Side Effects and Dosing

First a recent study that demonstrated the importance of individualized dosing levels -

Effective Doses of Low-Dose Naltrexone for Chronic Pain – An Observational Study... https://www.dovepress.com/effective-doses-of-low-dose-naltrexone-for-chronic-pain--an-observatio-peer-reviewed-fulltext-article-JPR

A comment about dosing - When we talk about the optimal dose we are generally talking about the Endorphin aspect. The ideal dose will yield 4hrs of blocking and 20hrs of rebound. Endorphins reduce pain, improve mood and support the immune system.

However it's possible that the optimal dose for the anti-inflammatory aspect is different. I suspect this is often the case when people find that higher than normal doses like say 9mg work for pain.

In that case the patient will need to find the best dose that gives overall results between the two aspects.

Adding this comment: Some may notice increases of pain or darkening of mood about 30 min after dosing. If that lifts in about 4hr. then the dose is right unless the effects are not tolerable. Some can sleep after dosing and thereby "miss" the blocking period.

Others' may need to keep slowly increasing and tracking the results. A journal is a good idea. Aside from LDN be sure to include notes about diet, sleep, stress, weather, other supplements/meds etc. -- we are complicated experiments!

At some point the results will perhaps not be as good as the previous dose. If the system doesn't adapt within two weeks one may need more time at the lower dose after skipping a day.

IMO lower the dose as needed rather than do a lot of skipping.

In case someone doesn't make it to the end of this long document let me post here an extended version of this worthwhile quote:

"TRUST THE PROCESS AND TRUST OURSELVES

Just as in Nature, decay must occur in order to nourish new growth, our bodies must tear

down old tissue and detoxify in order to regenerate. Expect that you will have ongoing

cycles of wellness interspersed with cycles of discomfort until you have reached a state of

stable, resilient health. At this point, you may still choose to integrate cleansing routines and

person-growth-stimulating therapies into your life on a regular basis. In doing so, you may

find that once in awhile you will again experience a release of something toxic, followed by a

feeling of being ill, followed by a feeling of being free and clear of whatever was released

(whether emotional or physical). In time, you will learn to welcome these events and to take

comfort and pride in them as affirmations that nature is taking its course.

You will most likely experience many healing events throughout the journey towards

reclaiming your health. As you understand the importance and predictability of these events

and learn to recognize when you are experiencing them, it will be much easier for you to

maintain confidence in your chosen healing path. Rather than trying to escape from the

experiences, you can relax into them with full awareness of their significance.

During these events, it is important to tune in to what you feel and need and to offer yourself

(or ask others for) all the love and care that you need to get through it. Your body is infinitely

intelligent. With adequate resources: healing, rest, clean water, fresh air, exercise, sleep, a

healthy emotional peace and an individualized healthy diet, it can work miracles in healing.

"For a long time it had seemed to me that life was about to begin...But there was always

some obstacle in the way, something to be gotten through first, some unfinished business,

time still to be served, a debt to be paid. Then life would begin. At last it dawned on me that

these obstacles were my life. This perspective has helped me to see that there is no way to happiness. Happiness is the way. So treasure every moment you have and remember that time waits for no one. Happiness is a journey, not a destination.” ~ Fr. Alfred D'Souza

About fillers:

Most reports of filler/ingredient trouble are with Avicel (Microcrystaline cellulose/MCC/cellulose) even though it may be tolerated in other meds/supplements.

Avicel and Other Fillers...

https://docs.google.com/document/d/171pT-q4ND3_RbdioLBvl-uCXWIelKtW98AEnH07H2Fs/edit?usp=sharing

Side Effects & Dosing of Low Dose Naltrexone (LDN) 1

Lots of info in this File. Please review as you are able, but here's a “Read this first” section with 5 points:

Dosing Comments…..

Doctors often seem to be in a hurry to get the what they think of as the “therapeutic dose” that they have seen in the studies – namely 3 or 4.5mg. While some do well even starting at those doses, clinical experience in the LDN groups indicates that for many it’s better to:

1) Start dosing at 0.5 or 1.5mg especially with conditions like Lyme, Hashi’s, CFS/ME, MCS or if the person seems to be generally sensitive to meds. Those with Hashi's may find that their thyroid begins to function better and they will need to do tests to adjust their meds to avoid going hyper. Starting low makes this possibility less intense. Generally speaking it's better to start too low and have to raise than to start too high and have to cut back. There have been exceptions where people had fewer side effects at higher doses. And some need to start even lower like 0.1mg or less. Sometimes it seems as if our systems need to first get used to the “idea” of LDN and then gradually increase. We know from ULDN doses that even a dose like 0.002mg has effects.

2) Spend at least two weeks at a given level before increasing. This gives the system time to adapt and initial reactions may settle down. If a person is feeling no effects either way they can increase more quickly. More sensitive users will likely want to increase in 0.5mg steps. Others might do 1.5mg steps.

3) It is more important to find the “right dose” for you than to get to the 4.5mg dose. Typically this may be anywhere in the 0.5 to 4.5mg range although it can be higher or lower for some. See more details and discussion of this below.

4) For anyone having problems the “easy suspect” IMO is the dose being too high or the filler especially if it is Micro Crystaline Cellulose (Avicel). See the File on this.

5) Set your own pace of dose increases. Even if you are doing well at some point it may be worth testing an increase (possibly in 0.5mg steps) to see if you can get more benefits. It’s often useful to keep a journal including factors like diet, sleep, weather effects, stress etc.

This document draws from a variety of sources. Because quotes were not always clear or were edited I have sometimes dispensed with quotation marks in the interest of making the document legible and available in a timely way. I have updated it with my understanding of current information. – Brian Haviland (Admin)

Additional reference links about side effects (may need to scroll to next page):

Side Effects & Dosing of Low Dose Naltrexone (LDN) 2

Survey from Walgreens….

http://bit.ly/2V1QLk0 LINK NOT WORKING - REPLACE WITH https://www.walgreensbootsalliance.com/news-media/press-releases/2015/patientslikeme-adds-information-about-patient-experiences-with-medications-to-walgreens-pharmacy-website?keys=4p%204p%204p&page=%2C68

Naltrexone: Friend Or Foe?…. https://www.prohealth.com/fibromyalgia/library/naltrexone-friend-foe 89485

Side Effects Reported from LDN Clinical Trials… http://ldnnow.com/55401.html

Because this document attempts to cover many of the possible side effects that we have learned about it might scare some new users. Please be assured that side effects are generally minimal compared to most medications. Here is a quote from Chris Kresser. You will see a link to a video from him later:

"The side effects are pretty minimal, in that in some of the double-blind, placebo-controlled trials, as I said, there was no difference in side effect between placebo and the treatment group, but I will say that in our experience, what we’ve seen in our clinic and other clinicians I know that work with it, there are some side effects that are fairly common, which are temporary sleep disturbance when a patient first starts taking it or vivid dreams and a mild headache, but these usually pass pretty quickly and can often be mitigated by starting with a lower dose, so if 3 mg or 4.5 mg is the ultimate dose that they end up on, starting at, like, 1 mg or 1.25 mg or something and then building up more slowly."

Most medications result in unintended reactions called side effects. LDN is no exception. Just as every relationship goes through an initial period of adjustment, so too does the taking of LDN bring about a

Side Effects & Dosing of Low Dose Naltrexone (LDN) 3

new order of things to which the body needs to adapt. Internal chemistry changes, endorphin levels increase, and the immune system is balanced – a generally beneficial process that can, nevertheless, take time getting used to. Fortunately, the side effects associated with LDN are usually mild and of a transitory nature and the rewards in terms of healing, restoration of function, and the cessation of pathology can be wonderful, even life-saving.

Dr. M.R. Lawrence is an English physician with multiple sclerosis (MS) who treats it with LDN. He also prescribes LDN for his patients. The following are his [edited] observations and advice regarding common side effects associated with taking LDN. While they refer primarily to people with MS, they also apply (with the exception of spasticity and possibly pain) in other situations involving the administration of LDN.

“When starting this LDN therapy in the treatment of MS, there may also be some initial transient, though temporary, increase in MS symptoms.

Experience in using this method has demonstrated most commonly, such as disturbed sleep, occasionally with vivid, bizarre and disturbing dreams, tiredness, fatigue, spasm and pain. These increased symptoms would not normally be expected to last more than seven to ten days [but your experience may vary].

Rarely, other transient symptoms have included more severe pain and spasm, headache, diarrhea or vomiting. These additional symptoms would appear to be associated with the previous frequent use of strong analgesics, which effectively create an addiction and dependency, thus increasing the body's sensitivity to pain. [Similar symptoms can also occur in people unknowingly allergic/sensitive/intolerant to gluten and/or dairy and who take those foodstuffs concurrently with LDN.]”

A friend was asking why she might feel worse after starting LDN and I [Brian] wrote this up for her. Thought I'd post in case others might find it useful or amusing:

Taking LDN can stir up many things. Think of your immune system as a clerk in a busy mail room. Their job is to receive the incoming packages and properly deal with them. If the clerk is not feeling well or doesn't have energy they may say "I can't deal with this package -- let me put it back here." Maybe that keeps happening -- even for years.

Then one day she has LDN and it's like she had a cup of coffee. She walks into the mail room and says, "Holy Moly! This place has gone to hell! Let me clean up some!" Pretty soon packages are flying out and things can get chaotic for a while. And many of the packages go to the detox systems so those can get overloaded or complain in their own ways. If they start getting too overloaded then the LDN dose may have to be reduced. But the good news is that the system is starting to "straighten up and fly right!"

For a more technical analysis see these articles about “herxing/retracing/detoxing”: https://chronicillnessrecovery.org/index.php?option=com_content&view=article&id=161 Herx........... http://www.silver-colloids.com/Pubs/herxheimer.html

Dr. Wilson's article on retracing.... https://drlwilson.com/Articles/retracing.htm

If you feel like you're dealing with herxing/detoxing/retracing be sure to read “TRUST THE PROCESS AND TRUST OURSELVES” at the end of this document.

It was previously thought when LDN started being prescribed in the 1980s that immunosuppressive drugs could not be taken in conjunction with LDN. Clinical trials with LDN that have been published for diseases such as MS, Crohns and Fibromyalgia, have shown this thinking to be incorrect as do the case studies doctors are writing up with various autoimmune conditions. WARNING: If you have had an organ transplant or stem cell therapy, please make sure your prescribing Dr understands that LDN inhibits cell growth and for this reason it may not be wise to combine the two.

Opioid drugs must be discontinued for at least two weeks prior to starting LDN. It is always a good idea

Side Effects & Dosing of Low Dose Naltrexone (LDN) 4

to take a complete list of your supplements and medications to both your doctor and your pharmacist so that they can evaluate them for your conditions and for any interactions. A pharmacist may sometimes catch a problem a doctor will miss. Some LDN users are able to use Tramadol for pain. See the “Pain” and “Tramadol” files for more information. However if a person has been using Tramadol for some time they may need to either taper down and do the same two week gap as with opiates or use ULDN.

Those that are currently unable to stop opiate use may want to learn about using very small doses of Naltrexone known as UltraLDN (ULDN) combined with the opiate doses. This actually makes the opiates work better and assists in the tapering process that one hopes will eventually lead to the use of regular LDN. Join this group for more information:

NOPE Non-Opiate Pain-relief Experiences. ULDN / Naltrexone & other options..................... https://www.facebook.com/groups/1593950197487522/

When starting the treatment it is essential that any untoward or adverse side-effects are reported immediately to your doctor so that the treatment process can be further assessed and, if necessary, modified.

Because LDN sometimes tends to initially worsen MS symptoms (especially spasticity), Dr. Skip Lenz recommends a nightly dose of 1.5 mg the first month, 3 mg the next month, and 4.5 mg thereafter. However if spasticity is an issue it may be better to stay at 3mg.

To quote Dr. Lenz:

“The reason we suggest a step-wise titration [for MS patients especially] is to AVOID SIDE EFFECTS. Three years ago, we found that EVERY PATIENT WHO STOPPED TAKING LDN BECAUSE OF SIDE-EFFECTS STARTED AT 3.0 MG OR HIGHER! There was only one patient who started at 1.5 mg who stopped because of side effects. Our efforts here should be to help the greater population. Now, there are some tough guys who can go straight to 4.5 mg and have no problems, but I betcha someone with a headache would feel differently or someone whose legs are screwed up in knots or someone who has had the bejeebers scared out of them with nightmares (me).”

One manifestation of LDN-related muscle spasms can be urinary retention.

Some members have found they needed to go to unusually low dose levels to get benefits with tolerable side-effects. Here's Elizabeth Aven:

“From what I've seen, it appears that some people fall outside of the typical dosing ranges on both ends of the spectrum. More so perhaps on the lower end. If someone is particularly sensitive, they might need under 0.5. Some may need as low as 0.001 for example which is generally referred to as UltraLDN or ULDN dose levels. I personally would decrease the dose as low as I had to in order to tolerate it. Assuming that fillers are not the issue, the dosing could be. I think that some people are missing out on the amazing benefits by not attempting to go low enough before giving up. One factor may be that people metabolize LDN at different rates and therefore need different doses. People can definitely still get positive benefits at this low of a dose if they find that it is their optimal dose. It may be best to stay at a given dose until symptom free before increasing.

I am taking LDN for Chronic Fatigue Syndrome/Lyme disease and I'm very chemically sensitive. These probably play a role in why I'm so sensitive to LDN. Some, but not all, with these conditions seem to need smaller doses. However, my mother, who is not sensitive to medication needed to start at 0.05 mg's in order to bypass nausea. She still had benefits at this dose. It's pretty individual. I think that your body will help to guide you to find your optimal dose. I wanted to make note of two more things- during the first few months on it, my hormones and cycles went a bit out of whack, but then that passed and now they are better than pre-LDN. I've seen some other women say the same thing. Once I got on LDN, I

Side Effects & Dosing of Low Dose Naltrexone (LDN) 5 needed to decrease other medications I was on as most of them felt a lot stronger.

Initially I started on 0.25 mg's and it was still pretty potent to me. Looking back, starting at 0.1 mg's might have been a better fit so I could have bypassed some of the initial side effects. I've been on LDN now for 8 months and am at 0.5 mg's and plan to stay at this dose because it is what works best for my body.”

Bente Wallace adds:

“My journey started with 0.5 mg at bedtime. From the get-go I really struggled. In hindsight this was due to MCS and having ME and later discovering that I am MTHFR. I wish I had started LDN at half that dose i.e. 0.25 mg or perhaps even lower. I am at month 7 now at a hard won 1.5mg dose trying to get to 1.75 with .25 mg capsules. Its very hard on me and I realize it's perhaps best to dose only every second day and perhaps it should be half of the . 0.25 mg increment and all along perhaps these steps to increase or decrease are just too big for me as I start to really flare.”

Two updates from Bente follow:

“I’d like to update my input in the above article

I have MCS, ME, FM, depression anxiety, general osteoarthritis, CNS sensitization, chronic pain, IBS, major intolerance to environment and activity, foods, chemicals, etc. I am now starting Year four on LDN. It’s been a long hard road but I hung in there.....I am doing best now at 3 mg, taken in the morning. I need to take magnesium bisglycinate malate for muscle spasms, and for sleep help. I take L theanine around 9 or 930 pm. My formula comes with magnesium. I take LDN for 3 or 4 days and then miss a day because I start more herxing if I don’t, as well as my fatique increases. A day off often really helps me. If I go higher than 3 mg, my anxiety severely increases, if I go below 3 mg, my inflammation is escalating. My osteoarthritis flares.

I started 3 mg just after a year had passed. I have tried twice a day, 3.5 mg , but I seem to do best at 3.

I can only say I’m better off with LDN, than without. I have much less pain, less inflammation, less depression. But the balance of LDN being helpful to me or not helpful is a fragile line, but I am grateful for the help I’m having even though it remains a struggle to find balance. Any increase or decrease is once a week or two by 0.125 mg, then twice, then three times etc. I need to move sloooowly. I have issues detoxing and clearing, but it is what it is. I’ll hang in as long as I will be able to. Because if I start to go off LDN my life becomes intolerable with symptoms flaring majorly.

Hang in there and give things a chance..and find your own path and be very patient. I’m glad I gave it a year when I started. I found the information in the Norwegian protocol very informative about inflammation and doses below 3 mg and why my inflammation wasn’t helped until 3 mg even though my pain was helped at .5 mg after a month or two.” And:

“I would add now that i still do best taking in am but have now found I've tweeked the dose as my body now is used to 3.0 mg and is now doing best on two days at 3.0 mg then 1 day 3.125 mg then 2 days 3.0 mg then 1 day 3.125

And then 1 day off no ldn

Then i repeat on a 7 day cycle

It is amazing how my body all of a sudden at 3 mg it stats to help less with inflammation yet if i add too much ldn at 3.125 i start to herx badly and major anxiety

Hopefully this routine will really help in the long term

I'll add my sweet spot after a while changes and needs very gentle tweeking”

Dr. Bernard Bihari was a New York physician who in his practice over a period of many years pioneered the use of LDN in humans. He determined that 4.5 mg was the optimal dose for the average person.

Side Effects & Dosing of Low Dose Naltrexone (LDN) 6

However the 4.5mg “ceiling” dose for LDN is not as solid as it used to be. Higher doses often seem to work better for pain, inflammation and certain mental conditions. 6 and 9mg doses are not that unusual. LDN pharmacist Stephen Dickson has mentioned doses up to 22mg! The current LDN brochure says LDN is any dose under 25mg. It's best to work with the higher doses with the advice of an experienced LDN doctor.

Another possible alternative for some is 2X/day dosing. Look for the File called “Alternative Dose Strategy from LDN Norway” or tag me if you can’t find it.

See: Low Dose Naltrexone 2018—US Information Pack…..

https://www.ldnresearchtrust.org/sites/default/files/LDN-2018-Fact-Sheet-USA.pdf

Note that the experience in the groups is that the cut-off level for a low dose that is effective has also moved. We used to see that many people were told by their doctors that any dose under 1.5mg would be useless, but we've had many members that have gotten results at 0.5mg and some lower like 0.1mg. Consider that ULDN (Ultra LDN) doses like 0.002mg still have effects!

Bottom line though is that each person needs to look for their "right dose" and most likely that will be found via experimenting. The most common "right doses" are still between 1.5 and 4.5mg, but there are exceptions both ways.

I think one factor that comes into play with LDN dosing is digestion. It may be that someone is dosing 4mg of only absorbing an effective 2mg dose. It such situations one might:

Increase the dose or

Switch from tablets to capsules or liquid or

Switch to a sublingual form.

Jayne Crocker of LDN Now with some thoughts on dosing:

“With cancer, it's the rebound effect or OGF effect that stops cancer cells from proliferating. So you want to capitalize on this. This happens once LDN has cleared your receptors (4 hours later) so the benefit and good things all happen for 20 hours (in a 24 hour period). A higher dose means a longer blockade time of receptors, and less time for the 'rebound effect'. Researchers who have worked with oncologists and studied LDN for over 30 years have recommended a dose of 3mg for the reason that the receptor blockade doesn't go over the 4 hour time frame allowing more time (20 hours) for the up-regulated levels of endorphins and enkephalins to stop cell proliferation....

Some find that after a while they are able to enjoy a longer duration of the rebound effect and need less help from LDN to stimulate the production of endorphins, OGF and receptors. In these instances it is worth considering lowering the dose and/or take it less frequently to allow the immune system to function as efficiently as it can on its own. ”

Following subsequent conversation with Jayne here's my [Brian's] understanding subject to correction. We get the most healing effect (OGF production) with a 4 hour blockage. It's tricky because the dose required to achieve this can range from (usually) 0.5mg to 4.5mg depending on metabolism. A lower dose than our "ideal" one will not produce as much healing effect. A higher dose will result in too much blocking time in each 24 hour cycle. At this point there's no test that can determine our ideal dosage so we all have to experiment.

However there is a second factor which can be thought of as "How much healing can we stand?" in terms of herx/retracing/detox that may be kicked up by the OGF production. One of the articles about herxing I read says the goal is "tolerable herx." So we want as much healing and clearing as we can live and function with, but if we get so ambitious that we incapacitate ourselves then we're overdoing it. If

Side Effects & Dosing of Low Dose Naltrexone (LDN) 7

the effects are too strong to tolerate then we may have to dial back the dose and pay extra attention to supporting ourselves via diet, rest, sauna, detox support etc. It takes constant adjustment and monitoring for some people. See the herx info posted earlier.

A complicating factor comes in if rather than reacting to the positive effects of LDN we are reacting to something in the fillers or possibly preservatives (with the liquid versions). So that is something to try to eliminate as a variable if someone is having trouble. More info below on this.

Occasionally we read about a patient or doctor using a dose higher than 4.5mg or sometimes dosing twice a day. There is some controversy about this and perhaps the best thing is to direct you to the two camps for their outlook. To read about the logic behind the different doses see the File “Alternative dose-strategy from LDN Norway group.”

As a counterpoint read the following from LDN Now on Dosing:

http://ldnnow.com/48501/90512.html

Some further thoughts about long term use of LDN:

LDN Rebound effect....

https://www.facebook.com/notes/ldnnow/ldn-rebound-effect/10152209009858391 and

Long term use from LDN Now.... http://bit.ly/2UUKsPg

For those having sleep problems aids include Chamomile tea, valerian, calcium/magnesium capsules, L-Theanine, GABA (NOW's True Calm is one verson), 5-HTP, and Natural Calm. . For best results, sleep aids should be taken about half an hour before bedtime. For additional sleep aids, visit http://www.naturalnews.com/044596_insomnia_healthy_sleep_quick_tips.html

breathing technique for sleep.... http://www.byrdie.com/how-to-fall-asleep-fast

http://www.huffingtonpost.com/mark-sisson/best-night-of-sleep_b_4233534.html

Some may find some useful information in this insomnia article:

https://www.juliarosscures.com/eliminating-the-top-causes-of-insomnia/

More information on insomnia, melatonin etc and be found in the “Insomnia” file.

This warning comes from the Low Dose Naltrexone Homepage:

Those patients who are taking thyroid hormone replacement for a diagnosis of Hashimoto’s thyroiditis with hypothyroidism ought to begin LDN at the lowest range [0.5mg] ). Be aware that LDN may lead to a prompt decrease in the autoimmune disorder, which then may require a rapid reduction in the dose of thyroid hormone replacement in order to avoid symptoms of hyperthyroidism.

Some people taking LDN have reported reduced appetite, a side effect that enabled them to lose weight. If weight loss is undesirable, small frequent meals are recommended.

In cases of autoimmune-related bowel disease, LDN typically leads to weight gain as the bowel heals and begins to function normally. Some may need to adjust their food intake and/or choice of foods.

Some people have reported a modest increase in blood pressure associated with taking LDN, while others have reported a decrease.

Aside from health improvements positive “side effects” that some individuals taking LDN have noted include an increased sense of well being, increased self-confidence, reduction of allergies and a stronger sexual appetite. For additional accounts to put the side effects in perspective look for the “Success Stories” File.

OPTIMAL DOSING TIME varies with the person. Best to experiment with different times and see what works best for you as an individual.

Side Effects & Dosing of Low Dose Naltrexone (LDN) 8

For some LDN is energizing -- they may have sleep issues with bedtime dosing but do well with morning dosing.

For some LDN makes them sleepy -- they will be too groggy with morning dosing but will do well dosing at bedtime.

Occasionally some will find the blocking period results in an increase of pain or a darkening of mood -- they will do better being asleep during that time.

Some sleep well but then are groggy in the morning -- they may want to try 9pm or 6pm dosing so as to give the LDN some more time to clear.

Etc.

The original thinking about dosing at night because of the Endorphin cycle has pretty much been put aside although the advice continues to circulate (see graphic).

As a general rule, if side effects are a problem, LOWER THE DOSE. If you want to adjust the dose before your next prescription here is what some users have done (may need to scroll to next page):

Side Effects & Dosing of Low Dose Naltrexone (LDN) 9

For more information about making a batch of doses look in the Files for the document “How to change LDN dose using capsules.”

Because of its unique mode of action in the body (the partial and temporary blockade of opioid receptors), achieving therapeutic results with LDN is highly dose-dependent. Too much or too little of the drug can definitely be counterproductive.

For children and pets: To compute the theoretical "ideal" dose in mg based on Clark's pharmaceutical dosage rule, multiply their weight in pounds by a factor of 0.03 . If liver functionality has been compromised, however, a dose lower than the computed dose may be necessary, and it can only be determined by trial and error.

Given the number of variables and unknowns involved, Dr. Tom Gilhooly, a Scottish physician, advises using the trial and error method at the outset, suggesting [building the dose] until the patient's symptoms start getting worse instead of better. At that point, the dose should be reduced by 1/2 mg and kept there until the symptom picture changes. Dr. Gilhooly has pioneered in the administration of split dosing (one dose in the morning and one in the evening at bedtime), and in doses as high as 25 mg. Some multiple sclerosis sufferers claim, for example, that a 25 mg dose of LDN at bedtime temporarily for a week or two is very successful at bringing them out of a relapse. But consult with your doctor about these unusual methods.

Some people who seem to be reacting to LDN may in fact be reacting to the filler used in compounding the medication. Talk to your pharmacist to see what was used and if there might be alternatives. My current impression is that sucrose is the least troublesome filler. Ginger may be a nice option. For a more extensive discussion see the File AVICEL AND OTHER FILLERS.

You may want to get a liquid version to start with because it will be easy to adjust the dose. My impression over time is that it is impossible to know your "right dose" -- it will have to be determined by

Side Effects & Dosing of Low Dose Naltrexone (LDN) 10

experience but it is likely to be between 0.5mg and 4.5mg.

Some issues have come up with some of the additives and preservatives in the usual liquid formulations. Some liquid versions have been found to contain sodium benzoate and ascorbic acid which is a potentially dangerous combination. May only be a problem if the mix gets hot. Added ingredients may not be any problem for you but sometimes it's hard to know if someone is reacting to the LDN or something mixed with it. So you may want to get the version made with pure Naltrexone powder (NOT crushed tablets) and distilled water with nothing else. This will eliminate any possible filler reaction. Check with your pharmacist about the life in the fridge. Since this version doesn't have preservatives it may only be good for 30 days (but check).Those with GI issues may prefer the sublingual drops.

We have a member that had quite a strong reaction to a compounded liquid LDN version but did better with the plain liquid.

Some question the effectiveness of the transdermal cream:

“ Can LDN be prepared transdermally in a cream form or patch? For LDN to work, the full LDN dose must be delivered to the body in one go. Transdermal delivery methods by nature result in slow continuous delivery of a drug. This will result in continuous opiate receptor blockade - quite the opposite of the purpose of LDN which is to deliver a very short term blockade in order to create the beneficial rebound effect.” From:

http://www.ldnscience.org/low-dose-naltrexone/questions-and-answers

"The efficacy of this product in adults is extremely dubious - as absorption into the bloodstream is very low. " From: http://www.ldnresearchtrust.org/sites/default/files/LDN%20- %20MS%20Fact%20Sheet%202015.pdf

We should note however that Dr. Jaquelyn McCandless said she had clinical success using the cream with autism. It's not clear how this squares with the above statements. See below (may need to scroll to next page):

Side Effects & Dosing of Low Dose Naltrexone (LDN) 11

Side Effects & Dosing of Low Dose Naltrexone (LDN) 12

It may be (?) that the healing mechanism with autism is different from other conditions. I (Brian) have seen some thinking that Autism indicates an excess of inner stimulation via Endorphins and higher or more frequent doses of LDN may be useful as they provide partial blocking. See the Autism File.

In rare instances, LDN levels can build up in a person and blunt or even negate its effectiveness. Therefore, a reduction in dose, or even skipping some doses, has been suggested in cases where LDN mysteriously stops working, or bothersome side effects return for no apparent reason. You can see a discussion of this in the “Skipping” File.

Naltrexone is an opioid receptor antagonist. It blocks narcotic painkillers from reaching their intended target, causing such painkillers to lose their effectiveness until the effect of the Naltrexone wears off. Since people appear to vary widely in their ability to metabolize LDN, Dr. Lenz currently suggests that you stop your regular dose of Naltrexone 7 days before any medical or dental procedure is scheduled

during or subsequent to which opioid painkillers are to be used or prescribed. Discontinuing LDN for 7 days might cause some loss of ground in terms of the condition for which a person is taking LDN, but apparently resuming LDN after that period at one's usual dose does not cause a significant return of unpleasant side effects. The body has already become accustomed to the drug. Many will be able to resume LDN 48hr after they discontinue the opioid painkiller, assuming they have not been using it to the point of becoming habituated to it. In the latter case, one should wait two weeks before resuming LDN, otherwise you may experience an unpleasant withdrawal reaction.

Regarding use of opioid medications in emergency situations. Linda Elsegood of LDN Research Trust was kind enough to exchange emails with me regarding this issue. She says,

"In ER they use high doses of opiates you don’t need extra high being on LDN. The standard dose they use is enough.

Over the last 11 plus years since I founded the LDN Research Trust, I have learnt from many doctors that we don’t need to carry warning cards in case of Emergency. If the worst happens we will be alright with the same treatment as those not taking LDN."

In a previous email she told me that pain specialist Dr. Pradeep Chopra had informed her that high enough doses of opioids will work in spite of the LDN. I suppose the dose used in a hospital emergency situation is typically going to be larger than a home dose. Nausea is sometimes an issue with opioids regardless of whether LDN is in the picture or not.

So bottom line is we don't need to worry about being on LDN in an emergency situation. If we have advance notice of an upcoming situation like surgery I think we should still follow Dr. Skip's advice and stop LDN dosing 7 days ahead of time.

However following that exchange I received these "contrary opinion" comments to the above Skip Lenz posted:

“I am involved, as an expert witness, on a case involving a patient on naltrexone going into an ER and basically being overdosed with an opiate. No pain relief at all. So with all due respect maybe I can give their names [Linda and Dr. Chopra] to the defense and we can duke it out in court. We always ask if you are on an opiate and if so you do not get LDN from us! end of story......

Tell the ER crew that you are on naltrexone and cannot take an opiate. There is a myriad of other drugs that can be taking in its stead....such as Ultram [Tramadol] or Ultracet [Tramadol plus Tylenol] either oral or IV.”

So the best advice we can give since people's reactions vary so much is to ask for non opiate pain relief first. If that is not adequate you *may* be able to use opiates depending on the extent of clearing in your system. It may be that higher than normal doses will be required.

Side Effects & Dosing of Low Dose Naltrexone (LDN) 13

In regard to taking LDN when pregnant or during breast feeding, Dr. Phil Boyle, a specialist in fertility care in Ireland, stated the following:

“I am confident that LDN is perfectly safe in pregnancy, and in certain cases will actually reduce the risk of miscarriage. Thomas W. Hilgers, M.D., of the U.S., who developed the fertility treatment I provide, has used high dose Naltrexone...up to 100mg throughout pregnancy and during breast feeding safely, without ill-effect to mother or baby, since 1985. I have been prescribing LDN regularly during pregnancy [for several years] and the results have been excellent. Clinical experience has proven to me that it is safe.”

However there are some counter-arguments – tag me to ask about this.

For best results when taking LDN, you may want to avoid gluten (see https://www.youtube.com/watch? v=DdJGqTVvBAM&feature=em-subs_digest),

genetically modified food, fried food (see

http://www.naturalnews.com/043619_fried_foods_trans_fats_whole_body_health.html ), and the foods discussed here:

http://www.naturalnews.com/042501_inflammatory_foods_disease_prevention_wheat_gluten.html . Some people have found it also helps to avoid nightshades (e.g., tomatoes, potatoes, peppers, and eggplant). You will find further discussion of various dietary protocols on the board.

Some people have also found it helps to keep Candida yeast overgrowth in check. Some research will be required to find the best way to do this for yourself. More info:

http://www.naturalnews.com/024209.html

5 Signs You're Suffering From Candida Overgrowth - and What You Can Do About It.......

http://health.usnews.com/health-news/blogs/eat-run/articles/2015-12-23/5-signs-youre-suffering-from candida-overgrowth-and-what-you-can-do-about-it

Candida Support and Information Group ….... https://www.facebook.com/groups/2319869614/

10 Signs You Have Candida Overgrowth & What To Do About It……

http://www.mindbodygreen.com/0-8376/10-signs-you-have-candida-overgrowth-what-to-do-about it.html?fref=gc

“Spit test”… https://www.doctorsbeyondmedicine.com/listing/candida-home-test

This info about Lufenuron is for those interested in researching this product that some people like. There is some controversy about it so it's up to you to research this with your doctor........ https://www.drmyhill.co.uk/wiki/Lufenuron_-_a_potentially_useful_treatment_to_treat_candida

https://lufe.info/

Copied from Francie Stull's post: “If you find a site that is against Lufenruon for Systemic Candida, it is somebody selling an expensive competing product, or copied from a competing site. There is really no down side to taking Lufenuron, which has been shown to be safe, relatively cheap, and totally effective.

It is pretty common knowledge that when starting the LDN, an already established case of Systemic Candida or yeast will get out of hand, so it is often recommended a course of Lufenuron as you are starting the LDN, or any time that a fungal issue pops up. There is lots of info here: Lufe.info and I buy from Shop4Lufe.com (the sister site), and the code for 10% is the year 2017 [maybe 2019 now??] I can't recommend it highly enough. It did a super job for me and lots of others, who were recommending it when I started the LDN.”

Side Effects & Dosing of Low Dose Naltrexone (LDN) 14

Against using Lufenuron…. https://www.candidaplan.com/1120/lufenuron/

You may want to search for other comments/reviews.

Some that have not been doing better with LDN test for Lyme disease. We recommend testing with a Lyme literate doctor (LLD). Unfortunately, some of the general tests for Lyme may not catch or diagnose it accurately. Many consider the most accurate test to be the Igenex version.

Doctors running clinical trials have discovered that low vitamin D levels can hinder the effectiveness of LDN. Many people are deficient in vitamin D. It might be a good idea to have your vitamin D level checked and, if need be, supplement your daily diet with at least 5,000-10,000 IUs of vitamin D3. If you do this you will likely need to add Magnesium and Vitamin K2. Look for the File on this and talk to your doctor.

Some people have a genetic defect that results in MTHFR and which might interfere with the action of LDN. Ask for my post on this.

Mold toxins can cause as well as mimic many health problems and undermine your success with LDN. For more information, visit: http://articles.mercola.com/sites/articles/archive/2011/11/01/recovery-from toxic-mold-exposure.aspx

As a summary of some of these points Dr. Jaquelyn McCandless was a physician who treated hundreds of autistic children with LDN. These are some of her edited comments regarding problems that she observed in her practice:

“Seldom is LDN a stand-alone treatment, but accompanies other strategies a person's body needs, especially a healthy diet. No sugar, dairy, or gluten. It takes some people longer to respond to LDN, and they may be colonized with pathogenic yeast and bacteria that could be slowing response. These setbacks usually do not last long unless something like a candida yeast infection is stubborn without specific treatment. Try to hang in for awhile longer.

LDN has been noted to aggravate yeast infections and other latent pathogens, viruses, etc., as the immune system is making early adjustments. It is good to have natural yeast remedies on board when LDN is started (grapefruit seed extract, Candex, lauricidin, hi potency probiotics, etc.) to help offset this possibility. (And of course a good dietary regime that does not encourage gut inflammation which is usually the predecessor to pathogen invasion.)

There is a phenomenon that happens to some people that as the immune system is shifting (usually from T2 to T1) right after starting LDN, the immune system drops and people get an infection, cold, flu, cold sore, etc., which is usually short-lived. Candida tends to overgrow or a virus will flare up. These infections are usually short-lived unless something like candida and gut bacteria needs treatment. If you are having adverse symptoms caused by LDN, would you be willing to stop all casein (milk products) and gluten (wheat, rye, barley, and oats) for a week and see if you feel better? A study done several years ago showed that 30% of us have some degree of celiac disease (intolerance/allergy to wheat) even though the clinical symptoms may not be obvious enough to alert most people to that. When anyone in that 30% of persons stops eating wheat, they feel a lot better. The LDN may be acting like the opioid antagonist it is and causing a withdrawal reaction from taking away your fix, even if only for a few hours. Many people who eat wheat and drink milk do not even know what "feeling good" is like until they remove these foods from their diet.

Anytime someone has a negative reaction to LDN, the first question I would ask is,"What is the diet like?" If I had a disease such as ALS or MS or other autoimmune disease, I would be more than willing to see if my dietary exogenous opioids could be causing the negative reaction to a drug that is helping most of these people get off all their other drugs without

Side Effects & Dosing of Low Dose Naltrexone (LDN) 15

progression of their disease. The reason this is a worthwhile trial is that this intolerance is affecting their general health and immunity in a negative way. Unfortunately, sometimes it takes up to 6 months to get gluten out of the system, so it is not so easy to test. Food is so emotionally entrenched in most people's notions of love and inner security, you would be amazed at what people will endure to eat the foods to which they are addicted! I have a huge respect for the power of addiction to foods and the difficulty in making radical changes from the diet we are accustomed to. Usually it takes an evaluation in the context of a serious illness for people to even consider changing, and even then many will not.”

You may like to watch this worthwhile interview with Chris Kresser. Here again is his comment about side effects and the link to the full interview:

http://chriskresser.com/low-dose-naltrexone-ldn-as-a-treatment-for-autoimmune-disease/

LDN user Elaine C.'s excellent post on dosing logic follows. Elaine has Hashi's so she is perhaps more cautious in her dose raising than some will need to be:

"Some people do find that a low dose like 1.5 is fine. What you can do is hold that dose for a while and see what it gives you - if the positive holds or not. I usually held my doses for several days or weeks but at 8 months in, I'm averaging about 1 month to 6 weeks of good response before it falls off and I start going backwards. At each of those points I just bumped up the dose a bit.

Being super sensitive, I did start quite low at 0.5mg (for Hashimoto's and adrenal dysfunction = exhaustion) and even at that low a dose had a nice subtle positive response of increase in energy and positive mood. I only held for about 10-14 days between my early raises so then up to 1.0, and 1.5mg. Once at 2mg, got a lot of negative symptoms, feeling unwell, depressed, out of sorts, some nausea (which is a key sign for me of too much LDN) - held it for 6 days to see if it would all pass but didn't and actually got worse. So dropped back to 1.5mg and all the negative cleared. Held at 1.5 for a while and then tried smaller increases below 2mg. Went to 1.75mg and got the best response ever - feeling like my old happy, strong self!

As I mentioned I had to tweak again after 4-6 weeks and went up by 0.05 a few times - so to 1.80 and now at 1.85mg. Feeling well. ......It's up to you what you want to do. Sometimes it seems like we have a good response and we just want to hold things steady. I know I always had some fear and trepidation with trying raises - but it really is so individual that it's only with experimentation that we can each find our best or optimal LDN dose.

The way I did it was I tried to stay tuned to how my body responded, regardless of what others might say is the ideal dose and timing. And in fact, the ideal is what works for your own body.

Another thought: the full extent of whatever that "ideal" turns out to be for you, is only seen slowly over time.

Side Effects & Dosing of Low Dose Naltrexone (LDN) 16

So my two key thoughts here:

1) It's an individual journey...

2) It's a journey, not a race! Find the "right dose" for you -- sometimes less is more.

I keep a journal with my dosing of meds, symptoms and vital signs (Temperature pulse and blood pressure - not every day mind you but those help me to discern what is going on with my thyroid issues - especially when things go off and I can sense changes). Keeping a journal also helps me to be objective about things as you can get mired in the present, especially when having a bad day (or week!), it may feel like you never feel well. But the journal helps me to keep perspective."

Addendum from Alfred Souza:

TRUST THE PROCESS AND TRUST OURSELVES

"Just as in Nature, decay must occur in order to nourish new growth, our bodies must tear down old tissue and detoxify in order to regenerate. Expect that you will have ongoing cycles of wellness interspersed with cycles of discomfort until you have reached a state of stable, resilient health. At this point, you may still choose to integrate cleansing routines and person-growth-stimulating therapies into your life on a regular basis. In doing so, you may find that once in awhile you will again experience a release of something toxic, followed by a feeling of being ill, followed by a feeling of being free and clear of whatever was released (whether emotional or physical). In time, you will learn to welcome these events and to take comfort and pride in them as affirmations that nature is taking its course. You will most likely experience many healing events throughout the journey towards reclaiming your health. As you understand the importance and predictability of these events and learn to recognize when you are experiencing them, it will be much easier for you to maintain confidence in your chosen healing path. Rather than trying to escape from the experiences, you can relax into them with full awareness of their significance. During these events, it is important to tune in to what you feel and need and to offer yourself (or ask others for) all the love and care that you need to get through it. Your body is infinitely intelligent. With adequate resources: healing, rest, clean water, fresh air, exercise, sleep, a healthy emotional peace and an individualized healthy diet, it can work miracles in healing. "For a long time it had seemed to me that life was about to begin...But there was always some obstacle in the way, something to be gotten through first, some unfinished business, time still to be served, a debt to be paid. Then life would begin. At last it dawned on me that these obstacles were my life."