Naltrexone and upregulation

[clicheguy]

So looking around the web, one can find a great deal of anecdotal reports and testimonies and even a few studies that low dose naltrexone can help sufferers with all sorts of conditions associated with chronic pain, and that ultra low dose naltrexone can slow tolerance to opiates, etc... and that these effects are likely the result of opioid receptor antagonism causing upregulation.

It is also theorized that other kinds of antagonists, e.g. dopamine antagonists, when taken long term in high doses are thought to induce changes that lead to tardive dyskinesia, as a result of dopamine hypersensitivity.

Now you might have already guessed, but my question is this: Is there a possibility that high dose, long term naltrexone could lead to a condition where one becomes hypersensitive to endogenous opioids?

Note: I am not an opiate user. The only high I want to enhance is my body's "natural" one

 

[Ligaturd]

Like a rebound effect? I would be interested to hear if this would happen as well but I think I would have read about opioid addicts that have had the Vivitrol shot and come off of it writing reports about some sort of high. I wonder if their opioid receptors would end up having reversed any conditioning brought on by opioid usage as well.

I read ULD Naltrexone is supposed to reduce tolerance build up and helps potentiate the effects of opioids by binding to the secondary opioid receptors rather than binding to mμ and forming a blockade(other than mμ) but leaving mμ for oxycodone or whichever other opioid. I was reading up on ULDN and Oxynorm is an Oxycodone formulation that is supposed to utilize ultra low dose Naltrexone for these supposed benefits but it doesn't seem to have become very popular and I wonder if it had anything to do with the efficacy or if doctors just aren't aware of it.

 

[clicheguy]

I think I would have read about opioid addicts that have had the Vivitrol shot and come off of it writing reports about some sort of high.

Well, under ordinary conditions, dopamine is constantly released at a low level, but the peaks of release occur when one anticipates a reward. Endogenous dopamine release (induced by placebo) is even strong enough to reduce symptoms of parkinsons.

Following this logic, sensitivity to endogenous opioids might not manifest in the form of a constant high, but it might enhance the experience of peak endorphin release, e.g. runners high, orgasm, eating your favorite food, etc...

This is anecdotal, but I've been taking Fluoxetine for over 9 months now and after the initial 6 weeks or so of adjustment, orgasm became difficult and even when it was achieved, on a scale of 1 to 10, the relief/euphoria was barely a 1. At times it just felt like I was peeing toothpaste. For the past two weeks, I've been taking 4.5mg of naltrexone before bed and not only are orgasms enhanced, my sleep has improved (previously, I would always wake after ~6 hours of sleep, no matter how tired I was) and I'm having dreams again.

So now I'm wondering if there'd be any benefit in taking things further. And of course, I'm not asking for medical advice, just wondering if my logic has any theoretical validity.