Naltrexone at low doses (LDN) and its relevance to cancer therapy

[Bigmls7890]

Naltrexone 2.5 mg , 2 days on 2 days off.

tandfonline.com/doi/full/10...

[Don_1213]

Fascinating article. I'm on my 3rd week of LDN. I started taking it for chronic pain from arthritis and nerve damage due to poor circulation (neuropathy). I'd read about it in an article in a local newspaper - and started researching it with Dr. Google. Many of the claims made for it sound too good to be true - but there were several double-blind studies done on it's use for chronic pain that made it sound like it would be useful.

The usual dosage is something like 1/10th the normal dose used to help control various drug addictions - and since it has very few reported side-effects the thinking is that at this low a dose, there shouldn't be any real risk of side-effects. So my GP who was interested in some of the papers I found on it was willing to write a prescription.

LDN isn't a buyable drug. No drug manufacturer makes it in the dose needed for LDN. It has to be compounded by a compounding pharmacy, who basically takes the full-strength drug, grinds it up, dilutes it with fillers, and casts new pills out of the mixture. There are also people taking the full-strength drug, grinding it up and diluting it with distilled water, and then adding it to something like orange juice in a mixture giving them the required daily dose.

It's suggested to take LDN at night before bed. A simplistic explanation of the working mechanism is - the drug blocks endorphin receptors, which then yell for more endorphins, which are produced. Meanwhile, the LDN clears from the receptors who then feast happily on the excess of endorphins, making the patient feel better and reducing inflammation, which is a primary component of arthritis (and many other chronic pains.)

I read about the potential for helping with cancer treatments - but when any drug or automotive engine additive promises to solve a multitude of problems, I usually am a bit cautious in believing all the claims made. So - I didn't count that in my decision to take it, I'm taking it strictly for pain relief since I can't take NSAIDs due to cardio issues.

So - what are my results? A test of 1 (which TA will tell you is strictly anecdotal and scientifically useless.):

The common way to take the drug is by increasing the dosage until you reach an optimal level. What's interesting in almost all the studies I've seen is that some of the effects of the drug are perceived almost immediately - within 24 hours of the first dose. The increasing dose is 1.5mg/daily for the first week, 3mg daily for the 2nd week, and 4.5mg for the continuing dose.

I should note - I'm a "night owl" - have been since I was a child. I normally don't go to bed before 1-2AM, and prefer to wake up about 7 hours later (usually 9AM.) Some people are morning people - I'm not one of them. so with that background here is my experience so far:

I took my first 1.5mg dose about 3 weeks ago - and found two things happened - I awoke from sleep at 7:20AM - feeling fine - and went back to sleep (I took the pill about 1:30AM.) When I woke in the morning at 9AM, I actually felt refreshed from sleep, something I haven't felt in a long time.

This pattern continued for the entire week at 1.5mg dose. After that week, I increased the dose to 3mg - and basically had exactly the same thing. Almost every night I'd wake up for a very short period of time around 7:10-7:30AM, fall back to sleep and wake up fully at 9AM feeling refreshed.

I also found I was in less chronic pain - a big enough improvement that my daily workout at the gym became easier (so I increased it).

About a week ago I got to the 4.5mg dose. The pattern changed - my chronic pain returned, I didn't wake at 7-7:30AM and I woke up feeling about like I did before starting the drug.

So last night I returned to the 3mg dose - and awoke at 7:20 briefly, then got out of bed at 9AM feeling refreshed.

As the article notes: "What seems to be important though is the ultimate outcome of treatment with naltrexone is critically determined by the dose and schedule by which it is used."

So - that's it so far. No side-effects that I can recognize and a general "feeling better" sort of reaction to it. The big reason I wanted to try it - was the chronic pain is enough to really restrict what I can do, and the next step in treating it would have been opioids and I didn't want to go down that path. The fact that I was able to increase my workout at the gym pretty much proved to me either the placebo effect is a real thing, or LDN was doing what was claimed for it - relieving pain. In either case, it beats opioids.

As usual - YMMV. If anyone is interested in a list of papers I've read about LDN, let me know and I'll put something together. There have been very few long-term large-scale studies of it since it's an off-patent drug and is very inexpensive and only available as a generic. IE - no drug company money to fund the studies.

What I found of interest - Columbia/Presbyterian/Weill-Cornell (my go-to oncology center in NYC) has a group that is using LDN for various purposes, and Memorial-Sloan-Kettering in NYC also has a page on their website as to the use of it for various cancers, so some "serious" cancer research centers are using and looking at it.

Any questions - feel free to ping me directly.

[Bigmls7890 in reply to Don_1213]

"LDN Research Trust - The Low Dose Naltrexone Charity"

ldnresearchtrust.org

[Don_1213 in reply to Bigmls7890]

Yes - I'm aware of them.

My problem with them is they are claiming that it is applicable to way too many diseases - often without any documentation to back up the claims. It's the "Slick-50" problem. It may be good, but it's looked askance at due to overly broad claims made for it. Just like "Slick-50"...

[Bigmls7890 in reply to Don_1213]

Where do u get your LDN

[Don_1213 in reply to Bigmls7890]

cfspharmacy.pharmacy/human-...

[Don_1213]

Here is the info at Weill-Cornell (NYC, my oncologist just happens to be from Columbia/Weill-Cornell): weillcornell.org/news/what-...

I have a tele-visit with my oncologist in a few weeks (Dr. Charles Drake), I'll discuss it with him. I do value what he has to say..

Another study - single blind but "crossover" (where the participants change their treatment to the opposite treatment part way though the study to see if results follow the treatment - or lack of treatment - aka placebo..)

academic.oup.com/painmedici...

The MSK writeup: mskcc.org/cancer-care/integ...

One other thing I noticed with my use of LDN. For at least the past year, possibly longer, I've had bowel issues where my stools looked like rabbit droppings. I tried probiotics, which did nothing for the problem. My WAG as to the cause was irritation of the bowel caused by the heavy radiation treatments I received as part of my PCa treatment. I mentioned it to a few of my doctors who recommended greater roughage and drinking more water. The drinking more water compounds continence issues so it wasn't entirely possible to do that. Roughage was consumed and perhaps had a small effect on the issue.

The issue resolved itself in the past 2 weeks. Can I attribute it to the LDN? Dunno - coincidence, maybe? One of the claimed diseases LDN is supposed to help with is Crohn's disease. Could LDN be relieving the irritated bowel? Don't know, but whatever caused it - it's nice to have that issue resolved.

[garyjp9 in reply to Don_1213]

How were you able to get a prescription to try this, if it did not come from your MO?

[Don_1213 in reply to garyjp9]

My MO isn't treating me for chronic pain. My GP has been treating it for about 20 years now, he's who wrote the prescription.

This used to be controllable or tolerable with Naproxen - but that's off the table thanks to cardio issues (possibly made worse by ADT.) So the choice was trying this - or - opioids - which I really resist using.

[Bigmls7890]

Did u have RALP or Brachy therapy

[Don_1213 in reply to Bigmls7890]

Are you asking me? No - I had 83Gy of IM/IGRT and 18 months of ADT (Gleason 10..) Current PSA floats around 0.17-0.22

[Bigmls7890]

Can you take ot with , metformin , statin, and melatonin?

[Don_1213 in reply to Bigmls7890]

Again - assuming I'm being asked... can't speak to melatonin since I'm not on it, but I'm taking it with metformin and statins. If you check at drugs.com for interactions - the strong full dose naltrexone has very few drug interactions - and I suspect the LOW DOSE naltrexone would have even less - but I'd suggest asking that of the MD who might be prescribing it for you.

[Hidden in reply to Bigmls7890]

melatonin yes . I do 20 mg mel with 4.5 Nal prior to bed . Per a Nat oncologist md.

[Hidden]

I’ve taken 4.5 per night for over seven yrs per my Nat doc . ✌️

[Don_1213 in reply to Hidden]

Interesting - that 4.5mg works fine for you. When I moved from 3mg to 4.5mg, the relief it provided disappeared almost overnight. And when I went back to 3mg - the relief also came back. I'm thinking about trying doing 2 doses a day, 3mg at night, then 1.5mg in the morning. A number of the papers noted the almost overnight response times when changing doses, and also how critical the actual dose is, that a difference can be seen with 1.5mg changes.

FWIW - tonight was the first time in a very long time (years actually) that I've walked some distance over soft ground without pain. That to me was amazing.

[Hidden in reply to Don_1213]

Interesting? First I’ve heard of this . Maybe I should cut to 3 . But my caps are measured at 4.5 ,a hassle to separate that ?. Good news walking without pain! Thanks

[Don_1213 in reply to Hidden]

There have been reports and papers on the use of VLDN and ULDN - VeryLow/Ultra Low Dose Naltrexone. About 1/100th--1/10th the amount we're taking. Apparently some people respond better to that range of doses, particularly for chronic pain. Maybe cut some in half?

ncbi.nlm.nih.gov/pmc/articl... - very interesting paper.

The results seem very similar to what I'm observing with my 3mg dose. Much less hip pain (sacroiliac pain was really awful before, now it's gone), reduced back pain, and solid normal looking stools (which is really a relief.)

Another interesting paper - ULDN - ldnresearchtrust.org/dr-joh....

There are lots more interesting papers if you ask Dr. Google "ultra low dose naltrexone"...

[Hidden in reply to Don_1213]

Thanks Don!

[Don_1213]

I thought I'd provide a follow-up since it's been about a month since I reported on LDN use.

I believe I'm now in my 6th week of LDN use. 3mg per day, taken at bedtime. I also started Omega-3 about the same time - so there may be some correlation of results.

My physical state before starting LDN:

- I had bowel issues where I was producing rabbit size pellets (the size of poops rabbits do), generally hard and dark. This was attributed to bowel irritation caused by 83 G of radiation for my prostate. Probiotics didn't help, additional water didn't help, nor did roughage. This was the case for about 18 months.

- I had very bad hip pain, bursa-related and sacroiliac joint pain, plus a badly out-of-shape back (some scoliosis) and compressed disks. This also wandered into sciatica with shooting pain down my legs and some peripheral neuropathy (feet in particular.) Arthritis run amuck basically. This pain was constant and disabling. Multiple treatments and PT have been tried to help this - with no success.

- I also had a shoulder with rotator-cuff issues. Extensive PT brought that down to an almost acceptable level - but moving it the wrong way still could trigger sharp pain.

- I had continence issues - with random leakage. This started after a urologist did a green-laser zap of my urethra to relieve not able to pee problems. I went from couldn't pee easily to way too easy to pee. Not severe, but requiring 1 Depends a day. This was being treated with drugs initially (didn't do anything good). And then with physical therapy, and eventually TEMS like electro-shock. The electro-shock seemed to help (it triggered kegals - strong ones.)

- I had a general overall feeling of exhaustion almost all the time, which kept me from doing lots of things I'd like to do. A nap daily was becoming a habit.

THEN I started on LDN.

- The bowel problem cleared up overnight and I'm doing textbook poops. It's been this way for the 6 weeks since I started LDN. LDN is supposed to suppress inflammation - and it appears it's doing it quite well.

- The hip and sacroiliac pain is generally gone. It can reoccur if I try to walk a distance, but that's getting better and the distance further, and I'm going much further on the recumbent bike at the gym. The back pain is gone except for a tiny twinge just before I get in the shower in the morning. Hip-bursa pain is gone. The back pain is of very long duration - over 30 years from my records. 2 Advil and it's gone all day. The neuropathy may be getting better - it really takes an effort on my part now to trigger it.

- Rotator cuff - no issue remains. I can move it however I want and use some heavier weights in my workouts without pain. I continue doing the PT exercises, they're easy to do now.

- Continence - today (the reason I decided to report in) was the first day in 18 months without Depends and in normal underwear. I also usually can go all night without having to pee, or at worse if I have some sherbet before bed - I might have to go once.

- Naps - I still take one once in a while, but the need for them is less urgent.

OK - so side-effects:

The most commonly reported side-effect of LDN is "vivid dreams" - that's a misnomer. What it is - is unlike without LDN - you remember your dreams on waking. I also awake every night (take the LDN about 1 AM - night owl) between 4:30-6 AM for about 5 minutes, feeling really good (very commonly reported by LDN users.) I don't usually have to pee, so I just turn over and go back to sleep. But whatever I was dreaming is still in my mind and easy to remember in some detail. Supposedly the LDN endorphin flood is supposed to take place about 4-5 hours after taking the LDN.

My first dream last night was about battling some alien organism that was a single-cell thick sheet of matter that could move.. it was a tad bizarre. My second dream from last night that I remembered when I woke up was about visiting a building I'd hung out in about 45 years ago - a motorcycle shop.. and thinking of buying it. Not as bizarre, but it did involve my arriving on my first big street motorcycle ('75 Norton Commando) and leaving on my present one (BMW R1200R.) It was a fairly pleasant dream actually.

As far as I can tell - that's it for side-effects. Not a big deal especially considering the positive results for the issues I described.

Can I say for sure it's the LDN? Nope - but the studies done have claimed that it does do two things - suppress inflammation, and give a general feeling of well-being. I am able to do a lot more around the house and have the ambition to do it.

Might it be the Omega-E lumps I down twice a day? Maybe, but I haven't heard about this sort of result from that. My GP wants me to take them, so I am.

I've discussed the results with my medical oncologist. He wasn't familiar with LDN, but he is now - he conferred with the pain management department at Columbia-Presbyterian who use it for chronic pain. He's quite interested in my results, and said "If it's working - keep taking it.."

I'll try to remember to do another update sometime in the future. Right now - I'm feeling much better.

[Don_1213]

Footnote: As of 11/7/22:

LDN appears to address many—perhaps most—of the major symptoms of long COVID, including chronic fatigue, cognitive deficits (“brain fog”), and persistent pain.

According to the news service Reuters, in an article dated October 18, interest in researching LDN for long COVID is spreading rapidly, not only to research centers but also to the NIH:

reuters.com/business/health...

Drawing on its use in ME/CFS and a handful of long COVID pilot studies, there are now at least four clinical trials planned to test naltrexone in hundreds of patients with long COVID, according to a Reuters review of Clinicaltrials.gov and interviews with 12 ME/CFS and long COVID researchers.

It is also on the short list of treatments to be tested in the U.S. National Institutes of Health's $1 billion RECOVER Initiative, which aims to uncover underlying causes and find treatments for long COVID, advisers to the trial told Reuters.

We were also heartened to learn of a new study out of Dublin, Ireland, originally published in the journal Brain, Behavior, & Immunity — Health in July. Out of a group of 52 patients, 38 began a course of LDN after contracting COVID and experiencing persistent symptoms beyond three months. Of the patients taking LDN, significant improvement was seen in 6 out of 7 parameters measured, including recovery from COVID-19, limitation in activities of daily living, energy levels, pain levels, levels of concentration, and sleep disturbance.

This was posted to an LDN Google group by:

Wishing you the best of health,

David Gluck, MD

Joel Gluck, MEd

LDN Website Editors