013 - Dextronaltrexone for Chronic Pain and Fatigue
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- čas přidán 21. 04. 2024
- Here is a quick update about my efforts to test dextronaltrexone in chronic pain, fatigue, and cognitive disorders related to brain inflammation. This substance has never been trialed in humans, and I want to tell you why it needs to be prioritized. - Jarred Younger
- Věda a technologie
also, I want to be frank, my appreciation for this channel is great. the fact that we get to see the face of someone who is engaged in actually helping us get a future works as suicide prevention.
That is very nice of you to say. I've seen some great science presenters on youtube, but I couldn't find frequent presenters who are actually carrying out the research. So I thought that could be an interesting view to present. I am very glad people are finding it useful! - Jarred Younger
I’m so grateful that you and like-minded researchers are trying to do this for us who are suffering so much. If I won the lottery big time, you would have it all.
I appreciate that! :-) - Jarred Younger
Dr Younger, there is a particularly blissful place in Heaven for people like you, who work so diligently and selflessly on easing the pain of others. The words thank you do not suffice in expressing our profound gratitude - yet I just need to say a mio. times thank you! ❤🙏❤ Many, many greetings from Denmark 🇩🇰
Lexington KY
I’m in the 25% of people with Dysautonomia ME/CFS w/ OI & PEM. I used to be very physically active before it happened. Now I’m pretty much housebound.
I have a background in research (genetics). I learned about LDN, & am trying it. I think it may be helping my energy some, but I’m on 4mg bid. I think it may be causing a bit of mood change as well, so I’m going to cut back to 2mg bid, based i what youve said.
When you do reach the point of doing dextronaltrexone human trials, If you ever develop a research partner for additional human trials in Eastern New York State, I would gladly volunteer to be an applicant. I feel like a prisoner of this disease. I can’t even speak out loud without it causing significant symptoms. It’s extremely isolating. I lost my career, everything. I’m deeply grateful you’re focused on helping people like myself.
Thank you for doing this work
Thanks for sharing that. I mentioned in another comment that unwanted mood responses to LDN *may* indicate a hypersensitive opioid system. If you have unusual responses to opioid analgesic "painkillers" like hydrocodone or oxycodone, you might have a hypersensitive opioid system. In those cases, the small blockade by LDN may actually be a big one for you. The signs of opioid withdrawal are anxiety and general malaise. Insomnia is also likely. In those cases, a reduction of dosage may be the answer. However, I need to caution that these potentials have not been explicitly studied experimentally, so they are just ideas to consider at this point. - Jarred Younger
@@youngerlab I understand. I think better safe than sorry in my case. I’d rather back off the dose, and slowly titrate back up, if I feel the need. I think your explanation of dextronaltrexone being a stereoisomer of naltrexone, makes enough sense to warrant my taking a more conservative approach. Appreciate the feedback.
I’m sure there are at least 200,000 chronic pain sufferers in the U.S. who have literally tried everything else to get pain relief, that would be willing to contribute $10 each to get your study funded and then volunteer to be enrolled in your clinical trial without needing to be paid to be in the trial. Although I doubt this would be allowed by the FDA. I just think there must be a better system of funding drug research in this country that moves things along more expediently and in a more inclusive way to those whom would actually benefit from the new drug! Rather than being an exclusively corporate profit centered motive. I think the entire medical system needs to be looked at thoroughly and adjusted to consider the will of the American people/ patients/public!
Of course, I’m an optimistic idealist 😂
Hi Dr Younger how can we thank you enough for your years of dedication to these illnesses. I’ve had ME since 2011. I was extremely stressed in court gastroenteritis. Since then I’ve had at times being bedridden and wheelchair bound for five years up to 2021. unfortunately then I had to have chemotherapy which took me backwards. quite a lot. UnFortunately, my hands (yes arms and legs too but nothing like my hands), are so bad I can’t virtually do anything with them literally nothing. I have this at the start of my illness in 2011 and couldn’t use them for 18 months not even once and I’ve got them back fully functioning through not using . They burn that much. I have to do zero and I mean zero for weeks to be able to use them a little bit again which affects my life so badly. I’ve never tried LDN as I’m so frightened that it might make, a dire situation even worse. I’ve always followed Ron Davis’ work and always heard your name. Is it too risky to try LDN? I know really it’s probably impossible to say yes or no as peoples reaction seems to be so different. I continue to watch your videos in the hope that there are things that we can try in the meantime. I’m 61 now so don’t know if what you’re doing would be in my lifetime, thank you so much. I’m so sorry about the ignorant peoples messages, to someone who has dedicated their life to science. Thank you
thank you for dedicating your time to this
Thanks! - Jarred Younger
I think it's very useful for ME patients and others to hear how you and others are working on our behalf! Thank you for your tireless work and sharing a piece of the picture every week!!
Such a huge decision for you and your lab. Thank you for your commitment & enthusiasm for helping find improvements for a huge number of patients going forward. I am really hopeful for your funding to allow this investigation 💙🙏🏼💙
Thank you! I have some good leads on funding, so I am optimistic this will happen. - Jarred Younger
@@youngerlab Thanks again Jared and all who support you behind the scenes for your continued effort. Yours, a very broken human.
Argh I didn't know it hadn't been tested in humans yet. That's a bummer. Long long road before it could be useful to us patients I guess. But I'm glad someone is trying hard to get funding to start that journey, that's great news. Good luck with it!
Man there's so much research that's just really progressing towards some good stuff right now in ME cfs, but science is slow and life goes fast, wish these funders would give you all more money for all this.
I think you just summed up a whole lot of discussion effectively in a few sentences. It always seems like a race against time to me. If just a million people are too debilitated to function for a year, that is one million lost years of productivity and well-being. And we know more people than that are debilitated, and for a longer time. The lost quality of life is staggering. But, you did note the most promising thing, which is that there truly is a lot going on right now, and at a much faster pace than ever before. - Jarred Younger
It all starts with the first step! Well done for being that person. Years down the road other researchers will be extremely grateful for your preliminary work.
Thanks! - Jarred Younger
I can only tolerate 0.2mg of naltrexone. My doctor and I suspected that increasing to 0.3mg was affecting my ability to walk - going back to 0.2mg has meant I no longer need my walking stick. I'm so very very excited about dextro-naltrexone. I wish we could convince some billionaire to put the money they would otherwise use to buy a superyacht into your research. What a legacy that would be, except they live in another world to us. Thankyou for doing everything you can.
Thanks. I like the ideas. Maybe someone has an old superyacht they can donate to be sold off for research. :-) I'm sure that would cover the research! - Jarred Younger
My heart-felt gratitude can, at best, simply echo what others have eloquently and enthusiastically written: thank you, sir, for your determination and perseverance. Cheers. --ddg
Thank you! - Jarred Younger
For fiunding please ask Taylor Swift... Her best friend Selena has Lupus and she's very generous... Thanks for your hard work on this better Right version of LDN...🙂
This might be the sort of thing pain clinic or chronic migraine researchers might be interested in Bc they run across this opioid problem in their pain patients with chronic illness and the use of LDN. 13:21 Peter Goadsby might be interested - he’s at UCLA now.
Thankyou so much Jarred. Your videos give hope that in the future others getting these illnesses will not be left suffering without treatment and sneered at because of ignorance . Thankyou for your calm, clear delivery of the information.
Thank you! - Jarred Younger
I have Long Covid and LDN has brought me a noticeable improvement for my cognitive fatigue, cognitive dysfunction, and PEM. The only thing I wish is that I could increase the dose. Have been curious about dextronaltrexone since I heard you mention it previously in a talk you gave - let us know if there's any way the patient community can help your support your efforts in this area!
Thanks - I will do that! I've been talking about d-naltrexone for a long time, and I should have pursued it more earnestly sooner than I did. But I am very glad LDN has been beneficial!- Jarred Younger
Thanks for trying stuff so thoroughly
As always enlightening! Thank You!!
GET THE WORD OUT!!! EVERY SOCIAL MEDIA PLATFORM!! GET THE INFO OUT THERE FOR YOUR FUNDING!!!!
😀
Thank you for the excellent presentation.
I'm on my 16th day of LDN for fibromyalgia. 3 days of 1.5 mg, 3 days of 3 mg and 4.5 mg thereafter. I seem to be a little more alert a few hours after taking it. No other effects so far. I know it may take months to work if at all.
I'm glad you are working on the dextro version. It'd great to have another option. Thank you for the update. Appreciate there are researchers like you and your dedication!
Thanks for saying that! I hope the LDN works well. You are right that it may take up to 3 months before you can gauge how well it will likely work. The time it takes to see benefits may mean something more substantial and fundamental is being addressed, rather than just an immediate effect covering symptoms. Someone may take an opioid and get pain relief in 30 minutes, but the opioid is not helping the underlying problem. - Jarred Younger
Thank you so much for trying to help us!!
🙂 - Jarred Younger
Finally a good explanation!
thanks! - Jarred Younger
i started low dose naltrexone, and it changed my life. i was bedbound from pain and fatigue for a year. i am now a functioning human
On the cutting edge again! Good luck!
Hey, thanks Cort! Well, you know how long I have been talking about dextro-naltrexone. Really past time to get things moving. - Jarred Younger
Wow! THE Cort Johnson, love your Health Rising content and have shared with my drs many times. 🙇
Even though I do not understand half of the stuff you are saying, I still love watching your videos, kinda cool to see an insight on how all of this stuff works
Thanks! - Jarred Younger
Thank you Dr Younger for your regular updates. Scientific research would go so much faster if everyone did this!
In our nicotine patch research we see that increased receptors increases signaling. That increases the effects (both good and "side" effects) of some other medications in some people.
I mentioned the increase in the effectiveness of amitryptiline to my Neurologist today and he had the same theory (without prompting him).
A lot of people who are trying nicotine patches are also trying LDN, but there have not been any anecdotes of effects on LDN either way... so far. Benefiting from LDN or not does not seem to correlate with how people respond to nicotine patches, but that is just anecdotal.... our data does not yet ask if people are responders to other medication...only if they take it or not.
Interesting. I never worked with nicotine and need to get up to speed on more recent uses of the compound. - Jarred Younger
@@youngerlab Feel free to contact me if you have any doubts or want to give feedback on our research.
I am a Fibromite since 1990. I am so excited at the work you are doing! You are offering a light at the end of the path. Thank you! Without being naive, would it be possible to start a Go-Fund Me page for your research? It's very grass roots, but there are so many of us with ME/CFS, Fibro, Gulf War Syndrome. I believe if we were to each donate and work on raising funds, we could make a dent in your financial need. I apologize for sounding like a Pollyanna, but we are usually overlooked because it is easy to forget us as we are not generally out in public. But fundraising can be done from the home, on the phone, while we are stuck in bed. Just a thought... Thanks again for all the work you are doing!
CDC says fibromyalgia affects 4 million US adults. If every other one of us donates a dollar, there you have 2 million dollars.
@@slomo4672 I promise that isn't how I came to the 2 million number. 😄 But I agree it is an obtainable goal. - Jarred Younger
Thank you! I think it is a great idea. I believe I will first secure a small number of donors to get us close to the goal-for example, $1.5 million- and then use crowdsourcing, like you said, to reach the final goal. I've never used that approach before, but it makes sense. I appreciate the ideas, and I will look into this option very soon. - Jarred Younger
Madness is no cure for despair, but it is often the result. I offer my condolences to the lost and raving. Compassion is not to be confused with condoning the behaviors. When the wrong raving shows up in the wrong place, it is a neon sign advertising unwellness. We would all do well to offer the compassion we seek, while speaking up for boundaries.
THANK YOU!
Thanks! I appreciate the little notes. - Jarred Younger
Awesome!
I hope it works! I'd love to take something different as LDN (low-dose naltrexone) has caused me to gain a lot of weight, despite my healthy diet and exercise regimen. LDN also causes me to retain water, so I'd love to have an alternative. There's nothing out there at the moment that I'd feel safe taking that eases the pain as much as LDN does.
This is cool. LDN (Low dose naltrexone) worked for me at a (pretty common) dose of 4,5 mg a day when I was much worse off than I am now.
It reduced my post exertional malaise from 2 days to a few hours. With time my system was stable enough and I stopped taking it, as it did nothing for me anymore at that point.
Curious if the other form would be in any way better. Or it would be pretty much the same, with the difference that people can take higher amounts. (Higher dose of LDN wasn't working better for me)
By the way, there're articles online describing people doing higher doses of LDN. I think up to 24 mg a day, if I'm not mistaken (2x12).
I vagely remember that I experimented going higher too, but I don't remember my max dosage. I didn't have any side effects, but no extra positive effects either.
So my levothyroxin is the left thyroid hormone? Love how you make this science accessible for everyone. Thank you so much!
It is true that levothyroxin is a left-rotated form of thyroxin, which is based on how the molecule rotates plane polarized light (doesn't have anything to do with the drug affecting the left versus right thyroid lobes). There is also a dextrothyroxin that is used medically, but not in the same way as levothyroxin. - Jarred Younger
I have no lobes. Born without a thyroid. Was even part of a study in the 70’s. They did an iodine test to check for thyroid tissue in all of the infants with low/no thyroid. Only one had no thyroid tissue at all. This girl. It’s weird reading a study and recognizing yourself. 🤣
Fascinating! And wow 😢 Medical care for you must've eventually been somewhat helpful but how long did it take? It's lacking now, can't imagine the deficits in 60s & 70s. @@ClaireCaoimheRaeMoonshadow
Very cool! You are probably correct about Federal funding sources. My son used to work for FDA. He said the worst thing was the slow approval process. I’ve been taking LDN for 4.5 years. I’m now taking 3.5 mg 3 times a day for chronic spine pain. I’ve been in bed with ME/CFS for 5 years and LDN isn’t improving my energy. I just had the Invitae mitochondrial genetic panel and it was negative. Did you know that they prescribe LDN in the pain clinic at Walter Reed? They even have a compounding pharmacy (Experimental Pharmacy) next to one of the hospital pharmacies. Dextronaltrexone sounds exciting. I hope it works!! 🙏🏻
I didn't hear specifically about Walter Reed, but it is interesting that these little pockets of LDN usage are popping up. I don't think the DoD/VA has adopted LDN generally, so there must be a specific physician who drove its use at Walter Reed. - Jarred Younger
I tried various doses of LDN from 0.5 mg to 4.5 mg over a year and a half. I couldn't tolerate it though regardless of dose, it did have some pain benefits and increased my physical endurance but I was so sleepy all the time like I was still in a dream state during the daytime. I also was all over the place from sometimes feeling improved mood to having severe mood swings and feelings of rage along with tachycardia. It also made me urinate like crazy and oddly enough gained weight. My mouth and eyes were so dry too on it, I actually started getting dental problems from how bad the dry mouth was. I really wish I could dry d-naltrexone though. Since it's not patented could this make it a candidate for a drug company with big pockets to consider funding trials? Since they could have the potential for a ROI?
I didn't know levo was left and dextro was right; hence words like dexterous, dexterity etc. Guess I'm levo-handed 😅 LDN helped me get to sleep for a while, but my doctor had to keep increasing the dose to get the same effect. Eventually no dose worked and I gave it up. Definitely makes me wonder what d-naltrexone or a combo of l and d would do at a much higher dose!! (As an aside, dextromethorphan helps my general payback & specific immune symptoms like weak legs, provided I take it 2 hrs before a shower or other activity. Hope you can research it one day!) Cheers from Melbourne Australia 😊
I did a small study with dextromethorphan in fibromyalgia as well in 2021. There seemed to be a meaningful benefit in some participants (mostly focusing on pain). It was a really small study, and we dosed only twice a day (the half-life is pretty short, unfortunately, so twice a day may not give adequate coverage). Anyway, I agree it needs more attention. The paper comes up with an internet search of PMID: 33542651. - Jarred Younger
Dr Younger, have you, by any chance, tested urotensin 2 levels in CSF in MECFS?
I've been taking LDN for the last 18 or so months, currently at 3mg, and have been experiencing anhedonia for a while now. I take it for Sjogrens disease and for a while I was in remission according to blood tests but recently my Sjogrens symptoms have been flairing up a lot, as if it is no longer as effective as it used to be. Even with anhedonia it is still the best autoimmune drug I've tried in terms of side effects. Really hoping it takes off and gets approved quickly. Hypothetically, would there be a way to volunteer as a candidate for human trials?
Would you have any theory as to why low dose naltrexone immediately severely crashed me (fatigue, brain fog, neck pain, depression)
I always thought the same! go to the future and get the cures!
Appreciate your time and work. I know you said LDN was an opioid antagonist can you explain what you’ve seen that cause in research subjects?
I did a study in fibromyalgia using 50mg naltrexone way back when I was a postdoc at Arizona State University. The fibromyalgia group showed more opioid withdrawal symptoms than healthy controls after naltrexone administration. These are signs like anxiety, stomachache, yawning, teary eyes, and a few other things. It seemed as if naltrexone was blocking their endogenous opioid system (beta-endorphins), causing symptoms not seen in people without fibromyalgia. But the difference was pretty mild. - Jarred Younger
You should use the time machine near a current large hospital - or library hoping it would still be there in the future and save some time since you only have an hour
Yeah, I guess a lot can happen in 100 years! I was wondering if there would still be books! - Jarred Younger
@@youngerlab true you might go and they'll just give you direct downloads of information - good luck - we're all counting on you.
Do you need free research subjects? I volunteer! I’m also close to you since I’m already a patient at UAB.
Hey thanks. It will be a while before we are at that stage, but yes we will be running individuals close to UAB at the start. When we are close to starting human participant research, I will do another video update! - Jarred Younger
So you can take it with opiates . I have arachnoiditis. Still trying fine a good pain dr.
🎉 Thank You
😃 - Jarred Younger
Hello Dr ! Have you ever seen a documentary ( I just saw one on Prime) called “ Resonance: Beings of Frequency?” I’ve maintained the belief that, being so previously synchronized to the earths magnetic frequency, this has truly disturbed and now magnified my “ fibromyalgia “ and I urge my fellow CML community to watch it. See German Drs Schumann , Berger (1940s-1960s) research on disturbance of frequency between human & earth’s magnetic field (7.8 hz) later in 2000, studies done on robins, and honeybees. Just a thought. We love your work!
This ties into some of the research from Michael Levin on bioenergetics and how life as we know it uses electrical blueprints to create life along with DNA. I believe we'll one day look back and people won't believe how myopic and naive our understanding about biology is when we didn't even consider or respect the fact electricity and frequencies are fundamental to our existence and health. His research is truly mind blowing.
@@MichaelMerritt exactly. This documentary says so succinctly what I’ve wanted to say- but have no “ research” to back it up as a layperson who is also a professional “ patient “ and they don’t teach this to anyone in medical school. As a musician, I came back to music in 2016, and thought 440 hz was dissonance! If we could but “ see” energy as the other beings here on earth “ see” it!! I hope this is one thing that this Dr will pursue as well.
Thanks! This is all new to me. I have been reading the limited research on using light in specific wavelengths, and other electromagnetic frequencies, to impact pain and anxiety, but I have not seen anything about sound pressure frequency. I will say that when I was very young - about 7 or 8 years old, I would occasionally get stomachaches. I learned mostly by accident that if I hummed at a certain frequency, the stomachaches would go away in a few seconds. I would just sweep the frequency range and I would know exactly when I hit it. If I missed the frequency even a little bit, it wouldn't work. I have no idea what frequency that was, but I know 100% it was doing something to my occasional stomach complaints! - Jarred Younger
@@youngerlab well very interesting how you “ followed your gut” response! I doubt my other reply will get through so if you have inclination, I urge you to watch: “ Resonance: Beings of Frequency.” It came up in my feed on Prime Video. It impacts all life forms.
@@youngerlab that’s extremely interesting and a pretty useful trick!
Reminds me of an urban legend that George Martin of the Beatles is quoted saying how Hilter would have rallies where they’d play ‘the brown note’ a very low inaudible frequency in the 15hz-37hz range. The human sphincter vibrates around 37hz so you’d start to feel physically ill when exposed to these frequencies for too long. As Hilter took stage they’d shut off the low frequencies and the audience would start to feel well again in his presence. It seems plausible enough that it could be true. Military uses sound for many purposes these days.
Thank you so much for all you do. I know there's no way of knowing exactly but if you get good results, roughly how long before something like this would be accessible do you think? This is a slightly unrelated question but I've been reading so many common brain symptoms between ME/CFS, CPTSD, ADHD (or ADHD mimicking), Lyme and (and there are probably many more). What do you think is the linking factor? Brain inflammation?
It will take about 2 years from now to complete pilot clinical research on individuals close to my research institution. After that, there would likely be a large clinical trial. I would try to do that remotely so anyone in the U.S. can participate. After that trial, a company would need to take over the manufacturing of the compound for commercial use. So, the short answer is that it will take many years before most people would have access to it. To your other question, yes, there is evidence of abnormal microglia activity in all of those conditions. I believe brain inflammation via microglia and astrocytes are the common points for these conditions, but it is not necessarily the case that they will all be treated the same. Microglia have many different receptor types that could be expressed abnormally. It could be that something like ME/CFS involves an abnormal Toll-Like Receptor 4 (TLR4), while Lyme involves TLR1 (just as a rough example). - Jarred Younger
@@youngerlab Thank you for the reply, that's so interesting about the microglia connection!
I thought the entire purpose of LDN and uLDN was to antagonize the opiate system so as encourage the body's upregulation of endorphines (natural opiates) by as much as 200% to 300% each night during circadian rhythm? Which I understand to be a kind of reverse to tolerance caused by taking exogenous opiate agonists. Wouldn't your medication defeat this important feature as well as its secondary benefit to improved immune function?
I've moved from the endogenous opioid system explanation to a microglia explanation, but a contribution of opioid antagonism has not been ruled out. There is good evidence that the opioid system is deficient in fibromyalgia (downregulated receptors in key cingulate brain regions). There is also good evidence of a microglia-mediated inflammatory environment in the brain. Since LDN works on both targets, we don't know for sure which action is leading to the beneficial effects. It could also be a combination of the two actions. But when we get d-naltrexone, we will be able to test both hypotheses against one another. Based on the animal literature, I am expecting d-naltrexone to be more effective than l-naltrexone. - Jarred Younger
@@youngerlab i personally believe the opioid interaction is what is helping me since i dont have the problem of feeling constantly sick fluish or poisoned, but i only have muscle weakness/anxiety/weird drained muscle feelings and lactic acid tremor left.
Can you explain the opioid system again, especially how one would know if they have an under sensitive opioid system vs hypersensitive? I'm on 12.5 mg of LDN and don't experience worse mood/anhedonia than without. But it does help with my pain.
Opioids have never done much for me after 35 yrs, but tnx to a video of yours, I know they have caused harm, so I quit, with no withdrawal. Could this mean that my opioid receptors are already not competent? Would this be a contraindication for any naltrexone, or a green light because the damage is already done, either by genetics or prolonged opioid use? I’m sure the cohort of we the afflicted who also have the damage from long term use is huge.
So if LDN works for us well (but not to remission) for fibromyalgia would you have them try dextronaltrexone and expect a better effect?
@melissanreynolds read my comment below - my daughter is in the same situation.
That is an important question we will need to test experimentally. There are three possibilities: 1) for those individuals, the l-naltrexone is superior for reasons we will have to determine, 2) they will experience a benefit switching from l-naltrexone to d-naltrexone, or 3) they will respond optimally to a mixture of l-naltrexone and d-naltrexone. It is possible there will be a ratio of the two forms that will have the best effect. Those should all be tested, but we can't know right now how it all will turn out. But you are asking the same questions we are. - Jarred Younger
Good luck with clearing the path to conduct this research. I have a question that might be dumb because I’m only about a month into learning about LDN, but isn’t the effects on the opioid system part of why it’s useful for treating chronic pain? Because it stimulates endogenous endorphins? I have heard of the side effects of this as you mentioned but I thought that this was the main reason for the interest in LDN. Tbh I was surprised and excited once I started finding material that mentioned the benefits of reducing inflammation and addressing autoimmune etc as I was reluctant to take another medication that would mess around with endorphins after a long and unsuccessful history of meds that work on neurotransmitters and similar. Do you expect dextronaltrexone to still have a similar effect on reducing pain or will it be achieved as a secondary effect of the changes to microglia?
That is actually one of the key questions about this drug. I gave a longer response to a similar question above. The short answer is that I think the opioid antagonist idea of LDN was popular before we really knew much about microglia. Now I think the data are leaning more toward the microglia idea of LDN. But if it turns out both contribute, we can combine l-naltrexone and d-naltrexone to get the benefits of both! Fibromyalgia will be the test case for figuring these things out, since pain is a primary complaint. My current hypothesis is that d-naltrexone will be superior to l-naltrexone/LDN in reducing pain, because I believe the microglia are changing neuronal function to increase the level of pain. I believe most people do not have a problem with their opioid system. But I could be wrong, so those two ideas will have to be pitted against the other directly. - Jarred Younger
@@youngerlab thank you. I appreciate your answer, your channel, and your work.
Hi Jarred, if you look through the comments on your previous video on naltrexone, I asked about dextronaltrexone for just the reason you stated here. My doctor has already increased my dose from 4.5mg/day --> 6mg/day. Unfortunately, I have no benefit from this small increased dose. It wouldn't surprise me if the required dose for me isn't an order of magnitude larger than what we can use with the levo sterioisomer. I cannot believe I'm the only one who might benefit and I am REALLY happy to hear this has percolated to the top of your priority list .... although my enthusiasm is tempered by the $2M pricetag you quote to get started. Maybe you can persue a grant out of the RECOVER funds already dedicated to long covid? Plus, how would this sterioisomer be produced and isolated from the levo form? Can you even tell them apart without polarized light? Can you link the work already done on dextronaltrexone you mentioned in the video? I think it would be an interesting read.
Hey - thanks for the comments. Yep, we are thinking the same way here. And it is a lot of money, but there are several groups dedicated to ME/CFS who could make that happen. I spoke with one funder earlier today who can contribute a large amount to this effort. Once I turn my full attention to it in July, I think we will be able to collect the needed funding pretty quickly. As to the synthesis question, my understanding is that l-nal and d-nal are created using separate processes, as opposed to the two stereoisomers being separated from a racemic mixture. I don't think the optical activity will need to be assessed. - Jarred Younger
You could try going higher. It's absolutely possible.
Google the article by health rising: The Strangeness of Low Dose Naltrexone.
Here's the quote:
"At 9 mg/day her abdominal pain disappeared and she was able to resume a full diet for the first time in years. She continued to experiment with dosage and for the past 8 years has taken 6mg/day two times a day - or almost three times the highest normal dose."
Once you start human testing, hopefully you won't find dextronaltrexone too hepatotoxic to be used in human beings? This may be discovered in the safety efficacy testing prior to human testing as well? Naltrexone is hepatotoxic at higher dosages and that is also highly dependant on the individual undergoing treatment. Some are more tolerant than others. This should be interesting? 🤔
Yep, I remember some old safety data showing an increased risk of hepatotoxicity around 300mg/day in people with comorbid conditions. The animal literature suggests that the dosages are roughly equivalent between d-nal and l-nal. So, I am hoping and expecting that we will be staying in a range of 1 - 50mg/day with d-nal. But there could be unexpected hepatic effects that will limit the dosage range (or limit the practicality of using the drug altogether). And good point about individual differences -- I sometimes see surprising adverse renal and hepatic effects of common botanical supplements, so the same may be seen with this new pharmaceutical. Thanks - Jarred Younger
When looking for funding, would it help to have some who this would benefit share their stories?
It does, and there is also a recent and big push to involve patients in research planning and conduct. - Jarred Younger
Can you take opioids and dextronaltrexone togethe, it would be nice and maybe get off of the opioids.
I read a paper or speech you gave and used what was in it for a while. Low dose naltrexone, dextromorphan and maybe something else. It work somewhat and help my back pain, but getting old sucks. Before someone goes on opioids that would be a good route to take IMHO.
Thanks for your work.
Yes that is a good point. Given the mechanism of action, it should be easy to take d-naltrexone together with opioids. And I suspect it would be a great aid to wean off the opioids. The d-naltrexone may counteract the negative effects opioids have on microglia. - Jarred Younger
Thank you doctor for your work and your video!!!!- I did try LDn all type of dosages it did work but was a disaster for my sleep - I was doing 4 hours a day and at the end I had to give it up :(
Yeah, if moving the dosing to the morning didn't work and low dosages around 1.0mg/day didn't work, then it is probably not the med to use. - Jarred Younger
I was under the impression that low dose naltrexone also helps stimulate endorphin production exactly because they interact with the opioid receptors? I have had temporary muscle strength improvement from ketamine which i assumed was because of the opioid interaction, and low dose naltrexone has helped similarly but with longer duration.
That is one explanation of the LDN effect, but I think the microglia are more important in most cases. Ketamine, as well as its weaker cousin dextromethorphan, and low dose naltrexone all push microglia out of their M1 "pro-inflammatory" state and into the M0 "resting" or M2 "anti-inflammatory" state. The benefits on pain, fatigue, and depression look likely to be due to that shift in microglia function. I started off adhering to the endorphin stimulating hypothesis of LDN, but the bulk of new research has shifted me to adopting the microglia hypothesis. - Jarred Younger
@@youngerlab I have experienced the effect of ketamine pushing my microglia outof that state as it ended my sore lymph node symptoms permanently, but the profound muscle weakness after exertion didn’t, and doesn’t coincide with any flulike feelings . I will get full strength back from ketamine but only for like an hour, same with kambo ( two days) and LDN (12 hours), opioid interaction being something they have all in common. But this is for fatigue and muscle weakness/anxiety, not for flulike feelings. I don’t have problems with feeling feverish or poisoned ever since I had ketamine infusions and TMS in combination. Tremor exertion induced brain fog anxiety muscle weakness and PEM are my remaining issues.
@@youngerlab also I have managed to get a baseline which is finally outof the constant horror of fight or flight that I was in for seven years with ketamine and a Stellate ganglion block, normalising cerebral blood flow and reducing sensory sensitivity. I have gone through so many treatments with varying baselines and results, but I have comorbidities that don’t qualify me for any studies yet I feel like I have a lot of observations that could be helpful to researchers, I would love to get in touch and talk just to see how much of my observations are coherent with where medical research is looking for answers.
Please tell me....has anyone here taken : OAA ( Oxaloacetate) and LDN ( low dose naltrexone in same 24 hours every day?) Many thanks ! :)
LDN did absolutely nothing for me even at a dose of 4.5mg. No primary or side effects. I’m hoping I might be able to respond on this new drug
I’ve tried LDN for long covid. I don’t notice much of a difference aside from improved sense of smell and taste
Firstly that alone is omggg huge!! If it varies w LDN treatment that might mean it repaired that part of your brain 😭😍!!! (Alternatively it might mean it repaired itself).
Secondly? Are you still on it or did you stop? Either way how long/what dose did you titrate to? I’m on 6 mg nightly lol -a lot of ppl as Younger says here need higher doses to start responding- and give up so soon they never get there!
Also Dr Younger would you agree that a lot of patients get worse- at first- on LDN as it leaches the inflammatory crap out of our brain/glia -before we get better? And that a lot of patients mistake this process for “side effects?”
Might it work for peripheral neuropathy? I also have ckd .
Some forms of peripheral neuropathy may respond to LDN better than others. Most forms of peripheral neuropathy involve inflammation to a degree, so d-naltrexone might reduce the severity somewhat. So I can see the possibility but I wouldn't make a prediction without some preliminary data. - Jarred Younger
@@youngerlab thanks. Mine is chemo induced.
Lipoic acid research that.. And cholesterol is needed to protect your coating around the nerves... Research that too
Check your vitamin D levels and copper levels a well
LDN is the only medication I would not wanna live without. I do hear from quite a few people that they cannot make it work, but I suspect it often has to do with the way they are advised to step up the dosage way too quickly. Or starting at a too high dosage. It requires a systematic approach and understanding that more is not better.
My experience was it worked like magic for a few months then just stopped working. I titrated up to 4.5mg over a month and it completely got rid of my mcas and fibromyalgia like symptoms and inflammation flares. I was so sad it stopped working. I waited a year and tried again and it worked for 1 day where I felt euphoric with no pain then didn't work anymore, flares kept coming the following days.
🙏🏼
I've never heard this POV before. What I read said that the mechanism for LDN was "reverse tolerance" on the opioid receptors. But your proposed study is hypothesizing that this has nothing to do with the effect!
"Dextro-naltrexone has been shown to have no activity on opioid receptors but is active on microglia receptors. The analgesic, anti-inflammatory, and neuroprotective effects of naltrexone do not appear to be dependent on opioid receptors as dextro-naltrexone has analgesic effects."
www.ncbi.nlm.nih.gov/pmc/articles/PMC3962576/
@@healMECFSthanks for posting
That is a good point and I forgot to mention it. There are two hypotheses about how LDN works. One is the reverse tolerance you mentioned, and the other is the microglia antagonist effect I was speaking about. Without going into the details, I believe the scientific evidence is weighted more strongly toward the microglia hypothesis. The opioid transient blockade idea was described before scientists really know how important microglia were in chronic disease. However, there are some respected scientists who do not adhere to the microglia idea. The great thing about getting d-nal is that we will be able to compare the two forms and will find out which hypothesis is right! It is also possible that they are both correct. In that case, the optimal drug will probably be a combination of l-nal and d-nal at a certain ratio (to be determined). - Jarred Younger
@@youngerlab thanks for the followup Jared. It is much appreciated
You would come back an angel and do well betting.
❤❤😮
Hes says i would try to grab a sports almanac. Lol😂😂 i hate to say it but so many cures have been found, but don't make the the medical industrial complex money.