Idea for lessening (or completely mitigating) tolerance from opioids...

[Doktah]

Hi everyone,

I had an idea the other day for mitigating tolerance from using opioids, and I don't have much time to post this, so I'll make it quick:

I have heard of many cases where people who go on Naltrexone have dramatically reduced (or reset) tolerances to various opioids when they stop taking it... what if we were to incorporate an opioid antagonist (like Naltrexone) into a daily dosing scheme - along with an opioid of choice - to reset any incurred tolerance from using said DOC... before the tolerance builds to any noticeable or significant level?

For example, "Tim" takes morphine once in the morning, and then again in the afternoon. Then, before bed (and after the effects of the morphine have worn off), Tim takes a potent opioid antagonist with a half-life that will carry him through until about the time he wakes up, at which time it's antagonistic effect has hopefully worn off, and Tim can take his morning dose of his opioid of choice (morphine for this example). Obviously this would only apply to people who do not rely on opioids for physical pain, and it would mean there would be short windows (aside from sleep) where you would not be on an opioid, but could this effectively reset the extremely small amount of tolerance that "Tim" would have accumulated throughout the day from using?

If this could work, I'm thinking that Naltrexone would NOT work, as it's half-life would be too long... that being said, what if you were to use a time-release formulation of naloxone - at a dose where it's effect is maximal? Could this not effectively eliminate (or greatly reduce) the carrying over of tolerance from one day to the next? Or are there definite reasons that this would not work? If you believe this wouldn't at least partially work, could you please provide legitimate reasons as to why this is? I'm very curious about this - thanks in advance!

 

[dopamimetic]

There is indeed some evidence that ultra low dosed naltrexone (in the range of 100 mcg), taken together with an opioid, has a potentiating and / or tolerance-slowing effect.

By taking naltrexone or naloxone at bedtime when the latest morphine dose was in the afternoon, you'll very probably find yourself in a hellish withdrawal. As afaik both of them are inverse agonists instead of simple / silent antagonists, I don't know if such one would cause less problems. As I felt absolutely indescribable terrible after snorting a crushed pill containing 50mg tilidine and 4mg naloxone - even without being physically tolerant to opioids or a regular user at this time! so I would really recommend to make a solution and begin tapering up in the microgram range if you're going to try this.

Also time-released naloxone would be difficult to make as when taken orally it gets almost completely inactivated by first-pass metabolism.

Other way to combat tolerance is by using NMDA antagonists, they are known to modulate mu opioid receptors and especially memantine proved to work in studies and for myself … but some experienced bluelighters have expressed concerns about the long time consequences of this. While I feel that using memantine vs. going through tolerance-withdrawal-PAWS cycles seems reasonable, it is true that the safety has not yet been established.

Some also report success from using low-dosed dextromethorphan which is easier to acquire (but less clean).

 

[sekio]

but could this effectively reset the extremely small amount of tolerance that "Tim" would have accumulated throughout the day from using?

Nope.

Antagonism of opioid receptors doesn't reset tolerance. That's the issue. Otherwise people would be going out left and right to buy naloxone to knock their tolerance down. Unfortunately, all opioid antagonism does is make you feel miserable, especially if you have some residual opioid in you. IMO, Any tolerance lowering effects coming from "normal dosed" naltrexone are a result of not being able to get high...

You can look at the spectacular failure rate of "anesthesia assisted detox" clinics for more evidence... there's plenty of clinics that will knock you out for a day or so, pump you full of Narcan, and then claim the worst is over and you're "not addicted". But they rarely, if ever, work. In fact they usually leave people ending up heading right back to dope.

 

[Nagelfar]

Ever heard of the artificial/synthetic opioid peptide D.A.M.G.O.?

https://en.wikipedia.org/wiki/DAMGO