Hi! I have central sensitivity/chronic pain and fibromyalgia, along with other chronic conditions, and I take LDN! It helped noticeably with my fatigue almost immediately when I first started taking it, but I can’t say I noticed it improving my other symptoms, i.e. GI symptoms and pain sensitivity. It’s still worth it for me though to help the fatigue.

When my PCP brought it up to me (she works in Integrative Medicine and has many patients with different chronic pain disorders), and I did a lot of research (otherwise known as Googling, carefully) before I decided to start it. She frequently prescribes it (I can also give you the name of the specialty pharmacy we use that is reputable and we found has a good price if that helps at all), and specially we agreed I would titrate slowly. That’s what she does with everyone, but for me in particular with my condition, we know already that my body is very sensitive to medication, new activities, environments, etc.

Our plan was to start at .5 mg and increase every 2 weeks by .5 mg until I got to a goal of 4.5 mg (or if it seemed like it felt like enough with less, that was also fine) and we’d see how that went for at least 3 months. The rationale was that of the studies she was aware of and that I found (though there aren’t many and they’re usually small), most found that there was no further benefit for those who took more than 4.5 mg. Some people had enough benefit at smaller doses—it seems to be very individual.

HOWEVER, it turned out that .5 mg was way too activating for me—I felt hyper-alert on my first dose. Unsure if it was a fluke or the placebo effect, I tried it the next day and then I couldn’t sleep, and just felt too uncomfortably “up.” So I had to slow my roll and go down to .25 mg. I titrated by quarter milligrams from there.

All that said lol (long way for me to get to your question), oddly with all my searching intermittently over a year and a half, I have not come across any Mayo Clinic information about it. Because there’s not as much “high quality” research on it, and LDN seemed to fly very much under the radar until all the long COVID cases, despite being so low risk, I’m doubtful there would be much out there.

When I was first looking into LDN, it seemed to me the recommendation to titrate was coming more from the personal experience of the providers, compounding pharmacists, and patients. My sense was it was a more practical approach to minimize any side effects, especially when most people turning to it already have problematic symptoms.

I doubt there’s a high risk to start right off the bat with 4.5 mg, but I’m almost never comfortable starting a new medication at the conventional dose because of my central sensitivity. I wasn’t comfortable running the risk of experiencing potentially uncomfortable (though not harmful) side effects (even though it happened anyway ha). It’s also harder to tell if you might have had a response with less medication—and since most people have to pay out of pocket for LDN from a compounding pharmacy, that might make more of a difference (it did for me).

It probably comes down to how comfortable someone is with the risk of starting with a higher dose.

This is from a few years ago, but a review mentions this about patient instructions to those in the study: “ A “low and slow” approach to titration of LDN dose was used, and patients were verbally counseled that, vis-à-vis LDN therapy, “more is not necessarily better.”

And there’s a link to a podcast episode on this page from Weill Cornell Medicine I came across when I first started researching. They interview the Division Chief for Pain Management; he mentioned he starts patients typically at 1.5 mg and titrates from there but some people need less. I could find any specific research to support titration specifically.

Sorry, this post is now getting super-long, but I almost wouldn’t have found out about LDN, so I always like to share my experience if it’s something that might help someone else.

If it helps at all: I mentioned above I had to start very low (.25 mg) because of my sensitive, and worked up to 4.5 mg, increasing st first by a quarter milligram every two weeks. At some point, I got impatient and if I didn’t have adverse effects after a week, then I increased again to speed up the process. I take it in the morning (again, leery of side effects), and found it helped with my fatigue.

Unfortunately, I got COVID last November and it exacerbated my symptoms. My fatigue returned with a vengeance, and my PCP recommended titrating to 6 mg because she inherited some new patients who take a higher dose with good results (she’s now the only person in the clinic who prescribes LDN after someone left). There are anecdotal reports of individuals taking 6 mg I found, but only research that said there wasn’t an additional benefit.

Now, I take 6 mg every morning. My dad has PMR (an inflammatory arthritis that causes extreme fatigue), and he takes 4.75 mg because when we tried to go past that point he was bouncing off the walls.

But, hope that helps, and hope you find some relief, whether it’s with LDN or another way. I do think it’s worth a try and agree titrating is the less riskier way to go.