Opioids Is it possible to reverse opioid tolerance?

[Swimmingdancer]

I often hear people say the only thing that can reverse tolerance to opioids is time without taking the drug, or that you can only slow the progression of tolerance, not reverse it, but I have seen a lot of animal studies where they were actually able to reverse tolerance using things like magnesium, DXM, other NMDA antagonists or CGRP antagonists. Is this possible in humans? Anyone have any experience? Do these things (presumably in correct doses etc) only "reverse" tolerance while you are taking them or for a short time after? Or can they actually effectively reset your tolerance back to zero? And if so, would that have implications for dependence?

 

[rymerkk]

things like NMDA antagonists will slightly lower your tolerance for the time said antagonist is active in your system, but nothing can reset your tolerance back to being an opiate virgin. also, in my experience taking NMDA antags give the high a slightly different character along with a small tolerance reduction.. not really a bad thing, but doesn't feel as "clean" (for lack of a better word) as just taking a straight opiate and nothing else. in my experience even taking a break without taking an opiates for a good while will reduce your tolerance significantly (the longer the better), but never back to absolute zero and will return back to original tolerance in a matter of days. again this is my experience in the matter.

 

[spacebound]

only time can reduce your opioid tolerance. you can obviously take something else to enhance your experience, but nothing will magically reverse your tolerance. it sucks, but i recently took ~1.5 month break and still had a fairly high tolerance (i was disappointed X_X).

 

[tricomb]

I take Chelated Magnesium (an NMDA antagonist) not for tolerance decrease but to prevent further increases of tolerance.

Of course these NMDA antagonists probably can't help people who are taking ever escalating doses.

 

[Ksa]

You can't really, it's our nature that was shaped through the survival of the fittest. Human beings define their reality through pain and misery so as soon as you add a substance that makes you feel better, the body readjusts. Like, say you're 10,000 years ago, and there's a restless guy feeling miserable and another guy feeling high, sleeping in his cave and enjoying life. The guy feeling miserable gains a sense of alertness, constantly trying to get out of that state, so he breaks into the other dude's home, kills him and steals his goods. So the calm, joyful and happy dude was never able to pass on his genes because he was overwhelmed by the dysphoric caveman which later evolved into the desperate American on the gold run and laying the foundations for our society of stressed/overworked individuals.

In a shell.

 

[chemical ali]

only time can reduce your opioid tolerance. you can obviously take something else to enhance your experience, but nothing will magically reverse your tolerance. it sucks, but i recently took ~1.5 month break and still had a fairly high tolerance (i was disappointed X_X).

i've taken 8-9 month breaks and still fairly high tolerance. the initial rush feels good but the high is the same old (taking the same dose as i would have before the break or even slightly more because money isnt an issue with a "once in a while" habit) i think the rush is good becase you receptors have been dormant for a while, but the high is the same because once they're activated a light bulb clicks on and they "remember." i am doing dilaudids

 

[brighton]

I take Chelated Magnesium (an NMDA antagonist) not for tolerance decrease but to prevent further increases of tolerance.

Of course these NMDA antagonists probably can't help people who are taking ever escalating doses.

Do you find it works well?? I found dxm to do nothing for my tolerance.

 

[tricomb]

Yeah I briefly tried DXM but much prefer chelated Mg. It's subtle, and probably can benefit people who take more or less the same dose of opioids daily. Plus, the magnesium should help with opioid induced constipation!

 

[Laughing Man]

Recent administration of naloxzone will temporarily reduce tolerance to all opiods for at least a week or two.
Of course naloxzone can also precipitate acute opiate withdrawal symptoms as well so it's a double edged sword.
I have empirical experience with this phenomenon because my brother took one of my 100 µg Duragesic patches and consumed the contents. He was overdosing within an hour. One week later he was shooting up 80 mg tabs of Oxycontin but his previously safe dose was now much lower like an opiate naive subject. He died exactly one week after being administered doses of naloxzone in the 24 hours he was hospitalized for the Fentanyl overdose when he resumed shooting up his previously safe Oxycontin dosages. This was in 2004. Since then I believe Oxycontin has been altered to gel like MS Contin so it is now more difficult to use via IV routes.

 

[Ashley]

What about ultra low dose naltrexone? Wasn't that shown to be effective in reducing/reversing opiate tolerance?

Ash.

 

[cdin]

using ibogaine will end up resetting your tolerance - but should be used as an adjunct for quitting, not getting higher. low dose it will blockade the opiate receptors - high dose it will reset them but it's a helluva an experience just to get your rocks off.

 

[RobotRipping]

i use magnesium for tolerance, doesn't help that much. it's been 5 months since i started opiates and using magnesium and my tolerance keeps going up, it sucks. It's either that or my desire to get high keeps increasing and since i'm always on opiates i get used to the feeling so it feels normal.

 

[Swimmingdancer]

So sorry to hear about your brother Laughing Man . I think when people are administered naloxone they should be warned that it may greatly decrease their tolerance and that if they are going to use opioids again to use much less than their usual dose.

I was more meaning are there any things you can do without stopping taking the opioids and, ideally that don't give major unwanted side-effects (like naloxone). People keep saying that it is impossible to decrease or reverse tolerance, that taking certain drugs/supplements will only slow future increases of tolerance, but what are we basing this on? Just that we personally have not been able to do it?

But what about all these animal studies? Here are just a few:

In these mice, the co-administration of memantine and MRZ 2/579, but not dextromethorphan, resulted in the reversal of morphine tolerance [to analgesia]. [Source]

These results suggest that LY274614 and MK801 [NMDA antagonists] do not alter the expression of tolerance but actually modify the development of morphine tolerance. Morphine-tolerant animals [given a subcutaneous injection of] LY274614 for 7 days regained their analgesic sensitivity to morphine. Furthermore, LY274614 also reversed the development of tolerance and restored morphine sensitivity in tolerant animals that continued to receive morphine.[Source]

A tenfold increase in morphine [tolerance] produced by morphine pellets was completely reversed by ketamine given subcutaneously. Intraspinal morphine produced a 46-fold increase in [tolerance], which was almost completely attenuated by the coadministration of intraspinal ketamine.[Source]

A single acute injection of lithium chloride (LiCl) or magnesium chloride (MgCl(2) at the same doses (5mg/kg) reversed the expression of tolerance to the anticonvulsant effects of morphine (1mg/kg, ip). [Source]

 

[tricomb]

I've always wanted to use ketamine as my NMDA antagonist but I don't have access to it so I'm stuck with the less-effective Mg.

 

[weekday warrior]

ive tried alot of these and from m/e taking breaks is the best way to reduce tolerance wait till w/ds start then take just enough to feel 'okay' wait, repeat, do this for two weeks or so and your tolerance will have decreased considerably just dont take any more than it takes to kill the wd feeling otherwise its exactly the same as your normal tolerance building routine.

 

[Swimmingdancer]

^^Yeah, I take magnesium too. I find its effects subtle. It did seem to slightly decrease my tolerance at first and perhaps appears to have slowed (but I'm not sure if it's actually stopped) the progression of tolerance. But I'm on methadone, which is already a mild NMDA antagonist and supposedly has relatively slow progression of tolerance already. Maybe I need to take more magnesium... Also I take a calcium/magnesium supplement and I'm not sure if the apparent decrease in tolerance could be due to that improving the absorption of the methadone in my digestive system.

I am just trying to take less and less methadone with as little suffering as possible.

using ibogaine will end up resetting your tolerance - but should be used as an adjunct for quitting, not getting higher. low dose it will blockade the opiate receptors - high dose it will reset them but it's a helluva an experience just to get your rocks off.

Do you have any evidence of this? I have found ayahuasca to seem to lower tolerance while under the influence of it, but I think it's actually just potentiating/synergizing with the opioid, as I go back to feeling withdrawals after it wears off.

 

[BiggDirty01]

I have used both DXM and Methadone for the purpose of NMDA antagonism and pain relief (methadone).

Methadone in single, large doses obviously does nothing but increase your tolerance but the way i take it for pain (20mg q8hrs) helps my tolerance from increasing AS FAST as it normally would.

I take DXM at night (nyquil for sleep) so I kind of double up on my nmda antagonism but in my opinion this doesn't reverse opiate tolerance BUT it absolutely slows down the pace at which tolerance increases and therefore has successfully let me lower my IR meds from Roxy 240mg to 180mg with about the same level of effectiveness.

 

[Swimmingdancer]

^Does DXM create dependence? Like do you get any withdrawal symptoms or rebound symptoms like worsened insomnia if you stop taking it?

 

[T. Calderone]

I think the best thing to reduce opioid tolerance is stop using them. I was addicted to oxy for nearly six years. I live in Florida where the pill mills were so easy to access and get scripts again and again. Gradually, I found a doctor who talked me into stepping down (not a pill mill guy) and he eventually prescribed hydrocodone after stepping down from 30 mg oxy four times daily and he cut off my xanax. It took some time to adjust my dosage but I am so glad he did me the biggest favor. The last time I took a 30 I was sick for hours so I guess that means my tolerance is way down and that's a good thing.

 

['medicine cabinet']

my moms accupuncturist told me there are techniques for reducing opiate tolerance by targeting specific spots on the body and namely ears. has anyone ever heard this before? seems like they say accupuncture can fix or heal just about anything, but it was the first time i had heard of anything other than time or drugs being able to effect tolerance.