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Low Dose Dextromethorphan (cough syrup) looks promising. Has anyone tried it?

Discussion in 'Latest ME/CFS Research' started by BeautifulDay, Oct 11, 2017.

  1. BeautifulDay

    BeautifulDay Senior Member

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    Doctors, researchers, and pharmaceutical companies are all looking into this path -- energy metabolism in the brain (glutamine, glycine, gaba, etc….) and brain inflammation and symptoms (cognition, fatigue, autistic features, etc….). Some of the researchers and doctors believe that low dose dextromethorphan looks promising for some individuals with chronic fatigue, fibromyalgia, cognitive loss, autism, etc…..

    I don’t believe low dose dextromethorphan is going to help everyone and I don’t believe it will be the cure all. However, for people who fit a certain criteria, low dose dextromethorphan looks promising for improving some symptoms in some people. If this is ultimately found to be the case, I expect pharmaceutical companies to develop better and more precise medications that will help with energy metabolism in the brain through similar means.

    I’m planning on trying low dose dextromethorphan (over the counter cough suppressant) to see if it has any impact on my fatigue and other symptoms (including cognitive issues). I’m the guinea pig in our family. Until the doctors find a cure, I’ve got to keep looking for items within my reach that can improve (even slightly) our symptoms. It’s very hard when one of our kids sobs that he/she is missing out on something because of severe fatigue or another related symptom.

    I’m not going to start low dose dextromethorphan until next week, so please post any thoughts, concerns, suggestions. Thanks!

    Here is a quick summary of my thoughts. I’ll post the more detailed science/research discussion in bite sized pieces in separate posts.

    There are many studies indicating that inflammation is higher in the brains of some people with CFS, Alzheimer’s, Austic Spectrum Disorder, Anxiety, etc…. Scientists have found that people with inflammation in the brain can have higher levels of glutamine or glycine or Gaba in their blood and/or urine. The question then enters – if my brain is not getting the glutamine, glycine, or Gaba it needs for energy, then 1) Does my body produce more to try to overcome what the body sees as a defect? 2) Will the amino acids that are not being absorbed in the brain show up as being higher in the blood or urine? I don't have the answers to those questions (I'm just thinking out loud).

    Across the board in our 5 family members with Mitochondrial Disease and Chronic Fatigue, we all have amino acid issues. Glutamic acid is low in all of us, while we all have various issues within our group from high Glutamine in blood and urine, high GABA in urine, and high 3-methylhistidine in urine. Everyone who has mitochondrial issues is different, even within the same family - so something that improves a symptom in one, may not work for everyone.
     
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  2. BeautifulDay

    BeautifulDay Senior Member

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    Autistic Type Symptoms and Autistic Spectrum and Autism are seen at higher rates in Mitochondrial Disease/Dysfunction patients.
    https://www.umdf.org/what-is-mitochondrial-disease/possible-symptoms/
    https://www.autismspeaks.org/node/113411
    https://www.cdc.gov/ncbddd/autism/mitochondrial-faq.html

    Several researchers have found that some individuals with autism have high glutamine and glycine in blood tests. For example:

    “Autism associated with elevated glutamine and glycine levels and clinical response to dextromethorphan.” “To competitively block his elevated Glu and Gly levels he was empirically treated with dextromethorphan (DM) at 5 mgm/kg/day (Delsym) divided BID. ….. Our data suggest some autistic children have consistent elevations of Glu and Gly and they may respond clinically to DM. Further studies are needed to determine the cause of these biochemical findings and the responce of other subjects to DM or other competitive inhibitors.”
    http://www.nature.com/gim/journal/v1/n2/abs/gim199914a.html?foxtrotcallback=true

    Keep in mind that in the above study, in screening a series of consecutive autistic probands, they only detected 2/60 who had elevated plasma levels of glutamine (Glu) and glycine (Gly). Therefore, this is not going to be across the board for everyone. Just another clue for some.

    In our family, glutamine is a real issue. However, our plasma glycine was all normal. Glutamic acid is low in all of us, while we all have various issues within our group from high Glutamine in blood and urine, high GABA in urine, and high 3-methylhistidine in urine. Only my glycine was high in urine. But then again, I’m high on most of them due to aminoaciduria. That could prove to be a renal or digestive/absorbtion issue due to having MitoD longer or it impacting me differently than others.
     
  3. BeautifulDay

    BeautifulDay Senior Member

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    This is a fabulous article on energy, mitochondrial function, and glutamate and GABA in Alzheimer’s brains. I find this article very interesting and worth the effort to read the entire source document. Here are some snipits.

    Energy metabolism and inflammation in brain aging and Alzheimer’s disease.”

    “The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. …….

    …. ATP generated by oxidative phosphorylation together with glutamate and GABA are critical for synaptic plasticity in brain. ….. Measuring glucose metabolism via 13C-MRS/NMR involves supplying a 13C-labeled glucose followed by measuring the glycolytic end product pyruvate and the downstream TCA cycle metabolites, neurotransmitters, and neurochemicals, such as glutamate, glutamine, GABA, and NAA. …. Thus, it is possible to follow the trail of glucose metabolism after glycolysis and estimate the amount of a specific metabolite (e.g., glutamate) generated directly from the labeled glucose. Moreover, MRS/NMR methods employing 13C-labeled substrates such as glucose and acetate allow direct assessment of neuronal and glial mitochondrial metabolism and facilitate distinguishing between them. ….

    Mitochondrial brain glucose metabolism investigated in aged rats using [1-13C]-glucose via 13C and 1H NMR spectroscopy revealed that the incorporation of glucose-derived 13C into glutamate, glutamine, aspartate, and GABA declined in aged brain [73]. The SAMP8 mouse model of accelerated aging is characterized by spontaneous age-related learning and memory impairments associated with gliosis as a function of age [74]. SAMP8 mice, administered [1-13C]-glucose and [1,2-13C]-acetate, showed that major mitochondrial metabolites such as glutamate and glutamine derived from [1-13C]-glucose and [1,2-13C]-acetate were both significantly declined during aging [75]. …..

    13C/1H MRS studies in healthy brains showed that elderly subjects had ~30% lower neuronal mitochondrial metabolism (assessed by glutamate-glutamine cycle flux and TCA cycle flux) compared to young subjects [71,76]. Interestingly, the astroglial rate of TCA cycle was ~30% higher in elderly group compared to young subjects, thus suggesting that normal aging was associated with a decline in neuronal metabolism along with an increase in glial metabolism as seen in astrocytes isolated from aged rats [14].

    There are several studies on mitochondrion-driven glucose metabolism (measured by MRS/NMR) in rodent models of AD. Tg2576 mice showed a decrease in NAA, glutamate, and glutathione in the cerebral cortex at 19 months of age, which coincided with widespread AD-type pathology [77]. 1H-[13C]-NMR spectroscopy analyses of the APPswe-PS1dE9 mouse model of AD showed a decrease in glutamate, GABA, and glutamine, which suggested an impaired glutamatergic and GABAergic glucose oxidation and neurotransmitter cycle in these mouse brains [78]. 1H-13C spectroscopy analyses of Thy-1-APPSL model, expressing mutant human APP, suggested that mitochondrial dysfunction may contributed to the glutamine synthetase impairment and increased metabolism of glutamate via the GABA shunt [79]. Glucose metabolism was clearly reduced by ~50% in a 3xTG-AD model as exhibited by the decreased levels of metabolites derived from the TCA cycle (glutamate, glutamine, GABA, and NAA) [80]. Clinically, a pilot study in AD patients receiving [1-13C]-glucose probed for glucose metabolism using quantitative 1H and proton-decoupled 13C MR brain spectra, showed reduced glutamate neurotransmission which might contribute to cognitive impairment [81].”
    http://www.sciencedirect.com/science/article/pii/S0891584916302167
     
  4. BeautifulDay

    BeautifulDay Senior Member

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    Dextromethorphan reduces some aspects of Fibromyalgia pain
    http://www.medscape.com/viewarticle/538238

    My ADHD mind is going in too many directions and I have two doctors’ appointments today and I leave tomorrow for the MitoD conference in Ohio. I’ll do my best to post the dozens of other articles on this issue later today along with some of the research being done and the pharmaceutical companies interest in the field. Yet, there are so many of you on PR with technical knowledge that it’s likely I’ll come back to find this thread already filled in – or on the flip side, the issue being shot down over a study or theory I missed.
     
  5. pattismith

    pattismith Senior Member

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    it looks interesting!

    On the other hand, I feel concerned by the side effects of this drug on cognitive functions and memory....
     
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  6. BeautifulDay

    BeautifulDay Senior Member

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    I'm just looking those up now. I'll definitely keep on the look-out for anything like that.

    Since I've taken name brand cough syrup over the years that includes dextromethorphan as an ingredient (Mucinex DM, Robitussin, NyQuil, Dimetapp, Vicks, Delsym, TheraFlu), and since my plan is to start at very small levels (and keep it low), I'm hoping that no side effects will pop up. I'm thankful for your pointing them out so just in case.

    Adverse effects per Wikipedia:
    "Side effects of dextromethorphan at normal therapeutic doses can include:[2][8][11]
    body rash/itching (see below)
    nausea
    vomiting
    drowsiness
    dizziness
    constipation
    diarrhea
    sedation
    confusion
    nervousness
    closed-eye hallucination
    A rare side effect is respiratory depression.[8]"

    Wikipedia then goes onto discuss neurotoxicity in intravenous use. I'm not going to be doing intravenous, so I skipped it.

    Wikipedia then goes onto discuss the adverse effects of overdose at 3-10 times recommended dosage. And also the side effects at 15-75 times recommended dosage. I plan on taking a smaller than normal dose (low dose), so hopefully, these won't be an issue.

    It also points out interactions with MAOIs, SSRIs, and grapefruit.

    Anyone who is thinking of taking over the counter dextromethorphan should read up on it first and check with his/her doctor.

    https://en.wikipedia.org/wiki/Dextromethorphan#Adverse_effects
     
  7. MAOAr297r

    MAOAr297r

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    I don't recommend you try it on your own without a medical professional. I did. It helped my depression but ultimately made me way to spacey because it's a dissociative. If you really want to hit it hard use DXMs big brother ketamine and have it prescribed by an MD. A gene involved in ME is called mTOR and there is it is under active in our disease. ketamine raises up the activity and also modulates glutamate among other things. I want to try it at some point. It's no cure but it might be a nice bandaid and help our quality of life.
     
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  8. BeautifulDay

    BeautifulDay Senior Member

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    Thanks @MAOAr297r

    Do you remember how much you were taking when you tried low dose dextromethorphan? Spacey definitely wouldn't be good. How long until that symptom showed up?
     
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  9. Londinium

    Londinium Senior Member

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    Just to flag:

     
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  10. MAOAr297r

    MAOAr297r

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    The standard doses and sometimes I tried 2x or 3x the standard dose too. It was not too bad at the standard dose.
     
  11. BeautifulDay

    BeautifulDay Senior Member

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    Good morning @MAOAr297r

    Your symptoms of it "ultimately made me way to spacey because it's a dissociative" wouldn't be surprising at 3x the normal dosage of dextromethorphan. Wikipedia states that these adverse effects can happen at 3 to 10 times the recommended therapeutic dose.

    euphoria, increased energy, increased confidence, mild nausea, restlessness, insomnia, talking fast, feelings of increased strength, dilated pupils, glassy eyes
    https://en.wikipedia.org/wiki/Dextromethorphan#Adverse_effects

    Since our family members tend to have adverse reactions to some common medications at normal doses, I'm planning on trying it myself at a low dose (lower than normal) and not going above low dose. In addition, I'm a big fan of giving the body a day off from medicines every week - that is when it won't be detrimental. For example, if someone was a diabetic, of course take your medication every day. For me with my blood clotting disorder, of course I'm going to take blood thinners everyday.

    However, with medications that people are known to build up a tolerance for (and larger doses are needed over time for the same effect), then why not have a day off every week to avoid the medication from not working in the future. https://en.wikipedia.org/wiki/Drug_tolerance

    It sounds like you might have started at normal dose and "it was not too bad." I presume, you had some positive symptom relief/reduction and kept taking it and as it worked less and less, you then tried it at 2x and then 3x the normal dose and had the adverse effects.

    For my experiment, my plan is to start at low dose (1/10th normal dose) and then take a day off every week from taking it to avoid the need for larger and larger doses to get the same impact. If it doesn't provide any symptom relief at the low dose (and I experience no adverse effects), then I'll double that dose (so that it's 1/5th a normal dose). If that doesn't work, then I'll stop the experiment. I have no plans to increase it to the normal dose.

    The pharmaceutical companies are conducting studies into low dose and of course changing it up so they can charge a lot more money. If they find something that works a lot better, then fabulous!!!

    Delsym Adult 12 Hr Cough Relief Liquid, Grape, 5oz states the adult dose is 10 ml every 12 hours. In each 5 ml, there is 30 mg of dextromethorphan. So a normal dose would be 60 mg of dextromethorphan - and at normal dose, that is taken twice a day for a total of 120 mg of dextromethorphan being considered normal in a day.

    I'm talking about starting at 12 mg of dextromethorphan in a day total. So instead of 10 ml every 12 hours, I would take 1 ml every 12 hours (with one day taken off a week). If at this very low dose I was able to get in an extra load of laundry a day or stay up for an extra hour to help with homework or have less cognitive issues, without the side effects, then I'll call the experiment a success.

    If there were no side effects but no improvement at this level, then after another week, I'd up the dose to 2 ml every 12 hours (that would be 24 mg of dextromethorphan a day) with one day a week taken off. If there is no positive improvements of symptoms or if there is any adverse effects, then the experiment would be a failure at that point in time..

    What is considered low doses of dextromethorphan in studies?
    There are many studies on low dose dextromethorphan. There are points that could be made in each study that are important.

    Therapeutic effects of add-on low-dose dextromethorphan plus valproic acid in bipolar disorder
    Study: Highlights:
    • Patients with bipolar disorder significantly increased plasma cytokine levels.
    • Patients with bipolar disorder significantly decreased plasma BDNF levels.
    • Dextromethorphan provided anti-inflammation and neurotrophic benefit in bipolar disorder.
    Low dose dextromethorphan was considered 30 or 60 mg/day.
    Study conclusion: "Conclusion: patients with BP have a certain degree of systemic inflammation and BDNF dysfunction. Treatment with VPA plus DM (60 mg/day) provided patients with BP significantly more neurotrophic benefit than did VPA treatment alone."
    http://www.sciencedirect.com/science/article/pii/S0924977X14002521

    The Intravenous Ketamine Test Predicts Subsequent Response to an Oral Dextromethorphan Treatment Regimen in Fibromyalgia Patients
    "After the ketamine infusion, computerized prescriptions for DX were entered into the pharmacy database on all patients, subject to approval by the anesthesia and pharmacy services. The starting dose was 0.5 mg/kg per
    os 3 times a day (TID), titrating up to 1 mg/kg TID "
    So in this study, they treat fibromyalgia patients with 1.5 mg/kg a day to 3 mg/kg a day of dextromethorphan. For an adult who is 160 pounds, that is 108 to 216 mg a day of dextromethorphan. In my experiment, I'll be starting with 12 mg a day and if that doesn't help/nor hurt, then I'll move up to 24 mg a day. That's still way under the dosage used in the patients with fibromyalgia.
    http://www.jpain.org/article/S1526-5900(06)00468-8/pdf

    In this unrelated study in an infant, low dose dextromethorphan was considered 0.25 mg/kg per day. https://www.ncbi.nlm.nih.gov/pubmed/8657542
    For an adult who is 160 pounds or 62 kilograms, that would be 18 mg a day of dextromethorphan. The level I'm talking about starting at, would be lower than my threshold at 12 mg a day (6 mg twice a day).

    Low dose dextromethorphan attenuates moderate experimental autoimmune encephalomyelitis by inhibiting NOX2 and reducing peripheral immune cells infiltration in the spinal cord.
    http://www.sciencedirect.com/science/article/pii/S0969996111002026

    Dextromethorphan and Memantine in Painful Diabetic Neuropathy and Postherpetic Neuralgia: Efficacy and Dose-Response Trials. In this study, the low dose dextromethorphan was considered to be 30 mg dextromethorphan administered four times daily (120 mg a day). That's actually the amount an adult gets from taking the normal dose of Deslym twice a day.
    http://anesthesiology.pubs.asahq.org/Article.aspx?articleid=1945108
     
  12. BeautifulDay

    BeautifulDay Senior Member

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    @Londinium I agree that recreational dextromethorphan has no use here. Recreational use is for those people who want to use it to get high. Dextromethorphan recreational use is at much higher levels than the low doses I am talking about in the above post to @MAOAr297r .

    I've researched the withdrawal symptoms in the low dose studies of dextromethorphan and I can't find any concerns at those very low levels.
     
  13. MAOAr297r

    MAOAr297r

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    You obviously know way, way more about this then me and it looks like you've done your homework. I know BDNF is really important in correcting mood disorders and it increases neuroplastisticy and thats really cool it inhibits NOX2 i had no idea. Let me know how it goes, I'd potentially like to try this.

    I know ketamine activates mTOR so I guess maybe DXM will too. It's a under active gene in ME. Ketamine works on systems outside the biogenic amines. It modulates glutamate for instance which binds to NMDA receptors and can invoke LTP in the brain. One of my neuroscience books has a large section on the molecular mechanisms behind ketamine. I guess thats what increases BDNF possibly. BDNF is really low in clinical depression too. They have done brain biopsies on suicide victims and find tons of them have super depleted BDNF, I did a paper on that in my psych class recently. Also a friend of mine is in a trial with a drug thats like a cleaner 2nd generation version of ketamine apparently but it's not out yet. I will ask her today what the heck the drug is. She said it's been helpful.

    Sorry if I already mentioned that, my memory is terrible. I need anything at this point. I'm going to ask my MDs about ketamine this week. Seriously update me if this helps you, it sounds fascinating at the very least from a molecular medicine perspective.
     
    Last edited: Oct 12, 2017
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  14. BeautifulDay

    BeautifulDay Senior Member

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    I definitely will. Thanks for all the great information!
     
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  15. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    I havent read the other posts here but dxm is a nmda antagonist which ketamine has this nmda blocking effect. So it can have pain relieving properties but its possible nmda antagonist like dxm, ketamine and memantine can lower drug tolerance to benzos, narcotics and stimulants. Worth research for that alone.
     
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  16. enduin

    enduin

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    My wife tried DXM at various dosages and unfortunately she didn't experience any improvement. I don't remember exactly now the regimen I gave her, but I think it was something like a couple of days at standard dosage, then ramped up over the following days to 4x the standard dosage (which is still perfectly safe, but it did make her a bit spacey). I'll tag her in case you wanna ask her follow up questions @Basilico
     
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  17. Basilico

    Basilico Florida

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    I only vaguely remember trying DXM, which means it had zero effect on me. But that's pretty standard for me, I seem to be a non-responder to just about everything I try.
     
  18. frederic83

    frederic83 Senior Member

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    I tried Dextromethrophan in a cough syrup. I remember I felt a bit drunk with something like 4x the normal dose. Nothing else to report for me. Did not change the CFS.
     
  19. DeGenesis

    DeGenesis Senior Member

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    DXM is dissociative, it causes depersonalization in healthy persons when taken at above recommended dosages.. MECFS have problems with DP/DR already. That's why I never experimented with it, because I don't want to trigger a relapse in my DP/DR symptoms. That is my warning, because almost nothing is worse than DP/DR.
     
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  20. BeautifulDay

    BeautifulDay Senior Member

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    I haven't been able to start my experiment with Low Dose Dextromethorphan yet due to the TMJ and the glass in my thumb. I want to give the experiment my full attention while not being burdened by other attention stealing health issues.

    (I had foot drop happen while going down the steps several weeks ago. I fell on the recycling glass I was carrying out and 15 stitches later in my thumb, I can't make any more progress in physical therapy until they figure out whether they are going to take out the rest of the larger glass pieces. The little glass splinters easily pop out on their own.)

    I haven't given up on the experiment. I'm just waiting for the best time to focus on it. :D
     

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