Narcotic (Opioid) Pain Medications Relieve Some of my Neurological ME/CFS Symptoms

[Tristen]

I also find it very odd that narcotic pain meds relieve some of my neurological symptoms. Not talking about pain....I get relief of other me/cfs symptoms like brain fog, clarity and memory, visual disturbances, tinnitus, and energy......even some of the PEM. It's not a cover up due to euphoria, it actually relieves some of the symptoms. As far as I understand, opiates would only affect those receptors and have nill to do with other neurological problems.....but they do for me. Must be some downstream effect like on endorphins or something. And it wasn't a fluke because I've had this happen years past as well. NSAIDS don't do this, so it's not an anti-inflammatory effect. I dunno, but I'm not willing to live on narcotics for this purpose. Gonna see what my me/cfs doc has to say about this.

 

[Hip]

I also find it very odd that narcotic pain meds relieve some of my neurological symptoms. Not talking about pain....I get relief of other me/cfs symptoms like brain fog, clarity and memory, visual disturbances, tinnitus, and energy......even some of the PEM.

That is extremely interesting, Tristen. Can I ask which narcotic (opioid) pain relief medication in particular brought this improvement in your neurological ME/CFS symptoms?

And can I also ask: after taking your opioid pain relief medication, how long does it take for the improvement in symptoms to appear (are we talking about an hour or so)? And how long did the improvement in symptoms last (perhaps 12 to 24 hours)?

The reason I ask is that I am currently researching the case of a mostly bedbound ME/CFS patient who was returned to virtually full health (full remission) within a few weeks of taking an obscure Amazonian Indian medicine called kambo, which contains some very potent opioid receptor agonists. He has remained in remission for a year now, while he continues taking this medicine. Ever since I read his story, I have been trying to figure out why opioid receptor agonists might provide such a dramatic improvement/remission in ME/CFS.

Notes:

It is interesting that the low-dose naltrexone treatment, which can help in ME/CFS, increases beta-endorphin. Beta-endorphin agonizes the mu-opioid and delta-opioid receptors. This study suggests that mu-opioid receptor stimulation decreases IL-6, whereas delta-opioid receptor stimulation increases IL-6.

This study says that in monocytes, mu-opioid receptor stimulation by morphine decreases TNF and IL-6. Conversely, this study says that morphine increases plasma IL-6 through autonomic activation of the adrenal cortex.

Natural killer cell activity is significantly enhanced by beta-endorphin (ref: 1), and of course NK cell activity is known to be low in ME/CFS, so this suggests that opioids might boost NK cell function. However, this study said that morphine suppresses NK function, and that heroin users have very low NK function.

 

[valentinelynx]

I also find it very odd that narcotic pain meds relieve some of my neurological symptoms. Not talking about pain....I get relief of other me/cfs symptoms like brain fog, clarity and memory, visual disturbances, tinnitus, and energy......even some of the PEM. It's not a cover up due to euphoria, it actually relieves some of the symptoms. As far as I understand, opiates would only affect those receptors and have nill to do with other neurological problems.....but they do for me. Must be some downstream effect like on endorphins or something. And it wasn't a fluke because I've had this happen years past as well. NSAIDS don't do this, so it's not an anti-inflammatory effect. I dunno, but I'm not willing to live on narcotics for this purpose. Gonna see what my me/cfs doc has to say about this.

Same it true for me. Has been for 18 years. I get grumpy whenever I read how "narcotics" (opioids) "don't work" in fibromyalgia or ME/CFS. Nothing else has helped me anywhere near as much.

 

[Tristen]

That is extremely interesting, Tristen. Can I ask which narcotic (opioid) pain relief medication in particular brought this improvement in your neurological ME/CFS symptoms?

And can I also ask: after taking your opioid pain relief medication, how long does it take for the improvement in symptoms to appear (are we talking about an hour or so)? And how long did the improvement in symptoms last (perhaps 12 to 24 hours)?

The reason I ask is that I am currently researching the case of a mostly bedbound ME/CFS patient who was returned to virtually full health (full remission) within a few weeks of taking an obscure Amazonian Indian medicine containing some very potent opioid receptor agonists. He has remained in remission for over 6 months now, while he continues taking this medicine. Ever since I read his story, I have been trying to figure out why opioid receptor agonists might provide such a dramatic improvement/remission in ME/CFS.

Notes:

It is interesting that the low-dose naltrexone treatment, which can help in ME/CFS, increases beta-endorphin. Beta-endorphin agonizes the mu-opioid and delta-opioid receptors. This study suggests that mu-opioid receptor stimulation decreases IL-6, whereas delta-opioid receptor stimulation increases IL-6.

This study says that in monocytes, mu-opioid receptor stimulation by morphine decreases TNF and IL-6. Conversely, this study says that morphine increases plasma IL-6 through autonomic activation of the adrenal cortex.

Natural killer cell activity is significantly enhanced by beta-endorphin (ref: 1), and of course NK cell activity is known to be low in ME/CFS, so this suggests that opioids might boost NK cell function. However, this study said that morphine suppresses NK function, and that heroin users have very low NK function.

Hi Hip, yea very interesting indeed. It was norco this time, but I have noticed the same effect in the past with other opioid pain meds like those containing oxycodone. It takes around 12 hours to affect the symptoms, and then on the second day more relief, third day even more. I get more clear cognitively that I've been in 20 years with me/cfs. The relief continues as long as I take the meds and will continue for 1-2 days after stopping the meds.

I'm glad to see others reporting the same because I've been truly baffled by this affect.....so much so that at first I thought it just coincidence. But I've now had enough experiences with this to know that these drugs are truly affecting some brain chemical (or some area of malfunction) other than just opiate receptors. The drugs affect something very connected to my symptoms.....I have pretty dramatic improvements.

I too have begun looking for a drug that may have the same effect, hopefully non-narcotic. I have tried tramadol for this reason because it is an "opioid like" drug and does act on some of the same receptors, but without the narcotic effect....but I don't get that same relief with it. LDN makes me very sick, even at miniscule doses......well, it did last time I tried it like 10 years ago. LDN is only an opiate antagonist....maybe the agonist like that found in the narcotics is needed for the effect. I'm currently looking at other drugs like Suboxone, which has both....not sure how I would be able to get ahold of that one though. After my experience with these drugs, I believe your amazonian recovery story very likely to be true.

I've become inspired to look into this issue more and I'm really interested in what you turn up with your research. Keep me in the loop, and I will do the same.

Thank you for sharing your experience on this too Valentinelynx. Really helps me to know we are really onto something good here.

 

[Hip]

Thanks for the info, Tristen.

OK, out of the mu, delta and kappa opioid receptors, the opioid pain medications you took act only on the mu-opioid receptor:

Oxycodone is a selective mu-opioid receptor agonist (like morphine is), with very little binding to either delta or kappa opioid receptors.

Hydrocodone (from Norco) is a selective mu-opioid receptor agonist.

(Norco contains a combination of acetaminophen and hydrocodone. Hydrocodone acts as a weak mu-opioid receptor agonist on its own, but hydrocodone metabolizes to hydromorphone, which is a strong mu-opioid receptor agonist.)

So it seems that the pain med drugs you are taking that improve your ME/CFS symptoms selectively stimulate the mu-opioid receptor only.

There is a large list of mu-opioid agonist drugs.

Given what you told me, I suspect that many drugs in this mu-opioid agonist list, provided they can cross the blood-brain barrier, will have similar benefits for improving the cognitive and neurological symptoms of ME/CFS.

Not all of these drugs in the list will be selective mu-opioid receptor agonists, though; some of the drugs will be non-selective, working on the mu-opioid receptor as well as the delta- and kappa-opioid receptors too. It may be best to use drugs that work exclusively only on the mu-opioid receptors. Also, it would be best to use drugs that have the least problems with tolerance, addiction, and withdrawal symptoms.


One question I would like to ask: if you take these opioid pain medications daily for an extended period of time of weeks or months, when you stop, do your ME/CFS symptoms just return to their normal baseline level before you started the pain medications, or do your ME/CFS symptoms become even worse than normal for a while? And do you get any tolerance, addiction, and withdrawal effects from these opioid medications?

 

[Marco]

NOTE: It might be an idea to ask the moderators to kindly move these opioid medication posts to a new thread entitled say "Narcotic (Opioid) Pain Medications Relieve Some of my Neurological ME/CFS Symptoms".

These opioid medication posts don't really fit in this thread, and need their own thread.

Agreed

How about mu opioids protect against glutamate excitotoxicity :

This may therefore indicate that mu-opioid receptor agonists have neuroprotective properties, especially in the excessive glutamate release that occurs under certain pathological conditions.

http://www.ncbi.nlm.nih.gov/pubmed/14618675

 

[Tristen]

Thanks for the info, Tristen.

OK, out of the mu, delta and kappa opioid receptors, the opioid pain medications you took act only on the mu-opioid receptor:

Oxycodone is a selective mu-opioid receptor agonist (like morphine is), with very little binding to either delta or kappa opioid receptors.

Hydrocodone (from Norco) is a selective mu-opioid receptor agonist.

(Norco contains a combination of acetaminophen and hydrocodone. Hydrocodone acts as a weak mu-opioid receptor agonist on its own, but hydrocodone metabolizes to hydromorphone, which is a strong mu-opioid receptor agonist.)

So it seems that the pain med drugs you are taking that improve your ME/CFS symptoms selectively stimulate the mu-opioid receptor only.

There is a large list of mu-opioid agonists drugs.

Given what you told me, I suspect that many drugs in this mu-opioid agonist list, provided they can cross the blood-brain barrier, will have similar benefits for improving the cognitive and neurological symptoms of ME/CFS.

Not all of these drugs in the list will be selective mu-opioid receptor agonists, though; some of the drugs will be non-selective, working on the mu-opioid receptor as well as the delta- and kappa-opioid receptors too. It may be best to use drugs that work exclusively only on the mu-opioid receptors. Also, it would be best to use drugs that have the least problems with tolerance, addiction, and withdrawal symptoms.


"One question I would like to ask: if you take these opioid pain medications daily for an extended period of time of weeks or months, when you stop, do your ME/CFS symptoms just return to their normal baseline level before you started the pain medications, or do your ME/CFS symptoms become even worse than normal for a while? And do you get any tolerance, addiction, and withdrawal effects from these opioid medications?

"

I've only taken them mostly short term like a few weeks at a time, but it did seem that my me/cfs returned to the previous baseline after stopping. Thanks for the link....huge list.

Agreed on the new thread.

 

[Tammy]

I also find it very odd that narcotic pain meds relieve some of my neurological symptoms. Not talking about pain....I get relief of other me/cfs symptoms like brain fog, clarity and memory, visual disturbances, tinnitus, and energy......even some of the PEM. It's not a cover up due to euphoria, it actually relieves some of the symptoms. As far as I understand, opiates would only affect those receptors and have nill to do with other neurological problems.....but they do for me. Must be some downstream effect like on endorphins or something. And it wasn't a fluke because I've had this happen years past as well. NSAIDS don't do this, so it's not an anti-inflammatory effect. I dunno, but I'm not willing to live on narcotics for this purpose. Gonna see what my me/cfs doc has to say about this.

I have found your experience to be true for me also and I agree it is not due to euphoria as I can take a very minimal dose ie(half a tab) and see the improvement and I have been taking that minimal dose for years.

 

[Dufresne]

I’ve noticed a decrease in ME/CFS symptoms with opioids as well. For me it seems to be working in the same way as benzos. It counters the excitotoxicity keeping my energy down. I believe Marco is bang on on this one, I highly suggest reading his article over at Health Rising if you haven’t already. (note to Marco: it’s all right to plug your own work)

http://www.cortjohnson.org/blog/201...fs-puzzle-the-neuroinflammatory-series-pt-ii/

He mentions a couple drugs that look particularly interesting, baclofen being one of them. As it's not an opioid, it could be a safer long-term therapy if it achieves a similar effect. It can be ordered from the following site http://www.alldaychemist.com/

 

[Tristen]

Really glad to see everyone chiming in on this. Hopefully we can come up with something helpful and practical for this purpose. I see my me/cfs doc (Peterson) next month and I hope to get the time to ask him about this. Meanwhile, plenty to follow up with on all this shared info. Thanks everyone!

On the use of Tramadol which I've tried hoping get the same result, yet without the narcotic effect, I do get a small amount of this relief, but nothing like with the other opioids. It also has some other what I consider undesirable effects....maybe due to it's action on serotonin and norepi. For me, a mu-opioid (thanks Hip) without the narcotic drug effect (buzzed) would seem ideal. Or some other compound having the same effect on whatever it is being targeted that brings the relief.

 

[Hip]

How about mu opioids protect against glutamate excitotoxicity :

http://www.ncbi.nlm.nih.gov/pubmed/14618675

Very interesting, Marco.

Though I found two studies (here and here) that said only delta-opioid receptor agonists — but not mu- and kappa-opioid receptor agonists — protect neurons from glutamate-induced excitotoxicity! So this is somewhat confusing.

 

[Little Bluestem]

I'd like to be a fly on the wall when you guys go to your doctors and tell them you would like to try out a variety of opioids to see which one makes you feel the best.

 

[Hip]

I'd like to be a fly on the wall when you guys go to your doctors and tell them you would like to try out a variety of opioids to see which one makes you feel the best.

This is a good point. Presumably those who are taking opioid pain medications received a prescription from their doctor because they were experiencing pain. However, for those without any pain symptoms, it may not be so easy to get opioids for this off-label use from your doctor. And I understand that the usual overseas pharmacies do not supply controlled drugs such as opioids.

So getting hold of opioids as a treatment for the cognitive and neurological symptoms of ME/CFS may be tricky.

Having said that, I recently saw a TV documentary about how some people in the US say they have pain when they have not, in order to get a prescription for opioid pain-relieving drugs, which they then use recreationally.

 

[Hip]

One study suggests a cautious approach when using opioids in fibromyalgia:

In this first study reporting on health related measures and opioid use in FM, opioid users had poorer symptoms and functional and occupational status compared to nonusers. Although opioid users may originally have had more severe symptoms at the onset of disease, we have no evidence that these agents improved status beyond standard care and may even have contributed to a less favourable outcome. Only a formal study of opioid use in FM will clarify this issue, but until then physicians must be vigilant regarding the multiple adverse consequences of opioid therapy.

Source: Opioid Use in Fibromyalgia Is Associated with Negative Health Related Measures in a Prospective Cohort Study

That study also had a useful opioid strength conversion guide:

10 mg morphine was equivalent to: tramadol 100 mg, codeine 100 mg, hydromorphone 2 mg, oxycodone 5 mg, and meperidine 100 mg.

 

[Marco]

Very interesting, Marco.

Though I found two studies (here and here) that said only delta-opioid receptor agonists — but not mu- and kappa-opioid receptor agonists — protect neurons from glutamate-induced excitotoxicity! So this is somewhat confusing.

Confusing's the word.

It also seems that as opioid tolerance develops so does an increase in glutamate. Short term opioid use may give short term benefits but longer term?

One way to prevent tolerance developing is to also take a glutamate NMDA receptor antagonist. Apparently resveratrol has the same effect.

Interesting effects though and worth digging into. Tinnitus I feel may be a handy marker of 'neuroinflammation'.

PS Thanks for the plug Dufresne

 

[Tristen]

Confusing's the word.

It also seems that as opioid tolerance develops so does an increase in glutamate. Short term opioid use may give short term benefits but longer term?

One way to prevent tolerance developing is to also take a glutamate NMDA receptor antagonist. Apparently resveratrol has the same effect.

Interesting effects though and worth digging into. Tinnitus I feel may be a handy marker of 'neuroinflammation'.

PS Thanks for the plug Dufresne

Good point about the tolerance issue. I haven't taken the meds long enough to make a call on that (well, maybe somewhat). This discussion also got me thinking about symptomatic baseline changes after their use. I said previously that I hadn't noticed any changes in my baseline condition after stopping the meds, which is true, but then I haven't been on them long term.

I'm sure it would be difficult if not impossible to find a doc to prescribe these meds for me/cfs symptoms, even the me/cfs docs. But then most of us have physical pain too. I can get them for arthritis pain. Regardless, I really don't want to be on narcotics long term. Easier said being back at the mild-moderate level of illness. I was willing to do anything when severe.......but really doubt I would have seen this affect then.

 

[Hip]

I really don't want to be on narcotics long term.

We can look at this from a scientific investigation point of view, as well as from a treatment perspective: if mu-opioid receptor agonists are producing a distinct reduction in the cognitive and neurological symptoms of ME/CFS, then this fact should be able to throw some light on the biochemical cause of these neurological symptoms in ME/CFS.

One way to prevent tolerance developing is to also take a glutamate NMDA receptor antagonist. Apparently resveratrol has the same effect.

This study says the same. So it might be a good idea to take transdermal magnesium (magnesium cream) when you take opioid medications, as the high doses of magnesium absorbed from the skin act as an NMDA receptor antagonist. (And transdermal magnesium is beneficial for ME/CFS anyway). Taurine (around a gram or two) is another useful NMDA receptor antagonist. Dextromethorphan and the supplement huperzine A are also good NMDA receptor antagonists.

Here is some more info on resveratrol's ability to reduce opioid tolerance:

In preserving the pain-relieving effects of morphine, resveratrol appeared to work in two ways. It reversed the increase in expression of a type of neurotransmitter (N-methyl D-aspartate, or NMDA) receptors associated with morphine tolerance. Resveratrol also blocked the increase of inflammation-promoting substances, called cytokines, in rats with morphine tolerance.

Source: Resveratrol May Preserve Pain-Relieving Effects of Morphine

 

[Hip]

It was norco this time, but I have noticed the same effect in the past with other opioid pain meds like those containing oxycodone. It takes around 12 hours to affect the symptoms, and then on the second day more relief, third day even more. I get more clear cognitively that I've been in 20 years with me/cfs. The relief continues as long as I take the meds and will continue for 1-2 days after stopping the meds.

In order to obtain some of the ME/CFS neurological benefits from opioid pain medications, but without taking these meds daily, what you could consider doing is taking a good dose of these opioid medications just once a week.

Since you say the neurological benefits of these opioid medications last for 1 to 2 days even after stopping the medication, this suggests that a single dose of the opioid medication, taken on one day, would give you around two or more days in total of ME/CFS neurological symptom relief. Two days a week with a clearer mind is better than nothing.

Taking an opioid medication just once a week like this should help avoid any tolerance issues, especially if you also take supplements like resveratrol, taurine and transdermal magnesium, which help prevent opioid tolerance.

Just an idea.

(Incidentally, the half life of oxycodone and hydrocodone is around 4 hours, so these drugs are going to be pretty much completely out of your system after 24 hours.)

 

[Dufresne]

In Dr Cheney’s 2009 Fairfax presentation he claimed hydrocodone was universally beneficial to ME/CFS sufferers, as measured by his ETM machine. From my personal experience with the supplements and drugs Cheney claims are beneficial, as well as those contraindicated, I can tell you that what his ETM machine is gauging is the degree of oxidative stress/excitotoxicity. For some reason the folks that actually feel this change in degree of excitotoxicity are in the minority. But those that feel it may be the ones that would most benefit from the therapies he recommends.

 

[Hip]

It also seems that as opioid tolerance develops so does an increase in glutamate. Short term opioid use may give short term benefits but longer term?

Marco: It does seem that both mu-opioid receptor agonists, and delta-opioid receptor agonists too, inhibit excitatory glutamate neurotransmission:

• Activation of mu opioid receptor inhibits the excitatory glutamatergic transmission in the anterior cingulate cortex of the rats with peripheral inflammation

• Mu-opioid-mediated inhibition of glutamate synaptic transmission in rat central amygdala neurons

• Activation of mu- and delta-opioid receptors causes presynaptic inhibition of glutamatergic excitation in neocortical neurons

So in regards to the excess glutamate model for the cognitive and neurological symptoms of ME/CFS that you have expounded upon here and here, the symptom reductions that ME/CFS patients say they experience when taking mu-opioid receptor agonist drugs (such as hydrocodone and oxycodone) could be explained in these terms, ie, by the fact that these drugs reduce glutamatergic neurotransmission.

Interestingly, morphine is able to inhibit microglial activation:

• Microglia-Mediated Neurotoxicity Is Inhibited by Morphine through an Opioid Receptor-Independent Reduction of NADPH Oxidase Activity

I personally suspect that the source of the excess glutamate in ME/CFS derives in part from microglial activation.