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

[Dufresne]

As it relates to Marco’s thinking on the subject, as well as taking something I knew to be risky for me, I thought I’d post a little about my experimentation with GBL and Baclofen.

With GBL I had no excitotoxicity. I also couldn't trigger PEM no matter how much I read, whereas a long paragraph used to cause me problems. Neuro-symptoms disappeared, and I enjoyed an increased tolerance for exercise.

GBL is a potent GABA-B agonist but it stimulates the hell out of endorphins too. You do develop a bit of tolerance to it within a week of regular dosing which leads to a slight rebound for a day or two, though hardly a remarkable worsening of excitotoxicity which is what I was expecting. Of course if one were taking it around the clock for an extended period of time I imagine the withdrawal would be similar to that of alcohol.

I started taking Baclofen, hopefully a sustainable GABA-B receptor agonist, and the results have been promising. I can get 80 mg/day prescribed here legally. Some of that wired feeling is dissipating.

I should add that I’m not endorsing GBL use or even Baclofen therapy, and I’ll have anybody reading know that I”m not combining these two. Just thought the effects might be of interest to certain posters on this thread.

 

[Tristen]

Thanks Dufresne, I've been considering the baclofen and appreciate hearing about your experience with it. Being non narcotic is a plus if it will work anywhere near as well as the opiates. GBL?

 

[Marco]

Hi Dufresne

GABA-B agonists do appear to be having an impact on some of your core symptoms which is suggestive. Rather you than me though - I really don't like the sound of that GBL!

 

[Dufresne]

What I’d like to find out is what aspect of my high protein diet is problematic, the glutamic acid or the ammonia. As I understand it both are able to get into the NMDA receptors. When I drop my protein intake down I really feel the Baclofen coming on. It’s great. It soothes this body-wide sensation of angst and does wonders for my social anxiety. Adjunctive therapies alongside the Baclofen might allow me to get by on a lower dose.

 

[heapsreal]

250-300mg of baclofen is a pretty big dose. if u ever need to stop your going to have to taper off it slowly. A common dosage i have seen used for muscle spasm in spastic type conditions is 25mg 3 times a day. I have used 75mg at night to help sleep and it did but i found 25-50mg more then enough, but i was only using it at night for sleep.

Have u looked into DXM Dextromethorphan as an NMDA antagonist and also supposedly can help with reversing tolerence to benzo's.

Theres a substance called GABOB (Amino Butyric Acid) said to work similar to GHB but without inducing unconsciousness, supposedly helps increase growth hormones etc. Ive never used it but it looks interesting and its sold here http://www.antiaging-systems.com/38-aminohydroxybutyric-acid-gabob-buxamin 1000mg seems to be the recommended dose which can add up if used nightly??

 

[xchocoholic]

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.

My reaction is within 20 minutes of taking the med and only lasts
it's normal alotted time. I'm assuming my reaction is just the normal carefree reaction
associated with these meds. I can't take these for very many days without feeling
sick / toxic tho. Because i have regular swelling hydrocodone works better thanloratab.

 

[Dufresne]

DM is effective but I don’t like the idea of taking it regularly, it's in the same books as GBL. This GABOB looks like it’s in the same family as GBL/GHB. Perhaps a good option to substitute for the massively overpriced Xyrem. Still one has to be careful with any of these. I hear Phenibut can be somewhat nasty to come off, and that can be ordered from IHerb.

What I like about the Baclofen is it’s apparently very specific to the GABA-B receptor. A hell of a lot better option than benzos. Those are horrible drugs.

The next drug I'd like to try is Tianeptine.

 

[Tristen]

Idea's, theories, links, on the cause of the NMDA excitoxicity or Glutaminergic storm, in me/cfs?

 

[peggy-sue]

If it's of any interest, I've been having to take co-codamol (500 mg paracetamol, 30 mg codeine) for sciatica over the last year or so.

I too, noticed a huge improvement in everything, even after I stopped the first time, for a short while, but it didn't last forever.
I started out just taking one tablet, the codeine was enough to kill the pain.
(I didn't want the paracetamol, it doesn't touch pain for me, never has).

However, the sciatica came back, I'm back on the tablets, I'm up to taking two at a time (never more than 5 a day, I am very wary of the paracetamol - and of addiction, to which I am very susceptible) and these improvements have not returned.

They do help my sleep.

 

[Marco]

Idea's, theories, links, on the cause of the NMDA excitoxicity or Glutaminergic storm, in me/cfs?

Tentative but here are some related snippets from my last blog on the subject :

In a review of immune findings in ME/CFS to date, Bansal et all, 2011 concluded: “Despite many years of intense investigation there is little consensus on the presence, nature and degree of immune dysfunction in this condition. However, slightly increased parameters of inflammation and pro-inflammatory cytokines such as interleukin (IL) 1, IL6 and tumour necrosis factor (TNF) α are likely present. Additionally, impaired natural killer cell function appears evident.”

You may also recall that Rönnbäck and Hansson’s description of ‘mental fatigue’ discussed in Part II suggested the role that pro-inflammatory cytokines may play in mental fatigue :

“we present the hypothesis that the proinflammatory cytokines tumor necrosis factor-α, IL-1β and IL-6 could be involved in the pathophysiology of mental fatigue through their ability to attenuate the astroglial clearance of extracellular glutamate, their disintegration of the blood brain barrier, and effects on astroglial metabolism and metabolic supply for the neurons, thereby attenuating glutamate transmission.”

The Japanese encephalitis virus (JEV) could provide something of a model for ME/CFS. This virus has been shown to cause encephalitis via a mechanism whereby TNF-alpha inhibits glutamate re-uptake leading to raised extracellular glutamate and excitotoxicity (Chen et al, 2012) :

“Our findings support a potential link between neuroinflammation and the development of excitotoxic neuronal injury in Japanese encephalitis. The link between neuroinflammation and excitotoxic death may involve a mechanism in which TNF-α released by microglia plays a facilitory role in glutamate excitoneurotoxicity via up-regulation of glutamate synthesis and down-regulation of glutamate uptake.”

Note that this process is remarkably similar to that proposed by Rönnbäck and Hansson to cause mental fatigue.

Regarding fatigue in primary biliary cirrhosis (as currently being studied by Julia Newton as a model for ME/CFS) Medscape states :

“The etiology of fatigue is unclear; although some evidence suggests that abnormalities of the hypothalamic-pituitary-adrenal axis, decreased release of serotonin, and increased production of proinflammatory cytokines (ie, interleukin-1 [IL-1], interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α] ) may be responsible.”

Medscape

Intriguingly, a just published paper (Raszeja-Wyszomirska et al, 2013) reports the association between polymorphisms in TRAF1-C5 – a gene regulating TNF-a with ‘sickness behaviour’ – fatigue, mental and physical function and mood in patients with primary biliary cirrhosis.

This finding appears to parallel increased polymorphisms in a TNF-a promoter gene in ME/CFS patients (Carlo-Stella et al, 2006) which led the researchers to comment :

“We hypothesize that CFS patients can have a genetic predisposition to an immunomodulatory response of an inflammatory nature probably secondary to one or more environmental insults of unknown nature.”

Read more: The Immune in Neuroimmune: Cytokines, Bugs and NK Cells – Part IV of the Neuroinflammatory Series Continues http://www.cortjohnson.org/blog/201...ls-part-iv-neuroinflammatory-series-continue/

 

[Tristen]

Fantastic, thanks Marco! My own labs showing very abnormal values with these particular cytokines, and my level of excitotoxicity, does seem to validate this information.

 

[Marco]

Fantastic, thanks Marco! My own labs showing very abnormal values with these particular cytokines, and my level of excitotoxicity, does seem to validate this information.

Thanks Tristen

I think it does hang together as a working hypothesis. Here it is in diagram form :

What to do about it though?

 

[Dufresne]

What to do about it though?

reduce dietary glutamate
transdermal or injectable magnesium as an NMDA antagonist
GABA agonists
wormwood for the cytokines (just a hunch - not sure how it works)
eliminate toxins to the best of one’s ability
kill bugs

 

[Marco]

Curcumin (or Etanercept) to reduce TNF-a?

or high dose thiamine : http://www.cortjohnson.org/blog/201...gia-mecfs-found-early-reports-spark-interest/

Plus lots of suggestions to come in my next blog

 

[Dufresne]

Curcumin (or Etanercept) to reduce TNF-a?

or high dose thiamine : http://www.cortjohnson.org/blog/201...gia-mecfs-found-early-reports-spark-interest/

Plus lots of suggestions to come in my next blog

Thanks for drawing my attention back to this article. I’d originally skimmed it and missed what was relevant to my thinking. It makes sense that Wernicke-Korsakoff which manifests as ‘wet brain’ is caused by excitotoxicity induced by alcohol withdrawal. I’d never thought that the correlation to B1 deficiency could suggest a possible remedy for ME/CFS. Just never thought it through. Thanks. I’ll try it.

I really look forward to your next blog

 

[Dufresne]

View attachment 5239

Does sympathetic dominance lead to pro-inflammatory cytokine production? I’ve often wondered if this were the case, but you’d think it would be the other way around, that it suppresses it. No?

 

[Marco]

Does sympathetic dominance lead to pro-inflammatory cytokine production? I’ve often wondered if this were the case, but you’d think it would be the other way around, that it suppresses it. No?

In a roundabout way. As I understand it, parasympathetic activity is anti-inflammatory so a relative absence of parasympathetic activity would be pro-inflammatory?

Which would explain why sympathetic ANS dominance is associated with cardiovascular risk and increased mortality generally.

 

[peggy-sue]

Wernike-Korsakoff is caused by Vit B deficiencies, not alcohol directly or alcohol withdrawal.
An alcoholic who continues to eat properly while continuing to drink will end up with non-Korsakoff alcoholic dementia (or primary alcoholic dementia - another name for the same thing), which manifests as severe short-term memory loss.
(my Dad had this)

 

[Marco]

Wernike-Korsakoff is caused by Vit B deficiencies, not alcohol directly or alcohol withdrawal.
An alcoholic who continues to eat properly while continuing to drink will end up with non-Korsakoff alcoholic dementia (or primary alcoholic dementia - another name for the same thing), which manifests as severe short-term memory loss.
(my Dad had this)

Maybe not the same thing but related. Alcohol withdrawal causes neurological kindling as, with the withdrawal of GABAergic alcohol, you get a neurotoxic glutamate spike that can provoke seizures amongst other potentially serious symptoms and repeated episodes of withdrawal cause permanent brain damage.

While W-K is due to thiamine deficiency (poor diet and poor absorption in alcoholics) the mechanism involves thiamine deficiency interfering with astrocyte glutamate transporters which normally clear extracellular glutamate resulting in neurological damage.

http://www.ncbi.nlm.nih.gov/pubmed/19565658

More than likely a thiamine deficiency will accelerate kindling induced brain damage.

Thiamine supplementation and my old favourite NAC can help prevent it.

 

[peggy-sue]

Yup, my mother was a binger, died from total organ failure caused by chronic alcoholism. She went through phases of being sober, then binging again - that was what killed her. The stress on her body of swapping from one state to the other, repeatedly.
My Dad was a steady drinker, I managed to get him sober after she died and he was quite happy to survive on just 4 cans of beer a day. There are 2 types of alcoholic.

Thankfully, although I'm a binger, I didn't bother with the sober binges and didn't do myself any permanent damage.
I am horribly familiar with the neurological kindling though. The tremors were vile until I could get some booze to stay down, sometimes I had epileptic fits and found myself coming to in hospital. I (thankfully) didn't get hallucinations.
(I did get sober, shortly after I started having fits. They were truly scary.)