Low Dose Naltrexone

[George999]

Here is a document with a lot of Low Dose Naltrexone information:

The Faces of Low Dose Naltrexone

- George

[slowandsteady]

Just a comment about the effects of Low Dose Naltrexone and time frames. I listened to Dr. McCandless on Mary Boyle Bradley's internet radio show (you can download it here or get it streamed from the site).

She's taken an active role in a study among HIV infected people in Mali, and has treated other immune related ailments like Cron's disease with Low Dose Naltrexone. In her talk she mentioned that the immune modulating effects really take 6 months to kick in, just so people are aware that the benefits for Peyronies Disease, if they materialize as hoped, probably will take a few months.

She had some interesting stories about Low Dose Naltrexone improving fertility, by the way, which has been a "side effect" of some participants who hadn't expected to be able to conceive in the past and who were in a Low Dose Naltrexone trial for an unrelated reason (although it's starting to look like immune function is playing a role in lots of 'unrelated' illnesses).

[George999]

Tim,  The way Low Dose Naltrexone works is that it acts on the brain by momentarily blocking key opioid receptors which in turn causes the brain to radically increase endorphin production which in turn strengthens and re balances the immune system.  This is why is it so powerful systemically.  It was initially decried as being snake oil as it was claimed to effectively treat so many widely varied diseases (multiple sclerosis, HIV, pancreatic cancer, autism, etc.).  However, now there are successful phase 2 trials for MS, Crohn's, and Fibermyalgia on the record and more people are beginning to pay attention.  This is also lending increasing credence to the theory that immune dysfunction is behind a whole array of health problems that get labeled discreetly according to their symptoms.  In any case, the effect of Low Dose Naltrexone is complex and systemic and not in any way dependent on the point at which it enters the body.  - George

PS - I would post a link here with more information, but each time I try to post a link with "L-D-N" in it, the posting mechanism arbitrarily modifies it to "Low Dose Naltrexone" and screws it up.  So much for being able to post links containing acronyms.

[slowandsteady]

Quoting from the lowdosenaltrexone.org site on How does Low Dose Naltrexone Work?:

Witness these statements from a review article of medical progress in the November 13, 2003 issue of the prestigious New England Journal of Medicine: "Opioid-Induced Immune Modulation: .... Preclinical evidence indicates overwhelmingly that opioids alter the development, differentiation, and function of immune cells, and that both innate and adaptive systems are affected.1,2 Bone marrow progenitor cells, macrophages, natural killer cells, immature thymocytes and T cells, and B cells are all involved. The relatively recent identification of opioid-related receptors on immune cells makes it even more likely that opioids have direct effects on the immune system.3"

Some of the cell types (natural killer cells, macrophages) make their way throughout the body and are presumably give rise to Peyronies Disease. The question is whether their are important changes that occur in the cells already circulating. And it can't hurt.

[Tim468]

cream may lead to systemic effects but should be highest activity locally where the absorbtion is. Is the theory behind it that we are modulating cell types that are circulating instead of fixed localized cells?

Tim

[slowandsteady]

What is the reasoning behind a cream?

It's great for giving to kids with autism, since 11pm is the ideal dosage time and you don't have to wake them up to take a pill.

I have some LND compounded into a cream. What the heck, I'll try it for a few days and report back.

[George999]

The effect of Low Dose Naltrexone cream is systemic NOT localized.  Thus using the cream has the same effect as using the pills, specifically that of deploying a brief opioid receptor blockade.  The reason behind to cream is to be able to use it on children since it must be administered late at night after children are usually sleeping.  Thus the parent or care giver will administer the cream to the forehead of the child while he or she is sleeping.   Since autoimmune disease is rare in children, use of the cream is more often for treatment of autism or HIV infection.  - George

[skunkworks]

To be honest I do not see what a cream would do.

The only way it could work would be if it was systemically absorbed, so you may as well get the dose right by taking it orally.

What is the reasoning behind a cream?

[slowandsteady]

Any thoughts on using Low Dose Naltrexone directly on the penis using the cream that is mentioned in the report?

Tim

It is a low molecular weight molecule (341 D), so might go transdermal. Where are the cells that naltrexone blockades though?

Edit: duh, of course it's highly bioavailable in transdermal form.

[Tim468]

Any thoughts on using Low Dose Naltrexone directly on the penis using the cream that is mentioned in the report?

Tim

[newguy]

Thanks for the recent Low Dose Naltrexone updates guys. Interesting info.

[slowandsteady]

I found her to be generous in providing answers too when I had a question about topical bases for Low Dose Naltrexone.

[skunkworks]

I am posting this with regards to a discussion me and George99 are having about Low Dose Naltrexone and its effect on pentox function.

I emailed a doctor who has run multiple studies on Low Dose Naltrexone and has measured tgf - beta 1 regulation in at least one of them. She replied in a matter of hours which I think is very good of her. Below is the question and answer. Sadly the answer was not all that definitive but it does suggest that Low Dose Naltrexone would not interfere with pentox function. I have bolded the important bit.

Through your research do you have any idea whether low dose naltrexone upregulates or downregulates TGF - beta 1 ? This information would be of great help to me in deciding whether or not to use low dose naltrexone, as it may interfere with the function of another drug I take, Pentoxifylline.

The studies I did were equivocal, and I understand that wherever you are in your disease process, TGF-Beta acts differently.  I would go ahead and use Low Dose Naltrexone if I were you.  Here is some info on my study.  Dr. JM

She also attached a document, which I have copied and pasted below:

        REPORT: LOW-DOSE NALTREXONE (Low Dose Naltrexone)


EFFECT OF LOW-DOSE NALTREXONE (Low Dose Naltrexone) ON LABORATORY IMMUNE VALUES AND SELF-ASSESSMENT TRACK-SHEETS FOR PHYSIOLOGICAL AND MOOD EFFECTS

PERIOD OF STUDY:  16 WEEKS MARCH – AUGUST 2006

PARTICIPANTS:  (20) ASD CHILDREN AND (38) ADULTS (PRIMARILY PARENTS OR OLDER SIBLINGS OF ASD CHILDREN), MARCH – AUGUST 2006


PRIMARY INVESTIGATOR:  JAQUELYN McCANDLESS, M.D., PRIVATE PRACTICE, CANOGA PARK, CA AND HONOKAA, HI

CONSULTANT:  ARISTO VOJDANI, PHD, DIRECTOR, IMMUNOSCIENCES LAB, BEVERLY HILLS, CA

EARLY INFORMAL ADVISORS ON THE STUDY:

JAAK PANKSEPP, PHD
PAUL SHATTOCK, PHD

STATISTICAL ANALYSIS PROVIDED BY DAVID GAYLOR, PhD,
ASSISTED BY JACK ZIMMERMAN, PhD

USE OF LOW-DOSE NALTREXONE (Low Dose Naltrexone) IN AUTISM 

I (DR JM) STARTED USING Low Dose Naltrexone IN A GROUP OF AUTISTIC CHILDREN PLUS A FEW ADULTS WITH OTHER AUTOIMMUNE CONDITIONS IN EARLY 2005 AFTER AN EFFECTIVE TRANSDERMAL CREAM WAS CREATED WHICH COULD BE APPLIED TO THE CHILDREN AT THEIR BEDTIME OR AFTER.  DOSES WERE 3MG OF Low Dose Naltrexone CREAM FOR CHILDREN AND 4.5MG CAPSULES FOR ADULTS PER DR. BIHARI’S DISCOVERY OF THIS WINDOW OF DOSING FOR OPTIMUM IMMUNE BENEFITS.

POSITIVE RESULTS IN THIS PIONEER GROUP AND THE LACK OF SIGNIFICANT SIDE EFFECTS LED ME TO DO A LARGER INFORMAL 16-WEEK STUDY FROM MAR – AUG 2006 WITH 20 AUTISTIC CHILDREN AND 38 ADULTS (ALMOST ALL PARENTS OF ASD CHILDREN).

A PLASMA IMMUNE PANEL WAS PERFORMED AT THE START AND FINISH OF THE STUDY INCLUDING TOTAL WBC’S, T-CELLS, B-CELLS, NATURAL KILLER CELL ACTIVITY, LYMPHOCYTE SUB-POPULATION, AND BRAIN AUTO-ANTIBODIES. 


TGF-BETA 1 UNSTIMULATED (12):   IMMUNOSUPPRESSIVE , CREATES
            SUPPRESSIVE CYTOKINES

TGF-BETA 1 STIMULATED (12): SUPPRESSIVE  TO ANTIGEN   



TGF-B:  THE TGF-B BEGINNING AVERAGE WAS QUITE A LOT HIGHER THAN THE MEDIAN OF THE NORMAL RANGE AND THE AVERAGE FINAL AVERAGE WAS LOWER THAN THE MEDIAN VALUE (ALTHOUGH, AGAIN, THIS CHANGE WAS NOT STATISTICALLY SIGNIFICANT).  THIS MAY MEAN THE IMMUNOSUPPRESSIVE EFFECT OF TGF-B WAS LOWERED ON THE AVERAGE BY THE Low Dose Naltrexone, WHICH COULD BE AN INDICATION THAT AUTOIMMUNITY WAS IMPROVED IN SPITE OF THE IL-10 FINDING, PROBABLY POINTING TO INFLAMMATION STILL BEING SIGNIFICANT IN THIS GROUP.  THEIR RELATIONSHIP IS AS YET UNCLEAR.

THE SIGNIFICANCE OF THESE VALUES RELATIVE TO THE USE OF Low Dose Naltrexone IS DIFFICULT TO UNDERSTAND EXCEPT IN VERY GENERAL TERMS.

AS IN MOST OF THE TESTS, TGF-B VARIABILITY WAS MARKED, WITH SOME CHILDREN MOVING FROM VERY ABNORMAL LEVELS INTO NORMAL RANGE AND SOME CHILDREN MOVING FROM NORMAL LEVEL INTO ABNORMAL RANGES.  WITHOUT A PLACEBO CONTROL OR A LARGER SAMPLE, CONCLUSIONS CONCERNING TGF-B CAN ONLY BE SUGGESTIVE.

[skunkworks]

Intense nocturnal and morning erections!

That in itself should help peyronies.

I have been considering a pde5 inhibitor like viagra but now am wondering if that could produce a too intense erection when combined with what Low Dose Naltrexone is already doing.

[George999]

Here is an interesting piece on the use of Low Dose Naltrexone in conjunction with ALA in treating liver disease.  The interview itself has a lot of fascinating information:

Burt Berkson, MD, PhD, Talks With Honest Medicine About His Work With Alpha Lipoic Acid and Low Dose Naltrexone

While this guy seems to be something of a pariah within his profession, I find it interesting to see what his patients think of him:

ratemds.com

- George

[newguy]

Yep, that's why I mentioned that it might result in missing out on the autoimmune benefits seen at lower doses (if higher doses are used). I suppose if it was found to have potent anti fibrotic uses in other organs then it could potentially be of use to us. It also depends on what benefits if any can be gained for peyronie's sufferers when using the autoimmune approach at low doses.

Even if it proves not to be all that useful for us, it still has great benefits for so many disorders that I'm sure it will eventually be something that more people have access to, which can only be a good thing.

[George999]

s&s - Interesting find. This would possibly rule out many the autoimmune benefits though (benefits in general, not specifically to our condition) and I'm not sure that it has anti fibrotic action in other organs too. If it does then it's certainly something of interest.

Remember, this study is pointing out the effects of Naltrexone, NOT low dose naltrexone.  The anti-autoimmune effects of low dose naltrexone derive from the endorphin cascade, NOT the naltrexone itself.  Naltrexone is thus an amazingly versatile drug.  - George

[newguy]

s&s - Interesting find. This would possibly rule out many the autoimmune benefits though (benefits in general, not specifically to our condition) and I'm not sure that it has anti fibrotic action in other organs too. If it does then it's certainly something of interest.

It does seem that in many issues relating to fibrosis, very good progress can be made. Unfortunately with peyronie's a failure to get a good grip on inflammatory processes appear to form a vicious cycle, where even if the drugs we take are working against fibrosis, the ongoing inflammatory processes do their best to make sure that further damage is done. That's not to say that nobody makes progress, but we still appear to have some pieces of the puzzle missing.

George - I notice that you mentioned a lack of availability of Low Dose Naltrexone through official routes. Yes, that is a shame considering that it appears have have very valid applications in some conditions.

The UK petition to the government for more research to take place now has over 6000 names. That will mean that the government will have to give an official response (anything over 500 names receives a response). I have thought about launching a peyronie's petition in the UK too, but all petitions are time limited and I think it' be a massive task to get 500 names down in a matter of months. That's where the more localised approach here could help in some small way I guess --> see 'Country of Residence' thread

[slowandsteady]

I don't know if this study has been mentioned, Naltrexone, an opioid receptor antagonist, attenuates liver fibrosis in bile duct ligated rats (PMID 16543289).

RESULTS: Naltrexone markedly attenuated the development of hepatic fibrosis as well as MMP-2 activity (p<0.01), and decreased the number of activated HSCs in BDL rats (p<0.05). The development of biliary cirrhosis altered the redox state with a decreased hepatic GSH/GSSG ratio and increased concentrations of hepatic S-nitrosothiols, which were partially or completely normalised by treatment with naltrexone, respectively. Activated rat HSCs exhibited expression of delta1 receptors, with increased procollagen I expression, and increased TIMP-1 expression in response to delta(1) and delta(2) agonists, respectively. CONCLUSIONS: This is the first study to demonstrate that administration of an opioid antagonist prevents the development of hepatic fibrosis in cirrhosis. Opioids can influence liver fibrogenesis directly via the effect on HSCs and regulation of the redox sensitive mechanisms in the liver.

Naltrexone is often used in alcoholics, many of whom develop liver disease.

s&s

[George999]

But I only wish I knew what it is that is going on.  Hopefully something easier to deal with than MS and not the other way around.

[skunkworks]

So there goes my easy ticket to Low Dose Naltrexone.  

I think I'll take no MS over no easy naltrexone any day of the week Glad to hear that George.

[slowandsteady]

Great news for you George. If you want to get some yourself, many on the Low Dose Naltrexone yahoo group recommend all day chemist.

I tried dosing when I woke up this morning instead of at 11pm. After a month I still haven't been able to sleep well with night dosing.

The good news is that, after taking 2.25 mg at 7:30, it's now noon and I have very good mood. The less good news is that it isn't turning out to be the anti-inflammatory I'd hope it would be, at least in the dose I've tried so far. My curcumin recipe is still tops in that category for me.

s&s

[George999]

Well, good news and bad news.  I just had an appointment with my neurologist and the tentative MS diagnoses is now off the table.  Apparently the initial testing that seemingly discounted a peripheral neurological problem missed something and that MRI results are showing something more benign, so next step is a battery of blood tests to try to figure that out.  So there goes my easy ticket to Low Dose Naltrexone.  But good news for me is that it is not MS and doctor is hopeful that the current remission of symptoms is indicative of recovery rather than just a remission and relapse syndrome.  I will keep you all posted.   - George

[slowandsteady]

Hi Johnd. I don't doubt what you are saying. I'm sure different people respond in different ways.

s&s

[George999]

For those interested in knowing more about Low Dose Naltrexone, I would recommend this series by Dr Skip Lenz.  It mostly pertains to MS since that is by far the largest population group using Low Dose Naltrexone, but it also covers quite a bit of information about Low Dose Naltrexone itself.  At the beginning of part 2, he covers the best way to start Low Dose Naltrexone as in dosages.  This is a very informational series and I recommend it to anyone considering Low Dose Naltrexone.

Dr Skip Lenz at Vanderbilt University 2007

Enjoy!  - George

[Johnd]

Hi Lads

Reading through your posts it would look like an autoimmune related illnesses. As some of you also have MS RA etc.
I personaly stated on 4.5mg 2 days before my wife just to see the side effects, because she has cancer 4.5 is the recomended dose. It took only 4 nights to get over the sleep problem, I took the Low Dose Naltrexone for about 2 weeks and stopped, about 3 months later I felt a cold comming on so I decided to try Low Dose Naltrexone to sort it out and took 4.5 again I had no problem with sleep so my body was still used to Low Dose Naltrexone. The good news is I never got that cold. So it will do you no harm to try it, the question is do you take the chance of going off the meds you are using and how long will you have to take Low Dose Naltrexone before you know if it is working. I have sent an e-mail to a doctor friend of mine asking her advice for you all as she wrote the list of disorders that Low Dose Naltrexone will help which is now on the www.ldndatabase.com. I am afraid at the moment  Peyronie is not there probably only because its rare

Best of look
John

[slowandsteady]

I wonder whether some of the conventional wisdom about Low Dose Naltrexone dosages are correct. For me, 4.5 mg just wrecks my sleep. Some people have reported success on doses like 1.5 mg.

[newguy]

I suspect there are multiple factors at play and that autoimmune may be one of those factors in some/all cases. I'm not sure that we're in a position to say with any certainty that autoimmune issues drives this condition. However, we cannot rule it out and as such it is impossible that when an opportunity to try to a treatment such as Low Dose Naltrexone comes along we give it a fair shot. We should not limit ourselves or become too rigid in our thinking though, as there is still much to learn about this conditon.

[George999]

I think it is also telling that the best medication out there for Peyronie's just happens to be an immune suppressant.  When you block TGF-beta1, you alleviate Peyronie's inflammation.  That is immune suppression going on.  That begs the question as to what the immune system is doing attacking the TA.  It is either autoimmunity or allergic response, one or the other.  And at this point, as far as I know, no allergens have been identified.  In any case, allergic response also reeks of immune dysfunction which brings us right back to the same place.  Those who insist Peyronie's is NOT an caused by an autoimmune response usually will claim either that the cause remains unknown or that it is caused be various phenomena that are actually typically associate with autoimmune responses.  This in turn makes these arguments rather weak.

The link noted by s&s should be:  The immunological features of Peyronie's disease.

More links:

Studies of Peyronie's patients have implicated an auto-immune component. It was shown that Peyronie's disease patients had at least one abnormal immunologic test (75.8%), alterations in cell-mediated immunity (48.5%) and in markers of auto-immune disease (37.9%). Another study found higher than normal levels of anti-elastin antibodies in the serum of patients with Peyronie's disease, suggesting an autoimmune etiology.

Pathophysiology of Peyronie's disease

Prevalence of diabetes mellitus is reported higher in patients with Peyronies disease and association with systemic sclerosis has also been documented in recent literature.  Etiology of Peyronies disease remains a mystery, and recent studies on HLA antigens and immunological features suggest the hypothesis of an autoimmune etiology for the disorders.  Peyronies disease co-existing with scleroderma and diabetes mellitus in the present case corroborates autoimmune basis of the disease.

Peyronies disease, scleroderma and diabetes mellitus


  - George

[slowandsteady]

I'm just curious as to why people are labeling Peyronies as an auto-immune disease.  I mean this has never been proven.  Has it?

There is some evidence, particularly the presence of leukocytes in Peyronie's plaques.

The immunological features of Peyronie's disease (PMID 7490821):

RESULTS: Circulating anti-penis antibodies were not found in any patient although antinuclear antibodies were present in 24%. Patients with early Peyronie's disease had IgM antibody deposition, marked T lymphocytic and macrocytic infiltration in the sub-tunical space, increased expression of adhesion molecules by endothelial cells and an increased human lymphocyte antigen class 2 expression by the cellular infiltrate, indicating cellular immune activation. CONCLUSIONS: These results show that some of the features of autoimmunity, in particular the cell mediated response, are present in Peyronie's disease

s&s

[hornman]

I'm just curious as to why people are labeling Peyronies as an auto-immune disease.  I mean this has never been proven.  Has it?

[Johnd]

Hi George

There is a list of doctors who will prescribe Low Dose Naltrexone from all over the world. If you send me a private email as to where you are I can reply with a few in your area. That goes for anybody here, and I do hope it works for you all

John

[George999]

John,  Some of us here are really hoping that Low Dose Naltrexone will be effective on Peyronie's at least to the degree that Pentoxifylline is.  Pentoxifylline is a cytokine blocker and is the only drug that is significantly effective to block the progression of Peyronie's for many of us here.  Like Low Dose Naltrexone, it is an off label use of an off patent drug.  But since the Peyronie's community is so small in the whole scope of things, it is very hard for many of us to get a prescription for Pentoxifylline.  Additionally, as a cytokine blocker, it belongs to the larger family of immuno-suppressants which makes it probably not the best choice even though its side effects are few.  It is definitely a problem for guys who already have some other infectious disease since they have to choose between keeping the infectious disease under control OR keeping the Peyronie's under control.  Low Dose Naltrexone, if effective on Peyronie's, could solve that problem neatly.  Additionally, it could join our community with the international people power movement that is effectively breaking down the walls of resistance to Low Dose Naltrexone in the medical community.  Since Peyronie's is auto-immune powered at its core, I am very hopeful that something good will come of this, but right now it is just too early to tell one way or another.  At this point there are just a small handful of us here giving it a try.  It has already been noted by one of our members here that it is hugely effective on RA.  I hope to join that handful soon.  I just recently received an MS diagnosis and am hoping that will get me a script for Low Dose Naltrexone without too much of a hassle.  According to a local pharmacist, our local neurologists are familiar with it and regularly prescribe it.  When I initially visited them, they alone were very encouraging on vitamin D use as well, so I am really hopeful on Low Dose Naltrexone.  Thanks for stopping by here and introducing yourself.  - George

[Johnd]

Hi George and Newguy and all

Yes I was talking about the www.ldndatabase.com, I cant take all the credit, It was my Idea and I got a lot of help with the questions from the Low Dose Naltrexone Yahoo group.
My wife really hadn't a chance with 5 tumours 2 of them were about to kill her and I found a hospital here in Ireland with Cyberknife and it dealt with them. The great news for everybody is the other 3 are shrinking on nothing but Low Dose Naltrexone, one is completely gone. The other 2 shrunk from 20mm balls to 14mm in 7 months. She had to come off Low Dose Naltrexone for an operation and because of complications had stayed off for 5 weeks and the 2 grew to 24mm, She is back on Low Dose Naltrexone now and it will start shrinking again

Thanks for the welcome

John

[newguy]

George - I assume that he's the owner of the site in my opening post, which appears to be linked to the yahoo group too.

John - I'm very sorry to hear about your wife, and I commend you for starting the database and for highlighting Low Dose Naltrexone in a meaningful way. I'll will be sure to post my results, good or bad when I start on Low Dose Naltrexone.

s&s -  It's good to hear that things are settling down for you. How are you feeling on the pain/discomfort front? Are you still taking curcumin, resveratrol and so on too ?

[slowandsteady]

I'm starting to sleep much better at a 3mg dosage. Those first few days I felt I was swimming in endorphins, though I've read that this feeling goes away once you get used to naltrexone.

s&s

[George999]

John,  Welcome!  I am assuming that you yourself do not have Peyronie's but that you are posting in order to inform us of your database and invite us to participate.  If that is the case, it might be helpful if you provide a link to the database site.  - George

[Johnd]

Hi All

I set up the Low Dose Naltrexone Database, The reason I set it up was because my wife has lung cancer and I was trying to find a way to see if Low Dose Naltrexone realy works. So I did not target people who Low Dose Naltrexone worked for as that would be stupid. I always ask people to fill it in good or bad. The people that Low Dose Naltrexone did not wofk for them are just as important. there are a few in the database that Low Dose Naltrexone didnt work for them. these show up easier on the graphs

Thanks
John

[George999]

Other petitions are out there trying to get government funding for Low Dose Naltrexone research:

Australia - http://www.gopetition.com/petitions/national-health-funding-for-low-dose-naltrexone-in-australia.html

Canada - http://www.thepetitionsite.com/1/funding-of-Low Dose Naltrexone-trials-in-Canada

USA - http://www.thepetitionsite.com/1/sign-support-the-campaign-for-research-trials-in-low-dose-naltrexone-for-multiple-sclerosis

[newguy]

Dr Chris Steele from ITV, a TV channel in the UK, is at the forefront of getting Low Dose Naltrexone recognised in the UK.

http://www.youtube.com/watch?v=CVpjsDK0LPA


There is a government survery for UK residents only, wishing to support a motion to use NHS money to conduct meaningful trials into its use:

http://petitions.number10.gov.uk/LowDNaltrexone/


This site has patient categoried Low Dose Naltrexone patient experiences. It's of course not particularly scientific, and I suspect attracts people for whom the medication works, rather than in those it doesn't, but I found it to be an interesting read:

 http://www.ldndatabase.com/index.html