Opioids Is it possible to reverse opioid tolerance?

[Ashley]

Naloxone is only worth it when it's naloxone or death.

Amen to that!

Suboxone can also save lives, due to the naloxone contained within the preparation. I have used it on occasion when absolutely necessary and it worked fine.

A.

 

[milagro]

This is turning into a megathread so I skipped to the end an apologize if this has already been discussed. I felt it necessary to relay something my doctor recently told me when discussing tolerance. I am a chronic pain patient and deal with tolerance constantly. Some develop it more rapidly and it is completely dependent on the individual.

The interesting thing that my doctor said was that there has been new research that demonstrates something many people probably already knew. It involves neruoplasty and the ability of the brain to repair damage once thought permanent. I wish I could site a specific study but they are all very technical and lengthy so you can research further if you wish.

Here's the scoop-It appears that the brain can and does repair receptors such as the opioid receptors. In fact, sometimes the brain will grow new, additional receptors if the old ones are damaged and cannot accept whatever molecule they are designed to bind with. So, tolerance will occur if a substance is continuously binding and saturating receptors. Tolerance is time oriented and you develop tolerance over time but it is definitely reversible, you just have to give the body time to regenerate.

I back off my meds when I notice they aren't working as well and find that taking a break for several days or a week makes my tolerance drop significantly. I hate how I feel during a fast taper but the end result is always the same. The meds work better when I return to my prescribed dose. Unfortunately, my brain and body have to go through a little hell to accomplish this. Is the lower tolerance the result of new opioid receptors being created? Only an autopsy

 

[skipsy25]

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.

luv this theory had me pissing my self thanks

 

[Swimmingdancer]

Thanks pontifexo01
Yeah, I can't handle DXM well either, even 20-30mg before bed produces noticeable effects, and I feel weird and groggy in the morning. I can't tell if it really is making a difference or not, although it does help me get to sleep better.

 

[Neuroprotection]

Sorry if this post is too long or in the wrong place. Also please beaware, if anyone tries any of the methods mensioned below, their may be a risk of leathal over dose as I have read about on other forums.

things like NMDA antagonists may work for a short time but they have their own side effectse.g. stomach discomfort with Magnesium and additional psychological/physiological effects with stronger antagonists like ketamine or dxm lessening the quality of the high for some people. However, other drugs such as endothylin antagonists have been shown to reset opioid tolerance back to 0 without their own phsycological effects. They do this by inducing rejoyning of uncoupled mu receptors to their associated gproteins. My only practical suggestions for lowering opioid tolerance are: take strong antioxidents e.g. ubiquinol, vitamin C in its lipid soluble ester form if possible, but most importantly if available, N acetyl cystineamide. This is because its a powerfull brain permeable antioxidant. Oxidative stress and resulting neuronal apotosis has been shown to be found frequently in the spinal cord of opioid tolerant animals. Torine has also been shown to prevent morphine tolerance both invitro and invevo in rats, thoe torine has little ability to cross the blood brain barria. Its preposed mechanism is antiapoptotic in nature. Another method proven in animals is use of Neuronal nitric oxide synthase inhibitors e.g. 7 nitroindizole or methalyne blue. Exessive nitric oxide production by NOS1 enzyme is a major downstream effect of NMDA receptor activation and contributes to the neurotoxicity of many drugs as well as tolerance induction and maintenance. NOS1 is activated by calcium influx into cells when glutamate receptors are activated, partly explaining why calcium channel blockers and NMDA antagonists may lower tolerance. It looks as if, if proven safe in humans, NOS1 inhibitors could lower opioid tolerance without too much interpherance in the phisialogical effects of opioids, possibly giving a "clean high" as stated previously on the thread.
Finally, studies have found that excessive cortisol releace can contribute too opioid tolerance, note that high cortisol concentrations are neurotoxic, and long turm opioid use has been shown to cause disfunction of the hypothalamic pituitary adrenal axis. This results in constently high cortisol levels, long after an opioid dependent/tolerant user has stopped using the drugs. However, it has been shown that, antiglucocorticoids such as mephepristone, or the safer alternatives metiripone and carbonoxalone prevented down regulation or conformational changes in a wide range of receptors, particularly the 5HT1A receptor, even when subject to a powerful receptor agonist. Serotonin is an important neurotransmitter in mediating both the annalgezic and mental effects of opioids, therefore protecting its receptors is vital to prevent tolerance and repareing them my be part of completely reversing opioid tolerance. The same may aply for mu receptors, that is, that glucocorticoid signalling is partly responsible for their down regulation and blocking such signalling may reverse this.

 

[Drowzey]

Ketamine also helps significantly.

 

[belfort]

imo its pointless to try and reduce opiate tolerance..the best way to do it is by taking time off...problem is, even if you take 2-3 months off and then start taking opiates again, you will feel great on lower doses for about a week or tops and then your tolerance will rise again quickly..

the best way to reduce tolerance is to not let it rise i the first place..lol..take opiates only a few days a week so they maintain the magic but hardly anyone i know can do that!

 

[Azblondie3467]

I have the same issue. I was prescribed percocet years ago for an broken bone and arthritis.. So as expected my tolerance rose. I can now take 3 or 4 oxy 30's, valium, alazporam, dilaudid and a popular herbal remedy.. LITERALLY one right after the other..and STILL not get much notable effect Even if I go thru the hell of detox, it still doesn't seem to change my tolerance. I've done grapefruit juice, cimetadine, avacado, heck pretty much everything to old wives tales but NOTHING works. I have to draw (my personal) line b4 heroin... So I'm hoping ANYONE can give some insight into something that actually works! I was even exploring the affect long term use has affected my dopamine production, etc... I'm even trying herbal DHA. Any suggestions for a true potentiator?? I'm not superhuman, so it's definitely become a major source of irritation that I can get no relief

 

[Opes]

I have the same issue. I was prescribed percocet years ago for an broken bone and arthritis.. So as expected my tolerance rose. I can now take 3 or 4 oxy 30's, valium, alazporam, dilaudid and a popular herbal remedy.. LITERALLY one right after the other..and STILL not get much notable effect Even if I go thru the hell of detox, it still doesn't seem to change my tolerance. I've done grapefruit juice, cimetadine, avacado, heck pretty much everything to old wives tales but NOTHING works. I have to draw (my personal) line b4 heroin... So I'm hoping ANYONE can give some insight into something that actually works! I was even exploring the affect long term use has affected my dopamine production, etc... I'm even trying herbal DHA. Any suggestions for a true potentiator?? I'm not superhuman, so it's definitely become a major source of irritation that I can get no relief

I don't suggest you or anyone else take anything I'm about to say as a recommendation, but I'm going to attempt to relay some scientific information about things you're wondering about.

First of all, I'm curious as to what the popular herbal remedy is you referred to. Is it perhaps kava? If so, I have yet to find a store bought supplement form of kava that produces any noticeable effects, be it capsules, liquid in a dropper bottle, or tea bags. All the ones I've tried are extracts, some containing what should be relatively high doses in the form of kavalactones. The only one that even produced the signature numbing effect was a certain liquid extract in a dropper bottle, but still there were no discernible psychoactive effects. Anyway, I have cold-brewed kava tea with milk in the past using fresh root powder and felt definite psychoactivity. I can't recall if I combined it with opioids ever, but I would venture to guess that the mellow, relaxed state the kava produced would synergize very nicely with them when used responsibly.

As for potentiators, I have lots of experience with the ones mentioned and others taken prior to opioid administration with perceived effect. However, they only potentiate opioids taken orally and even then the potentiation is not as pronounced as many people would like to believe it's going to be. Ime the peak plasma level of the opioid doesn't seem to increase as much as the duration of the experience seems to. I used to have an almost ritualistic regimen of drugs I would take around an hour prior to orally ingesting any opioids. Also, one has to remember that you don't want to attempt potentiation with prodrugs such as codeine because then they will limit the amount of active drug produced instead.

I used to use opioids on a daily basis and believe that messed with my dopamine and/or other neurotransmitters as well, be it directly or indirectly. Phenibut use seems to have brought the levels of those neurotransmitters back up to where they were prior to opioid and other drug use (drugs such as benzodiazepines, alcohol, and psychostimulants; drugs I believe also at least played a part in this possible neurotransmitter deficiency). Even after abstaining from phenibut this effect persisted and I felt more motivation, ambition, a lot less apathy, and an overall increase in mood.

I'll be receiving some tianeptine in the mail tomorrow which I know isn't a great example for studying typical opioid tolerance, but I've been taking a form of chelated magnesium along with some other supplements and will also be taking most or all of the potentiators I used to ingest prior to my opioid experiences. I'll post a general review of how it goes with said tianeptine in this thread within the next few days. I took tianeptine for two to three days in a row around a few weeks ago, but am hoping I didn't retain much, if any, tolerance from that bout. Prior to that, I hadn't used any opioid for months and even then it was here and there once in a long while and for one or two days, three consecutive days tops as I haven't used on a regular basis in almost two years.

Alright, time for me to get some sleep since I've been making use of phenibut's ability to cause me to feel well rested after only a few hours or so of sleep lately. Just figured I'd add my thoughts about all this.

 

[cdin]

Ok, I'm pretty informed on this topic - to my knowledge, the only things that really achieve the stated aims (and are fairly easily available) are - ibogaine/iboga (done it personally - will drop your tolerance a DANGEROUS amount, a complete reset if done at a flood dose, less but significant at smaller doses), and proglumide, a CKK antagonist. Anything else just potentiates it. If that's all your after, just use booze! (In moderation!)

 

[Ashley]

Ibudilast is a pretty newly researched compound that has been used to reduce tolerance to opioids and aid in reducing the symptoms of withdrawal. I believe some of the more expensive private rehabs utilize it for this purpose.

A.

 

[Neuroprotection]

Ok, I'm pretty informed on this topic - to my knowledge, the only things that really achieve the stated aims (and are fairly easily available) are - ibogaine/iboga (done it personally - will drop your tolerance a DANGEROUS amount, a complete reset if done at a flood dose, less but significant at smaller doses), and proglumide, a CKK antagonist. Anything else just potentiates it. If that's all your after, just use booze! (In moderation!)

What about Nigela Sativa Oil/thymoquinone or endothylin antagonists, what do you think of those. According to scientific studies, they may strongly reverse opioid tolerance.

 

[Ksa]

Topic is a bit vague, what are the amounts you guys tested on? Like, give some figures. If an opioid naive takes 5mg of oxycodone orally, what memantine and DXM doses must he take those 5mg with to achieve best results? Give me figures.

It's useless to say, memantine might work. We need a fractional factorial design with 3 unknowns so that the best dose combo is found as opioid + memantine + DXM. Memantine gets really good grades on ADHD forums, it's known to turn idiots into smart asses lately, very popular so there's definitly something there.

 

[Cosmic Trigger]

Has anyone tried Agmatine to reduce tolerance? I've read of some anecdotal success using this. I'm just starting to try this myself.

 

[John Baum]

First post. Long time lurker. Here goes. My tolerance went back to near 'virgin' after 1.5 years.

A little background: I was/am 5' 7" approx. 170lbs. Athletic build/muscular/low body fat. Had spinal fusion surgery, and like many folks became severely dependent to opiate painkillers. After two years of increasing tolerance, from feeling euphoria off 1-2 percocet 5mg in the beginning, to NO high at 60mg (15mg x 4) oxycodone hydrochloride 3x day at the end of year 2 of chronic use. Fentanyl patches were used on and off in place of the oxycodone during this whole fiasco. And like so many chronic pain folks, one day I ran out of meds early. Went through hell, thought I was going to die because of the withdrawal. Had never gone cold turkey, never gone into such severe w/d like that, ever. Never been so scared in my life. I was completely ignorant to any OTC type help such as Loperamide, DXM, etc. I didn't know jack squat about anything other than what my doctor/s told me/gave me. It never occurred to me that places like this exist for help/knowledge. Too stupid and naive to not check the dang internet. Anyhow, I digress. So...Finally got into see the pain doctor 2 days later. Got put on Methadone. After 6 months of very slow tapering, I was off any and all opiates. I was shocked. The pain was actually gone a long time ago, and I was simply hooked on the meds.

And so, after approximately 1.5 years of being clean, I injured my back again in the same area where the titanium screws were. Back to pain meds again. So 2 tabs of Percocet 5/325 got me high as a kite again--pain control was 90% effective. Back to square one, on pain meds everyday again. Ah shit. My tolerance rose sharply this time around, and after 4 months, it took about 45mg oxy hydrochloride (15mg x 3) to feel a slight buzz (pain control 'seemed' adequate). I had had enough, going down that path again. I was pissed. Was severe pain actually there? Deja Vu. So got on Methadone again, with a little bit of Clonidine. Tapered off the methadone, starting from 10mg x 3 per day. This time it took just about 3 and a half months to get off opiates. Today, I am in my mid 30's, I am 7 months clean. If needed Motrin 800 is adequate for aches/pain. Crossing my fingers that I stay 'healthy', free from any more serious injuries. The previous five years or so of my life was brutal. The hell, then normalcy, then hell again. I don't want to go through that hell shit again. Not a third time. For those who are fighting the fight everyday, you have my respect and my support. Keep your head up. Keep fighting.

Anyhow, back to the point of tolerance reversal, for me I found out not because I planned it, but things just happened. I don't know if my receptors needed 1.5 years to 'reset', who knows if 8 months or 1 year could've done the same thing. But fact of the matter, for me, after 1.5 years clean, my tolerance went back to near when I was a virgin to opiates. And the second time around, my tolerance curve was a lot steeper, ie. it happened much faster. No surprise there huh. I haven't touched a 'pill' for 7 months now, and I'm not sure where my receptors are at, I don't want to know.

 

[Psychedalienation]

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.

 

[Cosmic Trigger]

Agree with Ksa also on this. We certainly do define our reality through suffering. I always wondered why we do it to such an extent on the emotional level. I searched for answers for 40 years ( i'm 63) and then I found it. If you are interested get your hands on Ernest Becker's book, Denial of Death. It's all right there and it's not anything good.

 

[ColoradoBoy90]

What about ULD?? Only one person mentioned it.

It was proven In studies to reverse tolerance. I believe in people, too, not just animals.

What about progluadmine? That also in animal studies reveresed tolerance.

Both of the above do 10X more than Dxm ever can.... Even one of the drugs I mentioned had patent on them to reverse tolerance, and was about be be released -- but big pharma came in and took them away. They just disappeared. They don't want people less addicted. They want you more addicted.

There IS (or was) a cure for opiod tolerance but big pharma has surpressed it entirely.