You are absolutely right there is a sweet spot. The name “Low Dose Naltrexone” mislead me. After all, we are taking doses much lower than the drug’s prescribed dose for its primary intent.
I wasn’t paying attention when I ordered LDN. I order the 4.5mg dose and received capsules instead of the tablets I was expecting. It is harder to accurately adjust the dose with the capsule form. So this week I have been experimenting by opening the capsules and pouring some of the contents out.
~3mg before bed gave me a good extended deep sleep and I felt great the next day.
Last night I took 4.5 mg and I feel sleepy today with a queasy stomach.
To be honest when I read your first post about a sweet spot I was skeptical. Now I am a believer.
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Hi Paul
My team and I have used it on over 100 patients. Start at about 1.5 mg and titrate to 3.0 and then max of 4.5 mg. At these doses it may have cancer preventive properties, but may be cancer promoting,at least in theory, at higher dosing.
We’ve had success for chronic pain, MS, autoimmune issues, and even sweet craving control. Haven’t tried it for long Covid.
It’s easy for compounding pharmacies to custom make it for you.
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This is hot off the press from Cardiovascular Research Branch of NIH: https://twitter.com/EricTopol/status/1691173507869347841?s=20
"Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), named to reflect its “postinfectious” association, is a debilitating disorder characterized by exercise intolerance estimated to affect ~2.5 million individuals in the U.S. (1, 2). There are no clear abnor- malities by clinical testing to explain two prominent physical symptoms of ME/CFS, chronic fatigue and postexertional malaise, thus it is often a diagnosis of exclusion. 'The physical burdens of this disorder may also be accompanied by cognitive impairment, which further diminishes the patients quality of life. More recently, chronic fatigue has been associated with the post-COVID-19 syndrome (referred to as “long COVID”) and reported to bear resemblance to ME/CFS, raising the possibility that the pathophysiology of these two clinical entities may be related (3). Although the pathogenesis of ME/CFS has been extensively studied, no specific mediator molecule has been identified to explain the low aerobic capacity in this disorder. A number of ME/CFS studies have revealed redox imbalance and bioenergetic defects, both regulated by the mitochondria (4). Cardiopulmonary exercise testing of individuals with ME/CFS has shown decreased oxygen utilization and increased lactate accumula- tion, suggesting mitochondrial dysfunction (4-6). An important aspect of oxidative phosphorylation for ATP synthesis is the assembly of mitochondrial respiratory com- plexes into supercomplexes, which may reduce reactive oxygen species generation by facilitating the efficient transfer of electrons during respiration (7). Studies have shown that supercomplex formation in skeletal muscle is promoted by exercise and is positively correlated with mitochondrial oxygen consumption while metabolic dysfunction is associated with disruption of the supercomplexes (8, 9). During the clinical investigation of a patient with chronic fatigue, we found that WASF3, induced by ER stress, disrupts mitochondrial supercomplex formation and respiration by analyzing an aberrant sign- aling pathway observed in the patient’s cells. Our study provides a molecular explanation for the patient’s bioenergetic deficiency, which may be applicable to not only ME/CFS but also other conditions that feature chronic fatigue such as long COVID or rheumatic diseases associated with ER stress (10-12).
Significance Chronic fatigue is a debilitating symptom that affects many individuals, but its mechanism remains poorly understood. This study shows that endoplamic reticulum (ER) stress-induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance. Alleviating ER stress decreases WASF3 and restores mitochondrial function, indicating that WASF3 can impair skeletal muscle bioenergetics and may be targetable for treating fatigue symptoms."
An older paper (https://www.sciencedirect.com/science/article/abs/pii/S0304394006004502) showed that naltrexone can act through mitochondria. Therefore, it is possible that this may be related to the clinical observation that LDN can help ME/CFS and Long COVID via a pathway that is related to WASF3.
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Extremely interesting stuff Paul. Melatonin and ldn share some similarities. Melatonin also inhibits toll like receptors and is involved in mitochondrial health and function.
Of interest, WASF3 knockdown upregulates KISS1 in cancer cells which inhibits its invasiveness. Melatonin also upregulates KISS1. This could be a part of their anti cancer activity as well as the long Covid effects. https://www.cellmolbiol.org/index.php/CMB/article/download/2966/1435/6986
I’m wondering if a combination of ldn and melatonin might be synergistic.
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I’ve been pondering the high dose melatonin thing. Is it high dose at night, or melatonin all day long? I’ve used melatonin 0.3-3mg for sleep for 20 years, but have never used it during the day. I can imagine doing it on a highly active, outdoor day. But I can’t imagine sitting in my office with 30mg of melatonin in my blood. ZZZZZZZZZ.
I took melatonin for decades 1-10mg at night for a few months now I have been taking high doses at bedtime, typically 60 to 80mg, and another 10mg sublingually if I wake up during the night. Inspired by John Hemming and others in the thread: “Melatonin megadoses? - #46 by HigoMe33”
It feels no different to me than taking 1mg doses. It does not cause me any daytime sleepiness. A little too much LDN does.
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For prevention, it seems that people are using 100 to 180 mg at night. Studies seem to suggest that it’s safe . Melatonin, Beyond Sleep , is a pretty decent book by John Lieurance, written more for the lay person. Seems a little exaggerated, but still informative.
Better yet is the one by Russel Reiter called Melatonin. He’s one of the leading researchers in the field. It was also very informative.
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Thanks for the details. I’m tempted to try it. Maybe I wait to see what the LDN does first. (low low dose).
is there a US manufacturer/distributor making LDN? Just realized that you have to go to a compound pharmacy to get the low-dose Naltrexone which is a bit of hassle and compounding pharmacies could make mistakes. Did look into Ageless but the guy behind it had terrible reviews on the internet. Looks like it’s all marketing people for his website too.
I use Gethealthspan.com who I believe gets it from a compounding pharmacy. I ordered it but haven’t received it yet.
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Got mine from India. See the list of trusted suppliers.
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FWIW
I have been using AgelessRx for LDN for the past 6 months. Posted about this on another thread on this forum.
Cost $100.00 for 3 month supply{at 4.5 mg per day dose] delivered with a prescription.
I have no financial interest in AgelessRx, I am a user of their service.
If you look online you can locate a $30.00 discount code for your first order.
It’s not a big deal. Start at 1.5 mg and work your way up. If it makes you groggy, go down. If you’re using it for pain relief and the effect wears off, stop for a while and restart. I do the same with gabapentin as well. Agree with BobinUK it’s definitely about finding your personal sweet spot, probably based on weight, gender, age, and metabolism.
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I use it for Lyme disease complications and get it from compounding pharmacies. Here’s an interesting story on a long COVID treatment: 2 over-the-counter drugs reduce "brain fog" from COVID - Big Think
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Thanks. I’ll follow your advice.
As an update, I’ve been taking 1.5mg for 7 days. I take it around 9pm, and I haven’t felt anything yet. I have slept better, according to Oura as well as my own subjective feeling of having slept deeply. I don’t notice anything related to pain yet. I’ll be graduating to 3mg in a few days.
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why are you taking LDN?
For sleep enhancement, with fingers crossed on other possible benefits.
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what are your sleep stacks?
Melatonin, ashwagandha, glycine, theanine, jujube extract.
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