ultrarapid CYP2D6 metabolizer.”


115 Responses to Life as an ultrarapid CYP2D6 metabolizer

  1. I’m sad to say, I prefer the morphine. Codeine doesn’t touch me.

    • drfreddy says:

      I feel your pain 🙂

    • lawrence goldberg says:

      We all want a magic pill and perhaps there is one. I am currently on morphine sulfate as my pain mgmt was smart enough to notice on my drug screen it appeared that I was not taking my oxycontin. He then did a genetic swab test and came up with the CYP2D6. this comes up with the last 4 pain mgmt not having a clue why my opiate levels were near nil and this shows their stupidity. there was a hunt and peck and there was one time when my pain was managed to the affect that i was pain free. So the only clue that I have is to move from morphine sulfate which I currently take to hydromorphone.

  2. Toad says:

    Atomoxetine (Strattera in the U.S.) is another drug significantly metabolized via CYP2D6. It is used primarily in children with ADD/ADHD, who are typically started at a low dose, then that dose is increased in increments until an effective dose is found for the child. However, those kids that are “slow metabolizers”, which is a substantial percentage of at least the Caucasian population, are at risk of developing severe (usually cardiovascular) side effects. Once the concentration of parent drug saturates the capacity of the 2D6 enzyme to remove it, the drug concentration continues to build up rapidly over time. The problem is, if CV effects are not noticed quick enough, even taking the child off the drug does not immediately remove the systemic drug concentration until additional 2D6 is made by the body; and, this can take some time. I’ve seen it take a good 2-3 weeks for the side effects to dissipate. The wide variety of 2D6 mutations and heterogeneity in their substrate binding and instance and severity in the population make this a more difficult issue to deal with – a simple test wouldn’t necessarily tell you much.

    • drfreddy says:

      Interesting. I didn’t know that. A close friend of mine has his kid on Strattera (maximum dose), but nothing unusual there, knock on wood.

      Another fascinating aspect with codeine that didn’t make it into the main post is that it is also a potent CYP2D6 inhibitor (even at therapeutic doses), which means that you could say that it has a built in safety system. A second dose after 2 hours usually has little or no effect. You have to wait the full 4-6 hours until you take it again, or it won’t work.

  3. Jayde says:

    So what on earth does it mean when nothing works, no codeine, no morphine, no Tylenol, no Advil, no dental freezing ( or any other kind of freezing), I can drink several shots of espresso and fall asleep. My dentist called me an alien when neither freezing, nor “conscious sedation” had any effect whatsoever at the legal limit. Fortunately I only get sick once every 20 years, unfortunately I get wicked migraines, for which I have no solution. Whatever my liver enzymes are doing, they aren’t helping me. Modern medicine has no ideas, and I’ve been a lab rat for too long.

    • claude says:

      I’ve been searching the internet around the subject of migraines and
      cyp2d6 ultra extensive metabolizer variant obviously in such a case codeine should be overly potent as a pain killer but most standard longterm treatments should be negatively impacted propanolol amitryptiline flunarizine all seem to be processed by cyp2d6 have you had any novel insight since ?

      • Debra says:

        I get migraine and am a UM. I find Fiorocet, in only slightly higher doses than normal, helpful and actually the only thing that has worked for my migraines.

      • GC says:

        I finally found that Topamax took my Migraines down 3 or 4 a year from as often as every day at 3:05 pm. I am lucky that my Migraines aren’t very painful so I can just ignore the pain and go on with what I am doing after my vision comes back in 15 or 20 minutes. I usually had to take something to get to sleep around 1:00 or 2:00 a.m. I was pulled in on failling project that had a hard dead line. I was working 16 hours a day 7 day a week for about 3 months. The headaches started about half way in. I couldn’t take any pain killers for them and do any work. The headache started as soon as I relaxed a little at the afternoon coffee break.

    • amanda says:

      I know this thread is old, but are you RH negative by chance?

      • Paulina says:

        Does RH factor into this?

        • Debra says:

          I 7nderstand that there are tests for example the OATS test that tests for rh and should be administered beside the chromosome tests and could affect the therapies but I have found my insurance company will not allowy doctor to perform it. Crazy! If you can get tested for rh I do understand it can be very enlightening and helpful!

        • Timothy Lee Coffey says:

          What I have read most of the Caucasians are from middle east and Northern Africa where most RH negs come from. I am A-, and as a point of intrest Tutancommon, King TUT came back as A-. So yes I would think RH factor might play a role? But I am not a doctor, just put it together from Wiki on the enzyme, and what I know from being Basque/Northern African . Morocco/ basque have the most RH negs.

    • I hope you have found help! If not look in to connective tissues disorders such as Marfan’s or Ehlers-Danlos.

    • Teri says:

      have the same issue, I’ve had genesight testing and am an ultra rapid metabolizer, but I knew already, waking up in middle of surgeries, codeine, fentanyl, etc lasting a third of the regular time, coffee has no effect… get tested, your Dr can do it, as for dental, laughing gas on high, started at least ten min beforehand… local anaesthetic with stopping once or twice for more works for me. are you a redhead? ginger pain studies help me figure it out prior to DNA testing… only the redheads at Drs office needed the extra oomph and I didn’t get why people drank coffee

    • Ben says:

      A small percentage of the population has inactive CYP2D6 enzymes, that cannot metabolize any CYP2D6 substrates, (medications, or foods, whatever). They may respond partially when the drug is metabolized by a number of different enzymes, and sometimes in these situations the other enzymes can compensate to some degree for the inactive CYP2D6. You might want to get genetic testing from a company like “Genesight” to figure out what medications may work for you.

  4. Susan says:

    UNfortunately for me, my CYP2D6 is so compromised that NO pain medications I take orally works for me AT ALL. Worse, the only route(s) by which I can get any opioid relief, say, from acute post-surgical pain, is by IM injection or IV infusion. Needless to say, walking into an ED and saying, “HI! I need 2 mg of dilaudid (standard adult dose)and 4 mg of Zofran” doesn’t usually go over very well!!. I have been labeled a “liar,” “malingerer” – although I don’t know how anyone who has just had their ulnar shortened and had the block wear off in four hours could be said to be malingering – a “drug-seeker,” and several other impolite names by physicians in various emergency departments. And it’s always someone else’s “job” to figure this thing out. Frankly, ED physicians haven’t done their homework with regard to individual patient response to opioid treatment needed for acute pain experiences. They have no clue about the differences of metabolic issues which can cause patients to respond to IV/IM medications and NOT respond to oral administration. And, from my own experiences, I think I can state that they really don’t care. It is simply easier to, as I said, say it’s someone else’s “job” or suspect drug abuse. I’m allergic to the adhesive used in the patches too, so that’s out as well. I’d much prefer the pain in the A#$ injection than what I have to deal with from pain in the A$# emergency department physicians!

    • FriendofCats says:

      Michael Jackson pink elephant took dxm recreationally and at 150mg had signs of slight CYP2D6 deficiency as motor control was impacted strongly but head clear but almost on verge of second plateau at a higher range of the 1st plateu dose by weight. But Michael Jacksons pink elephant also takes codeine and as far as she is aware her reponse to codeine is about normal and it does relieve pain at the stated doses, not exactly indicative. What recreational drugs (i.e above medical rec doses )shuld MJPE take to work out for sure if their CYP2D6 is slow or normalish and if it may be their CYP2A enzyme that is slightly slow or non active rather than their CYP2D6 or if conversely their CYP2D6 is slightly slow but their CYP2A is slightly fast… Micahel Jackson pink elephant is as much intrested in this from a scientific point of view to roughly work out their rough different enzyme abilities as they are to try recreational doses.

    • Dr. Sloane says:

      Perhaps your problem is tolerance? You no longer feel the effects of your oral medication. The reason you feel Dilaudid is because of its iv/IM route and lack of tolerance to this drug. If you really believe your problems are a result of what you have stated, you need to have testing to prove your theory. Nobody will be able to argue with you at that point

    • Dee says:

      Um hi if you dont know already but you might have Ehlers danlos..

    • Nancy Cramer says:

      I feel your pain. I’m a small person but a rapid metabolizer. Most pain meds don’t help at all. I’ve had 2 knee replacement surgeries. IV meds fine, but oral meds did not help at all. I guess a different pathway. In any case, they cut you off the narcotics. I can’t take any NSAIDS, as they give me stomach problems.

    • Erin Herold says:

      I have found my TRIBE!
      For 53 years I have had a feeling of aloneness and feeling that I am the only person who has this painful, awkward, and bizarre relationship with my body, and a body that doesn’t work like everyone else’s.
      My skin also blisters with bandaids (or ANY adhesive – even the “delicate skin” stuff), and tears off right along with the adhesive; I have awakened twice during surgeries and in both cases, instead of receiving compassion, docs were angry with me – with ME!; my dentists didn’t believe me when “laughing gas” didn’t work, even though I was fully aware and cognizant; and NOOOOO – painkillers DO NOT WORK!
      I was DX at 38 with Ehlers-Danlos and Fibromyalgia, and have since added several other fun maladies, including being a CYPpie.
      As a redhead, this of course adds another layer.
      This article, and these comments – especially yours, Susan – are like a beacon in a hurricane.
      This is absolutely the best, most reassuring collection of experiences, CYP anecdotal knowledge, and affirmation letting me know that I am not alone in this disorder.
      What an incredible gift! I’m so, so grateful!
      Being that it’s older and was buried a bit, I’m going to post this on Twitter and hopefully help others like it helped me. Bless you all!

  5. Debra says:

    I have been swab tested by my therapist/MD because he was trying to treat me for ADHD and I told him I was not feeling anything from the Adderall dosage even after he had increased it to the highest recommended. I told him when we first started my treatment that I had a super high tolerance to all pain killers, alcohol, Novocain… At the time I did not know why, I just knew I did. My swab was conclusive that I am a CYP2D6*2xN (UM-Ultrarapidmetabolizer). CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs. Ultrarapid metabolizer – multiple copies of the CYP2D6 gene are expressed, and therefore greater-than-normal CYP2D6 function. In my genotype, *2xN the N stands for the number of alleles and could be anywhere from 2 copies up to 13 (that they know of.)

    Interesting fact about depression and CYP2D6 UMs: we have statistically lower than normal levels of Dopamine, a neurotransmitter that helps control the brain’s reward and pleasure centers. And serotonin, many researchers believe that an imbalance in serotonin levels may influence mood in a way that leads to depression. What is really sad is that the instances of failed therapies from antidepressants is extremely high in CYP2D6 UMs because the drugs have no effect unless administered at super high doses and most physicians are not aware of the CYP2D6 UM anomalies thus are not willing to administer remedies in the high doses necessary.

    These gene tests seem to be gaining popularity, so there is hope for us UMs although, I don’t like the side effects from the super high doses that are necessary… I may need to stick with natural remedies… and do like I have done all my life, just don’t get sick and or have a super high tolerance to pain and learn to live with it, in lieu of being called a drug monger, or addict. Even the dentists have called me a lier, saying there is “no way” you still feel that… Honestly, why would I lie to the dentist? It would have been nice to have these test results to stick in the A** H*** nurses face after I woke up the morning after a serious car accident from which I had a compound fracture repaired the night before. I was in SEVERE pain and the nurse told me to shut up and that I was on a morphine drip so could not have pain… Funny thing is, Morphine might as well be water to a UM. And don’t give us Codine… it very possibly could kill us as it turns to super high doses of morphine. Go figure…

    I hope this was helpful, your not crazy…

    • FriendofCats says:

      Michael Jacksons pink elephant took dxm recreationally and at 150mg had signs of slight CYP2D6 deficiency as motor control was impacted strongly but head clear but almost on verge of second plateau at a higher range of the 1st plateu dose by weight. But Michael Jacksons pink elephant also takes codeine and as far as she is aware her reponse to codeine is about normal and it does relieve pain at the stated doses, not exactly indicative. What recreational drugs (i.e above medical rec doses )shuld MJPE take to work out for sure if their CYP2D6 is slow or normalish and if it may be their CYP2A enzyme that is slightly slow or non active rather than their CYP2D6 or if conversely their CYP2D6 is slightly slow but their CYP2A is slightly fast… Micahel Jackson pink elephant is as much intrested in this from a scientific point of view to roughly work out their rough different enzyme abilities as they are to try recreational doses.

      • Arden Poirier says:

        I am missing the cyp2d6 chromosome also and i had cancer in my uterus, ovaries, lymph nodes was suppose to be 1 surgery, asshole surgeon cut my ureters off ,cut nerves and 12 repair surgeries and im in bad pain and I am on minimal pain meds and always still in pain. I’m pissed bc a doctor fucked me up and it is not fair i have to feel like a pos bc thats how they look at you.

    • Bruce says:

      I had a gallbladder attack and the ER doctor gave me the recommended dose of painkiller. I told him I was a URM and needed to increase the dosage. It wasn’t until he spoke with my doctor that I finally got relief.

    • Candice Sundkvist says:

      Hi. This is so wierd. I feel like im talking to myself. They have drugs for that but they dont work on me. Hahaha. Ive been on exsira a low dose first time ive ever been on a low dose of anything and its working well. I use toplep for pain and migraines and fibro and finally im ok. I ever woke up halfway through surgery once. So yes i get the stupid dentists thing. I was on oxy and that was a joke did nothing.

  6. julie says:

    Thinking I may be a high metabolizer but not sure. I can’t take any type of opiate (I’ve had several surgeries to come to this conclusion) morphine made me hallucinate(I was told I was quite hilarious of course I have no recollection) and pass out so that pca pump was not needed, hydro’s, vicodin, percocets they all make me deathly ill talking instant puke. I was on straterra at a pediatric dose for my adhd and it knocked me out, couldn’t stand up, had to hold the wall to walk to bed. Dextromomethorphan (DM in cough suppressants) causes me to vomit like a person who just drank while on antabuse. Claritin makes me look like I am on cocaine (I’m a psych nurse I’ve seen it all). I would presume since all side effects occur in 30minutes or so I am an ultra-metabolizer? However Benadryl has no ill effects on me. I can take it and it helps allergies but doesn’t knock me out. Background- White living in North America, 5ft2in, 110lbs. So what medications do I need to avoid if an ultrametabolizer? Substrates, inhibitors? Any info appreciated.

    • Debra says:

      Julie, I believe you need to ask to have your chromosomes tested. Your symptoms do not sound like any Ultrarapid Metabolizer symptoms I have ever heard of. Actually you sound more like a poor metabolizer in some circumstances, however not all of the scenarios you have described would fit that either. I have found a doctor who actually loves working with me/ testing me and then being able to discover how my body will react to certain therapies. He does this because he wants to be aware and be able to help others similar… altbough, he will not run across many like me, it’s the fact that he sees the many anomalies and uses them to help not reject his patients. I hope you can find a great one as well.

      • Kate says:

        I can’t find a doctor now that mine retired. May I ask whom you found? How you found him?
        I need a doctor asap.
        I have painful pleurisy – will last 4 weeks they tell me at urgent care….and no one to treat me… I’ve fired or been fired by more doctors than I care to recall

        Its horrible as we all know, to be treated always like an addict when we can’t even get addicted

        • Quin says:

          I got my test done at the psychiatrist; who wanted to know what effect I would get by mixing the drugs that pain management were giving me with an increased antidepressant.

      • FriendofCats says:

        Michal Jacksons pink elephant took 150mg dxm and lost all her motor control but was still thinking clearly this was after around 4 hours.Psychoactive effects where neither lower or significantly higher than normal. MJPE can drink a lot of alcohol for 62kg 5ft 4
        and only uses alcohol every 2nd week on a saturday yet high tolerance of around 20 units 5-6hrs to get drunk 24-25 to be sick, more again to get as drunk as MJPE’S much taller friends. MJPE was once in hospital, eventually morphine did cause the odd mild hallucination, wasnt instant it was ongoing admin over hours that caused it by IV.
        Codeine appears to work about normally. All this makes for a mixed picture.
        What’s the bet on MJPE’s CYP2d6 status? Whats the bet on MJPE’S CYP2A status?

    • Kate says:

      I don’t think you’re an ultrametabolizer…. I think you’re deficient! You don’t have the enzyme to utilize the meds so you get sick. Also, you might have combination of other enzyme deficiencies like I do. Get tested for pseudocholinesterease — an enzyme that helps break down Esters. My dad was deficient, he had similar suffering. I am an UEM, it takes a boatload of narcotic for slight pain relief. When having surgery the usual general anesthetic meds don’t work they have to also give that poisonous gas…
      Bad news
      Plus I can’t find a doc who knows of this or believes me when I tell them.. I never know how to handle that… it makes for never having adequate pain relief.

  7. Glenda Alexander says:

    Ijust found out that I am a Ultra Rapid METABILIZER, after years of nothing working on me for pain and other disorders.I have had a Thoracotomy with a lung removed and ribs.I have been on everything you can name to no prevail.I worked in the medical field most of my life.There is no use to go to the ER BECAUSE THEY DO NOT UNDERSTAND.it took years for my doctor to figure this out.He did a DNA and found it out.I have a pain pump in with Fentanyl in it and also take Percocet.I might as well take a baby aspirin.Maybe some day they will be able to do something about it,meanwhile I guess we will have to live with the hand we were dealt.

    • drfreddy says:

      Ask your doctor for a written certificate, unless you haven’t already. To show the staff in the ER for example. It is quite rare, and must be horrible, to be “immune” to all kinds of pain medication. Are you sure your current pain is nociceptive (traditional), and not neuropathic? Sufferers of neuropathic pain often get little or no relief even from strong opiates. Have you tried Lyrica (pregabalin), for example? I am not a medical doctor, so don’t take this as medical advice, but in your shoes I would ask my doctor for a neuropathic pain evaluation. Nerve damage is not unheard of after major surgery.

      • Kate says:

        How do you find a doctor who understands and agrees to treat this?

        • Quin says:

          They are specialists in Pain Management. You usually need a referral to one, and in the USA they test you for drugs at every visit. But they do understand the ultra/non-metabolizers, the difference between pain from a source, pain from a nerve pinched somewhere else, and pain that doesn’t have a cause but hurts anyways.

          Me, I’ve got some pinched nerves and some pain that is a result of more than 10 surgeries. My pain specialists never doubted me, since I had more than 20 years of doctor’s notes where I complain about pain and they look for it without finding a physiological problem to ‘fix’. Don’t expect the same, expect instead that they will have you tested for drug use, and send you for a CAT/MRI/PET scan to look for a physical problem. But they do know how to treat it even if they can’t find anything obvious.

      • Arden Poirier says:

        It is awful and so much pain from the botched cancer surgery, and to make it worse missing that chromosome makes your risk of cancer drastically higher.

  8. Jonny C says:

    I was a pain patient in Pittsburgh for 22 years and was on 390mg of methadone after taking blood tests to prove that I could metabolize 200 in under 4 hours. Codiene doesn’t work for me, I’ve been given
    12x10mg tabs with no effect. Right now I’m on 120mg of morphine 3x and 120mg of roxycodone every 4. I still feel pain, and I’m not remotely feeling these meds (not that I want to I just want to be out of pain) I do take 4 x 500mg of the most powerful nsaid, with some help. I’m called a super metabolizer, by the docs I’ve seen, but I can’t get into another pain place.

    It’s unfair that we have to live with pain beside of pressure on doctors to not write for us. I guess
    If we are all ultra rapid metabolizer, we should join together and protestor our cause.

    • Glenda says:

      I’m with you Mr! None of my Doctors understand or want to even try…. they make you feel like you’re only trying to seek out drugs, only because of all the drug abusers out there. so the rest of us that aren’t seeking them for their reasons (just to get high)We are in serious cronic pain, as for my self I have a pain pump in my back and had taking just about all you can take for pain that would killll a normal person. I had a DNA ran under my Doctors order not mine. I AM a URM. My liver eats up not only pain meds, but just about anything I take. No wonder people like us get so depressed. These Doctors need to do more research on this!!!!! We need HELP with our pain!”just saying”

    • Arden Poirier says:

      I’m a rapid metabolizer also and I am so fucking sick of being looked at like a drug addict, I just wish I never had cancer surgery and died.

  9. George says:

    Ultra rapid metabolisers will get more pain relief and more chance of euphoria from the oral medication. The clue is in the name, if you metabolise something you are breaking it down. Codeine needs to be broken down to work. And it’s broken down into morphine. This is what provides the euphoria and pain relief. If these pills have no effect, you have a CYP2D6 enzyme deficiency. This is why you get no pain relief.

    • Kate says:

      This is incorrect. UEM metabolize so quickly narcotic never gets a chance to connect to the receptor site.

      • Quin says:

        Depends on the opioid narcotic. Codeine in all it’s forms need to go through the CYP2D6 or CYP2D7 enzymes to be turned into morphine (and other junk) and work. After that, morphine works until the liver gets it again and the UGT2B7 and UGT1A1 cleave it into glucronides that can then be processed and excreted in bile.

        I say this as a 2D6 ultra-rapid metabolizer who has been researching how this affects me. If someone is getting no benefit from codeine I would first guess a low metabolic rate on 2D6; but if morphine didn’t work either the guess would have to switch to a high rate on one of the UGT pathways. Methadone, tramadol, and fentanyl all avoid any secondary pathways, and avoid the CYP2D6 and UGT pathways and may be drugs available to someone who gets no relief from codeine/morphine/dilaudid.

        • Erin Herold says:

          QUIN! You will be a LIFESAVER to so many people!

          I only wish that I had seen your post 14 years ago! (lol)
          I’m a CYPpie who has ZERO response to any of the codeines, “laughing gas,” etc., and am wicked allergic to morphine.

          However, fentanyl patches worked pain-wise, but with the adhesive and EDS, it caused the skin around and underneath the patch to blister and erode. Tramadol worked for a long time until my body caught on, and now Methadone is 100% a savior!

          It’s such a frustration with docs who think they know everything and insist that dilaudid will “do the trick” for post-surg pain – even when you have explained the CYP issue to them.
          After all, PTs can’t know about their OWN BODIES, right?!

          Methodone, which I was slightly reluctant to try simply for the – I don’t know – ?stigma? – had been my personal Godsend.
          It works, no brain fog, and IT WORKS!
          Did I mention that IT WORKS FOR CYPPIES?!!!

          Outstanding, informative, and easy to understand post, Quin – thank you so much!

  10. Glenda Alexander says:

    Morphine or Lyrica neither one work on me and tobacco makes things worse. I am trying to quit, but it is about the only thing I can do when I get anxious from the pain. The m.d. said it breaks the medicine down too fast. Good luck everyone.

    • glendaalexander says:

      I am o negative.What does that mean?

    • Jamie says:

      Your so right Glenda. I have cypd26 genotype. Had the test also. They swabed the inside of my cheek. I was just taken of butran patch 20mcg and put on zohydro and it don’t do crap for me. Called the dr left a message and said it doesn’t help at all. So I’m thinking I don’t matabolize it.

    • Jamie says:

      This does suck by the way. Even tho it shows my dr I don’t metabolize opiates they still keep me on the norco and I eat them like candy. They had me on 8 a day until they put me on zohydro bumped me down to 4 a day which isn’t working. Still in pain.

  11. Anial says:

    In reply to Debra,
    Funnily enough, I have substantial reason to believe that I am a extremely poor metablizer. I get intended and side effects from various mental health and pain medications (which are notoriously involved in CDY2DS), even at the lowest available doses, sometimes in under an hour. These have included some serious effects such as palpitations and extreme nosebleeds (from citalopram) and a hysterical cry-laugh-cry state from amitriptyline which felt like I had just drunk 50 coffees. The result is ultimately the same; I can’t have medication. Full stop. Some GPs have accused me of making it up. Others have been very understanding (to be fair you can’t fake many of the side effects so they all should be understanding). I think it basically boils down to whether the GPs are informed or ignorant about the vast variation (up to 1000 fold in some cases) in metabolizer ability for certain drugs derived from certain genes.
    However, I just wanted to voice on here that us under and over metabolizers are essentially in the same boat, because medicine still only caters for the average.

    • Debra says:

      Anail, you are so right. In my research I have found much more information about poor metabolizers because PMS make up about 25% of the population whereas UMs… 1%. In my opinion, from what I have read, it is much more dangerous to be a PM because you can OD without knowing it and there are physicians who will continue prescribing higher doses b/c of a lack of response as oposed to testing the patient for genotypes. Although testing is incressing, I am shocked at the lack of medical professionals who are chosing not to educate themselves about the different reactions caused by genotypes which would make them more comprehensive as a person who supposedly went into a profession to help people. Thank you for your response. As we, UMS and PMs continue our dialogue and begin to be card carrying geno-atypicals, hopefully we will be taken more seriously and not treated with such disrespect

      • Devin says:

        I am a poor metabolizer but have faced depression and suicidal thoughts since I was a teenager. (the way I found out I had this condition was when NO medications were working and were actually making the condition even worse.) I have been trying to do so much research but do not know what to do in my case.

        • Susan says:

          Devin, have you gotten any relief from your depression through medication since this post? My 16 year old daughter was tested and she is an Ultra Rapi Metabolizer. We have been completely unsuccessful in getting her relief from her depression.

          • AJ says:


            I’m a UM. After trying SSRI’s and having a bad reaction to tamoxifen that was related to switching SSRI’s and, and.. anyway, I fell into the hands of a psychiatrist who did the cheek swab on me, and we discovered this. She switched me to an SNRI (pristiq) and this has worked better (meaning I notice if I don’t take it, and things are better with it).

            In the interest of full disclosure, I also take methylphenidate (ritalin) (*SUPER* small doses) morning and afternoon for chemo brain/menopause/undiagnosed-ADD, and clonazapam (sp?) at night to help with anxiety.

            This “cocktail” has worked wonders for me. I hope your daughter is as lucky as I eventually was and finds what she needs!

            Hope this helps!

          • Bruce says:

            Devin, You are not alone. I have to take mega doses of Pristiq for it to be effective.

  12. Anial says:

    P.s. George it depends on drug action.
    Metabolism (which is defined in science as the sum of all chemical reactions in an organism; including both anabolism building molecules, and catabolism breaking down molecules).

    Further, some drugs are activated by breaking down, whereas some are inactivated by breaking down, and some are make more removeable (e.g. easier to excrete) by breaking down, whereas some are made less so.

    So being an ultra/poor metabolizer has different effects on different drugs. Please don’t over simplify it, as you may actually confuse people reading this, who have problems they are trying to understand.

  13. Anial says:

    Sorry for typos no glasses on.

  14. Liam says:

    I’m completely unresponsive to Paracetamol, Ibuprofen, Aspirin, Naproxen, Amitriptyline and Cyclizine. I go into respiratory depression if I’m given opiates such as Tramadol, Morphine, Fentanyl and Codeine, and the former two make me extremely physically sick and give me headaches unlike any cluster I have ever had. My mum is the same. I swear we must be Ultrarapid CYP2D6 metabolisers but I’ve only just found out about this so I haven’t had a chance to ask my doctor yet.

    Needless to say, I have had some weird experiences. In the ER last week, I got a disbelieving look when I said that I don’t respond to any ‘normal’ painkillers (they probably thought I was looking for a high) but then I was faced with a look of confusion when I rejected opiates! They gave me Entonox but I felt like I was losing control of my body and worst of all my breathing so I quickly put an end to that. They tried IV Paracetamol in a drip which had no effect at all, and then resorted to Codeine which worked (of course) until my BP and RR fell and I began to feel very sick.

    I don’t know…should I get checked for CYP2D6 ultrarapid metabolism or is it just me?

    • Quin says:

      Yes, get checked if you can. That depressed heart and respiration rate at a ‘normal’ codeine dose is a trademark of ultra-metabolization on CYP2D6.

      Other common symptoms of URM that I’ve learned: benedryl causes hallucinations, so do almost all old antihistamines. An adult dose of detromethorphan cough syrup is an invitation to see the walls bend and change colors. Lots of older antidepressants (prozac, paxil, effexor, and others) cause withdrawl daily.

      • Jo says:

        Happy to find this info. I’m starting to look into having my daughter tested because she’s Ethiopian and 30% of Ethiopians are Ultra Rapid Metabolizes. Interesting that you say that about dextromethophan cough syrup. When I was a child I had some crazy hallucinations after taking Vicks44DM. I’ve never taken it again. I also metabolize anesthesia at the dentist, requiring several injections (for a root canal) and usually reaching the “max” dose. I’ve been prescribed hydrocode afterwards, but only ever take a half of one that day because they make me really loopy. I seem to have a pretty high pain tolerance. I’ve never had any surgeries or serious pain issues, so I have no experience with other meds.

      • Sandra says:

        Glad to see this. My 3 year old was bouncing off the walls last night after a normal dose of Benadryl. Then when he finally fell asleep, he was very restless, twitchy, and saying a bunch of weird stuff if I woke him up to check on him. He’s taken Benadryl before and I thought I noticed him being a little hyper. It never made him sleepy. However, last night, it was VERY obvious. He went from feeling bad and being lazy to full blown jumping on the trampoline and turning flips 35 mins. after taking the med.

  15. Bronwyn Maddison says:

    Hi!Am from Australia & have not heard of anyone else with this problem,just that my dr says I have it,& have actually felt really victimised & traumatised by the attitudes,as described above,by ignorant medical staff.So am pleased to connect with some others…..however it would be good to hear from anyone from down here,especially re ANYWHERE that does understand the problem?I suppose the first step is getting the test done.Am just about to have surgery & feel a bit scared re how “the mix” is going to go!

  16. Kathy says:

    Hi, my name is Kathy and I’m an ultra-rapid metabolizer… Kind of makes you feel like you are introducing yourself at an AA meeting of sort! 🙁 But yes, this is what I am and it does SUCK BIG TIME!! As like previous writers have written, doctors just blow you off and think you’re a drug-addict looking for a fix… GODS!! I wish that were the case!

    Also, if you guys don’t already know it, it’s hereditary, so chances are your children also have the same problem with medications that just don’t do what they are suppose to. All that happens is that my liver breaks everything down super-fast and I’m basically peeing out pure morphine or whatever, without getting any of the relief said medications are suppose to deliver to your system. Add to that, I have life-long PTSD and same goes for those medications.

    Something that makes life really a pain in the A** at times, is the fact that both of these conditions trigger WILL each other… Chronic pain, will worsen PTSD as well as depression, anxiety etc. etc. etc… and the other way around…

    I have now FINALLY 20 years later managed to get my doctor as well as my psychiatrist to send in the necessary paperwork to get ALL of the tests done to PROVE that I am in fact an ultra-rapid metabolizer… Will in no way recommend HOW I managed to get them to understand that I am telling the truth and not just out to get multiple prescriptions of drugs that don’t work anyway. I sat in my doctors office and just told him ok, now WATCH CLOSELY…. I poured 10 pills of 100 mg Tramadol retard/similar to Oxy, a synthetic morphine (the strong, long lasting ones)into my hand and swallowed them before he could react… He of course hit the alarm button but over here in Sweden at least, they are not allowed to treat you if you are conscious and refuse treatment. So they are legally forced to wait until you are unconscious… I sat there in front of him and told him that if I in any way or form become either unconscious or “high”, you have my permission to do whatever you want… 1 hour later and one wide eyed doctor, he wrote the necessary paperwork for me to get a TOTAL evaluation on WHY my meds don’t work. Was it dangerous what I did? of course it was! But if I don’t get any form of relief soon, I will end up killing myself… Not intentionally but mixing and matching all sorts of stuff, just to get at least 5 minutes of relief… :'(

    But… I also have a son which also suffers from PTSD, as well as the same freakin chronic back-pain I do and he is going through the exact same crap from the doctors. So, if for no other reason, I want my son to be able to get the help he needs and not have to cope with both pain and anxiety the same as I do everyday!

    So, did I get high or affected in any way or form from the handful of pills I took, that SHOULD have knocked an elephant out… Nope, didn’t phase me at all, which was the point I was aiming to prove and yes, I even drove my car home after the doctors appointment… One good thing more that came out of this whole ordeal, I know have a doctor that is highly motivated in LEARNING more about the various mutations on the CYP2D6 gene….

  17. HelenR says:

    Hi, just wondering if anyone can recommend which company they used to get tested?

  18. Kate says:

    I have this condition – the UEM on CYP2D6… How can I get tested so I have something to show MD’s (as if that will help anyway because I can’t find an MD replacement who has ever heard of this!! My rocking MD retired)

    Can anyone share where I can get tested – preferable online/mail in…

    Can anyone share where I can find an MD who is even vaguely familiar with this or thinks outside the box enough to manage this?

    Previously I had to go out of state and I will again to get the right care.
    I have this plus other enzyme deficiencies making my life hell with regard to any kind of medical care.

    • Quin says:

      Psychiatrists and Pain Management specialists have access to a cheek swab test. As far as I know it isn’t something you can get over-the-counter and test yourself for. But my psych was glad to run the test since it would also affect what antidepressants I could take.

    • abrahim says:

      I don’t know how it is in the US, but in Canada they are some companies that offer this type of testing. A quick google search for pharmacogenetic testing canada gives you some companies such as medcan, geneyouin, medicnematch, dyncare – and you can easily order online too

    • Jane says:

      One company that does this is called Genelex, at genelex.com. They’ll send a free packet to your doc with cheek swabs and return envelope, you do it in the doc’s office and the doc sends it back to them. Both you and the doc get copies of the report. It may or may not be covered by your insurance; you have a better chance of getting approval if you have a history of adverse drug reactions. If it’s not, you can pay out of pocket. But you need the doctor’s order to get it done. (I have no financial connection to this company, I just happen to know two people who used them — feel free to look around for others, of course.)

    • Bruce says:

      Have you been successful in finding anyone who is willing to help you?

  19. Jonny C says:

    I finally found a doc to help me and just as l got up to 1Gm morphine and 80-120mg Oxycodone every 4-6 hours, my f-ing insurance disembarked me. I was cooked.. I’m now on subutex 120mg most day until Sept 1….i feel you all.. We need to do something. I’m tired of ER DOCS calibre me a seeker! That’s fucked!

  20. Don says:

    Codeine causes nausea and hydrocodone makes me feel like Mike Tyson hit me in the gut, so a doctor told me to list them under allergies on medical forms. In 1991 I had a C section and awoke with a patient regulated morphine IV in my arm. Soon the anesthesia wore off and the tremendous pain hit. I pressed for a dose of morphine and nothing happened. My pain grew worse and worse. I then just kept pressing frantically and nothing. By then I was off the pain scale charts when a nurse came in. She gave me a dose off morphine through the IV herself and nothing happened. She left and hurried back with a shot of demerol which immediately started easing the pain. I don’t understand why codeine and hydrocodone make me sick when morphine did absolutely nothing…it might as well have been water!

  21. Don says:

    Don = Donna.

  22. Blanche says:

    Interesting site and as I had a glimpse here a few months ago when preparing for some surgery I think it could be interesting if I post me recent experience.

    Having learned my lesson with Dextrometorphan (Bexin) and every cough-remedy containing codein I avoided this stuff for all my adult life until about 10 years ago I got an attending pharmacist who for ONCE listened carefully and could explain the different metabolism-types to me. He also mentioned to me to be careful with other opioids, but as I never needed strong painkillers I probably forgot about that and also made no further research on the issue. Then once I got Tramadol from a dentist and it nearly knocked me out. You know the stuff; suppressed breathing, extreme nausea, cold sweat and to make things worse: no pain relief at all. Thank god that only lasted for about 20 minutes, then I felt as before, took some Mefenamic acid (Ponstan) which brought the searched for pain-relief. It was then that I remembered that talk with the pharmacist but again saw no reason to react until recently I was facing some surgery and thought it necessary to adress my suspicions of being an ultra-rapid metabolizer to the anaesthesiologist. Well, I thought I made everything right; he understood emediately as a professional but also as he’s got an ultra-rapid metabolizing dog. But he also said that he would put an opioid called Petidin together with some strong drugs against nausea in reserve which should be bether tolerated (at least by his dog). Just in case, no need to worry… We agreed for a spinal anaesthesia with no suplementing sedatives and I really had absolutely no worries when entering the OR that morning, feeling perfect during the surgery and was in really high spirits when I got in the recovery room and the nurse informed me that she would give me now some Ibuprofen and as a substitute for the opioides a Metamizole- infusion, a substance which is btw. banned in many countries…
    Still all was well, until I got back to my room, and the operation surgeon warned me on his visit not to take the pain easily and ask immediately for some more painkillers if it started to rise, as otherwise it could endanger the healing process. I then told him that I was afraid of the use of opioides and he answered, that there was still the Metamizole – then he saw the infusion, frowned and told me: that, as this has been the maximally allowed dose, there was not much to chose from now on. The day went on, the pain increased and the nurses pressed me to give in and let them use the Petidin. As expected that was no good, the first few doses had no effect as a painkiller, but I got nice waves of sickness… Then I called for the anaesthesiologist which was of course not the same I talked the whole matter through. She offered me to use Morphine instead, no effect again, but also no side-effects… An hour later the pain still increasing I called for her again and she offered to block the affected nerves as a final solution, but that this was quite unusual and not good for the recovery of the tissue. So not a real option then… I had then some morphine in regular intervals with no effect at all, but as the night went on the pain really got too strong and finally I gave in as a nurse explained to me, that with some people they had to reach a certain level until it started to work. So I got that medications against nausea and dose after dose of morphine in 10minute intervals both intravenous and subcutaneous. Actually after about the 8th or 9th dose I started to feel a certain damping effect on the pain. It didn’t go away, but seemed to be like something further away and not so direct. Not bad – but by then I also started to notice the first signs of nausea. I refused further doses but the following 8 hours were awful, I never ever felt so sick in my life. I was just lying as still as possible, breathing very low, and even the slightest movement of the head or someone bumping against the bed triggered a stormy ride an a rolling ship, I even reacted on lights going on and sudden noise. Slowly it got bether and from the moment I was able uplift the upper body a bit the puking started. Sounds awful, but was in fact a relief as from then on only a slight sick feeling remained. So Fazit: Morphine can have some pain-reliefing effects when highly dosed, but for me it is only a very poor solution. At least I know what I’m going to face next time (and unfortunately there will be a next time…) and maybe this new information also helps an able anaesthesiologist to determine the optimal therapy…. But on the other side, there seems to be a growing number of people aware of our problems, at least compared to the time I first started to talk to my GP or pharmacologists about it 15 years ago…

  23. Jo says:

    Hi all, it’s confirmed that my 6 yr old daughter is a CYP2d6 Ultra-rapid metabolizer.I’m doing tons of research, but not finding much info. She has a dental procedure coming up, so I need some advice. Will Lidocaine (and similar local numbing agents) work on her? If not, what is the alternative? Dentist typically prescribes Tylenol with Codine for pain management after the fact, but I said no to that. So frustrating how little info there is. I really don’t want her to have a painful/traumatic experience. 🙁

    • Lorraine says:

      I’m an ultrametabolizer (was just officially tested this week). After years of passing out or having breathing probs after getting numbing agents or gas at dentist’s, I found a dentist who believed me when I said I was super sensitive. Find one of those, someone who listens. Someone who will go very light with meds. For pain: I’ve been ok with Ibuprofen, a quarter dose. I used an entire Ibu when I sprained my ankle, one, one time, and I’m not one who likes to suffer it out. I’ve been in touch with siblings who also confirm that about a quarter dose is plenty. I’ve checked out some lists of affected meds and haven’t seen lidocaine on the list, but I haven’t studied all the info out there. I’m currently studying mindfulness meditation for pain relief. Perhaps your daughter would benefit by that, it’s a good life-long tool.

  24. Peri says:

    Thank you so much for this page – I just got my DNA results back and I have major SNP’s in CYP2D6, CYP2C9, CYP2C19, CYP3A4 (homozygous)COMT, MTHFR C677T homozygous and more. I am on morphine and swear I do not feel it whether they increase my dose or turn it down – same pain level just the same. From what I read about phase 2 meds….is it possible I have trouble with morphine? Seems like Morphine is one of the drugs they recommend for folks with SNP’s? I seem to be a poor metabolizer and possibly rapid metabolizer in several areas. A LIFE full of over-reactions and under-reactions….now validated. But cannot figure out the morphine issue and doc cannot understand why I am on such a high dose and report high pain. (major nerve damage from back surgeries, 11 years now.) Thanks for any help.

  25. Pat Damico says:

    I have been DNA tested and I too I problems with Doctors saying they understand the issue and that they will make adjustments to my pain melds post surgery. Right! While I suffer the Doc then just tries different things to no purpose. Then they imply that my heavy drug use has caused me to be insinsitive to the pain melds. As all of us know, most CYP2D6 people take very few drugs because they simply do not work. I did get a Doctor that has a wife with the same kind of issues and he worked with me. Turns out Talwin, which is a very old school drug actually works at a half dose.

  26. Cynthia says:

    I was DNA tested at a former pain clinic, came back as an URM. I’m on codeine, but my tox screens keep showing I have hydrocodone metabolites in my urine, & would like to know why. I’m giving some history here, please bear with me.
    I’d been on morphine for a decade, began self-inj 9 of those years, the only way to get any relief. That clinic closed, went to another & was given Opana (20 mg 12-HR, which gave no relief. They gave me 3 morphine IR/day, which worked better. Then had a false screen for cocaine (I’m on 4 different BP meds, I’m not about to use it at my age!), I was discharged & had to find a dr fast. The one I’m going to now is an injection-freak. She wanted to burn nerves, I said NO! I think if she had her druthers, she’d spend all her days shoving needles into spinal columns. I did get Botox for migraines 2 months ago, it’s already wearing off. I have Imitrex injections & discovered they provide a rush like nothing I’ve ever had before! Think that’s why insurance only allows 2/month -if word got out on the streets, they’d be selling it on street corners!
    I’m also bipolar, & can’t take the regular meds (had NMS & Strvens-Johnson syndrome), so take Neurontin (not metabolized in the liver), Trileptal, Buspar, Primidone (also have CVS, Cyclical Vomiting Syndrome, which is treated with Primidone, a combo of 2 barbiturates). Also on the 4 BP meds, plus diazepam & triazolam. I take Benadryl, which doesn’t make me sleepy -has the opposite effect.

    I’ve tried just about every pain med out there. The oxy-anythings have me bouncing off the walls, can’t stand that. Make me want to crawl out of my skin. Hydro-anythings are a little better, but not much relief. Tried fentanyl patches, no help at all.
    Dilaudid was ok (if injected), but the coming down takes no time at all. 3 hours of relief, then suddenly the pain is back full-force.

    So, all I’m on (pain-wise) is codeine & Excedrin (I add Primidone, as that’s the combo in fioricet/codeine). Still, have a lot of pain, have 1 torn & 4 bulging disks, fibromyalgia, stretched ligaments (so bones, especially my knees, will pop out of joint), Osteo AND Rheumatoid arthritis, spinal stenosis, migraines, diabetes (with severe neuropathy), as well as the other conditions I mentioned. This pain dr says I cannot possibly be in enough pain for anything stronger than codeine, tramadol, or Butrans (tried it, no relief). My PCP told my yesterday to find a different pain clinic, but with more & more shutting down, or becoming franchises (so if you’re discharged from 1, you can’t get into another in the same chain, they won’t see you).

    Another question – Benadryl doesn’t make me sleepy, but when it wears off I start yawning like crazy. I’ve tried googling that, but no answers. Also, why are my tests showing hydrocodone? (The CYP2D6 wasn’t my only anomaly, I have several others) Would it be more beneficial for me to remaine on the codeine or ask for tramadol?

    • Nancy Cramer says:

      My doctor told me to take Tylenol PM to help me sleep at night after knee surgery. It affected me opposite, like I had 5 cups of coffee! I couldn’t get to sleep until 3:00 am!

  27. Brittany says:

    Hi Im Brittany, I am a URM, i have had almost every pain med and depression med tested and none work. I have had the feeling og hydrocodone and oxy didnt work all of my life. The first time at 12 with my first surgery, tonsilectomy. They gave me hydrocodone and i cried for a week. I remember it all. I kept telling my mom the pain meds isnt working and nothing being able to be done… fast forward to me today, im constantly in pain and my pm keeps telling his np im to young for high levels of fentayl… i had 3 back surgeries and a 6mm kidney stone last year. i have not found ONE drug that works yet 🙁 also usually URM dont get any relief bc its out of your system before you can feel anything, so maybe the OP is a poor metabolizer which puts more of the meds in your system for a od.

  28. Bruce says:

    I am a URM and require a mega dose (off-label) of Pristiq to control my clinical depression. I was fortunate enough to find a psychiatrist who knew about URM and was willing to prescribe the dosage I require. He has just retired and I’m in search of a new doctor. Every time I go to see a new physician as soon as they see the dose I’m taking they tell me how dangerous it is and they refuse to take me as a patient. I’ve been on this dosage for over 3 years and have no ill effects. I have blood work done and everything is in the normal range. My BP runs in the 120/80 area and that is without and high blood pressure medication. It’s frustrating and scary because I NEED that dosage to totally control my depression. Through research, it is my understanding that a doctor can prescribe a medication off label if in their opinion it will be beneficial to the patient and do them no harm.
    Any suggestions or feedback would be greatly appreciated.

  29. Seanchai says:

    I’ve been a URM all my life, the number of medications that effect me with a normal does is less than 10%. I now suffer from Chronic Tendonitis and finding the medication that would dull the pain is Nil, how ever there is a medication that does lower the pain levels 2-3 places downward so an 8 or 9 day drops as low as a 5 or 6, the amount I have to take suck because I also have A.D.D. so when medication does work often the side-effects are reversed, so things like Morphine give me a mild high where most of you get sleepy I develop Insomnia.

  30. S. Mom concerned says:

    I think you need to be careful giving advise about 2D6, my daughters was diagnosed at 4yrs old. And a Codine caugh med put her into a morphin based comma. She could not be woken. She was unresponsive. After hours in the children ER, a spinal tap, and gene testing…..we found out of the 2D6 RM. And found out it is geneticly inherited thru myself and my mother. My mother later was also tested and treated for her cancer focussed for her genetics.
    People if you believe you have this condition…..please please ask a Dr to test you. It is NOT to be messed with. Today my daughter who is now 11yrs old was in the ER….and even through I told the staff about the 2D6…they stillgave her a medicine that is NOT allowed for her condition.

  31. Jerold says:

    I, too, have just become aware of this. I have had drug screens in the past come back negative for oxycodone which was puzzling to me. I take anywhere up to 30mg of an evening for severe refractory restless legs (and arms) syndrome. I have been puzzled by the fact that the effect of controlling the unpleasant (and indescribable to someone that has never had it) sensations last for less that 90 minutes and often much less rather than the 4-6 hours I am supposed to have. I am a person in recovery, so I am very careful using this class of drugs. I was in the hospital last week and again had a negative drug screen within a few hours of taking 20mg of oxycodone. I also have never gotten the undesired buzz from it despite taking the entire 30mg within an evening. Is that also an observation in a rapid metabolizer?

    My sleep medicine doctor wants to put me on Methadone. In light of this new fact about being a rapid metsbolizer of oxycodone, will I have the same issue with Methadone?

    • Bill W. says:

      Yes, unfortunately. Though CYP3A5 directly effects methadone more so than the CYP2D6, you will probably still suffer the same affect with methadone.
      You might want to consider having your genes mapped. It might help your Dr’s. in knowing more so what to prescribe and at what levels and how often.

  32. Stephanie says:

    I am a ultra rapid metabolizer and my dr and I have been trying to get my dosage right on my adderall. I use to be on 3!e30 mg adders a day before I had the test but the psychiatrist just decided not to prescribe that any more do I went back to 2 30 mg a day which was horrible and would not stay in my system long at all. I had the genetic testing done and my family dr mov e me up to 3 30mg a day which I’ve been in before and it doesn’t last me. I need to find a psychiatrist who will do 4 a day so I csn run my business and work and take care of just everyday task. Have you ever heard of someone getti
    G 4 30mg a day and any suggestions on what to do to get a dr to prescribe those besides the proof from the test.

    • Anita Rønning says:

      I just red you askes of adderal.
      Hav you found any medisin that workshop for you.
      I am a UM CYP2d6 and have Adhd.
      I try to find how to dose Aduvanz.
      Anita Rønning

    • Anita Rønning says:

      I just red you askes of adderal.
      Hav you found any medisin that workshop for you.
      I am a UM CYP2d6 and have Adhd.
      I try to find how to dose Aduvanz.

    • Debra says:

      I found the side effects Gato be too extreme at the high doses that it took to help with the ADHD. Was not worth it.

      • Debra says:

        Oops, delete “Gato”

      • Anita says:

        Hi, thank you for the answer. Can you please tell me more about how to found out how to get information? Have you found any medicine that you can use? What about the bad symptoms when you use medicine, can you explain me more about how you feel it? Do you know anyone that can more about this? Hope for you to answer my questions, or anyone else that have found information about UM Cyp2d6 and treatment for ADHD?

  33. Bill W. says:

    I have had my genes mapped as a test participant at my Dr. Office. I AM an ultra-rapid metabolizer of CYP2D6 which affects both codine and morphine.
    Although, both take affect much more rapidly than in the average person, that affect does not last very long either. Taking an extended release form of the drug helps some, but not a lot.
    Unfortunately, most Dr’s. are hesitant to prescribe a higher level of a drug just because you are a ultra-rapid metabolizer. SO, long story short, I do not achieve the relief that a normal netabolizer by this gene would.
    I cannot take a higher dose, I need to take a regular dose more often, this too is out of the norm for most Dr’s. to prescribe…

  34. Mark says:

    I’m 68, with treatment resistant rapid cycling/mixed state bipolar, along with non-restorative sleep and non-combat PTSD. I suspected, several years ago, that there was something malfunctioning in the way I metabolize drugs. My new psychiatrist wants to do genotype testing. Along with all psych meds and sleep meds, I can’t tolerate pain meds and have minimal tolerance of alcohol. Ironically, if I inject too much rx testosterone at one time, I can smell it in my urine, so I need to inject small, daily doses and even with that, I overaromatize it to estradiol. Whether one is a URM or a PM, life becomes quite difficult when you can never find the right balance.

  35. […] Life as an ultrarapid CYP2D6 metabolizer. F. von Hieseritzky. Synthetic Remarks. […]

  36. Sarah Rimkunas says:

    I think it can be confusing as many doctors don’t even know all that much about this. It is very complex. For ultrarapid metabolizers, particularly children, a standard dose of codeine (such as that typically given post tonsillectomy) can be a fatal overdose because of its rapid conversion to morphine. So, it is far more complex than the need for more painkiller or painkillers don’t work. If you show evidence of metabolizing CYp2d6 in an unusual way, the best bet is to get genetic testing. A wide variety of pharmaceuticals are processed by this enzyme including many psychiatric medications. Also, while ultrarapid metabolizers are quite rare among White people of European Descent, for other populations such as North African and Middle Eastern persons, this mutation is MUCH more frequent like 30%.

    • CKavanagh says:

      Agree. I can’t get a doctor to look at the report. I have basically been told years ago before 3 recent spine surgeries, I have bad DNA, bad genes and bad bone and that I just have to live with it! in the end, the report validates that I am medication resistant so I guess I do have to just live with it! But I keep trying to find effective pain management in hopes of a better quality of life. 25 doctors in 2 years and no further ahead, actually a step or two back.

  37. Dark Web says:

    Thanks for sharing this.

  38. Michelle says:

    I just found out I am an ultra rapid metaboliser after years of not understanding why almost all medications leave me with nothing but side effects. A codeine tablet for example can keep me up all night, and its not a fun experience.. its amazing to actually find out why this happens to me!

  39. Nancy Cramer says:

    I guess I’m a rapid metabolizer.Normal doses of pain med just so-so. I’ve had 2 total knee replacement surgeries. If I request more pain meds my doctor looks at me like I’m a drug addict. I never take any medications. Can’t take NSAIDS. They all give me stomach issues.

  40. Amy kelly says:

    I am a UMR verified. I have cyclic vomiting and extreme pain nothing seems to work. Any suggestions on depression meds as well? Have other tried high levels of thc to see if it effects you as it should? Is there a book I can read?

    • chris says:

      I hate being a 2D6 Ultra Rapid Metabolizer(also am a 2C19 and 1A2 rapid metabolizer). Wellbutrin-XR should work for depression. Avoid all SRI’s, they’ll likely give you flu-like symptoms.

      • CKavanagh says:

        Over 25 years I have tried Prozac, Effexor, Paxil (hell of a withdraw when discontinued) Cymbalta and Bupropion (aka Wellbrutin) Also tried a long list of analgesics, antidepressants, anti-seizure meds, opioids, CBD,OTC vitamins and minerals.
        Finally did the Pillcheck Pharmacogenetic test last January after being accused of drug seeking behaviour.I am an ultra rapid metabolizer CYP450 pathways for most analgesics, antidepressants, opioids…
        Wishing you luck finding pain management!

  41. CKavanagh says:

    Tried it all!
    I am an Ultra Rapid Metabolizer to CYP2D6, CYP2C19, CYP1A2,CYP2B6,CYP2C8, CYP2C9, CYP3A4, DRYD, OPRMI(decreased sensitivity to opioids)Morphine/hydromorphone ineffective in pain management but affects mental health – hallucinations/delirium.
    I am interested in how DNA affects our body. After years of taking various medications offering no pain relief and being accused of drug seeking behavior, I decided to take the Pillcheck Pharmacogenetic DNA test last January. My suspicions were verified! The pharmacist opinion letter reports that I am an ultra rapid metabolizer for most common medications and have a decreased sensitivity to opioids. Even medications listed as normal metabolization are ineffective. I was told I need extremely high doses and may never find an effective dosage risking overdose. I am forced to live with chronic pain – osteoarthritis, advanced degenerative disc disease, tarlov cysts, fatigue, hot flashes day/night, no energy, low mood, irritability. I also took the Puregenonics DNA test and it was reported I have some nutrient issues, vitamin deficiencies (B12 listed but bloodwork normal, high insulin fasting, GGT now close to normal(I don’t drink but have NAFLD)) iron overload and low dopamine; however, I eat healthy and exercise. I found if I take supplements and vitamins I get increased diarrhea and bad odor on skin – especially my hands, and my mental health declines. There is no change on constant physical pain no matter what I try to do. I have been told that I have bad DNA, bad genes and bad bones and that I just have to live with it. I have unexplained physical pain. My diagnoses are Osteoarthritis, Myofascial Syndrome, Somatic Pain Disorder, possible Ankylosing Spondylosis. Alternative therapies have also been ineffective – PT, OT, Chiro, Massage, Acupuncture, Dry Needling, Heat Cupping, TENS, Nerve Block/Trigger Point, Naturopath. A lifetime of pain and trying to find effective pain relief (I am now 54), 25 healthcare professionals in the last 2 years following 2 spine surgeries and no pain management. Is my chronic pain rooted in my DNA and there is not enough research to prove this to the healthcare professionals?

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  44. Mayah Beeson says:

    Hello, my pain doctor told me I’m a super absorber. I overdosed on 1/4 dose of vicodin as well as tramadol. I recently took a 1/2 dose of benedryl and felt drunk. Is that a Ultra Rapid Metabolizer problem?

    Also, 2 of my three children react to all antibiotics. One of them has a strange reation to Tylenol since birth. She goes unconsious and is unresponsive. Doctor diagnosed as a seizure but she only gets it with tylenol. It happened as a baby and again in late teens when a boyfriend gave her tylenol for menstrual cramps by mistake. Same exact thing. Out cold for about an hour. Anyone know why that would happen with tylenol?

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  47. Santay says:

    Hi DRFREDDY, I’m so glad to come across this post. Why don’t doctors know this stuff? Three days ago I had total hip replacement surgery. I had told the surgeon at my pre-op visit that from previous experience I know that the only pain reliever that works for me is hydrocodone. I told him a DNA test years ago indicated that I was a “super-uptaker” (as the doctor doing the tests at that time called it). My surgeon wouldn’t even let me get the words out, he was so totally uninterested. I persisted – could he give me hydrocodone? He said if the other drugs didn’t work he could give me that. So here I sit at home with Tylenol 3 and Tramadol. The Ty3 makes me a drooling idiot until I fall into a heavy sleep and wake up later with every muscle aching from lying in one position. The Tram, I may as well not even take it. Absorbine Jr works better, and it’s a derivitave of horse liniment. (Actually, it works very well for sore achy muscles.)I don’t know why hydrocodone works, but it is amazing – no pain, but not slobbering on myself. There were two enzymes that the doc who did the dna tests circled on my report. I don’t know which ones they were, but it finally made sense when she told me about it. I am so mad now. The surgeon bald-faced lied to me. When I called the surgeon’s office this morning to ask for hydrocodone his answer is that he NEVER prescribes it. I’ll give his name here because I’m so mad: Dr Daniel Vande Lune, Sun City Orthopaedics in El Paso, TX. I’m madder that he lied to me than I am for not getting the meds. I have spoken to several friends and acquaintances who have had similar surgeries, and most of them were offered Oxycodone after the procedure. Oxy makes me feel like I’ve had a dose of LSD. Am I crazy to ask for hydrococone? If you are looking for a doctor who will take you seriously and do the testing necessary to find solutions to your health problems, I highly recommend you see a holistic doctor. The one I went to years ago is Kari Rollins, DO, in Fort Worth, TX. PS I suffer from depression and over the years have tried many drugs and combinations. Effexor 75 mg seems to work now.

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