Some People Get More of a Kick From Opiates Than Others

The strength of opiates varies from person to person depending on individual genetics as describe below.  Doctors assume that they are ‘tipped off’ to narcotic abuse when a patient says ‘codeine doesn’t work for me– I need vicodin’.  The more we learn about opiate metabolism, the more it appears that doctors may be making a mistake and under-treating pain in some individuals.  The following case illustrates that point and also discusses opiate tolerance.

A patient question:

hi doc,

I have been on suboxone and was doing fairly well, despite chronic pain issues and trying to find alternative ways of dealing with migraines and fibromyalgia.

a week ago,,, (details of injury removed for confidentiality). my prescribing doc said it was fine for me to use pain medication but would need a much higher dose. so i am taking like 1o dilaudid suppositories a day to just keep the discomfort level down, with no feeling of being high, other than light withdrawals when it wears off during the night.

i am planning to return to suboxone as soon as possible, but on the other hand, am not so great at handling pain. i know once i return, it is pointless to use opiates. btw: i was using as much ibuprophen as i could tolerate but ended up with wicked stomach cramping despite eating with my pills.

this might sound strange, but dilaudid suppositories are the only opiate i have ever been able to tolerate without feeling absolutely bat poop crazy. my addiciton kicked full force in after a medication switch this past spring to opana, having used dilaudid for years as prescribed. i ended up snorting the drug, for some ungodly reason that i rationalized that i needed a stronger route of administration. its just the addict in me that suddenly wanted to be totally high, as opposed to just pain free.

my question is this: my tolerance is obviously high since being on suboxone. will it suddenly drop once its finally out of my system? i am hoping to only be on pain meds for a few more days. i just don’t want to end up being left in pain…

what are your thoughts. i feel ok for the most part, like i said, the opiates are working for pain, but in twice the amount i have ever used when i was actively on opiates. (i was always under doctor’s care, and for a few years, the opiates actually improved my quality of life, being pain free, until i decided to abuse them.

i am currently in out-patient treatment…



My Response:

That is interesting that the dilaudid suppositories are the only thing you tolerate. The rectal route of administration does provide a more potent way to get things into your system. The small intestine blood supply drains into the portal vein, which carries absorbed substances directly to the liver for destruction or metabolic processing; the distal large intestine blood supply drains into the systemic circulation, avoiding what is called ‘first pass metabolism’ by the liver.

I looked up dilaudid out of curiosity and found a couple interesting things… Vicodin or ‘hydrocodone’ is metabolized by an enzyme in the liver called ‘P450 2D6’ to form hydromorphone, or Dilaudid. Over the past 10 years or so we have become more aware of the genetic differences in drug metabolism; these differences can effect potencies of various narcotics in certain ways, explaining why some narcotics work in some people and not in others. For example codeine is metabolized to morphine; I read a study some time ago that reported lower enzyme activity in African American patients. The result is that codeine is a bad choice of pain reliever in those patients. I am sure many times when minority patients tell their doctor that ‘the pain meds aren’t working’ the doctor assumes that the patient is abusing them– when in reality there are reasons that they may not be effective. Morphine is metabolized in varying degrees in different people to a substance that is 50 times more potent than morphine, some people will have much more profound analgesia with morphine than other people will.

Demerol is well known for causing toxicity– the breakdown product is ‘normeperidine’ which is a neurotoxin that can cause seizures. Dilaudid also has a toxic breakdown product that can cause seizures– hydromorphone-3-glucuronide or ‘H3G’. It increases over time, and is thought to reduce the analgesia caused by Dilaudid by acting as an excitatory substance in the brain. Taking Dilaudid by suppository is probably much safer than orally, as you avoid the direct path to the liver where that substance is formed.

OK, enough tidbits… It takes much longer to get buprenorphine out of one’s system than people generally expect. I have had several patients who stopped Suboxone for surgery, and even after a week opiates are blocked to some extent. By ten days, though I would expect the buprenorphine to be gone for the most part. The opiate potency of buprenorphine at the ‘ceiling’ dose is equal to about 30 mg of methadone. This in turn is comparable to 10-25 mg of Dilaudid. These numbers can vary in different people but they get us to a ballpark estimate of your tolerance– if you are used to Suboxone, your tolerance would be equal to what you would get taking 10-25 mg of Dilaudid every 6-8 hours. In other words, that amount of Dilaudid will get you to the ‘break even’ point, and higher doses would be needed for analgesia.

Most of the opiates that people commonly use for pain work at the same receptor in the brain and spinal cord, called the ‘mu receptor’. They are all ‘cross-tolerant’ meaning tolerance to one equals tolerance for all. So the answer to your question (finally) is that no, your tolerance will not drop as the Suboxone leaves your body (it is probably already gone). The reason is because the activation of the receptor caused by buprenorphine is being replaced by activation of the receptor by Dilaudid. Your neurons don’t know the difference– the receptor is activated to varying degrees by all opiates, and the activation results in different amounts of a ‘second messenger’ substance created by the portion of the receptor inside the neuron. The neuron ‘doesn’t know’ if the increase in amount of ‘second messenger’ is from a more potent opiate or from higher doses of the regular opiate.

Tolerance and withdrawal are closely connected; as one reduces tolerance, withdrawal symptoms occur. You can’t have one without the other, and the reverse is generally true as well– whenever a person is in withdrawal, the person’s tolerance is in the process of going down. Likewise when a person is ‘high’ or free of pain from injury, tolerance is always on the way back up again. Some day there will be meds to block tolerance– there were clinical trials of ‘morphidex’ some time ago that failed– although I don’t know in the long run if such a discovery will be a miracle cure for pain and suffering… or the end of humanity as we know it.

Take care, and I hope you recover soon.


A Reply to Chronic Pain:

I feel that I have a good understanding of suboxone…. With the exception of the pain issue. The reason for my lack of confidence in that area is because first, I have seen less-consistent results in pain patients, and second, some of the claims made by patients just don’t make sense!
Suboxone has several characteristics that make it different from opiate agonists (like oxycodone); the ‘ceiling effect’ combined with the long half-life results in a very stable subjective experience—there is no up and down, but rather there is a constant level of opiate effect over time. Tolerance occurs very rapidly—that is a good thing for addiction treatment, as the person taking suboxone feels ‘normal’ within a few days. But just as the person becomes tolerant to the sedation, respiratory depression, and other side effects of buprenorphine, I would expect tolerance also to the analgesic effects. So theoretically it should not be a good pain drug because the rapid tolerance would eliminate the analgesic effect after a few days.
In reality, though, patients will claim relief from suboxone for an indefinite period of time in many cases. I have no explanation for such an effect; perhaps it is all a placebo response, or perhaps (more likely probably) the pain control system is much more complex than we imagine. The other odd thing is that pain patients will often claim that the analgesic effect of buprenorphine increases linearly with dose, without reaching a ceiling and leveling off. That makes no sense to me either—the analgesic effect of opiates occurs at the mu receptor, which is the site where buprenorphine binds as a partial agonist, and so the ceiling effect should apply to the analgesic actions of buprenorphine. I suspect that in this case the placebo response is the reason for the patients’ perceptions.
Suboxone certainly has advantages over other opiates, if it is found to be effective. The tolerance with buprenorphine is limited, whereas the tolerance to a pure agonist has not limit—so there is a lower amount of withdrawal if/when the drug is eventually discontinued. The stable blood level prevents the temporary ‘highs’, the miserable lows, and the cravings that can accompany the use of agonists. The patient feels much more clear headed on suboxone compared to opiate agonists. And suboxone can be dosed once per day, which has a couple effects—first, it just is less trouble to take, but more importantly the absence of ‘as needed’ dosing all day long will help prevent the patient from focusing as much on the pain.
As far as the personality effects… many people have told me that suboxone seems to work as a ‘mood stabilizer’—they feel less labile, more regular, and generally a bit happier on the drug. There are case reports of opiates treating depression or precipitating mania, but buprenorphine doesn’t seem to push people to euphoria, but instead seems to ‘level’ their mood. Maybe that is what you have seen in your friends. I think that part of the effect relates to cravings; cravings can manifest as mood symptoms, and as suboxone eliminates cravings, it also eliminates some of the mood symptoms. This raises the issue of whether buprenorphine should be used to treat mood disorders… and for that I will leave the readers to do their own research. A couple years ago there was an article in Elle magazine by a woman describing her treatment of depression using suboxone. I do not know of any large clinical studies that support such use at this point.
Chronic pain is a very difficult issue, and I wish you the best. I encourage you to avoid opiates as much as possible—there is generally little future in opiate treatment of pain, since tolerance always chips away at the effects of the opiate over time. I am sure that at some point we will have ways to prevent tolerance, which would be quite a thing for people with chronic pain. On the other hand I can imagine many dangers associated with such a discovery. Thank you very much for your question; I am going to go ahead and post on my blog, , and on the forum at (without your real name).

Why Not Just Take Narcotics for my Chronic Pain?

I received a letter today– a person discussing the use of opiates by a family member with chronic pain.  I was not sure if the letter was asking questions about my opinions, or was instead arguing that my ideas were off-base.  In either case it is worth publishing, as several topics are discussed.  As per usual, the names were blocked to keep things confidential.
Here it is, with my answers:
Why is it wrong to take pain medications for pain?  Especially if you have INTRACTABLE CHRONIC PAIN.
Medications for pain are not ‘evil’—the only way I approach the issue is from a quality of life position.  There are many problems with pain meds as they are now.  At some point I expect we will find a way to avoid tolerance to opiates—that will truly revolutionize pain treatment.  But as things are now, tolerance is the basis for the problems with chronic use of narcotics for pain.  Any person taking narcotics, either for pain or for ‘fun’ (although there is nothing fun about opiate dependence after the first few weeks), will become tolerant to the effects.  The medication will become less and less effective, requiring increases in dose to get the same pain relief.  The dose cannot be increased forever—eventually the patient would be chewing on pills every minute of the day—and so the doc must limit the pills.
If I give enough medication to satisfy a person who is 40 yrs old, what will I do when the person is 42 years old?  Tolerance develops very quickly—this leads to tension between doctor and patient, and eventually the patient takes too many and asks for early refills.  This annoys, angers, or frightens the doc, who therefore eventually stops the narcotics or quits seeing the patient.  The patient, meanwhile, thinks he is being deprived, and gets mad at the doc, mad at all docs, and mad at the world.  Finally, pain meds get inside the head of everyone who takes them, whether they are being taken legitimately or not.  The patient becomes more and more focused on the meds, getting the meds, the pain, and the withdrawal.  Relationships suffer.  Depression develops.  The patient eventually becomes a one-dimensional shadow of who they once were, where the biggest relationship in the patient’s life is the relationship with the pain pills.
I have seen this all happen many, many times, with every patient who takes narcotics.  I do treat with opiates, but I do tell the patient all of this, so they understand what they are taking on.  This is why opiates are always the last resort.  Any good pain doc will tell you that they have seen patients who complain of terrible back pain, who ask for narcotics repeatedly and think they need them…  who get detoxed for some reason and after getting past the withdrawal are surprised to find that the pain is gone, or very small.   I have seen it many times, and I cannot explain it, other than the body trying to trick the person into thinking he needs pain pills as part of an addictive process.
For cancer pain, by the way, none of this is relevant—with a limited life span the doc should just give what is needed to control pain.  But for non-malignant chronic pain, I have never seen opiates improve a person’s quality of life in the long term.  And I have seen many lives destroyed.  The patient may not see it—he may insist things are great on the pain pills, even as his marriage falls apart and his kids disappear.
Why would you want to withdraw, if the pain was being controlled and it lowered your blood pressure?
We have plenty of ways to lower blood pressure—narcotics should never be used for that purpose, except in the case of acute myocardial infarction, when morphine has a number of helpful effects including lowering blood pressure.
What if the patient was limited, and could not do alot of physical therapy to get the benefits of endorphins to work for them.
Patients can do much more than they think with physical therapy.  They need to be taught patience, and they need to work at it every day at home—not only at the therapy center.  Physical therapy is so valuable—but patients generally look for short term solutions.  That is unfortunate.  As far as endorphins go, I caution people against getting wrapped up in thinking about what their brain chemicals are doing.  It is much more complicated than magazines suggest–  endorphins, for example, do many things besides pain control—including things that have nothing to do with pain.  Yes, they have been shown to be released by exercise, but… so what?  We don’t know if that release actually does anything helpful for people.
Like you said, there is a difference between dependency and addiction.  My family members suffer from chronic pain due to chronic pain conditions, that we were either born with or developed.
There is a difference early on, but over time the differences go away.  A person who I see for a congenital pain condition who takes loads of narcotics has very few differences with a person who started pain pills ‘for fun’ and who takes tons of narcotics.  If anything, the addiction is worse in the pain patient, because they are convinced they need the pills, and cannot see the destruction they are causing.  A person who starts ‘recreationally’ is more likely to truly hate the pills, and is often willing to go to greater lengths to get off of them.  That person hates the pills, where the pain patient thinks he loves them.
So, intervention should come, if I am just lying around getting HIGH in a chair, like the rubbish I have been reading
I don’t know what you mean by this sentence.  If you are referring to addicts as ‘rubbish’, you are off base.  Yes, some addicts have bad characters, just as some non-addicts have bad characters.  It sounds like you see a difference between ‘good people’ on pain pills and ‘bad people’ on pain pills.  That difference does not exist.  Over time, any person on pain pills becomes a slave to them, and desperately wants to be free from them.  For some people, it takes longer to seek freedom; some people never seek it.   I can assure you, though, that opiate addicts are not sitting around enjoying themselves—not after they have been doing it for a few months.  They are scrambling for money to get something to avoid being sick—stealing, prostituting, whatever.
OR should it be, I take the pain meds, and I can walk around in the house, function a little better than suffering in pain.
That is your decision.  But it is more complicated than you would like to believe.

I wish you the best, and hope things work out.