Opioids Opioid tolerance reducers/Opioid Potentiators list

[bookshelf1]

There are some ways to reduce opioid tolerance and inhibit amounts of tolerance and use opioid high more days
but they don't work perfectly
but it has worth for someone who need more badly

1-Proglumide
it is hard to find
Reference: Wikipedia reference / International Association for the Study of Pain

2-Pregabalin
i tested it sometimes works great,Gabapentin works too but its weaker and doesn't work like pregabalin in my experience
Reference: Pubmed / British Pharmacological Society / Wiley-European Journal Of Pain / Korean Journal of Anesthesiology

3-Ultra Low Dose Naloxone(ULDN)
tutorial of how to do this is on bluelight
Reference: Bluelight / Science Direct-European journal of pain / Research Gate / Sage journals-Clinical insights of medicine

4-Dextrometorphan
i tried 30mg of it 3 times with oxycodone and worked a little bit
Reference: Science Direct / British Pharmalogical Society

5-Ketamine
i tried intravenous and intramuscular and intradermal injection with 1mg to 10mg but didn't work with oxycodone 15mg to 30mg
Reference: Science Direct / International Anesthesia Research Society(IARS) / IARS-2 / Wiley-Journal Of Neurochemistry

6-Cannabinoids(Dronabinol, JWH-133)
Cannabinoids have mixed effects on opioids,they potentiate opioid high and reduce pain but simultanusly decrease the analgesic effects of opioids
Reference: International Anesthesia Research Society / Sage journals

7-Memantine
Personally i tried 10mg and 20mg memantine and didn't work at all
Reference: Springer / Nature

8-Papaver Rhoeas(Common poppy)
I tried it,its bitter and a little hard to eat or drink its tea,it worked for me awhile and made me more sleepy at opioid high but recently stopped working i don't know why,maybe we should use it when we have no tolerance at all.
Reference: SID(Scientific Information Database)Journal: KOWSAR / SID(Scientific Information Database)Journal: PHYSIOLOGY AND PHARMACOLOGY / SID(Scientific Information Database)Journal: Journal of Medicinal Plants

9-Vitamin B+Omega3
I found it for the first time on the internet,it works great if you find right dosage but may doesn't work if you have tolerance to opioids,you can withdraw opioids for awhile and start again with it
Referenece: Bluelight

10-Tumeric
i took 3 full spoon but didn't work
Reference: Plos One / Journal of pharmacology(ASPET) / Science Direct

11-Blackseed(Nigella Sativa)
Personally i used it couple times and worked but stopped working after awhile
Reference: Researchgate / Pubmed

12-Stimulants(Amphetamines,Ephedrine)
Not well documented
Reference: Science Direct-Journal of pain and symptom management / International Association for the Study of Pain / Springer Link-Psychopharmacology

13-Benzodiezepines
Beware of overdose danger
Not well documented
Reference: Science Direct / Science Direct-European Journal of Pharmacology

14-Grapefruit
Beware of overdose danger
grapefruit doesn't reduce or inhibit tolerance.
Grapefruit can potentiate lots of drugs by influencing on enzymes,grapefruit juice increases serum levels of opioids,grapefruit inhibit some enzymes and If the drug's breakdown for removal is lessened, then the level of the drug in the blood may become and remain high.
Reference: Pubmed / Wikipedia


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and its strange why there isn't a list like this on the internet after all these years(2024)...having lots of sites about drugs and addiction on the internet they all write unnecessary and repeated subjects with no new word to help us.most of sites focus on how to not use drugs and prevent using drugs instead of supporting people who need drugs for their life.

 

[9Bar_of_Jenkem]

No mention of grapefruit juice?

 

[bookshelf1]

No mention of grapefruit juice?

thanks,i added it

 

[DeathIndustrial88]

Be careful, stuff like gabapentin can actually decrease the amount of opioids in your blood, specifically stuff like hydrocodone, while potentiating others.


- Stimulants can potentiate opioids. Although I find DRI stims to dampen opioid euphoria, where as dopamine releasers like amphetamine potentiate or synergize with the euphoria.
- Ephedrine, although technically a "stimulant", it's not in the same category as amphetamines in terms of effects, but I find it can potentiate buprenorphine quite a bit. Why though, I'm not sure.
- Diphenhydramine (aka Benadryl) is often touted as an opioid potentiator but I find it can cause extreme drowsiness which just over rides any opioid effects.
- Drugs like clonidine can slightly potentiate your opioid, but mostly just the sedation & possibly a tiny bit more pain relief.
- Laying down. Some times if I'm not feeling the opioid I took very much, if I just lay down in bed & relax for a minute, it can bring the opioids effects a little more to the forefront.
- Benzos can be hit or miss. Some times they synergize nicely & other times benzos can completely dampen the opioid euphoria & make it feel dull & boring. It can also be a dangerous combo for people who don't know what they're doing or don't know how to accurately assess their tolerances & own individual metabolisms.

 

[bookshelf1]

Be careful, stuff like gabapentin can actually decrease the amount of opioids in your blood, specifically stuff like hydrocodone, while potentiating others.


- Stimulants can potentiate opioids. Although I find DRI stims to dampen opioid euphoria, where as dopamine releasers like amphetamine potentiate or synergize with the euphoria.
- Ephedrine, although technically a "stimulant", it's not in the same category as amphetamines in terms of effects, but I find it can potentiate buprenorphine quite a bit. Why though, I'm not sure.
- Diphenhydramine (aka Benadryl) is often touted as an opioid potentiator but I find it can cause extreme drowsiness which just over rides any opioid effects.
- Drugs like clonidine can slightly potentiate your opioid, but mostly just the sedation & possibly a tiny bit more pain relief.
- Laying down. Some times if I'm not feeling the opioid I took very much, if I just lay down in bed & relax for a minute, it can bring the opioids effects a little more to the forefront.
- Benzos can be hit or miss. Some times they synergize nicely & other times benzos can completely dampen the opioid euphoria & make it feel dull & boring. It can also be a dangerous combo for people who don't know what they're doing or don't know how to accurately assess their tolerances & own individual metabolisms.

i couldn't find enough document for these you mentioned but i addeed them
if you have good scientific page/article please write for me

 

[DeathIndustrial88]

i couldn't find enough document for these you mentioned but i addeed them
if you have good scientific page/article please write for me

A lot of these are just anecdotal but some have scientific truth behind them.
Google is garbage for any drug-related research now a days. You'll be bombarded with anti-drug, pro-drug war propaganda any time you try to look anything up.

It use to be well known that stimulants enhanced pain relief from opioids. I mean you're taking two drugs that release dopamine at the same time, so you're going to get a stronger effect than taking either alone. There use to be pills with both an opioid & stimulant in them prescribed for pain, but of course they don't do this now a days anymore.

Here's some more info -

"It has been long-established that amphetamines and other stimulants have an analgesic effect in their own right and significantly enhance the analgesic effects of opioids.¹⁻⁹ The first person to suggest this combination was probably Dr. Herbert Snow of London (in 1896) who recommended an oral mixture of morphine and cocaine for patients suffering in agony from an advanced disease.¹ In the 1920s, the “Brompton Cocktail” was invented at the Royal Brompton Hospital in London.¹ The cocktail consisted of morphine or diacetylmorphine (heroin), cocaine, ethyl alcohol, and chlorpromazine (e.g., Thorazine ® ) for nausea. It was usually reserved for terminally ill patients with cancer or tuberculosis. Dextroamphetamine and morphine were found to be an excellent combination for pain relief during World War II.³ Also, during this war-time period, it was found that stimulants would counteract the respiratory depression and sedation of opioids.⁴˒⁵ Although the use of this combination was known, it was seldom used clinically and essentially unreported in the medical literature after the war. Instead, researchers, commercial producers, and practitioners turned their attention to combining stimulants, including caffeine, into single commercial products.⁶⁻⁸ This interest led to the development of popular combination drugs consisting of weak stimulants with opioids and/or inflammatory agents."

- https://www.medcentral.com/pain/chronic/simultaneous-use-stimulants-opioids


It is my own anecdotal experiences that DRI stimulants (Ritalin, Welbutrin, etc..) blunt/dull the euphoria from opioids, but dopamine releasers (like amphetamine) potentiate opioids. I don't know if anyone's looked into the science behind this, but my guess would be that DRI stims block the reuptake of dopamine that's generally already in your brain & I wonder if this also means they will block dopamine release in other areas of the brain caused by taking an opioid on top of it. Making the euphoria blunted or not apparent at all. Of course the research I just posted, they used a lot of DRI stimulants for their research. So it's possible that even a DRI stim would enhance the analgesia of opioids, but not necessarily the euphoria. Where as dopamine releasing stimulants probably provide both enhanced analgesia & more euphoria.

 

[daturetard]

Basic, or alkaline stomach conditions are better for absorption.
Also might want to add something about the CYP2D6 enzyme. It converts codeine to morphine, hydrocodone to hydromorphone, and oxy to oxymorphone. I believe valerian used long term is a weak inducer of this enzyme (as well as combination of it and hops having an agonistic effect on the opioid system, the only well known, strong inducer is glutethimide, which supposedly made codeine feel like heroin.

 

[DeathIndustrial88]

Here's some info about clonidine, although from my experience, the potentiation isn't all that phenomenal.

"Clonidine is an α2-agonist that produces analgesia independently and when administered in combination with opioids. Clonidine blocks the conduction of nerve fibers and has also been demonstrated to induce enkephalin-like substance release at peripheral sites."

- https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/clonidine

This might not apply to oral clonidine. Sounds like epidural route is used for analgesia.

More info -

"Lastly, clonidine enhances neuraxial opioids and, in combination with fentanyl, interacts in an additive manner, which can reduce the dose of each component by 60% for postoperative analgesia."

- https://www.ncbi.nlm.nih.gov/books/NBK459124/

I have no idea what a "neuraxial opioid" is, but I'd love for some one to tell me.

 

[bookshelf1]

Here's some info about clonidine, although from my experience, the potentiation isn't all that phenomenal.

"Clonidine is an α2-agonist that produces analgesia independently and when administered in combination with opioids. Clonidine blocks the conduction of nerve fibers and has also been demonstrated to induce enkephalin-like substance release at peripheral sites."

- https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/clonidine

This might not apply to oral clonidine. Sounds like epidural route is used for analgesia.

More info -

"Lastly, clonidine enhances neuraxial opioids and, in combination with fentanyl, interacts in an additive manner, which can reduce the dose of each component by 60% for postoperative analgesia."

- https://www.ncbi.nlm.nih.gov/books/NBK459124/

I have no idea what a "neuraxial opioid" is, but I'd love for some one to tell me.

neuraxial opioid is when you inject opioids to your mainstream nerve(spinal,epidural),its just a no needed word to make medicine look more complex

Basic, or alkaline stomach conditions are better for absorption.
Also might want to add something about the CYP2D6 enzyme. It converts codeine to morphine, hydrocodone to hydromorphone, and oxy to oxymorphone. I believe valerian used long term is a weak inducer of this enzyme (as well as combination of it and hops having an agonistic effect on the opioid system, the only well known, strong inducer is glutethimide, which supposedly made codeine feel like heroin.

actually i think i should remove that cytochrome part,it makes it complex and not necessary

 

[Keif' Richards]

There is not currently a substance or process that resembles what I believe you actually want. You want to revisit the days when you first started using. Those were the best days for all of us.

There is no magic spell. The only way you will ever get back to what you're looking for is by lowering your tolerance.

Cannabis is a lot similar if you'll follow me here. I also think it's much more common in the general population to have had a high Cannabis tolerance followed by abstinence. My hope is that more people will understand what I'm saying through this analogy.

With no tolerance, you can take one hit off a joint and be pleasantly high for hours. The experience is deep and vivid. You start smoking more. Pretty soon you're smoking a joint at a time. It's been a couple of weeks of regular intake. In that joint, let's say there are 10 or so of those same small hits. You are forced to admit to yourself that you now are using 10x the amount in a sitting and you're not even getting as high as that first little toke you took weeks ago.

Pretty soon, you're mixing Hash Oil with your bud. Then you start taking straight dabs. You eventually start taking huge dabs in order to be high for 15-20 minutes followed by 40 minutes of afterglow.

I have done the same thing with Opioids. Your tolerance gets to the point where you can no longer experience any positive effects. At this point you can only reduce your dosage or continue with the numbness.

You need discipline to reduce and discipline to use responsibly. Opioids can be used, chronically, without causing any physical or mental damage to a person.

Once your tolerance is back to zero, you could feasibly use again with the same effects you got initially. However, the Kindling Effect is going to make what would already require a great deal of discipline, require 10x more discipline to keep from getting out of control. Unfortunately, this leaves most people either unable to use at all or as full-blown junkies.

I believe that if you aren't managing your own supply, it can be a lot easier to make this kind of thing work. For instance, I know plenty of people who are successful on Methadone. They can easily get more Methadone, but they don't. It's that extra element of control that helps them keep some rigidity to their schedule. This is another reason why I believe Heroin/Hydromorphone prescription programs could be our only way out of this mess.

 

[daturetard]

Agmatine is great for tolerance reduction. It's like low doses of dxm with less nausea, no snri properties, and it's naturally occurring, which I know is a plus for some like myself on here.
Also, it's an amino acid that you produce, as well as being neuroprotective (i believe) and antioxidant.

 

[Halif2]

Hey daturetard beat me to the agmatine sulfate mention!

I found that to be pretty good with irregular use. DXM can also be a good one but it's going to require more than 15mg. If I'm getting it from cough syrup, I find around 60 - 100mg effective.

Overall though it's like Keif Richards said: None of these things are going to produce a miracle. Personally, I find the best use of potentiators is as an occasional booster situation. Trying to use any of them on a regular basis just leads to reduced effect at best, and a potentially a second addiction at worst.

 

[daturetard]

Hey daturetard beat me to the agmatine sulfate mention!

I found that to be pretty good with irregular use. DXM can also be a good one but it's going to require more than 15mg. If I'm getting it from cough syrup, I find around 60 - 100mg effective.

Overall though it's like Keif Richards said: None of these things are going to produce a miracle. Personally, I find the best use of potentiators is as an occasional booster situation. Trying to use any of them on a regular basis just leads to reduced effect at best, and a potentially a second addiction at worst.

Why did you keep the agmatine irregular? Does it form tolerance?

I personally would recommend a sub-intoxicating dose of DXM. I think anything over 40mg starts to take the spotlight away from the opioid euphoria and starts dissociating you from the good feelings. (However I am sensitive to DXM and I believe I have a strong CYP2D6 as I can notice recreational effects from just 60 MG codeine.

Also, the CLOSEST drug to a miracle when it comes to opioid tolerance/potentiation, hands down, ULDN. Naltrexone is super easy to get in order to stop drinking.

I've tried taking low doses of lope to clog gut receptors. Not sure if it worked or not. I'd like some input on this from others.

DLPA and blackseed oil have significant agonistic effects on the MOR. One last suggestion, if you choose to use a gabapentinoid, go with phenibut or pregabalin. Gabapentin decreases the absorption of opioid. If you intend to use gab, take it at least an hour post-opioid.

 

[Psychlone Jack]

My simple go-to's when I need to stretch a dose are diphenhydramine and dxm, as with this morning; 100mg and 60mg respectively.

And also, kinda surprised not to see a mention of it already, but black seed oil. Mixed reviews just as with everything else, but I personally found it indispensable for pretty much the entirety of my last taper.

 

[chippermonk]

Also might want to add something about the CYP2D6 enzyme. It converts codeine to morphine, hydrocodone to hydromorphone, and oxy to oxymorphone....the only well known, strong inducer is glutethimide, which supposedly made codeine feel like heroin.

I actually have a couple ancient glutethimide ( Doriden) tablets around from my grandmother's medicine cabinet. I know they are supposed to work well with codeine, oxys and hydros, but I never really can bring myself to try them out, having a very low opi tolerance. I sure can't take them at the dose level people did with Dors-and-4s back in the old days. Maybe someday I'll give them a try, if I can ever get some solid HR advice.

 

[Halif2]

Why did you keep the agmatine irregular? Does it form tolerance?

It seemed to stop being noticeably effective after three or so days and - this is completely subjective - I felt strange when I stopped using it. I know that's pretty vague but it was just a kind of drop in mood. Unfortunately, most of my agmatine experience was when I was taking a bunch of other things because I was tapering and detoxing, so it's harder to say what it was or wasn't doing. If I use it now and then I find it fairly effective and there are no negative after effects, so I like to keep it as a 'now and then' thing.

Also, I should have mentioned that I have a residual tolerance to dissociatives because I took boatloads of them a while back (I miss MXE so much). So 40 - 60mg of DXM for potentiating opioids is probably a safer range. For me, it's at 150 - 200mg that the DXM effects become noticeable and can potentially mess with the opiate effects.

I'll have to look at blackseed oil after the positive mention from a couple of people here.

 

[bookshelf1]

I have used NSAIDs specially Naproxen for tolerance reduction of Oxycodone and it worked sometimes greatly when together with vitamin B+Omega3 but i couldn't find any reference and scientific article about it.