Chronic Pain and Methadone/Opiate Pain Management

Dr. David Arneson, N.M.D. (Naturopathic Medical Doctor) Chronic Pain and Methadone/Opiate Pain Management Methadone (dolophine) is a synthetic long acting morphine (Last updated on 8/1/08)

I’ve decided to write a few words about this subject since it seems that I’m spending and inordinate amount of time responding to the unfortunate that have found themselves in this impossible situation. There will some who think this is the answer—more so because they have been told this is the answer to their long-term problems. It is interesting that of the in-house patients that I have detoxed from methadone, and all manner of opiates, those put there for pain management, a full 85% are out of pain within 3-6 weeks after their last methadone/opiate dose. It is also true that there are some that can be on opiate therapy for years and it seems to continue to work for them. These words are not meant to convince anyone that they should, or should not be, on pain medications. If it works for you over the long term and your physical ailments are irresolvable then by all means do what needs to be done. Yet there seems to be more questions than answers involving pain management. So this small addendum is an educational forum, if you will, on what is known and unknown about this subject matter. All these facts are documented in current literature.

First of all, Methadone, as well as all opiates, have a caustic, negative affect on what is called the hypothalamic/pituitary/adrenal axis…it also acts as nor-epinephrine and serotonin reuptake inhibitor in the brain not unlike being on a anti-depressant or other psychotropic drug for months or years. Literally what this means is that methadone negatively affects all hormone/neurotransmitter driven systems in the human body/mind…especially negatively affected is the adrenal glands—located on the superior margins of each kidney…all this leads to the cardinal symptoms of chronic fatigue, depression, anxiety, and other related symptoms. In other words, ALL methadone patients suffer from chronic adrenal fatigue. In addition, since methadone has a negative affect on the production of neurotransmitters, ALL methadone patients will eventually suffer from depletion of neurotransmitters and the receptors that these neurotransmitters work on leading to chronic depression and anxiety. More importantly, since sufficient amounts of serotonin are needed to block the production and release of a brain molecule called Substance P—which positively affects the pain pathways—methadone users will suffer increased levels of pain over the long term…eventually leading to more methadone which eventually just makes things worse for the patient. In my clinical experience treating methadone patients detoxing off the drug…when using focused high dose amino acid therapies to rebuild the serotonin and dopamine circuits…I find that a full 85% of these patients are pain free in 3-6 weeks…it is an extremely rare case for the pain not to diminished greatly in the others. This includes all fibromyalgia cases that have been put on any class of opiate therapy for pain. The reason for this is clear. One cannot make more serotonin with anti depressants such as Prozac or others of their class—and methadone certainly causes these negative affects on brain neurochemistry. When one is depressed over their emotional/life conditions, due to the chronic pain, or because of on-going caustic drug therapy—the traditional treatment is an anti-depressant. Anti depressants DO NOT MAKE MORE serotonin, dopamine, norepinephrine, or epinephrine. Initially, they just move around what you have…and the patients is more than likely already depleted or low on these vital brain chemicals…these drugs only take from one place and put it in another. Fundamentally, all this does is set up the mind to try and reach some sense of normalcy. The DNA is the master blue print—it is set up to keep things in some set of boundaries so survival is optimized in each human being. In a normal functioning human brain neurotransmitters are released from one nerve (into what is called the synaptic space) to interact with the receptors on the next nerve and than reabsorbed with in manners of micro seconds (150-250 one/one thousand of a second). When any drug, or situations occurs, that impedes this process the mind reads this as having too much neurotransmitter. When this happens the brain starts producing a molecule called monoamine oxidase which breaks down the “excess” serotonin or dopamine (both are monoamines). Since dopamine is the precursor building block for nor-epinephrine and epinephrine these neurotransmitters also get down regulated. Why this doesn’t make any sense to the standard medical profession defies all logic. Yet these types of therapies are all they know. It is sad the in most of these cases they do more harm then good. The answer for the majority of patients facing these issues is simple—nutritional biochemistry.

The lack of interest and the basic ignorance of good oral nutrition by the “best medical system” in the world are beyond belief and comprehension. The only way the body/mind can truly heal, to the level it is capable of healing itself, is by the very nutrients you take in everyday. This is not discounting that some have genetic problems severe enough to require modern chemistry. We see these people in crisis management and typically they are danger of self or the community at large. As was stated earlier, 15 % of the patients on a particular psychotropic probably need to be there. The other 85% need other alternative therapies. Yet even in those that need chemical therapy it rarely works well. We managed, more that anything, to utilize the medications as chemical straight jackets. And rarely do we even consider nutritional therapy. In my four years working with the severely mentally ill in crisis stabilization I never once saw a person allowed to do a multiple vitamin with the exception of the occasional pregnant female who was allowed folic acid. In fact, if the patient came in with vitamins there were ceased as contraband and return only on their discharge from the facility. There are cases where supplementing a B-complex vitamin has totally reversed the symptomlogy of bi-polar disease. There are studies now that show the addition of Vitamin B-12 and folic acid makes Prozac more effective in those that don’t respond well to the medication. The question should be why we didn’t start with the B-12 and folic before the Prozac since it is common scientific knowledge that deficiencies in B-12 and Folic are found in some cases of depression.

Methadone, as with any opiate, negatively affects critical physiological processes in other organ systems in the human body. One of the most negatively affected organ systems is the gastro intestinal tract. Normal gut function does not exist in a methadone treated patient. It matters not whether this is treatment related to opiate drug abuse or treatment related to chronic pain or post surgery. Methadone also slows heart rate and therefore decreases blood flow through the GI tract. If the GI tract is fundamentally unsound how does one absorb the necessary nutrients needed for repair to take place any where else in the body—or the mind? I’ve seen opiate therapy patients that have gone through back surgery where the primary incision takes months to heal—a process that should be completely in 10-14 days at the maximum. As long as one is on opiate therapy (methadone or otherwise), these physiologic processes will NEVER work at their optimum. So if we truly want to treat the deficiencies than we need to understand one thing clearly…like the house that has been damaged in the storm we need the proper building and repair materials. The body/mind house only knows nutritional building materials…one cannot say absolutely that all will respond completely to such nutritional treatment regimes…yet in our experience, well over 80% or more do respond favorably to such nutritional focus. The reason for this is quite clear…the only way to repair the damage, or to facilitate the return to normal function, is to utilize the knowledge of nutritional biochemistry…in wholistic medicine this is known as functional medicine, or molecular medicine, or in some circles–cellular medicine…a logical question put forward by many is, “why doesn’t standard medicine utilize this nutritional knowledge to facilitate the return of health to the individual?” The Harvard medical school looked at this issue and discovered that over 70% of their doctors received no nutritional biochemistry in medical school…other studies calculate that only 5% or so of the standard medical doctors in this country have any nutritional biochemistry in medical school…this is usually an elective of 20 hours or less. There is absolutely no financial reward to the pharmaceutical companies, or the doctors that rely on these same companies for their income—to do anything different for the patient.

Methadone is a long acting synthetic morphine. Its recognized half life is 24-36 hours on the average. This means if you are doing 100 mg of methadone, and you have liver function capable of metabolizing the dose in 24 hours—than 24 hours after taken 100 mg that you will still have 50 mg of the original dose in your system. In the next 24 hour period you will still have 25 mg in the body. Extrapolate this out and one can see that on the average it takes 7-10 days just to get the methadone out of the human body. Remember, 24-36 hours for the average person. Some are poor metabolizers and some are rapid metabolizers. When one abruptly quits methadone the onset of the acute withdrawal symptoms can take from 3-12 days in the cases I’ve seen. I call this—“hitting the methadone withdrawal wall”…it is different for everyone. It is crucial in the detoxing of this drug that nutritional treatment begin early and last for 2-3 months.

As long ago as 1969, terms were being used about a protracted withdrawal syndrome. Today, this is known as post acute withdrawal syndrome (PAWS). The idea behind PAWS is that the average patient continues to have underlying symptoms of withdrawal long after the original drug or alcohol has been metabolized out of the system. These symptoms can include depression, lack of concentration, mental fogginess, anxiety, sleep issues, fatigue and immune system dysfunction. It is also noted in the literature that these symptoms can last from six months to two years in the average patient if they do nothing more than just quit the drug or alcohol.

The level of signs and symptoms of this withdrawal are different with respect to the following conditions: 1) type of drug, 2) amount of drug taken, 3) duration of drug use, and 4) genetic makeup of the individual. Without a doubt, withdrawal symptoms are the primary reason for chronic relapse into the drug of choice. In my clinical practice, both in-patient and outpatient, it is rare to see these symptoms last longer than three to six weeks in the average patient utilizing focused nutritional biochemistry as the primary treatment. Yet, nutritional therapy is a complex issue. Clinicians that wish to pursue this level of treatment for their clients must understand extensive information on metabolism and genetic function. Without understanding the intricacy of molecular functions and how they are activated and manipulated through nutritional treatment, the clinician is likely to create more harm than good. Even if harm is not caused to the client, treatment often fails to produce the desired result. Just taking one particular vitamin or amino acid to address health issues in detoxification and recovery is much akin to supplying the client with just Prozac to “cure” their depression. Majid Ali, MD, says it best: “… No molecule exists in biology alone, functionally or structurally. This is self evident. And yet we physicians insist in diagnosing ‘a nutrient deficiency’ to understand ‘a disease’ which we can then treat with ‘a nutrient therapy’ … The central issue here is: Mono-nutrient therapy has no place in the clinical practice of molecular medicine.”

ALL levels of opiate therapy, whether methadone or others, will cause the body to down regulate the production of the bodies own internal opiates (enkephalins and endorphins) and also the receptors these opiates work on to block pain transmission (this is called building tolerance to the dose or the drug). The longer one is on opiate therapy…the more down regulated these systems become—necessitating the need for higher and higher doses to obtain the same affects. One day, as many of the patients on these therapies find out, it seems as if nothing works…once again necessitating higher and higher doses. What becomes evident is that all long term opiate therapy patients remain in chronic low grade pain…many times this pain is found away from the original injury. Because there are not sufficient amounts of opiate receptors left to interact with the opiates, whether these are internal opiates generated naturally by the body or taken externally, to help us through the day from the normal wear and tear that occurs on our muscular-skeletal system. Opioid-induced hyperalgesia[1] or opioid-induced abnormal pain sensitivity[2] is a phenomenon associated with the long term use of opioids such as morphine, hydrocodone, oxycodone, and methadone. Over time, individuals taking opioids can develop an increasing sensitivity to noxious stimuli, even evolving a painful response to previously non-noxious stimuli. Some studies on animals have also demonstrated this effect occurring after only a single high dose of opioids.[3] The need for dose escalation in opioid therapy may be as a result of tolerance, as a result of opioid-induced hyperalgesia, or, more likely, a combination of both. Thus patients receiving medications to relieve pain may paradoxically have more pain as a result of their medication.

This phenomenon likely results from changes in NMDA receptors in the dorsal horn of the spinal cord. Research on the mechanisms underlying this phenomenon is ongoing, as are attempts to identify NMDA receptor antagonists, which may be able to prevent or attenuate this effect.

If an individual is taking opioids for a chronic non-cancer pain condition, and requires increasing doses, yet still do not achieve pain relief, they may be experiencing opioid-induced hyperalgesia. If so, they may benefit from complete withdrawal from opioid therapy. Many individuals report reduced pain levels when opioids are withdrawn.[4]


1. Angst, MS & Clark, DJ: Opioid-induced hyperalgesia: A qualitative systematic review. Anesthesiology 2006; 104:570–87

2. Mao J: Opioid-induced abnormal pain sensitivity: Implications in clinical opioid therapy. Pain 2002; 100:213–7

3. Celerier E, Laulin J-P, Corcuff J-B, Le Moal M, Simonnet G: Progressive enhancement of delayed hyperalgesia induced by repeated heroin administration: A sensitization process. J Neurosci 2001; 21:4074–80

4. Wuitchik, M. & Feehan, GG: Opioid withdrawal versus opioid maintenance for persons with chronic non-cancer pain: The experience of the Canmore Pain Clinic. Rehab Review 2006; 2:19-21

All this being said, two things must be understood before starting…1) Keep it simple…movement from the simple therapy to the complex therapy will allow the physician, or patient, to move to the level of complexity needed in any particular case without overwhelming the patient, 2) Stay the course…many get discouraged because they want to be “well” now. Ask yourself, “How long did it take me to get here…” and more importantly, “how long, am I willing to commit to this process of healing and recovery?” I have my patients commit to 6-weeks of intensive nutritional therapy…we assess every two weeks and change what is necessary. At 6-weeks, I ask for another commitment of 6-months to one year. Approximately 80% of those who make the initial 6-weeks make the longer commitments. Remember, it takes time to reestablish and heal adequate neurotransmitter/biochemical function…one day at a time.

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