The sources are patents. 2014a and 2014b.

It is interesting that the benefits were retained over a large dose range. Oddly, full doses (when combined with benzos) can help treat tardive dyskinesia. Thus, it seems plausible that the benefits for RLS are retained at even higher doses. I've not yet checked the sources to see if higher doses were tested. That is, doses over 1 mg. I doubt they were, because it would probably have been mentioned here.

It's not often you find effective treatments for negative symptoms. As a schizoid myself, this looks like a valuable tool. I'd be fascinated to see how LDN and ULDN perform.

Interesting. They were using full naltrexone doses, not LDN. I'd expected full doses would make movement disorders worse.

From the full text, they used 5 micrograms of naltrexone. Naltrexone dose is very finicky. There's low dose (LDN), very low dose (VLDN), and ultra-low dose (ULDN). This is a ULDN. I believe the type of effects I'm looking for occur at VLDN and LDN doses. If I recall correctly, I think 2 mg is optimal for analgesia, but I don't remember whether this was with or without morphine. 0.125 mg and 0.25 mg are effective in opioid withdrawal when combined with methadone. Thus, it's not too surprising that 5 mcg had little effect. At those doses, the effects it does have are like mediated by different mechanisms.

This is important because it suggests mood-brightening. Contrast this with combining L-type calcium channel blockers with opioids, which appears to limit tolerance to opioid analgesia that does not correspond to mood brightening.

Based on water intake of 10ml per 100g body mass, that should translate to 0.5 mg/kg. This is one of the few studies using LDN as opposed to ULDN.

The question, then, is whether the opioid receptors are involved at all in this upregulation. For example, it could be mediated by TLR4 or filamin A.

2 mg appears most effective. download PDF here.

I would not expect doses this small to impact the opioid receptors.

Symptoms in the treatment group continually improved, whereas symptoms in the placebo group plateaued. Thus, I'm interested in seeing a longer treatment period. Projecting from symptom scores, elimination of symptoms would occur in about 10 days.

Interesting. Conventional doses of naltrexone appear effective for sleep apnea. I'll be interested in seeing if LDN fairs well.

The full text describes how ultra-low-dose naloxone and naltrexone enhance opioids at very slim dose margins. A mere two fold difference on naltrexone dose can determine efficacy: 2 micrograms is effective whereas 4 is not. What's more, this optimal dose changes with sex, mouse strain, opioid agonist used, etc.; this making precise dosing challenging. The mechanism suggested is that filamin A has two binding sites, where only 1 has the desired effect.

This sentence appears to indicate equal potency between the two drugs.

So, naloxone has a 200 times higher potency at Filamin A compared to opioid receptors, but I need clarification on whether naltrexone achieves similar potency.

Standard LDN is 4.5mg. According to this data, that may be orders of magnitude too high. Nevertheless, LDN has been found effective.