Reversing Opioid Tolerance

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Myrmidon
New Member


Date Joined May 2010
Total Posts : 5
   Posted 5/23/2010 2:30 PM (GMT -7)   
I have been using opioid (tramadol, hydrocodone and oxycodone) for 6 years, initially to manage pain related to a car accident (hip, sacroiliac, sciatic nerve) and then for my scoliosis (which didn't cause me any problems until my late 30's). I'm now 42.

As I expect to be on pain meds for the rest of my life, I am concerned about the future efficacy of the meds. As it is, I spend a fair bit of time lying down and not taking any breakthough medication just to help reduce the rate of tolerance development. My pain doc provides me with enough to take 1-2 per day but I usually just use 1/3 -- creeping into 1/2 of what he prescribes. In addition to Ultram ER, I use 10-15mg of hydro or 7.5mg of oxy for breakthrough pain.

I've searched online to gain an understanding of the mechanisms underlying tolerance and what research is out there regarding how to reverse it. I have no background in biochemistry, but have put together a basic picture.

From what I can gather, there's a short-term mechanism and various long-term mechanism of opioid tolerance.
The long term include both a reduction of opioid receptors and desensitization -- the latter primarily as a result of a number of mediating processes related to NMDA and glutamine.

As for research of reversing tolerance, I've looked at clinicaltrials.gov and some pre-clinical work. It seems that ketamine and to a lesser degree dextromethorophan have been key targets of research (NMDA antagonists). But it does not look as if they offer more than a temporary change in receptor behavior. Opioid antagonists (e.g. naloxone and naltrexone) likewise don't reset the receptors for the long term. Though there are drugs to permanently reverse tolerance for benzodizepines (for instance), I cannot find something which will do that -- or even make much of a dent in opioid tolerance.

Other than the above, reduction of dose frequency, and opioid cycling, I am wondering what else can be done. Has anyone here looked into the research and can give me some leads?

Thanks.

Tirzah
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Date Joined Jul 2008
Total Posts : 2203
   Posted 5/24/2010 9:48 PM (GMT -7)   
I'm not sure about what research studies are out there, but you could go off the opioids for a while. My PM puts me on a "drug holiday" for 2 weeks each year. Yes, they are miserable (though he does give me meds to manage the withdrawals), but I have been on the same dose of medication for over 6 years & it is still just as effective as it was on day one.

Hope that helps!
frances

PS -- The best source of information is your PM. S/he should be able to give you information about what is safe & healthy for you.

Myrmidon
New Member


Date Joined May 2010
Total Posts : 5
   Posted 5/25/2010 3:29 PM (GMT -7)   
Thanks for the reply. I have likewise taken such "drug holidays" in the past.... including my daily maintenance Ultram ER.
Definitely, when I restart, the efficacy has increased, but then settled back fairly quickly.

For 4-5 years, I didn't notice any tolerance developing. It has only been for about the last year or so that I've found a need to increase my dose. But it has been perhaps 2 years since I took my last "holiday". I'm going to stay on the Ultram and see if no hydrocodone or oxycodone for 2 weeks will help restore the efficacy -- for more than just a short period.

If that doesn't work, I may then try with no Ultram. Dosing out over 3-5 days--- diarrhea, cramps, etc! But also, I probably won't be able to get any work done for days... something I can't do at the moment.

Thanks for the recommendation

Tirzah
Veteran Member


Date Joined Jul 2008
Total Posts : 2203
   Posted 5/25/2010 4:00 PM (GMT -7)   
Maybe your pain is getting worse. On rare occasion, I have been on a higher dose for a month or so. But then my PM runs tests & starts brainstorming other ideas to manage my pain. After a couple of weeks, we are able to cut back down to the lower dose.

Not really sure whether that's what's going on with you, but even if your not developing a tolerance the low dose might not be enough for you anymore. Conditions do worsen & that is the most common reason for needing an increase in meds.

take care,
frances

PS -- have you tried Promethazine for the stomach issues? it is an anti-nausea med especially for withdrawal nausea. it has been a godsend for me. i use that & catapres patches and the two together keep away all the symptoms except the creepy crawly feeling in my legs. it makes it much more manageable to face the drug holiday.

Myrmidon
New Member


Date Joined May 2010
Total Posts : 5
   Posted 6/7/2010 3:49 PM (GMT -7)   
Some board members may be interested in the results...

I followed Frances_2008's suggestion -- at least in part.

I continued with my Ultram and went one week without taking any breakthrough meds. I wanted to take two weeks, but I've not been able to get enough work done due to the pain and I have a project which must be finished asap (my concentration is not impaired by opioids).

Anyhow, I took 10mg of hydrocodone today and its effects are greater than what that dose had been offering. The short break seems to have scaled back at least a short-term tolerance mechanism. I'll see what happens over the next few days when I take another breakthrough dose.

Also, the added pain motivated me to buy a few books on yoga (haven't arrived yet) as well as purchase some hot/cold gelpacks (have arrived).
Other board members may be interested in the gelpacks. They are "Elasto-Gel" and there are ones for the cervical spine, lumbar, and for the whole back. Here's a link to a few: http://www.elastogel.com/product_catalog.php?category_id=1&subcategory_id=6&page=1

tmjpain
Veteran Member


Date Joined Oct 2008
Total Posts : 2021
   Posted 6/7/2010 6:05 PM (GMT -7)   
I have had three cycles of intravenous ketamine to start resetting my receptors and am now on dextromethorphan four times a day to continue this process. I am also weaning off my oxycodone as it has not been effective for my pain. At this point I am not sure how long he is keeping me on the DM and what the next plan is. I am almost afraid to ask.
   
SUZANE
      
 Chronic, severe and continuous bilateral temporal headaches since April 2000.
 Poor prognosis, seen thousands of doctors, been on dozens of meds and tried all forms of treatment with no success.
   May 2010 to present taking DM, dextromethorphan, 4x/day, to continue to reset the receptors, weaning off of oxycodone as it did not help with my pain, pain continues to be terrible every minute of every day!
  Feb to end of April 2010:3 cycles of IV Ketamine infusion via a PICC line and pump at home, this was to try to break the pain cycle by resetting the receptors
 Meds: oxycodone for breakthrough, cymbalta, vitamin D, B12, magnesium, omega 3, melatonin
 Profession: Part time registered nurse on Long term disability and applying for permanent disability thru CPP
 52 yrs old, female, married, two boys 19 & 21, live in Ottawa, Ontario, Canada
 
           


Myrmidon
New Member


Date Joined May 2010
Total Posts : 5
   Posted 6/7/2010 7:32 PM (GMT -7)   
Suzan,

Thanks for letting me know about the treatment. Do you think the ketamine made a difference?

Do you know of any clinical trial data for it or DXM? What dosage are you using?

Let me know if the DXM helps.

RobertB
New Member


Date Joined Nov 2011
Total Posts : 1
   Posted 11/10/2011 8:45 PM (GMT -7)   
Tale a look at this link about the study by Jane Loitman in 2006. It might help you people tremendously. Here is a link to an article discussing the report:

http://www.prohealth.com/library/showarticle.cfm?libid=14502
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