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Pain Management Versus Opioid Abuse: Glimmers of Light

Doc Gumshoe follows up on A Troubling Quandary

By Michael Jorrin, "Doc Gumshoe", October 18, 2017

[ed. note: Michael Jorrin, who I dubbed “Doc Gumshoe” years ago, is a longtime medical writer (not a doctor) who writes for us a couple times a month about health issues and trends.  He does not typically focus on specific investment opportunities, but has agreed to our trading restrictions… as with all of our authors, he chooses his own topics and his words and opinions are his alone]

At the end of the first installment on this subject I promised to lift the curtain on some glimmers of light that have emerged in this troubling picture.   Before getting up to launch velocity, I need to do a bit of review.

First, we need to understand one simple, basic, underlying truth: in most cases, our pain response is an essential survival signal.   The sensation of pain tells us that something is amiss and needs to be remedied.   This is true of both the fast type of pain, which is a response to mechanical or thermal events (bangs, cuts, burns, etc), or the slow type of pain, which is a response to something wrong systemically, whether something relatively trivial like indigestion, or any of a huge and intimidating range of non-trivial conditions and diseases.   Those two general types of pain are transmitted by different nervous systems.   Fast pain impulses get to the brain in less than one tenth of a second after the incident, while slow pain impulses begin to trickle into the brain several seconds after the chemical agents reach the nerve endings, and then increase over longer periods, sometimes as long as hours.

The most immediately useful response to pain is to determine the cause and try to deal with it.   This is generally fairly simple with fast pain.   If you burn yourself picking up the cast-iron skillet without a pot-holder, you can run cold water on your hand and then put on some lotion; systemic pain medication is usually unnecessary.   But if you develop a severe pain in your lower back, and it gets worse overnight and doesn’t go away, you might need to consult a health professional to try to find the cause.   And if, despite the interventions of the health professional and short-term pain medications, the pain persists, you might find yourself in the situation I described in the previous installment.

That situation embodies some inherent conflicts.   As noted in the previous Doc Gumshoe sermon, chronic pain affects close to one third of the US population, and the most effective drug treatments for pain are agents that address the μ opioid receptor, but opioid abuse is endemic here in the USA, and opioid overdoses kill about 175 of us every day.

Lots of different cohorts contribute to this situation in many different ways.   People in pain increase their opioid doses in an attempt to cope with their lives, perhaps unknowingly flirting with addiction, while others knowingly risk addiction in the search for pleasure and a good time.   The economics of the health-care system may make it easier to treat pain with cheap opioids than with some relatively more expensive alternatives that may be less addictive.   And shady characters in quest of easy money provide people with those more addictive drugs.

The pharmaceutical outfits that make and market opioids attempt to dissuade users from becoming addicted to their products mostly through formulation – either by compounding the opioid with one or more other substances that are intended to minimize addiction, or by making slow-release tablets that deny users the immediate rush of pleasure that rewards addicts.   For example, oxycodone, which by itself is an immediate-release agent, is available in seven different formulations intended to deter addiction while perhaps augmenting the basic pain-relieving activity of the opioid itself by adding other analgesics.   In theory, bringing down pain levels by multiple mechanisms would reduce reliance on the opioid channel and thus perhaps lower the odds that the patient would take another opioid pill when the pain level increased.

The formulation strategy is very limited in its effectiveness.   Addicts quickly learn how to crush or dissolve their pain pills and take them in such a way as to get that quick rush that they crave.   And, paradoxically, putting other agents in the mix can add risks.   Both oxycodone and hydrocodone are available in forms compounded with acetaminophen (Tylenol).   Taken regularly over long periods, both the oxycodone-acetaminophen pill (Percocet) and the hydrocodone-acetaminophen pill (Vicodin), will likely elevate liver enzymes and can cause significant liver damage, especially when taken with alcohol.   And large doses of those drugs, in the amounts favored by addicts to provide that immediate rush, are thought by some to be a leading cause of liver failure, leading to liver transplants, and in some cases, death.   There are formulations consisting of 5 mg. of oxycodone compounded with 325 mg. of acetaminophen.   A dozen of those would put a person at 3900 mg. of acetaminophen, which is right up against the 4000 mg. danger marker, while only yielding 60 mg. of the opioid – nowhere near enough for an addict to get a rush.   So, sometimes it’s not the opioid that kills the addict, but that supposedly benign little pain killer that we give our kids.

So, is there a way to deliver the pain relief that opioids can provide without also increasing the risk of addiction?

Maybe less is more…

A small pharmaceutical company has developed a drug that – perhaps! – accomplishes just that.   The company is Nektar Therapeutics (NKTR) in San Francisco, and the drug in question is NKTR-181, unnamed as of this writing.   (Before I go on about this drug, let me state plainly that I have no expertise whatever in assessing the economic potential of Nektar, other than to say that it is a quite small company, and that if their pain medication scores a hit, the company itself could do well.   But I have not bought any shares and do not plan to for the foreseeable future.)

At first glance, NKTR-181 would seem to be a total bust.   It is about an order of magnitude less potent than opioids like oxycodone and hydromorphone, and it is afflicted with many of the common side effects that come with other opioids.   It is inherently very slow-acting due to its molecular structure, and therefore unsuitable for the treatment of acute pain.   So why is it viewed as a promising drug?

Exactly for some of those reasons.

How quickly a drug begins to deliver pain relief depends on the speed with which it reaches the pain centers in the brain.   These centers – the analgesia systems of the brain and spinal cords – are highly complex, and also highly sensitive to opioids.   About half a century ago it was discovered that really miniscule quantities of morphine, injected directly into certain areas of the brain, result in an extreme degree of analgesia – a nearly total suppression of pain impulses.   As research into this matter has continued, a number of naturally-occurring opiate-like substances have been discovered in the nervous system, and many areas of the brain have opioid receptors.   Opioids are indeed our natural, built-in pain suppressors.

The fast-acting opioids that are commonly used for pain management reach those opioid receptors in the brain pretty quickly – in the case of oxycodone, it can take as little as fifteen minutes for the drug to enter the system, get absorbed in the blood stream, travel to the pain centers in the brain, and elicit a response.   That depends on the dose, of course – the drug trickles in over time, and with a larger dose, the amount required to elicit a significant response gets to the target receptors that much sooner.

That’s where NKTR-181 has this entirely counterintuitive advantage.   Where it takes oxycodone a quarter of an hour to start delivering results, NKTR-181 can take as long as eight hours.   That’s because the molecule itself is very slow to be absorbed into the circulation – sometimes as long as four hours – and then, very slow to cross the blood-brain barrier – again, perhaps four hours.

So there’s no way for the would-be drug abuser to get a rush by taking NKTR-181.   And the slow onset of the opioid effect is not due to any formulation, but to the inherent structure of the molecule.   Therefore, it is extremely unlikely that tampering with the drug itself would increase the potential for abuse.

The low potency of NKTR-181 is also, in a sense, an obstacle to abuse.   Whereas for certain chronic pain patients, 40 mg of oxycodone per day would be a dose adequate to keep their pain levels under control, the amount of NKTR-181 needed to attain the same level of analgesia would likely be about ten times that amount -400 mg per day.   But 40 mg of oxycodone in a 24-hour period is nowhere near enough to provide the same gratifying effects that addicts crave, nor would the equivalent amount of NKTR-181.   And the higher the dose, the greater likelihood of encountering the kind of side effects that are not dangerous, but definitely disagreeable – nausea, vomiting, and so forth.   So, even if patients boost their dose, there’s no immediate rush and they could feel lousy for a few hours.

A clinical study comparing NKTR-181 with oxycodone and placebo used the Drug Liking Visual Analog Scale and found that at all dose levels, NKTR-181 had significantly (P < 0.0001) lower Drug Liking scores than oxycodone, and about the same scores as placebo (Webster L, Pain Medicine  03/10/2017).    At the 2017 PAINWeek conference in Las Vegas in September, Nektar presented results from its SUMMIT-07 trial, which reported that more than 98% of patients taking NKTR-181 experienced no withdrawal symptoms whatsoever, either during the trial, or after discontinuing the drug at the conclusion of the trial.

In terms of efficacy – which is, after all, what the legitimate pain patients want and what the medical community is looking for – NKTR-181 can deliver about the same amount of pain relief as the standard opioids, although, of course, at a higher dose.

The effectiveness of NKTR-181 was confirmed by the SUMMIT-07 trial, which  enrolled more than 600 patients with moderate to severe chronic back pain who had never used opioid therapy.   Four daily dosage levels of NKTR-181 – 100 mg, 200 mg, 300 mg, and 400 mg – were compared with placebo.   These doses would be approximately equivalent to 10 mg, 20 mg, 30 mg, and 40 mg of oxycodone daily.   Pain levels were based on patients’ self-assessment of their pain on a scale of zero, meaning no pain at all, to 10, meaning the worst level of pain imaginable.   At the start of the study, the mean pain level reported by patients was 6.73.   All patients went through a two-week open-label phase during which they received one of the four dose levels of NKTR-181.   At the conclusion of this phase, the mean pain scores for all patients declined from 6.73 to 2.32, a reduction of about 65%.   At this point, the patients were randomized to NKTR-181 or placebo, and the patients at all dose levels of NKTR-181 maintained pain scores below 3.0 to the conclusion of the study.   The primary efficacy endpoint of the study demonstrated improved chronic back pain relief with NKTR-181 compared to placebo, with results considered highly statistically significant (P = 0.0019).

Are you elevating your eyebrows at the notion that pain can be measured accurately to two decimal points?   If so, Doc Gumshoe agrees with you.   Perhaps a better way of describing the results of that study might be to say that at the start, the patients were mostly experiencing considerable pain, somewhere above the midpoint of a pain scale – let’s say severe, but not agonizing.   But then, after getting gradually increasing doses of this drug, their pain level subsided, to a level that might be considered a bit more than negligible, but quite tolerable.   When patients were asked to put a number to those pain levels, the arithmetical mean for the pre-treatment pain level came out to 6.73, and that mean for the pain level after the drug’s effects were felt came to 2.32.   What made it possible for those numbers to be stated out to two decimal points was that there were more than 600 patients involved in the study.   So, in language that actually represents what most of those patients felt, we could say that NKTR-181 lowered their pain from severe to tolerable.   That, after all, is the kind of benefit that people want from pain pills.

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A couple of other points regarding NKTR-181 were that, at the dosages used for that degree of pain management, the side effects were mild, and similar to those accompanying the usual doses of other opioids – constipation, nausea, somnolence, headache, vomiting, dry mouth, and fatigue.   Very small percentages of patients in the study dropped out due to adverse events, and the incidence of serious adverse events was quite small – a total of 5 in patients treated with NKTR-181, compared with 7 in placebo patients.

The bottom line, as I see it, is that NKTR-181 can be an effective pain medication in patients with moderate to severe chronic pain, that it is accompanied by side effects similar to those affecting other opioid pain medications, but that it produces those results with essentially no risk of leading to addiction.

NKTR-181 has not yet been gained FDA approval, but it has been granted FDA fast-track designation, so approval should be forthcoming fairly soon.

Nektar Therapeutics is a quite small company and will almost certainly seek partnership with a larger pharma outfit for the marketing of their agent.   Doc Gumshoe has no clue as to the financial fortunes of Nektar, which will, to some degree, depend on the nature of whatever business deals they make to market that particular drug as well as others they have at various stages of development.   As I said earlier, I do not own any shares in the company and have no plans to acquire any at this point.

And now for some entirely different glimmers of light …

Another avenue to combat substance abuse

One of the most troubling aspects of addiction is that the victims often are unable to resist falling into patterns of abuse even if they are completely aware of the risks that continuing abuse presents.   They may be “clean,” but they are at high risk of relapse.   They absolutely know that they could lose jobs, friends, family, homes, their freedom, and even their lives.   But their brains have somehow changed, in ways that are only now beginning to be understood.   It appears that the pleasurable responses that they experienced in drug use, over time, become strongly linked with certain environmental stimuli – the places or the social milieu where they took the drugs, or sometimes other factors that have no essential connection with the drugs, but which have become associated with their drug experience at some deep level in their brains.   What happens is that despite their best conscious efforts, brain mechanisms override their caution and they go back to drug abuse habits – in other words, relapse.

Based on animal studies, scientists have now found certain epigenetic factors that appear to influence this behavior.   Before going further down that track, let me (briefly, I promise!) try to explain something about epigenetics, which is a highly promising line of investigation in a number of medical areas, especially cancer.

A short epigenetics backgrounder, if  you’re interested

The cause of the changes that result in the formation of cancer cells has traditionally been thought to be random errors in the transcription of genetic material in stem cell division, such as mutations, which can result in the loss of the genes that suppress tumors, or in the over-expression of the genes that promote cancer cell growth, termed oncogenes.   (Needless to say, some of these errors have external causes, which we all know about.)

However, not all cancers are the result of changes or mutations in the genome, which is the DNA material that encodes the genetic characteristics of the organism.   More recent research demonstrates that changes in the activity of genes can be triggered by agents external to the DNA strands themselves, but within the capsule containing the DNA strands, which are tightly wound around proteins called histones.   In turn, the histones are organized into tight clusters called chromatins.   The full DNA double-helix, consisting of 146 to 147 base pairs of DNA, would be over 2 meters long extended to its full length, but the diameter of the chromatin is about one 6-millionth of a meter.

Chemical changes can affect the histone as well as the DNA itself, without changing the essential DNA.   The agents that bring about these changes are called epigenetics, meaning “upon” or “over” genetics.   At least three classes of proteins that interact with histones have been identified.   These have been classified as writers, which modify the histone through chemical changes; erasers, which can remove those modifications; and readers, which can recognize the histone modifications and can deliver enzymes that can modify histones or DNA.

Several types of epigenetic chemical changes have been identified.   Among those of particular interest are DNA methylation and histone acetylation and deacetylation.   Methylation is the binding of a methyl radical, consisting of a single carbon atom linked to three hydrogen atoms, or CH3.   Similarly, acetylation is the binding of an acetyl radical, consisting of the methyl radical plus one more carbon and one oxygen, thus COCH3.   Deacetylation is the term for removal of the acetyl radical, which is carried out by means of an enzyme, deacetylase.

These changes are termed epigenetic changes.   They are not intrinsic to the DNA, but they persist as the chromatins divide in the process of cell division, forming chromosomes.   Thus, the new cells formed by division of the cells that have sustained epigenetic changes retain those same changes, and if those changes, such as unchecked cell reproduction, are characteristic of cancer, then those new cells carrying those epigenetic changes are cancerous.

Although epigenetics has been studied primarily as a way to treat cancer, anything that affects our DNA will have other consequences, perhaps including the way we respond to drugs that give us pleasurable sensations.

Epigenetics and the mechanisms that lead to relapse in drug users

The research we’re discussing here was done at the Medical University of South Carolina (MUSC) and published a couple of weeks ago (Taniguchi M, Neuron 09/27/2017).   Researchers were working with cocaine-addicted mice, which had been exposed to certain specific light and sound stimuli in conjunction with their daily cocaine fix.   These mice then learned to depress a lever which dispensed cocaine in their habitat, and when they pushed that lever, a light would go on over the lever and a particular sound was emitted, so that they associated that light and sound with their cocaine treat.   In time, when the mice were exposed to those same stimuli, they would respond by seeking out the cocaine dispensing lever.

The researchers then investigated what genetic factors might be involved with this behavior.   Among other findings, they focused on the above-mentioned epigenetic enzyme histone deacetylase 5 (HDAC5), which removes the acetyl radical from the histone protein around which the DNA strand is wound.   HDAC5 does appear to inhibit the mouse brain from forming those associations between the cocaine response and the light and sound stimulus.   But when mice in which that association had already been established – we might call them addicted mice – were given a form of HDAC5 which traveled straight to the nuclei of neurons, their drug-seeking response when they were exposed to the light and sound stimulus did not diminish.   So, while HDAC5 might work to prevent the mice from forming those associations in the first place, once the associations were formed, it did nothing to reduce drug-seeking behavior.

However, when mice which had previously been exposed to cocaine and had formed the association with the stimuli, went through a period of abstinence, the results were markedly different.   Mice given HDAC5 after having been off cocaine for a period – mice that had been in “mouse rehab” – were exposed to that stimulus, but they demonstrated a much lower level of drug-seeking behavior.   They pushed that lever much, much less.

The researchers at MUSC are using that finding to investigate what genes in the DNA genome are affected by HDAC5, and they have identified several.   A protein, NPAS4, which encodes for one particular gene, seems strongly linked with addiction, at least in the mouse brain.   Mice with more NPAS4 took less time to form the association between drug-seeking behavior and the external stimulus.   HDAC5, the epigenetic factor, seems to inhibit NPAS4, as well as other proteins that favor addictive behavior.

Nobody is saying that treatment with that epigenetic protein is going to be the decisive answer to drug addiction.   But the signs are hopeful.   Human brains share many, many genes and enzyme pathways with mouse brains, and the mental links that favor addiction are probably similar in other addictions beside cocaine.   Addiction could be described as the formation of an extremely strong link in the brain.   If a way could be found to weaken that link, it would be good news indeed.   That might turn out to be a cure for addiction.

Other possible approaches to managing pain

Our brains possess an active and, at best, highly effective way of suppressing pain, known as the analgesia system.   Neurons in areas of the upper brain and the medulla can send signals down the spinal cord to a complex located in the dorsal horns of the spinal column, where pain signals can be effectively blocked before entering the brain.   Those portions of the spinal column secrete serotonin.   Serotonin in turn stimulates neurons in the spinal column to secrete enkephalin, which is an opiate-like substance that causes inhibition of the synapses of incoming pain fibers where they link to the dorsal horns of the spinal column.   The synapses, as you may remember, are the little connections between nerve fibers.   When the connections are closed, the signal flows across, but when the connections are open, the signals can travel no further.   The effect of enkephalin essentially is to open those connections, blocking the pain signals.

Several opiate-like substances have been identified in the brain, including the enkephalins and endorphins, and multiple areas of the brain, especially in the analgesia system, have opioid receptors.   These receptors are where exogenous opioids exert their pain-controlling actions.

The analgesia system can be mobilized by external tactile stimulation of sensory nerve fibers leading from peripheral tactile receptors.   Or, to put it in simpler language, rubbing or massaging the painful or achy region can result in significant and effective pain relief by opening the synapses.   Addressing those nerve fibers is also the way acupuncture works.

A review of 105 clinical trials conducted by scientists from the National Center for Complementary and Integrative Health (NCCIH) at the National Institutes of Health supported the effectiveness of nondrug approaches to pain management.   The researchers found that for several classes of pain, the following approaches were at least somewhat effective, and were not associated with significant adverse effects:

  • Acupuncture and yoga for back pain
  • Acupuncture and tai chi for osteoarthritis of the knee
  • Massage therapy for neck pain and for short-term benefit
  • Relaxation techniques for severe headaches and migraine.

According to the NCCIH researchers, massage therapy, spinal manipulation, and osteopathic manipulation may provide some relief of back pain, and relaxation approaches and tai chi might help people with fibromyalgia.   Evidence was weaker for those forms of therapy, but overall, the nondrug approaches were thought to be promising.

Another approach to suppressing pain is external electrical stimulation.   Electrodes can be placed on the skin, or implanted over the spinal column, as ways of stimulating the sensory column of the dorsal spine.   In some cases, electrodes have been implanted in areas of the brain that are part of the analgesia system.   Patients may be thus able to control the amount of electrical stimulation they receive.    Some patients have reported that their pain levels were reduced almost to the imperceptible level, and remained there for a full 24 hours or even longer.   Obviously, this is not a form of treatment that is practical for chronic pain patients who need pain treatment in order to permit them to continue with normal life activities.   But it can provide relief for some terminal cancer patients, whose final days would otherwise be spent in agony.

Mind over pain: can this work?

It worked for me, up to a point anyway, during the recovery from my two total knee replacements, which I described in previous Doc Gumshoe posts.   For the first couple of days after the surgery I was so heavily sedated that I felt only the dullest of a dull ache.   The pain only really began when I was sprung from the hospital to the residential treatment facility, and only really ratcheted up when I reported to the twice-daily physical therapy sessions, which started in earnest on day three after surgery.   But the uptick in the pain level, despite a considerably high level of oxycodone dosing, was colossal.

After a 20-minute limbering up ride on the stationary bike, the physical therapist, Lorenzo the Magnificent, would work on my flexion and extension.   In other words, how much could I bend the leg, and how straight I could get it.   Lorenzo would bend the leg up to the point where it would begin to hurt pretty badly.   He would then ask me to tell him when it started to hurt too much.   I, being a good Boy Scout, would stand it as long as I could, and then, when I gasped out something like “now, now,” he would keep pushing to the count of five.   This was agony, something like being drawn and quartered.   Then the same procedure with straightening the leg.   Lorenzo would press down on the knee with all his considerable might, ask me to tell him when it hurt too much, and when I did tell him it hurt too much, continue pressing to the count of five.

And here’s how I tried to deal with it: in my mind, I pictured the pain as being “Down There,” somehow not really part of my essential self.   It was not in my head, not in my gut, not in my heart, not in any vital part of me.   It was only in my knee, almost outside of me.   It still hurt, of course, but it didn’t feel like a dreadful invasive life-threatening presence.   It wasn’t frightening.   It was almost no more than an interesting sensation.   But I was pretty glad when it stopped.

Is this “mind over pain?”   Perhaps so.

Several prestigious medical treatment centers have endorsed “mind over pain” as ways to manage pain without drugs.   Dr James Campbell, a neurosurgeon and pain specialist at Johns Hopkins, suggests avoiding the “catastrophizing” of pain – not immediately assuming that the pain represents something disastrous.   “If the pain is not an indication that something is seriously wrong, you can learn to live with it,” says Dr Campbell.   And at the Mayo Clinic’s pain rehabilitation center, Dr. Wesley Gilliam says much the same thing: “Pain is an interpretation by the brain.”   The brain becomes addicted to dramatizing pain, and dwelling on the pain reinforces that addiction.   The recommendation for chronic pain without a clear, remediable origin, is not to dwell on it, and not to try to fix it.   Eventually, the mind should just let go.   The Mayo Clinic’s program includes techniques that may strike some of us (your faithful servant Doc Gumshoe among them) as rather New Age-ish, like focusing your mind on your breathing rather than on your pain.   I did not do this, I’ll confess – I don’t even want to think about my breathing.   But it has been reported to work quite well for some people.

* * * * * * *

Many thanks, once again, for any and all comments.   I certainly hope reading about pain doesn’t aggravate your own aches and pains; sorry if it did!   In any case, in the next installment I’ll try to talk about something a bit more pleasant.   Best to all, Michael Jorrin (aka Doc Gumshoe)

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rubber
Member
rubber
October 18, 2017 10:12 pm

Here is the home remedy that worked for my arthritis and other minor pains.
6 medium size carrots grated, level table spoon of grated garlic, level table spoon of
turmeric , half table spoon of ground black pepper. Mix them well and refrigerate.
Take one tablespoon in the morning on empty stomach 1/2 hour before eating.
Try for a month, you may not need pain medications any more.

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R K LAKHOTIA
Guest
R K LAKHOTIA
October 19, 2017 7:27 am
Reply to  rubber

Hello rubber
I entirely agree with your approach. Also ingest pineapple on alternate days It will reduce the knee pain. Gradually reduce reliance on ‘pain killers, to the extent possible. Go to nature please.

jbnaples
October 19, 2017 5:51 am

Doc,
Been taking 10-325 x4 daily for many years for severe joint pain.
Just switched to 5mg prednisone daily. No more pain or 10-325.
Wondering which is worse. Any thoughts?
BTW: Had 2 organ transplants 18 years ago. Thanks. JB

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deboruth
October 27, 2017 9:28 pm
Reply to  jbnaples

jbnaples, the prednisone will reduce your immune function on top of whatever reduction your transplant anti-rejection medicine is doing. This is a very serious matter. 10-325 impacts the immune system negatively, but nothing like steroids. Also prednisone can make you mean and nasty. You already know the drawbacks of 10-325. Your might want to get a little more medical opinion vis-a-vis that joint pain. Maybe get some of the longvida curcumin developed at UCLA which is the most bioavailable kind.

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irabidermandds
irabidermandds
October 19, 2017 8:41 am

any idea about ACRX? I know they just got another CRL from the FDA. Seems the machine for patients to give themselves the pill is causing more problems, what about the pain medication itself? thanks in advance

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SoGiAm
October 19, 2017 9:07 am
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Don Hawkins
Member
Don Hawkins
October 19, 2017 9:12 am

Thanks doc for this topic i am one with chronic pain & im tired of
being treated like a ” JUNKIE! some people need this medication & are treated so unfairly SOMETHING NEEDS TO BE DONE ASAP.

wcdave
wcdave
October 19, 2017 10:04 am

If it is appropriate, I’d like to share this article from Thomas Kline MD, PhD
THE OPIOID REFUGEE CRISIS: CAUSES and RECOMMENDATIONS revised 10–13-17
https://medium.com/@ThomasKlineMD/the-opioid-refugee-crisis-causes-and-recommendations-9-4-17-4b8453656f55

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Jamie
Jamie
October 19, 2017 5:43 pm

On this topic.. anyone have experience with kratom? I live in a small town in FL and there is a store/bar that serves kratom and kava. Far as I can tell is that a high percentage of their clientele are folks getting off their opiod addiction. Just curious?

wmikemarshall
October 19, 2017 10:33 pm
Reply to  Jamie

I just ordered KRATOM via an old friend’s wife who is a cancer researcher++ and recommended trying Kratom for weaning down on vicodin of which I take for blown back disc, also claims it helps with anxiety, pain and depression. Makes weaning off opiates easier. I just ordered per her advice from KRATOMUSA.COM and going to give it a try when it arrives any day now to address all of the above issues of which I suffer from. Excited about having something natural do so much good. I’ve had great luck with testing natural supplements VS Big Pharma poison and have fixed 2 separate health issues, one lasting 20 years, one for 35 years, both cured in ONE day with 2 simple OTC supplements. Hoping for the same good luck with Kratom! BTW, it was $50 for 100 tablets but not sure on dosing yet and going to take what my friend did who was successful in using it. Good luck.

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VICKY G LEWIS
October 20, 2017 10:57 am

How does the Cannabis Drug Cara is coming out with Compare to NKTR drug for pain. They have high hopes of helping out the Opioid Abuse problem?

kteed1
Member
kteed1
October 22, 2017 2:36 pm

I too have chronic pain from Failed back surgeries x3, Fibromyalgia, Osteoarthritis thru my body and just diagnosed with Autoimmune connective tissue disease disease. I’ve been on all kinds of pain pills and now take a long acting Morphine for last few yrs. I’ve been able to wean down somewhat but that’s as far as I think I can go and still be able to function. My BIG problem is being CAUGHT up in this fight. My insurance company as a CRACKDOWN thinks all of a sudden I should be able to not be in pain by only taking X amount of the medicine per day even though they’ve approved what I’ve been on for the last 5 years. Now to pay out of pocket is costing me almost $1000 a month and that’s generic! I’m disabled, my hubby is retired, a lot of the other pain meds didn’t work for me, nor did injections or modalities as tens, etc. The ins co’s and others need to remember there’s those of us who follow the rules, play by the law but we either have hi tolerance to pain meds, low tolerance to pain or perhaps both or neither it’s just how we are. But there’s no co-morbidity for us. We just want to live our lives and function as best we can with at least pain as possible. My blood work gets done routinely to make certain no problems, eat healthy, exercise as I can use ice heat stretch etc,but stop treating me as an addict!

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kteed1
Member
kteed1
October 22, 2017 2:40 pm

I just wanted to add that I hope to move to a state that has legal M so I can try that and also other kinds of treatments come to mkt like the one discussed here NKTR, that might be one. Keep informed. Thkx.

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John
Member
John
October 23, 2017 2:44 pm

If it actually works, the DEA will be right on it, declaring it harmful (no medical studies required), using their authority to declare it a controlled substance. The DEA, constituted as an agency of government overreach, is the heart and soul of our “drug problem.”

John
Member
John
October 23, 2017 5:17 pm

Didn’t like that one ? Too close to the truth ? Marijuana might reduce opioid usage ? DEA will hold the line. Reefer Madness forever.

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William Moser
October 24, 2017 6:16 pm

‘Decatastrophysing pain’ makes a lot of sense.

A major sociopolitical issue is the fiction that physicians are wise enough to deserve the command-and-control prescribing privileges which infantilizes patients and artificially keeps their waiting rooms full

Narcotics efficacies and dangers are well established but most MD’s are a bad combination of judgmental and ignorant when it comes to pain management. It’s all about ‘turf and money’ and in this regard they are no better than any other industry seeking to keep competition (naturopaths, nurse practitioners, chiropractors) at bay.

Since controls are politically expedient, there should be some kind of ‘registered addict’s program ‘ so this class of drugs can be obtained without the waste of time and money dealing with drug-seekiing behaviors and ‘legitimate’ pain patients don’t have to fear the suspicions, accusations and condescension so prevalent in medicine.

deboruth
October 27, 2017 9:36 pm

By the way, y’all, my PA tells me that CVS has decided they now have the right not to sell you pain medicine. They have declared a maximum of, I think, 90 morphine equivalent per day — that would be 3 of 10-325 oxycodone, not the 4 tablets one reader mentioned taking. Actually, I found CVS generally unwilling to stock any controlled drugs for years, requiring weeks of waiting for a prescription, etc — basically they don’t want the expense of paperwork,, regulated handling, security. Gosh, serving medical needs of patients, they’ve found, is an unnecessary downside to the profitable business of selling lipstick and Halloween candy. I switched to Duane Reade in New York, now part of Walgreens.

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backoffice
Irregular
October 29, 2017 12:40 am

I suffer from neuropathy of the feet and both legs up to the tops of the lower legs just below the knees. I’m not diabetic and had HepC in the early 90″s and was put on Rebetron. I rapidly began losing weight, developed PTC which was diagnosed as a skin disorder after a biopsy was done.The Interferon was causing the problems yet was continued. The doctor I had at the time felt I had amyloidosis and told my wife to get all my things in order, I went into the hospital as an outpatient and had a broviac tube inserted into my chest and was sent home on a morphine pump to control the pain I was in and wait for the inevitable.I could feel my life slowly ebbing away and to get around outside the home I needed a wheelchair. What I failed to realize at the time was that once you accepted Hospice you sign over your health care and they control everything. I was asked if there was anything in life that I had wanted to do but didn’t I told them that I had always wanted to learn how to play guitar. Do you know they tried to set me up with guitar lessons? It was after this that I decided to fight. I had 2 kids and a wife and I was to young to die.
Through the internet and friends I was able to get into contact with a doctor in Texas who looked at my lab reports and had me contact a Doctor at Columbia who suspected PTC and upon verification began treatment with Aralen which is used to treat malaria.I was off Hospice care by then and began seeing a different group of doctors, I was even evaluated for a liver transplant thanks to Dr. Tobias of NYU, who has been one of the best Physicians that I’ve encountered. It was a long time recuperating, I’ve been left with neuropathy to deal with and now a government
that’s out to deprive me of the medication that allows me to function.

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vickyg43
October 30, 2017 2:47 pm

I’ve been on Oxy for 20 years, after breaking my back and Neck, and many complications, and operations, from Michigan State to Cleveland Clinic. Some very grave out comes for me after doctor eras. Then I was Allergic to many of the pain meds. After being talked out of heavy pain meds by the 3 therapies Sisters I took the highest dose of Motrin till it litterly burnt the lining of my stomach out. After not being able to take that anymore and the pain was litterly wrecking my life, my Doctor talked me into taking 20 mg of Oxy 3 times a day. I’ve never taken more then 2 a day because it makes me itch. Anything over 20mg.of oxy makes me itch like crazy. I’ve went on to have many other health issues and I’m in chronic pain daily, really bad at night. I could write a list of everything I’ve tried, its really is to long, topped off with I’m allergic to most of the other pain meds. I’ve thought about trying CARA’S pain meds or either NKTR, pain meds, which one do you think will be the BEST FOR PAIN? It would be wonderful to be able to get off OXY. Even having insurance, they still are charging me $443.00 a month. Between my Beta blockers, Asthma drugs and Oxy, Im paying over $1200.00 a month for drugs. I’m always in the donut 4 months after the 1st of the year. My co-pays are high as it is, but they are almost getting to the point where I will not be able to pay them in the future with my insurance charges. Hopefully the cannabis based drugs will be cheaper and I’ll be able to buy them. Do you have idea of when they will be ready for market? How long does this take? Any help would be greatly appreciated. Vickyg

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Robyn
Member
Robyn
October 31, 2017 12:28 pm

Thank you for this article and your knowledge and insight. Due to injuries from multiple motor vehicle accidents, i have been taking pain medication for years, including opiates. Because of the opiate addiction problem, the insurance company will no longer pay for these medications for me. i was told that i was an addict and forced to get into a drug addiction program. This was so demeaning and horrifying! Before these injuries, i wouldn’t even take aspirin! Thankfully, the experts at the addiction center determined that i was not an addict, and that i just needed it for pain. The insurance company (workers compensation), is still fighting it, despite their findings, I am in serious pain all the time, cannot sleep, can’t be productive and I don’t want to live like this anymore. It is no kind of life. Hopefully, this NKTR-181 will be approved and the insurance will allow me to take it. Thanks for the true “Glimmer of Light”.
I really enjoy your articles and your humor is wonderful, too. Please keep up the great job you are doing!

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edski
Irregular
June 18, 2020 10:58 pm

Sounds like you basically have another opioid drug that possibly causes a lot of the same symptoms as full strength ones already in use, just not getting the high from taking the real thing. And what symptoms will this drug be prescribed to alleviate other than pain? Is it formulated to work on different causes of pain, say Osteoarthritis, arthritis, herniated disc?

There are always new drugs out there being tested in clinical trials, and I have been following one in Australia, which is about to go into a double Phase 3 trial here in the US and in Europe. It has been tested on over 750 people in Australia, and results from 10 retired NFL players will be out soon.

I started a Topic a while back titled,” NON OPIOID DRUG GOING TO BE A GAME CHANGER IN OSTEOARTHRITIS? ” https://www.stockgumshoe.com/2020/05/microblog-non-opioid-drug-going-to-be-a-game-changer-in-osteoarthritis/
I add information to it every now and then and give links to a sight in Australia that has discussion groups. It is free, just sign up. It trades on the Australian exchange as: PAR, or Paradigm Biopharmaceuticals Limited. It costs more as a foreign trade, but it is also listed on the pink sheets as PBIGF. I would not purchase pink sheet stocks though, because it is so thinly traded, you might never get your trade exercised for a LONG time.
Go to the sight and read the posts. I do not plan on answering many questions, as I have offered you plenty of links to do your own due diligence. I am an old time Gummy and thought about sharing my information with my old family here at Stock Gumshoe. This has not been touted and talked up here in the states yet. YET. It will, and I am not making any promises, just offering information. Yes…I am a share owner. This particular drug, Zilosul, has been used in veterinary use for over 60 years for osteoarthritis, and has worked well.
This is not investment advice! I make no promises. Take your time and research the product. Pharmaceutical investing is not for the weak. Many things go can wrong along the way towards FDA approval. They can also go very well.
I hope that you find PAR interesting and hopefully, in the near future, available as a NON OPIOID treatment for Osteoarthritis the world over. Stay well and good reading. Ed

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