LDN. ... BACKGROUND Low dose naltrexone (LDN) is an antidote to modern life. In any condition in which the gut is involved, or the brain is inflamed, I often consider LDN. It seems to completely stop neuroinflammation driven by bacterial endotoxin of gut origin, and it acts regeneratively on wounded tissue. There has been considerable confusion into the mechanism of LDN. The most common idea is that it's an opioid antagonist, and the withdrawal of it causes a rebound increase in endorphin, producing the common quality-of-life improvement. This has led people to erroneously believe it will make you feel bad until withdrawal -- so they take it at night. This is a mistake. I've seen no case reports of people taking LDN during daytime and suffering any negative feelings. If anything, they immediately feel better and more clear. Forgetful people usually do not forget to take their LDN. LDN tends to disrupt sleep if taken too late in the day. Case reports indicate that you can "get over the sleep issues," but what this really means is that you become so deprived of quality sleep that you can fall asleep despite the LDN. It does not have this effect when taken in the morning. The role of endorphins actually seem to be relatively minor in its pool of effects. The most important anti-opioid effect it gives is in the case of wound healing, where endorphin can increase scar tissue formation, and naltrexone can block its action. In this case, due to endorphins, you would want to postpone the naltrexone withdrawal rather than experience it. LDN seems to mostly work through two pathways: 1. TLR4 2. OGFr 1. TLR4: This is the receptor for 'endotoxin.' Endotoxin is a component of bacterial cell walls that triggers an inflammatory reaction. The extreme of endotoxin poisoning is known as sepsis. If you have a leaky gut, or have rapid growth and turnover of bacteria in your gut (SIBO, for example, or if you eat highly fermentable fibers), endotoxin is likely leaking into your blood with no real threat of infection. This was not as common in ancestral times due to higher quality foods, so your body is right to overreact. Now, though, you don't want your body to overreact, and LDN can be a much-needed bandage as you sort out gut issues. It blocks TLR4 and prevents the endotoxin-mediated inflammatory cascade. 2. OGFr: This is the opioid growth factor receptor, and naltrexone blocks opiod growth factor from binding to it. Despite OGF being called a growth factor, it inhibits regenerative growth. Blocking the OGFr can promote repair, but only during naltrexone binding. You likely don't want permanent growth, repair, or cell division, so it's good that LDN is cleared out relatively quickly. You get a window of repair, and then revert to baseline. It's very tunable and generally safe. The anti-cancer effects of LDN are likely a product of the phase where naltrexone is not bound to the receptor, for example, but blocking the receptor does not give you cancer. This will give us some insight into the protocol below. There are many purported off-targets -- SIRT1, Bax/Bcl-2/caspase-3/PARP, etc., though the effects are generally positive and often are downstream of TLR4. At the time of writing, I've been privy to some unreleased data from AgelessRx, who are actively running LDN clinical trials. Nearly everyone in these trials reported an improved quality of life in multiple aspects. Whether people use it for fatigue, aging, multiple sclerosis, or migraines, it seems to be truly condition agnostic and improve quality of life. As for a personal anecdote, I had a background pain in my head since I was a child, which could rapidly worsen and become a migraine. LDN was the first thing to ever give me relief from that background pain. ... PROTOCOL LDN can be acquired from AgelessRx. LDN might be considered, conservatively, for the following issues: - Migraines - Chronic fatigue - Fibromyalgia - Multiple sclerosis - Psoriasis - Autoimmune conditions - Leaky gut - Depression - Anxiety - Aging - Atherosclerosis It's part of my regenerative healing protocol along with BPC-157. If you sustain a severe injury, naltrexone and BPC-157 immediately taken will improve prognosis. As for how to take it: - Start with 1.5mg, and titrate up to 4.5mg (as AgelessRx recommends) if conditions do not improve. - On a consistent basis, take in in the morning only. - If you are severely injured, take extra doses every ~8 hours until the injury heals. Withdrawal may slow healing, but extra doses accelerate it. - It may be worth experimenting with 'ULDN,' ultra-low dose naltrexone, if the initial dose is too much. If you cannot use AgelessRx or get a compounding pharmacy to make 1.5mg tablets, you can dissolve it in water and use a syringe to measure out the dose. It's stable in water, but I like to freeze part of it for storage once I make it like this. Quick protocol for that: - Crush up 150mg naltrexone tablets - Put in 100 mL water (measure with a measuring cup) - Add the 150mg naltrexone to 100 mL water, mix vigorously - Store in any liquid container you can use, preferably glass The fillers in the tablets may not dissolve, but the naltrexone likely will. I think it's still a good idea to resuspend the fillers and make sure the solution is visibly homogenous before removing your dose with a syringe. With this solution, you need to only take out 1 mL (or 1 cc) to get 1.5mg -- so it's good for 100 doses. This can be done with any standard insulin syringe. You can then throw it into water or food to dose. I see LDN as both a magic bullet and a crutch -- it's better if you don't need anything external, but it may give you the energy and clarity to figure out how to fix the root cause of your issues. There's a good case for staying on it for life, though, especially for aging. ... -- anabology