Why 3 mg. Low Dose Naltrexone Might Be Best

Why 3 mg. Low Dose Naltrexone Might Be Best

The above title should probably say 3 mg. being the best dose in those with liver disease, cirrhosis or cancer.  More evidence is being produced on why a lower dose of LDN might be best.  Jayne Crocker of LDN NOW has been in touch with Dr. Ian Zagon over the years (he discovered LDN and OGF) and she has shared his thoughts on why 3mg LDN is the optimal dosage and not 4.5. Particularly in those who have problems clearing LDN from their systems or liver.  Dr. Zagon also said that some may benefit from every other night dosing but at the maximum of 3 mg.


Remember, the discovery of LDN came about through research of an opioid system that has remarkable effects on mood an d *cell proliferation*. I highlight *cell proliferation* as I can’t stress enough the understanding of this. When anyone asks how LDN works, we always seem to tell them ‘it modulates the immune system’, which is correct, but let’s break that down a bit and explain what this actually means for cancer.



Once you are diagnosed with cancer, your body lives with cancer cells. These cells have a tendency to grow. The effect you want from taking LDN is to *regulate* cell proliferation, do what you can to stop the cancer cells from spreading. If taken at a low enough dose, LDN can stop the cancerous cells from proliferating by putting a stop to them spreading. In other words, it works by preventing cells from reproducing.

In order to achieve this effect from taking LDN, you need to allow as much time as possible for that endorphin OGF to do its magic (rebound effect). Endorphins are found in most cells of your body and are an important regulator of cell growth. OGF is the one endorphin that has been found to have an influence on cell growth (meaning it can put the brakes on) – which is a good thing!


Now, the duration of the ‘rebound effect’ which happens once LDN clears your system (hopefully in 4-6 hours) is usually around 20 hours, which is why people then take another dose of LDN. It very much is a supply and demand protocol. Once the rebound effect wears off, you take another dose of LDN and 4-6 hours later you allow the endorphins to to go to work for another 20 hours or so.

If for whatever reason you are not clearing LDN out of your system in 4-6 hours, you are diminishing the amount of time you are giving yourself for OGF to do all the good work (it’s not LDN that’s helping you here, but OGF). LDN is just a decoy! There are numerous people with compromised immune systems who cannot metabolize LDN efficiently at a dose of 4.5mg. It is the experience of Dr Zagon, that no more than 3mg will have this positive effect for everyone and I believe he is very adamant about this, especially those using LDN for cancer.

Dr. Zagon email:

The 4.5 mg story.

In 1983 after we published a series of papers in Science announcing our discovery of LDN/HDN - and opioids as growth factors - I received a telephone call from a Dr. Bihari. He was director of medical affairs at Downstate Medical Center in Brookl yn. He thought what we were doing was fabulous and should be used on patients immediately. He asked me what dosage to use. In our patents that were filed, we estimated 1--10 mg/day of LDN - this was based on human pharmacology work with naltrexone that others had done. I said to take a 50 mg tablet and cut it down to around 5 mg. He called me the next day and to my amazement he told me he took it the night before and awoke feeling terrific (remember, you get an endorphin high because LDN raises the endogenous opioids). Apparently, he then went on prescribing close to this dosage - 4.5 mg - to patients as an off-label drug. And, it was working. Now, in fact 4.5 mg probably is not maximizing the window of effect, and is prolonging the naltrexone in the body longer than it should be. That is why 3 mg is best - keeps to a short window of 4-6 hours for NTX, and then 18-20 for the opioids to react with the receptors.

Dr. Zagon


It is my understanding that Dr Smith obtained funding and approval to go ahead with the Crohns trial at a dose of 4.5mg when it was thought that 4.5mg was the best dose to take, but you can see from Dr Zagon’s explanation that in order to get the benefit from the OGF effect, a dose of 3mg is preferable. Dr Smith’s trial also had patients combining LDN with steroids. Now, with all the latest research done and knowledge base we have as of todate, one has to ask if this trial would have produced more favourable results if patients were taking 3mg?


Remember, the minute you take LDN, it is doing everything you do not want it to do (activates cells). In other words as soon as LDN blocks the opioids, it becomes a negative. Increasing the dose means you are increasing the time of the blockade period. You want to control cell activation, not encourage it and this only happens when LDN clears your system and OGF goes to work. The goal from using LDN is to get the maximum effect from the Opioid Growth Factor (OGF), not Naltrexone itself.

Let’s say if you take 3mg you are blocking the opioids for 4 hours, You then have to allow for another 4 hours for OGF to undo all the activity that LD N has done. So 8 hours later you are really benefitting from the OGF for the remainder of the 24 hour cycle. This means 16 hours of great work. Increasing the dose of LDN to 4.5mg means the blockade will last longer, maybe 6 hours. So you then have to allow another 6 hours for OGF to get your body back to what it was prior to taking LDN (12 hours), so you then only have 12 hours of benefitting from taking LDN as opposed to 16 hours with taking a dose of 3mg. And 24 hours later we start again.


And over the last few years it seems that by and far most folks with liver issues and elevated enzymes all do very well with LDN, with great reduction in their lft's.  However, in a few folks, usually in those with cirrhosis, they have reported elevations -  and I believe that all of them were taking 4.5mg.  The couple that did know their ferritin levels also reported high levels (350+).

How do we know if we are clearing the LDN?  Good question - but again, another reason that each person needs to find out what dose works best for them - and not think that one must take 3mg or 4.5mg.  Experiment with dosage if you can.  More later..

Thanks Jayne!