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Side Effects and Dosing of LDN

Side Effects and Dosing of Low Dose Naltrexone (LDN)


Most medications result in unintended reactions called side effects. LDN is no exception. Just as every marriage goes through an initial period of adjustment, so too does the taking of LDN bring about a new order of things to which the body needs to adapt. Internal chemistry changes, endorphin levels increase, and the immune system is upregulated--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 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 (Low Dose Naltrexone) 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.]

In addition, because LDN will also block the analgesic effects of any opiate drugs (includes codeine, dihydrocodeine, morphine, pethidine or diamorphine) presently being taken, the use of LDN will initially greatly increase the level of pain experienced [or worse, result in a potentially dangerous withdrawal reaction]. It is therefore advisable [in cases of dependency] that any opiate-like drugs be discontinued at least two weeks before this treatment is initiated [to allow a "drying out" period].

When starting the treatment it is essential that any untoward or adverse side-effects are reported immediately [to your LDN prescriber] so that the treatment process can be further assessed and, if necessary, modified.
Italian researchers conducting a four month clinical trial (N=40) of LDN in the treatment of MS made this statement about side effects:
Transitory haematological abnormalities (increase of liver enzymes, hypercholesterolemia), mild agitation and sleep disturbance were the commonest adverse events.
There is a good deal of confusion in regard to LDN dosing, in particular, the best time to take it. The biggest misconception is that clinical studies show it does not matter what time you take, you will get the same benefit regardless. In actual fact, there are no such studies. Some studies show it works if taken in the morning, but we already knew that from anecdotal reports. But, there has NEVER been a study that deals specifically with morning vs evening dosing.

Dr. Skip Lenz graduated from Massachusetts College of Pharmacy. He received his doctorate with highest honors at the University of Florida after completing a rigorous Pharm. D. program. He has about eighteen years' experience dispensing LDN to literally thousands of patients.

Writing in the "Questions and Answers" section of the newly published The LDN Book he recommends taking LDN at BEDTIME. Most of the LDN clinical trials used evening dosing, and the Low Dose Naltrexone Homepage recommends taking it between 9 pm and 3 am.

Because LDN tends to initially worsen MS symptoms (especially spasticity), Dr. Lenz currently recommends a nightly dose of 1.5 mg the first month, 3 mg for the next two months, seeing how you are doing, and then re-evaluating with your doctor whether you should increase to 4.5 mg. Some people do not fully respond to LDN at doses lower than 4.5 mg, which is why most of the LDN clinical trials used that dose. Click here for information about cancer doing. To quote Dr. Lenz:
The reason we suggest a stepwise 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).
"Start low and go slow" is how one patient put it.

People who have multiple chemical sensitivities are advised to start LDN at a dose of .5 mg at bedtime, and increase it by .5 mg every two weeks. Some authorities also suggest a starting dose of .5 mg for Hashimotos, Chronic Fatigue Syndrome, PTSD, and fibromyalgia.

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 at bedtime was the optimal dose for the average person. Most of the LDN clinical trials used that dose. Some people, however, do well on 3 mg, but others only do well on 4.5 mg. The bottom line is that we each have to find the dose that works best for us, the one which gives the maximum benefit with the fewest side effects. As will be discussed later, not everyone can tolerate a dose as high as 4.5 mg, or, in some cases, even 3 mg.

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

Sleep aids include Chamomile tea, valerian, melatonin, calcium/magnesium capsules, Lunesta, L-Theanine, GABA, 5-HTP, and Natural Calm. My personal favorite is earthing/grounding.

I would also recommend taking an afternoon nap. Studies show that daily naps have definite health benefits, and I believe that is particularly true for people on LDN.

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 (1.5mg for an adult) [some authorities are now recommending .5 mg]. 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 people have reported a modest increase in blood pressure associated with taking LDN, while others have reported a decrease.

Additional side effects that some individuals taking LDN have noted include an increased sense of wellbeing, increased self-confidence, and a stronger sexual appetite.

People who have bipolar disorder should be sure to check in with their psychiatrist and be monitored closely for any signs of imbalance (mania, depression, or a mixture) during or after starting LDN. It is especially important to avoid insomnia, which can precipitate such an imbalance.

The Mayo Clinic has extensive information on the side effects of much larger doses of Naltrexone (25 mg and up), the kind used to treat alcoholism and drug addiction. Some of these side effects (like dizziness, thirst, itching, rapid heartbeat, and urinary problems) may also apply in rare instances to LDN. To learn more, visit


Because medications are metabolized in the liver, if that organ has been damaged by toxic chemicals, pathogenic microorganisms, previous drug therapy, or alcoholic addiction, there will be an increased likelihood of unpleasant side effects.

The optimal dose of LDN for the average adult is deemed to be 4.5 mg taken between 9 pm and 3 am. To control for the difference between Daylight Savings and Standard Time, some people take it between 10 pm and 2 am. The optimal dose does not suit everyone, however, as will be discussed later in this site.

LDN should not be taken with food. The medication needs to be rapid release, and food prevents that, because it is delayed during the process of digestion and consequently presented piecemeal to the body's opioid receptors. For the same reason, LDN should not be compounded with the filler calcium carbonate, as it tends to cake and prevent rapid release.

To quote Dr. Samyadev Datta (a pain management specialist):
It is recommended that naltrexone is administered at night. It should be done on an empty stomach [at least two hours after eating] and patients are NPO [nothing by mouth] for 1 hour after administration of medication. This allows for better absorption and best results. Administration at night allows synchronization with the diurnal rhythm. Maximum endorphin and enkephalins are then released early in the morning. In addition low-dose naltrexone may need to be titrated to higher doses.
In regard to daytime dosing, of all the clinical trials of LDN conducted with humans, only one used daytime dosing for all participants--a German study with a group of 60 MS patients. While about a third of the group did experience limited benefit, this is the comment made about the trial by Dr. David Gluck, webmaster of http://ldninfo.org:
Unfortunately, because of some early complaints of sleep disturbance, the principal investigator of this trial switched all of the study group to taking LDN at 9 am in the morning, a questionable dosage time. It is generally recognized that the most effective time to take LDN is at bedtime, between 9 pm and 3 am, due to the fact that the endorphins for each day are always produced at their peak rate in the pre-dawn hours.
In a presentation made by Dr. Bernard Bihari in 2002, he gave this perspective on LDN dosing:
The reason the hour is important is that 90% of the endorphins are made in the middle of the night, between 2 and 4 in the morning. If a small dose of naltrexone is taken in the late evening, generally at bedtime, generally endorphin production is boosted as much as threefold, 300%. The naltrexone itself is gone in about 3 hours, but the endorphins remain elevated all the next day. So the naltrexone doesn't significantly block the endorphins but does cause them to rise.
To test the hypothesis that evening dosing is preferable to daytime dosing, Dr. Skip Lenz compared the results of two studies, both of which involved LDN in the treatment of progressive forms of MS. One study, the German trial mentioned above, used morning dosing, and the other, the Italian trial mentioned earlier, used evening dosing. Based on his comparison, he concluded that morning dosing was a "poor substitute" for evening dosing. To quote Dr. Lenz:
You want LDN to be in your body and working during the period of time at which your endorphin levels are increasing naturally.
I personally have known people who switched from evening to morning dosing, only to have their symptoms return. This is the experience of a woman in an LDN discussion group:
I switched from bedtime to AM dosing because of discussion on this board about how AM dosing may be equal to or even superior to PM dosing. I lost all the benefits I was getting. When I switched back to PM dosing a couple of weeks ago, my pain levels immediately began decreasing and now I have negligible pain. The timing, I have concluded, is of utmost importance to me.
This is the experience of a woman with a number of afflictions:
On morning dosing I quickly experienced a reversal of my improvements of my autoimmune conditions. I started getting RA pain back in my knuckles within a few days. My inverted psoriasis came back a few days after that, along with ringing in my ears returning (autoimmune ear disease). My thyroid started to change back to a hypothyroid state with no changes in thyroid medication dose and my thyroid gland started physically getting noticeably thicker, more inflamed again after about 8-10 days. I also got a cold and got a return of my cold sore after about 7 days of morning dosing. I concluded that morning dosing of LDN is not effective, or not as effective, as night time dosing for me.
This is still another testimony about the benefits of evening dosing:

I started taking LDN for MS in December. At the end of January I switched to morning dosing (based on a Medical Assistant’s suggestion from the prescribing office🏻) and lost all benefits, so switched back to pm dosing about 10 days later. I felt yucky for a month [due to morning dosing] and my hair started receding, so in my experience, pm dosing is the only way to go for the full endorphin benefit. It really is the gold standard, like they say.

This is the experience of the organizer for the very first LDN Conference in 2007:
After being on LDN 2 years, I one day decided to see if daytime LDN dosing would keep me in remission. Just a few short days being on daytime LDN, I started coming out of remission, and by the end of the week I knew if I didn't get back on night LDN dosing, I was headed back to that nightmare I had suffered with for so many years. So, back to night dosing I went. In a few days I was heading back into remission.

My grandmother when she was living had advanced Alzheimer's and on 4.5 mg LDN. My aunt changed the timing of the dosing from 10 pm to earlier and we noticed a rapid decline. Got my grandmother back on her 10 pm LDN dose and she gained back abilities she had lost when her dosing was changed and she stabilized again until her death years later. So, if you do daytime dosing and are not getting good results with LDN at 3 mg or 4.5 mg, try night dosing at 10 pm for a good 6 months and see if that makes a difference.

I used to suffer chronic insomnia before LDN, after LDN I generally sleep quite well. There are many natural sleep aids available. A combo you might try at bedtime is 500 mg of magnesium, 1000 mg calcium (as citrate), and some potassium to relax your muscles.
I also know of people switching from morning to evening dosing and experiencing much better results. Morning dosing does work for some people, but I would not recommend it except for a short period as a means of helping the body adjust to the medication, or in split doses as a means of increasing one's daily intake of LDN. For example, Dr. Bihari found that the main endorphin producing period in humans is between 2 am and 4 am. However, Dr. Lenz has observed that there is a minor period around 10 am. For more information about split dosing, see the reference to Dr. Tom Gilhooly's work later in this site. Before switching to morning or even split dosing, however, I would give evening dosing a thorough trial. It still is, according to Dr. Lenz, the "gold standard."

In an online eBook written by Cris Kerr, there are 51 case studies of people greatly helped by LDN. All, without exception, used evening dosing. In view of the above considerations, had each used morning dosing, it is highly unlikely that they would have achieved the benefits they did.

As a general rule, if side effects are a problem, LOWER THE DOSE. If all you have is a supply of 4.5 mg capsules, while you are waiting for a revised prescription from your doctor, what you might do is empty the contents of ten capsules into a glass jar containing 45 ml of distilled water (three tablespoonfuls), shake well, and store in the fridge. Each ml of solution will contain one mg of Naltrexone. In measuring out the distilled water, be sure to a measuring spoon, NOT regular tableware. Use a baby medicine dropper to draw up the desired dose.

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.

Although the optimal dosage of LDN for the average adult (presumed to weigh 150 pounds) is considered to be 4.5 mg, some patients do much better (i.e., have fewer side effects and a better response) on a lower dose. [To compute the suggested dose for children and pets, multiply their weight in pounds by a factor of .03.] Adult dosage can be affected by a number of factors, including liver functionality, age, and metabolic rate.

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 a dose of 1 mg for the first month, 2 mg the second month, 3 mg the third month, and so on 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.

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. It appears that some people who have taken LDN for an extended period may also need a lower dose to achieve the same therapeutic benefit.

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. At low doses, the blockage only lasts about 4 to 6 hours. However, some people are "slow metabolizers," which means Naltrexone can remain active much, much longer. Therefore, since people can vary widely in their ability to metabolize LDN, Dr. Lenz currently suggests that you skip your nightly dose of Naltrexone a week before any medical or dental procedure is scheduled during or subsequent to which opioid painkillers are to be used or prescribed. Discontinuing LDN for a week 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. You should be able to resume LDN the day after you discontinue the opioid painkiller, assuming you have not been using it to the point of becoming habituated to it. In that case, you should wait 10 days to two weeks before resuming LDN, otherwise you may experience an unpleasant withdrawal reaction.

In regard to taking LDN when pregnant or during breast feeding, Dr. Phil Boyle, a specialist in fertility care in Ireland, stated the following in 2008:
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 100 mg 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.
This site offers helpful hints to people for whom LDN does not seem to be working:


For best results when taking LDN, I strongly suggest that you avoid dairy and gluten (see http://tinyurl.com/dump-dairy-and-gluten), genetically modified food (see http://tinyurl.com/dump-gmos), sugar (see http://tinyurl.com/sugar-feeds-cancer), fried food (see http://tinyurl.com/dump-fried-food), and the foods discussed here: http://tinyurl.com/inflammatory-food. Some people have found it also helps to avoid nightshades, e.g., tomatoes, potatoes, peppers, and eggplant (see http://tinyurl.com/dump-nightshades).

Many people have found it helps to keep Candida yeast overgrowth in check. If the overgrowth is confined to the gastrointestinal tract, this site can help:


In cases of systemic Candida overgrowth, Lufenuron can help. For more information, visit


Some people have been greatly helped by earthing, an inexpensive drugless method based upon directly connecting to the earth. For more information, visit


If you are afflicted with any condition and are not a praying person, now would be an excellent time to start. Prayer changes things, and there are a number of scientific studies that show it can hasten healing, both mental and physical. For more information, visit:


If you have questions, comments, or suggestions, please feel free to contact me at


Very sincerely,

Dudley Delany, R.N., M.A., D.C.