Why am I immune to all medication?

June 2, 2012 1:37 PM

I have been almost immune to most medications for as long as I've been taking them, particularly pain medications, anesthesia, anxiety medications, benzodiapines, and psychotropic drugs (this one is iffy because sometimes they don't work on people anyway). I feel literally nothing even on high doses. Wtf?

Asking for a friend:

"I have been almost immune to most medications for as long as I've been taking them, particularly pain medications, anesthesia, anxiety medications, benzodiapines, and psychotropic drugs (this one is iffy because sometimes they don't work on people anyway). I feel literally nothing even on high doses. I required more anesthesia for my first surgery when I was a small child than an adult male brain surgery patient and my body continued to move around after my mind was unconscious. I then regained consciousness. Many similar incidents have happened since. I have ruled out tolerance because the given medications don't even work the very first time I take it. Data points: I can smoke a million joints and not get high, but eating weed makes me really high. I get inebriated easily from alcohol. The same exact drugs that don't work in pill form even crushed up through a J-tube work much better (but still not to a normal level) when I receive them intravenously. I'm thinking I must be missing receptors in my brain, at this point. Is that something that can happen? If so, can anything be done to fix/regulate/stimulate receptors/something? I've heard the hypothalamus can be related to this - any legitimacy to that? I need quite a few medications for serious medical issues and I'm starting to feel completely hopeless. I've tried taking them on an empty stomach, full stomach, with lots of water, everything I can think of. Can anyone please suggest anything?"

posted by jitterbug perfume to Health & Fitness (21 answers total)

This is a question for your doctor. If you have already discussed this with your doctor, what did they say? If you have not discussed this with your doctor, why not?
posted by jessamyn at 1:46 PM on June 2, 2012

Response by poster: I don't know what kind of doctor to discuss it with. A neurologist? My GP has no ideas or suggestions. My psychiatrist says I must not have receptors but offers and possesses no further advice. That's why I'm asking here... like, who do I even ask? If the receptor thing is true then it seems neurological but if not then that seems not the right path.
posted by jitterbug perfume at 1:54 PM on June 2, 2012

Response by poster: Or maybe if anyone has any personal experience with this.
posted by jitterbug perfume at 1:55 PM on June 2, 2012

I know someone who is resistant to morphine - he makes a point of having that in his medical records since its potentially life-threatening. So it can be a real medical condition.

However, "I can smoke a million joints and not get high, but eating weed makes me really high." strongly suggests to me that a lot, if not all, of this is entirely in your friend's mind. I've met a few people who make the same claim and they obviously aren't inhaling properly.

If your friend is concerned about potential complications from medicinal ineffectiveness, definitely bring it up with the family doctor (if available, respected, and trustable) who can then make recommendations or even referrals to specialists.
posted by porpoise at 2:16 PM on June 2, 2012 [5 favorites]

Do you happen to have red hair? I am a redhead and need a LOT of anesthetic when I have had any sort of surgical thing done. Its a known phenomenon that (I think) has something to do with melanin affecting receptors.

I am not a scientist/doctor.
posted by joan_holloway at 2:35 PM on June 2, 2012 [4 favorites]

Do you, or have you ever had, any naturally red hair, any place on your body? The rs1805007 mutation causes some strange interactions with drugs that people can view in all sorts of ways until they know for sure what is happening.
posted by jwells at 2:37 PM on June 2, 2012 [1 favorite]

Get a liver function test done.
posted by gorcha at 2:49 PM on June 2, 2012

I'm not a doctor or scientist. Your mention of anesthesia and pain meds made me think of a friend of mine who's got Ehlers-Danlos Syndrome. Some of her symptoms/complications include resistance to local anesthesia and requiring more powerful or larger-dose (I'm not sure which) of pain meds. I'm not suggesting you have EDS necessarily, just that there are things that can turn off or reduce a medication's efficacy.

I would ask for a referral to a neurologist; even if the cause isn't based in neurology, I'm betting s/he would have better specialist recommendations than your GP.
posted by asciident at 2:52 PM on June 2, 2012

porpoise: "However, "I can smoke a million joints and not get high, but eating weed makes me really high." strongly suggests to me that a lot, if not all, of this is entirely in your friend's mind. I've met a few people who make the same claim and they obviously aren't inhaling properly."

For what it's worth, I know someone who has this "problem," and it's not an inhalation problem. She also finds opiates to be less effective than Advil. Lidocaine works, but only in extremely high doses. She's about as far from redhead as you can get.
posted by wierdo at 3:13 PM on June 2, 2012

I will also echo that your friend should seek professional advice from a physician. There is not enough information here and in your friend's situation, advice from a random stranger on the interwebs is going to be almost useless.

However, if I were your friend, I would talk to the treating specialists/physicians and candidly discuss with them the perceived lack of efficacy of the medication.
posted by scalespace at 5:21 PM on June 2, 2012 [2 favorites]

I have similar issues in some ways - needing more anesthesia to knock me out than was anticipated, Advil works MUCH better for me than codeine but both Nyquil and Dramamine knock me out like I weigh about twenty percent of my actual mass. Just tell your doctor; this isn't completely insane and is absolutely something a prescribing physician should know about.

And don't eat or smoke marijuana while taking other prescription drugs (or at least let your doctor know what you're doing.) Because that kind of behavior could potentially mess with what you're taking (so can, for instance, taking Vitamin C.) Always, always, always make sure there's at least one medical professional who knows all the stuff you're taking, including supplements and recreational substances.
posted by SMPA at 7:26 PM on June 2, 2012 [2 favorites]

My aunt is like this; She has woken up during surgery twice after having a huge amount of anesthesia to finally knock her out. Klonopin does have an effect on her, though.
She started having this issue after dealing with liver issues (was an alcoholic for 30 years).
posted by KogeLiz at 7:59 PM on June 2, 2012

Response by poster: From my friend:

However, "I can smoke a million joints and not get high, but eating weed makes me really high." strongly suggests to me that a lot, if not all, of this is entirely in your friend's mind. I've met a few people who make the same claim and they obviously aren't inhaling properly.

No, this is legit actually. Consuming marijuana is way different than smoking it. You can tell the body receives it differently just by the high. And just for the record I'm not on here to complain about not getting high, but I use cannabis for medical purposes and felt this was relevant info.

And don't eat or smoke marijuana while taking other prescription drugs (or at least let your doctor know what you're doing.) Because that kind of behavior could potentially mess with what you're taking (so can, for instance, taking Vitamin C.) Always, always, always make sure there's at least one medical professional who knows all the stuff you're taking, including supplements and recreational substances.

My doctor does know what I'm doing as far as this and it was his suggestion - I had never even tried it recreationally. My GP as well as every other doctor I see has a full detailed list of everything I take, prescription or otherwise (like supplements or herbs).


If your friend is concerned about potential complications from medicinal ineffectiveness, definitely bring it up with the family doctor (if available, respected, and trustable) who can then make recommendations or even referrals to specialists.

Already did this :)

Sounds like I need to look into liver issues. Also, yes, I am a bright redhead.

Does anyone know of any other diseases or conditions - like the one mentioned - which make one need more medication or have a tolerance or not have receptors, etc?
posted by jitterbug perfume at 9:01 PM on June 2, 2012

An enzyme known as CYP2D6 can affect your ability to metabolize various drugs.
posted by Serene Empress Dork at 9:44 PM on June 2, 2012

You could be what's called a "fast metabolizer", ask your doctor about this.

One of my doctors mentioned this when I was having similar issues with various drugs he was prescribing. Relatedly, the one time I had surgery I ripped the anesthesia tube out of my throat when I came out from anesthesia faster than expected.
posted by volition at 11:43 PM on June 2, 2012

This is genetic. Basically different polymorphisms within genes for things like CYP enzymes (things in your liver that break down drugs) or neurotransmitters change how your body processes various chemicals (food too). Pharmacogenomics is a term you could look up to find out more about this, nutrigenomics is the food focused counterpart. This also is what volition is referring to as a 'fast metabolizer', that term is actually so general that it's meaningless but the idea is that you metabolise some drugs faster because of a specific polymorphism in the relevant gene. (e.g. I have the 'slow' version of CYP1A2 that processes caffeine so one cup of coffee keeps me awake for up to 12 hours).

Being a red head means you already likely have the rs1805007 polymorphism mentioned upthread that affects anaesthetic and pain response, you may also have other variants that are contributing. Checking your liver function is a really good idea to make sure there isn't something systematic going on too.

I'm not surprised the doctors aren't helpful, there is still a lack of understanding in general medicine about these effects even though genetic variation can contribute a really gigantic amount of how different drugs work in different people. To be fair, this is largely because there is still so much we don't know and research is still relatively new in this area. Without well validated genetic tests and phenotype/genotype correlations there isn't much a doctor can do anyway, but it should be well known by your medical professionals that some people just don't respond to chemical intervention in the same way as the general population.

Assuming liver function is good and the red head thing isn't enough to cover your response, you might be able to find a research group investigating this stuff who can either tell you more or who is interested in finding more about you (e.g. a group doing genotyping of relevant populations). It's outside my field so I don't know who researches this stuff, but look around in the literature if that's something you may be interested in.
posted by shelleycat at 2:46 AM on June 3, 2012

Response by poster: There are a ton of helpful suggestions, thanks so much, if anyone has any more please still post them. A few questions:

About CYP2D6 - is there a way to know if this is an issue? If it were, would it be overproduction of it, or?

About the rs1805007 polymorphism - Is this literally only in redheads?

voliton - What did they end up doing to help you, if anything?
posted by jitterbug perfume at 4:14 AM on June 3, 2012

I required more anesthesia for my first surgery when I was a small child than an adult male brain surgery patient

Although it is hard to know what this means without knowing a lot more detail ("anesthesia" and "brain surgery" are very broad terms), it is a little known fact that young children are relatively insensitive to inhaled anesthetics (as measured in units known as MAC) and the sensitivity increases with age (all other factors being equal). This is discussed in some technical detail here.

The same exact drugs that don't work in pill form even crushed up through a J-tube work much better (but still not to a normal level) when I receive them intravenously.

This is to be expected in everybody, due to first-pass metabolism.

Finally, given that your friend had surgery when very young, has (or had) a j-tube, and has been on a large number of different medicines means that there are all sorts of possible interactions that may be going on between his medical condition(s) and multiple medicines. Polypharmacy can be a real problem if he doesn't have one physician and/or pharmacist looking at all his prescriptions and monitoring for interactions. Finally, as mentioned above, he does not sound like someone who should be drinking or smoking pot. I generally have an open mind toward both activities, but adding two more drugs to this mix (pain medications, anesthesia, anxiety medications, benzodiapines, and psychotropic drugs) only complicates the picture.
posted by TedW at 6:26 AM on June 3, 2012 [1 favorite]

About CYP2D6 - is there a way to know if this is an issue?

It's probably due a genetic polymorphism so you find out by genotyping. Same goes for the s1805007 polymorphism and any other one that might be relevant. Small changes in amino acid sequence can change the structure and/or chemical properties of proteins making things like their enzyme activity or signalling action more or less efficient. Turns out those changes can sometimes be really pharmacologically relevant (and quite often totally inert, heh).

Of course, there are huge numbers of enzymes working at all kinds of levels and we don't even really know the full extent of genetic variability present, let alone how they all interact to affect phenotype, so it's pretty complicated. And, as TedW points out, administering multiple medications is complicated as it is. Genotyping may or may not be worth doing depending on the state of current knowledge and whether it would change your treatment anyway, but definitely do some reading about the red head thing at least since that seems pretty likely to be relevant here. Plus it's cool.
posted by shelleycat at 6:57 AM on June 3, 2012

My Mother in Law has similar problems with anesthetic and pain killers. They had to give her a huge dose of anesthesia when she had her hipped replaced and the only pain killer she could take that did anything while recovering was Tylenol. The doctors could not pinpoint why she was having the problems, but she has had several major brain surgery for neurological problems and while it had been a bit of a problem before there was a dramatic increase in her resistance after her last brain surgery. So your friend is not alone, I would seriously suggest they speak to a doctor about it, his family doctor or GP would be where I started.
posted by wwax at 1:08 PM on June 3, 2012

> About the rs1805007 polymorphism - Is this literally only in redheads?

That's hard to answer. I was a redhead as a child but the hair on my head looks brown now, unless you catch it in the sunlight. My beard has some red and blond though, and I have the mutation. Hair is weird like that. It changes so often that even the genes don't tell the full story. So it's probably safe to say the mutation coexists with red hair, but one doesn't necessarily lead to the other.

Also, be careful of what you read. Studies tend to focus on only one thing or another, and miss the larger picture. Weirdly, dentists seem the most knowledable about red hair and drug effects, thanks to this. Mine perked up and told me about the study when I mentioned that my hair was red as a kid. I had a cavity, and due to the study they used so much Novocaine (w/o epi) that my nose went numb. Very weird not being in pain for it. I guess that's a little like what non-redheads experience it like.
posted by jwells at 8:17 AM on June 4, 2012