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.

Fibromyalgia Neuroinflammation Finding Could Open New Treatment Options

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.


younger -UAB

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:

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