Dr Bihari was of the impression (in 1994) that anywhere between 1.0mg and 10.mg was sufficient, with the therapeutic effects below 1.0mg being quite small. He suggested that 1.5mg to 3.0mg was the dosage “at which Mu receptor sites are substantially blocked while the Delta sites are substantially unblocked”. Dosages above that would cause “the effect of the preferential blocking action against Mu over Delta receptor sites (to) disappear, since the amount of the drug is large enough to cause at least substantial blocking of Delta sites while the Mu sites remain fully blocked.”
Ultimately (for whatever reason), he started recommending 4.5mg as the optimal dosage, and nothing over that as a rule.
Another of Dr Bihari’s recommendations was that we take LDN between 9pm – 3am, because our “POMC mRNA levels were elevated during the dark period, reaching a maximum level at 0200 h that was 2-fold higher than that occurring during the light period”. What difference that makes, I'm not sure
. . . but this was apparently how he came to the recommendation that we should take it during those hours.
He further recommended suggested that LDN was not compatible with the interferons.
I know there are people who aren’t (or can’t) follow those guidelines, and LDN is working in spite of that. However, those are the “exceptions” vs. the rule, and it would stand to reason that we would TRY to follow the rule, where possible.
For years now, the plan was for people to start at 3 mg LDN (or 1.5mg for those who were particularly sensitive to meds), but once they were managing that dose they would attempt to increase the dose to 4.5 mg. For some, there is a transient increase in MS symptoms when we are upping the dosage, such as weakness, stiffness, changes in sensation, muscle spasm, pain, sleep disturbances, fatigue or tiredness. These symptoms usually disappeared within the first week of treatment, but apparently
in less than five percent of people, these side-effects may be more severe or
last as long as several weeks. This is considered “normal”, or at least nothing to be concerned about . . . but many people give up too early when they don’t see immediate improvement with NO side-effects.
Rarely, symptoms may persist for two or even three months and in this situation, the ultra-low 1.5 or 2 mg dose is recommended, but still not as a permanent solution . . . as a gentler “introduction” to the med. However, normally, once the body adjusts to LDN the dosage can be increased.
Over years of trial and error of trying to follow these recommendations, some men (and petite women) found they experienced ongoing side effects at 4.5 mg, and were better off at 3 mg . . . and some like me (and Sally) had to try a few times before we were able to tolerate “optimum”. In my case, I also have to drop LDN down at the start of the cold season . . . so obviously not everyone can stay consistently at 4.5mg, even if they are normally perfectly fine at this level.
Ideally, everyone DOES want to TRY to persevere to 4.5mg (or min 3.0mg), but I suppose if they try for several times, for several weeks and still CAN’T adjust . . . then so be it. I have run into several people who have not seen any great improvement for several months, or even suffered with some side-effects for that long, but EVENTUALLY their bodies adjusted and LDN worked for them.
Those people (who are very sensitive) are very FEW and far between though, and most do try to get up to between 3.0mg and – 4.5mg. I would imagine that 2.0mg could be helpful anyway, especially for some symptoms, and perhaps maybe even for the disease process. I haven’t met anyone who is on that level of LDN (alone, without using Copaxone too), and where it has proven successful for reducing relapses/progression in the long run. Most I've run into at that level are on combo therapy (use LDN for symptoms only), or they quit after a few years because they don’t feel it is helping the disease process.
I certainly would stick with a low dosage if that was all I could handle, but I wouldn’t give up trying to get to optimal just because of a few transient side-effects. I just hate to see people give up so easily, and not get the benefit of a dosage which may ultimately be therapeutic for them.
Cherie