LDN

This article is for informational and educational purposes only, and is not to be used as medical advice.

Acknowledgements:

For more information on LDN, please visit:

Low Dose Naltrexone Homepage  

This is Dr David Gluck's page, and I consider it one of the very best resources on LDN. 
As such, I do not feel the need to replicate what is done there, but simply refer people to it.

Thanks also to Drs Ian Zagon and Patricia McLaughlin, for their copious and excellent research on naltrexone.

More LDN resources:

Dudley's Low Dose Naltrexone Sites

Low Dose Naltrexone and chronic pain - Pradeep Chopra, MD

https://www.ldnscience.org/research

Naltrexone ‘Changed Life’ of Fibromyalgia Patient

What is the difference between regular dose naltrexone 50 mg vs low dose naltrexone 4.5 mg?

Regular dose naltrexone 50 mg blocks the opiate receptors in the brain all day long. Opiate activity is blocked.

Low dose naltrexone (LDN) 3 to 4.5 mg is designed to block these receptors for only a few hours.

This difference is critical.

When low dose naltrexone blocks the opiate receptors only temporarily, the body is tricked into thinking that endogenous opiates are low. Thus, the body ramps up production of natural opiates. Opiate activity is increased.

It is this increase in opiate activity that gives many of the beneficial effects of LDN. As with all medication, not everyone will respond. However, due to the low side-effect profile and relative safety of LDN, many people try it.

What are the side effects of low dose naltrexone (LDN)?

The 2 main side effects seen are:
1. Temporary slight increase in insomnia.
2. Temporary increase in pain (in people with chronic pain).

People report that both these side effects may be minimized by starting on a much lower dose (0.5 or 1 mg) and gradually increasing.

What is the dosing of low dose naltrexone (LDN)?

The usual dose of LDN is 4.5 mg at bedtime. There are reports that people with multiple sclerosis may do better with 3 mg instead. The ideal dose may vary slightly between individuals.

Some people with insomnia prefer to dose LDN first thing in the morning. Reports are conflicting regarding whether this gives as good a benefit as dosing it at night.

It is common practice to start with a lower dose (0.5 to 1.5 mg), and work up to 3 or 4.5 mg over a few weeks to months. This is called titrating. People who are super sensitive to medication may go slower, and those who are not so sensitive may go faster. Some just start at 4.5 mg and do not bother with titration.


Contents:

Part 1:  How to make LDN at home

Part 2:  my notes on LDN

How to make LDN at home

if you do not have access to a compounding pharmacy or if funds are limited

Where possible, it is always best to get your LDN from a compounding pharmacy.

However, if you live in a country or area with no available compounding pharmacies, you may have to resort to making LDN yourself at home.

This is a method that I came up with, and is by no means perfect. Nor is it the only possible method.

The following directions are strictly for educational purposes only, and are not intended as medical advice or recommendation. 

If you chose to follow any of these instructions, you do so completely at your own risk, and agree to absolve me of any and all liability, direct or indirect. You must also make sure to be in compliance with any applicable local laws.

Do not take any medication without first checking with your physician.

How to make liquid LDN yourself

First, you will need to obtain a supply of commercially available Naltrexone 50 mg tablets. In many countries as well as in USA, this will be by physician prescription only.

Then, you want will to get at least 2 amber glass dropper bottles in either the 1/2 oz or 1 oz size or a combination of sizes. E-bay is a good source for these bottles. 

Make sure the droppers in the bottles you use are all about the same shape, as this may affect the size of the drop.

Also, you will want a label for your bottle, and some clean drinking water. If no clean drinking water is available, 7-up or ginger ale or similar soda can be used.

Do not make big batches, as there is no preservative, unless commercial soda is used, then there will be some sodium benzoate in it.

Optional: a container such as a graduated measuring cylinder or precise weighing machine.

[This will save you from having to count drops again and again]

Concentration:

Aim for either 0.5 mg per drop or 1 mg per drop.

If 0.5 mg per drop, use 100 drops per tablet. If 1 mg per drop, use 50 drops per tablet.

Method:

Have a cup of clean drinking water. 

Break a tablet in half, drop it in an amber bottle. 

Count the desired number of drops of liquid, and add to the bottle. Just in case a mistake in counting is made, count the drops into a different container before adding.

If there is concern that volume will be lost from clinging to sediment or the container, add an extra drop or two per tablet, but no more than that. Whatever method is used, do not change it from batch to batch.

If desired, stevia liquid can be used in place of water.

Let sit overnight or longer to allow things to dissolve and settle. Usually there will be a white layer at the bottom, and a semi-clear liquid on top.

Take a new bottle, and extract the semi-clear liquid, leaving the sediment behind. This will be the administration bottle. Label it.

Low Dose Naltrexone

These are more my notes for my benefit, and not meant to be an article on naltrexone..

Indications for LDN include

Poor or slow wound healing

Chronic Lyme

Naltrexone metabolism

After oral administration, plasma levels peak in about 1 hr. Naltrexone is very well absorbed orally (about 96%).

Major metabolites are conjugated naltrexone and nonconjugated and conjugated 6 beta-naltrexol. 2-Hydroxy-3-O-methyl-6 beta-naltrexol is a minor metabolite.

Excretion of naltrexone is mainly by urine and less than 5% in stool.

The liver enzyme dihydrodiol dehydrogenase (DHDH or DD) metabolizes naltrexone to 6ß-naltrexol. Other metabolites include 2-hydroxy-3-methoxy-6β-naltrexol and 2-hydroxy-3-methoxy-naltrexone. Further metabolism is by glucuronidation.

The cofactor of DHDH is B3.

Half-life

The major metabolite of naltrexone has a longer half-life than the parent compound.

The half life of naltrexone is about 2.7 hrs if given IV, and 8.9 hours is given orally (about 4 hours for the parent compound and 12 hrs for beta-naltrexone).

One study reported the half-life of sub-cutaneous naltrexone as 1.68 hrs for the parent compound and 8.8 hours for the major metabolite, 6 beta-naltrexone.

Naltrexone disposition in man after subcutaneous administration.

Metabolism and disposition of naltrexone in man after oral and intravenous administration.

Bioequivalence, dose-proportionality, and pharmacokinetics of naltrexone after oral administration.

6ß-naltrexol vs naltrexone

6ß-naltrexol is slower to start working compared with naltrexone, but lasts longer. Part of the efficacy of naltrexone in humans is likely due to 6beta-naltrexol.

6β-Naltrexol acts as a potent, peripherally selective opioid antagonist, and works in the gut to block constipation due to morphine.

In vivo characterization of 6beta-naltrexol, an opioid ligand with less inverse agonist activity compared with naltrexone and naloxone in opioid-dependent mice. :

"6beta-Naltrexol was roughly equipotent to naloxone and between 4.5- and 10-fold less potent than naltrexone in blocking morphine-induced antinociception and locomotor activity, showing that 6beta-naltrexol enters the central nervous system. In contrast to naloxone and naltrexone, 6beta-naltrexol precipitated only minimal withdrawal at high doses in an acute dependence model and was approximately 77- and 30-fold less potent than naltrexone and naloxone, respectively, in precipitating withdrawal in a chronic dependence model. 6beta-Naltrexol reduced the inverse agonist effects of naloxone in vitro and in vivo, as expected for a neutral antagonist."

6beta-naltrexol preferentially antagonizes opioid effects on gastrointestinal transit compared to antinociception in mice.

In vivo and in vitro potency studies of 6beta-naltrexol, the major human metabolite of naltrexone.

6β-naltrexol, a peripherally selective opioid antagonist that inhibits morphine-induced slowing of gastrointestinal transit: an exploratory study.

Naltrexone vs Naloxone

Naltrexone's longer duration of action compared to naloxone has been considered to be due partly to its major human metabolite, 6beta-naltrexol.

Comparative potency:

naltrexone >> naloxone > 6beta-naltrexol

Pathways of action

LDN works through the OGF-OGFr (opioid growth factor) pathway.

Naltrexone is a mu opioid receptor antagonist.

Naltrexone and wound healing

...note in progress...