Jarred Younger – the creator of the Neuroinflammation, Pain and Fatigue Laboratory – is committed. He knows neuroinflammation plays a role in fibromyalgia (FM) and chronic fatigue syndrome (ME/CFS) and his lab is dedicated to showing that.
So far – he’s been quite successful. His groundbreaking heat mapping study showed widespread neuroinflammation in ME/CFS and he pioneered the study of a putative neuroinflammation buster – low dose naltrexone.
He believes that taming the fires should provide relief to a brain that’s on high alert – pouring out inflammatory substances that are causing pain (and other symptom) producing nerves to respond to every little stressor.
Younger believes an overactive immune system may be causing the symptoms in fibromyalgia.
He’s had his eyes on dextromethorphan – a drug used to suppress coughs – for quite some time. In animal studies, dextromethorphan has been shown to protect neurons from toxic levels of glutamate and low oxygen levels (hypoxia and ischemia). It was also able to inhibit the big neuroinflammatory producers (the microglia). In animals, at least, it seems to be hitting some big potential hot spots in FM and ME/CFS.
Humans, of course, are different, and even the best animal studies more often than not do not translate into successful human trials. One estimate found that only 37% of successful animal trials were subsequently replicated in humans. As a cancer research said, “If you are a mouse and you have cancer, we can take good care of you.”
Younger pointed out two ways dextromethorphan might be reducing pain. Like ketamine and memantine, both of which have shown to be at least somewhat helpful in fibromyalgia (and possibly ME/CFS), dextromethorphan (DXM) is able to tamp down activity in the NMDA receptor. The receptor for glutamate – the primary excitatory neurotransmitter in the brain – NMDA receptor activation could be causing central sensitization.
Younger believed, though, that DXM’s ability to calm the immune cells of the brain – the microglia – would likely be the key to its success in FM.
Dextromethorphan had been studied in FM, but at a much higher dose (200 mgs/day), which apparently reflected the researchers’ attempt to calm down NMDA receptor activity. The study had some positive effects but also quite a few adverse ones. Younger chose the other path.
The Study
“The aim of this pilot study was to determine if DXM should be further investigated as a possible treatment for FM.” Murray and Younger
The exploratory nature of the “Low-Dose Dextromethorphan for the Treatment of Fibromyalgia Pain: Results from a Longitudinal, Single-Blind, Placebo-Controlled Pilot Trial” should be noted right off. It was too small (n=14) to be generalizable to the broad FM patient population. While the participants were blinded to which treatment (placebo or Dex) they got, the researchers weren’t. Since only one dose was used, we don’t know how effective other doses would have been.
The study used low doses of dextromethorphan because an animal study found that low doses were more effective and higher doses were not effective in reducing neuroinflammation.
Fourteen women with fibromyalgia received a placebo for five weeks, then 20 mg DXM 10mg (2x’s/day) for ten weeks. Daily symptom reports and physical activity were taken. The last four weeks of the placebo and the drug were then compared using those reports.
Something strange occurred on the way to tabulating the results. The endpoint of the study focused whether the people on the last four weeks of DXM treatment arm had significantly fewer symptoms, and/or engaged in significantly more activity, than when they were taking the placebo.
It turned out that they didn’t. The odd thing was was that Younger et. al. had been tracking DXM vs placebo results throughout the entire trial. Using all the patient scores (instead of focusing on the last month) suggested that the drug did help reduce generalized pain and high pain scores by about 30%. The drug also seemed to work better in those in more pain. (It did not significantly help with fatigue and other symptoms).
The odd decline in effectiveness when looked at over the last four weeks of the ten-week trial could be explained by a couple of things. The fact that the researchers had a lot more data to work with over 10 weeks than in the last four weeks may have helped particularly given the small size of the trial. The drug could also, for some reason, be more effective in the short term.
As often happens in these studies, the scores tended to improve in both the placebo and treatment arms; i.e. there was a placebo effect.
Conclusion
Younger has pioneered the efforts to combat neuroinflammation in fibromyalgia.
Dextromethorphan, at best, seemed to have a moderate effect on pain and did not markedly affect other symptoms; i.e. it wasn’t an overwhelming success or a resounding flop: it was somewhere in between.
Whether that’s enough for bigger trials with more statistical heft to emerge from this pilot trial is unclear.
Since Younger didn’t have the funding to assess brain functioning, we don’t know if DXM tamped down neuroinflammation or not.
For all the interest in neuroinflammation in FM, this is just the second time a potential anti-neuroinflammatory drug has been studied in FM. (Low dose naltrexone was the first – and Younger pioneered that study as well).
Younger has been beating the bushes for ways to reduce neuroinflammation in these diseases. He tried (and failed) get the NIH to fund a dextro-naltrexone study. His large botanicals study, however, has finished up and will hopefully be published soon – and potential neuroinflammation busters are being studied in several neurological diseases. This is just the beginning of the hunt to tamp down neuroinflammation. Check out many other potential brain inflammation busters below.
Microglial Inhibiting Drugs – Providing Hope for Fibromyalgia and Chronic Fatigue Syndrome (ME/CFS)?
Note: As of September, Younger’s Neuroinflammation, Pain and Fatigue lab was looking for people with FM to participate in a study assessing levels of neuroinflammation. To find out more about that:
IMPORTANT NOTE: Readers who take fluoxetine should be aware that taking dextromethorphan can cause a bad reaction resulting in serotonin syndrome. It did for me and I ended up in the emergency room. The dextromethorphan in my cough syrup affected the metabolism of my antidepressent. Many people are not aware of this reaction.
Dear Amy, thank you for that useful information. There seem to be so many things which react with fluoxetine yet no one tells us about it. It also means there are many things I cannot then try for the CFS/ME/Fibro. May I ask what dose of Dextromethorpan you took and if you know anything more about this?
This study reminds me of Martin Pall’s work on the NO/ONOO cycle. He also suggested Dextromethorphan.
Why are men left out of the study?
That’s typical in fibromyalgia studies. Because men and women have somewhat different biology’s it makes it simpler to just assess women – who make up the lion’s share of FM patients. Plus when you have a smaller study like this you want to do everything you can to limit the number of confounding factors.
Thanks Cort. Do you think this approach will prevent going into the Post Exertional Malaise reaction? I sure would like to know the molecular processes that get the reaction to happen in the first place. It seems like reducing the brain inflammation probably mostly minimizes symptoms, which would be good, but maybe the brain inflammation actually kicks off and maintains the PEM? I get a ton of brain inflammation symptoms during a PEM but not so much otherwise. Although I do have peripheral neuropathy so that would be worth trying for that too.
why you guys going around ?
neuroinflammation is well responding to the IVIG
LOOK AT THE corona virus neuroinflammation—all of them use IVIG
In the US, it’s mainly because of cost.
you really don’t need high dose 1-2 gram/kg.
you only need 1 gram per wk.
low dose is much more effective than high dose
it do not cost too much
May I ask where you are geographically? I trust not NY, where we have a hard time getting IVIG without meeting very specific criteria that FM and ME patients do not tend to meet.
Let’s hope we get some good IVIG long COVID studies and those translate over to FM and ME/CFS studies.
Dysautonomia International is doing studies on IVIg as well. I’m an IVIg patient. It definitely helps though I still have symptoms. Treated now for over a year. A new study by Dr. Grubb shows greatly elevated inflammatory markers (TNF-a, IL-1B, and more) in POTS patients, but the question of why still eludes research.
Corey, I saw your reference to Dr Grubb. where did you find the info on him? Does he have a website? I saw his NP a long time ago and was never able to get an appt. again. Now I would not go but would like to know what he is doing about POTS. thanks in advance if you see this.
I saw Dr. Grubb talk at the Dysautonomia International conference and he has published studies as well. He’s an expert in POTS. Definitely trust him.
what is your exa t regimen regarding ivig for me/cfs please?
IVIG? Does that mean gamma globulin infusion?
I tried it several times- too much. Ended up with migraine for whole month.
Is it possible to take a small dose by injection?
Thank you. Fascinating info.
Yes, I believe they are the same. I don’t know about smaller doses.
Tough to get Medicare to pay for IVIg for these conditions
I tried NyQuil caps which have Dextromethorphan, Doxylamine (anti-histamine) and acetaminophen. I noticed that it makes me feel like I have gotten good sleep (as opposed to the usual unrefreshing sleep and can help improve my mood. This applies if I take it once in a while. Less good effect if I take it days in a row. However, it does make my brain fog much worse. Other antihistamines like Benadryl or hydroxyzine alone do not have that affect and make my brain fog bad, is it makes me wonder about the dextromethorphan. It bums me that the study was so small, but I would imagine funding is the reason why.
Apparently, ingesting salicylic acid can cause the dexmethorphan to not work.
There are ME/CFS/FM/POTS patients who benefit from anti-epileptic drugs. Lorazepam also has an anti-epileptic and calming effect on the brain. Everything in a low dose.
I suffer from involuntary body jerks that are apparently brought on by stress/anxiety due to having a long history of those issues. I had it checked out by a neurologist and nothing came up. Hence the stress relation. Just another manifestation I guess. Anyhow, lorazepam helps stop them pretty quickly (usually within an hour) when they occur (I once had them non-stop for 36 hours before being diagnosed and given a prescription, NOT fun). Yes, lorazepam causes a huge calming effect haha. It usually causes me to sleep, a lot more than I usually would. No, it doesn’t help me feel rested, unfortunately.
Lorazepam is a benzodiazepine. Should not be used long-term. This class of drugs are known to be highly-addictive.
I think he should focus on Silent Migraine drugs & anti-epileptics are also used. Any type of Migraine is devastating what’s worse about Silent Migraines one would not know they had these & they can occur daily & destroys lives
And consider CBD oil, widely available, legal, and for me, very effective for preventing migraines. Also, a good brand of hemp oil does not need to be expensive. (Also, butterbur for preventing migraines, found in Migracontrol. Butterbur and CBD oil was the winning combo for me. Sorry if I’m getting off topic, but these two things have really helped me tremendously and I hate to think of people suffering if these things might help them).
PS CBD oil was found to be clinically effective for preventing/controlling a certain kind of epilepsy in children. Hence people started connecting it to possible migraine prevention in the general population.
Thanks for passing that on Cameron. If you haven’t please consider posting a review on our ME/CFS and FM Cannabis survey
https://www.healthrising.org/treating-chronic-fatigue-syndrome/drugs/cannabis-fibromyalgia/cannabis-fibromyalgia-chronic-fatigue-entry-form/
Check out the reviews so far here:
https://www.healthrising.org/treating-chronic-fatigue-syndrome/drugs/cannabis-fibromyalgia/cannabis-fibromyalgia-chronic-fatigue-reviews/
Wish I could afford any of that. I’d much prefer a natural product like this over man-made medication. However, it’s a major out-of-pocket expense for me and one I cannot afford.
Went the MJ license route and was given a prescription. That’s how I found out how expensive it would be. It is legal in Ontario too.
It may not be so effective for ME and fibro, but it’s definitely worth promoting for Covid.
I took steady doses of DMX (Mucinex) when I had a horrendous case of Covid that lasted for 2 months. I am convinced that this medication kept me out of the hospital and kept me alive through the worst of it.
Ha! Good to hear. I hope you’re over it.
When I saw the comment about the person taking Nyquil caps for sleep, I cringed. Doxylamine, one of the ingredients in Nyquil, was an ingredient of the medication, Bendectin that caused thousands of children to be born with partially missing limbs. We got it off the world-wide market in 1982 as cases went through the courts reaching verdicts as high as $95 million. To show the power of the pharmaceutical companies, every verdict was overturned on appeals that the drug company took to higher and higher courts, eventually the supreme court.
Once the court cases were resolved in favor of the drug company, they wanted to bring a version of Bendectin back on the market. We blocked this for 13 years with a Citizen’s Petition based on cancer studies in rats and mice done by the government. Liver tumors were found in both species. We also found several human studies connecting childhood cancers to products with doxylamine taken by mothers during pregnancy.
According to the law at the time, no drug or chemical that caused cancer in test animals could remain on the market. However, at the FDA hearing that I attended, the ad hoc committee decided not to take doxylamine off the market and not to even put a warning on products like Nyquil and knockoffs with the same ingredients.
The question is how safe is doxylamine for people who have immune system problems related to ME/CFS?
The medical director of Vicks quit the company over the development of Nyquil calling it a witches brew that combined a highly sedative antihistamine with alcohol (in the liquid form).
Can you link a source?
You can find stand-alone Dex. I took around 10mgs daily, didn’t feel much benefit as a result. Male, ME/CFS
I’m no expert but I don’t believe 10mg is enough to have an effect. Case in point, I was prescribed 120mg a day prescribed by my PM doctor.
10mg-15mg is the dosages mentioned in the study for pain relief. If you go much higher it has no or less of an effect.
I tried dextromethorphan after it was first mentioned years ago, had zero effect for fibro pain for me. Also, it’s a highly anticholinergic drug that, if you’re over 65 and worse’ if you’re also taking other anticholinergics, will cause cognitive decline and possible Alzheimer’s disease. Look it up.
BTW, Ivermection, a powerful anthelminthic and antiviral, taken via horse paste if necessary due to lack of prescription, actually has an excellent curative and prophylactic record for Covid, many observational studies, some clinical ones. Suppressed by TPTB because doesn’t fit the party line of needing government help and Big Pharma. Don’t see how dextromethorphan could do anything.
Does it do anything for Epstein-Barr?
Good question, no idea. Same as with ME and long haul Covid…folks trying it for those also. .unfortunately doesn’t pass blood brain barrier, though, so seems unlikely, to me, to affect our problems. Nevertheless, I just tried six days of 12 mg equivalent ivermectin horse paste to see if it did anything for severe fibro pain…no luck. No side effects, tasted terrible but, according to the protocols, I’m immune to Covid for a few weeks.
My local doctor, a naturopath, got Covid and treated himself successfully with Ivermectin.
Let’s be frank – this doesn’t sound promising at all, nor does Younger’s research in general.
I would not be surprised if a bigger trial doesn’t result from this. While there were some positive results I don’t think they’re strong enough to produce that. It’s possible that the study was just too small to give positive results.
I have a lot of hope for Younger’s research though. He developed thermal mapping of the brain – a non-invasive way to assess neuroinflammation. Younger is also currently using new technology to determine if immune cells are making their way into the brain in MECFS. He’s also assessing neuroinflammation in fibromyalgia. Pretty good stuff…
Maybe. But he’s been ‘promising’ for more than 5 years now…
I was really hopeful about Younger’s research – years ago! But so much time has elapsed since then. It doesn’t help that other problems, like GWS, compete for Younger’s time and research budget. And the pandemic obviously has thrown him a curve-ball as well.
But ME/CFS is proving to be well beyond the intellectual resources of current researchers. Look at the most famous person in the field – he can’t come up with anything after 7 or 8 years besides trying a drug that’s been around for 20 years and obviously does not get at the root of the problem.
The brightest star in the field, IMO, is Bhupesh Prusty. He’s looking at single cell RNA and other really cutting-edge stuff. If anyone can crack this, it’s this man.
Hi, this group is full of info I’ve been chasing for 40 years.
Thank you!
I live in NJ/NYC area. Do you have a list of physicians who are up to date as are you.
Sadly I’ve wasted a lot of time with tired old doctors who can’t think outside a box.
Hi Kathleen:
In July of 2019 I was lucky enough to get in to see a Physician by the name of “Dr. Roger Mazlen.” He has offices in Roslyn, NY & Downton NYC. I live in Virginia and was able to see him in his Roslyn offices every few months, until COVID hit; now we do ‘phone appointments.’ My experience is that he is a very dedicated physician who encourages email updates and any communication as we work together to try different things. He is serious about wanting to help and after a year and a half, almost 2 years, even though I’m getting worse in some areas, he encourages me to keep in touch with him, via email and/or phone, so he can continue to monitor my situation. I feel so grateful to have someone to talk to about my on-going brutal difficulties who actually cares about my well-being. Bottom line: During this past year and 1/2, Dr. Mazlen has been only a phone call away with an incredible “bed-side manner,” that I haven’t experienced by a physician in over 10 years. And, by the way, he has a wonderfully caring staff.:)
You can check him out online and his website outlines his protocols for people like us. Its been an extremely difficult year and 1/2+ for me due to my specific combination of illnesses.
From what I gleaned in my Google search, in 2019, he has been in the “game” fighting for ME/CFS patients and trying to help “us” become well for 30+ years.
I don’t know if he would be a good fit for your needs, however, I couldn’t pass up giving you his name since you live in the area. All the best…Annie
I have ME. I take 30mg dextromethorphan 2 hours before showers and other activities that I know will produce PEM. It definitely helps a bit, maybe 25-30%, which is equal to or better than most stuff I’ve tried for this god-awful disease. Haven’t noticed side-effects.