List of supplements and drugs that improve ME/CFS within hours or days

[Hip]

An ME/CFS patient asked me if I have any idea of which supplements or drugs for ME/CFS work within hours.

He made the good point that patients could run through a list of such treatments and quickly determine which ones work for them. So for new ME/CFS patients, these fast-acting treatments might be the best ones to try first. By contrast, testing treatments which take many months to yield results is a much more lengthy process.

So to my knowledge, here is a list of supplement or drug treatments with a track record of helping ME/CFS which work within hours or days:

Piracetam — this supplement at 600 to 2000 mg daily is usually effective for reducing brain fog within two hours for most patients. Piracetam is not a stimulant; it is classed as nootropic supplement (cognitive enhancer). One common side effect is increased emotional blunting, but this can be minimised by taking low doses of only 600 mg daily.

Dr Greg Russell-Jones vitamin B12 transdermal oils — can be effective for brain fog for some patients within a few hours. Success rate though is probably less than 50%.

Oxaloacetate — at a dose of 500 to 2000 mg daily, this supplement often greatly boosts energy and improves brain fog by its mitochondrial effects. It works for approximately 50% of patients, but is very expensive (about $6 for the typical 1000 mg daily dose). Proven effective for ME/CFS in clinical trials, see here and here.

High-dose vitamin B1 — at daily doses from 200 to 1500 mg, 66% of ME/CFS patients observed major improvements in their fatigue, PEM and brain fog with B1, according to a survey by Health Rising. A study demonstrated that high-dose vitamin B1 is effective for treating the chronic fatigue of IBD.

Pyridostigmine (Mestinon) — for many ME/CFS patients, this drug increases energy, reduces PEM and alleviates POTS and orthostatic intolerance within hours to a few days. Dosing is typically 30 to 60 mg taken two to three times daily, though often patients will start with lower doses, such as 15 mg twice daily. However, for many patients this drug does not work at all, and for some, it creates intolerable side effects.

Low-dose Abilify — some ME/CFS patients find Abilify (aripiprazole) at low doses of 0.2 to 2.0 mg daily leads to major improvements in their symptoms within a few days to a week. But for others, the benefits take a 2 to 8 weeks to arrive. Unfortunately in some cases, the benefits of Abilify fade after a few months (Abilify poop out). When poop out occurs, taking a break from Abilify for several months can restore its benefits. A study on Abilify for ME/CFS noted promising results.



Further reading:
List of ME/CFS Recovery and Improvement Stories

 

[Rufous McKinney]

Thank you for this valuable summary, @Hip

 

[Wayne]

So to my knowledge, here is a list of supplement or drug treatments which work within hours or days:

I get almost immediate results from being inside an mHBOT chamber. I usually detect a notable shift within minutes, and often a more profound shift after 20 minutes. Sometimes I will continue to feel better and better the whole time I'm in, which can be 1-2 hours. The increased energy I experience usually lasts for several hours afterwards. I attribute at least part of the profound relaxation I feel afterwards to being able to shift into parasympathetic mode.

I also get almost immediate results from doing a coffee enema, to which I add approximately 10 grams of sodium ascorbate. I used to think I would feel immensely better because of the purported detoxification effect, but I've come to believe it's a combination of that, plus the fact that enemas stimulate the vagus nerve. Which for me, seems to balance out the entire neurological system, and like mHBOT, allows it to go into parasympathetic mode.

AI had some suggestions--in the link below.

Spoiler: AI Suggested Fast Acting Treatments

Additional Fast-Acting Treatments for ME/CFS​

1. Low-Dose Naltrexone (LDN) – Typical onset: 1 day to 1 week (some report within hours).
Dose: 0.5 to 4.5 mg at night. Benefits: Immune modulation, reduced pain, better sleep, improved cognition. Mechanism: Microglial inhibition, endorphin upregulation, TLR4 modulation.

2. Methylene Blue – Typical onset: Within hours.
Dose: 0.5 to 4 mg/kg/day (start very low). Benefits: Mitochondrial support, cognitive boost, antimicrobial. Notes: Can worsen symptoms in some due to MAOI effects or serotonin syndrome risk with SSRIs.

3. Caffeine + L-Theanine – Typical onset: Within 30 minutes.
Dose: 50–100 mg caffeine + 100–200 mg L-theanine. Benefits: Quick boost to cognition and alertness with reduced jitteriness. Note: Some ME/CFS patients are paradoxically worsened by caffeine.

4. CoQ10 (Ubiquinol Form) – Typical onset: Within a day or two for some.
Dose: 100–300 mg. Benefits: Mitochondrial support, energy. Notes: Best absorbed with fat; often used in combo with carnitine or NADH.

5. NADH (e.g., Enada) – Typical onset: Within a few hours to 1 day.
Dose: 5–10 mg sublingual. Benefits: Energy production, reduced fatigue. Study: Shown to improve symptoms in a subset of ME/CFS patients.

6. Rhodiola Rosea – Typical onset: 30–90 minutes.
Dose: 100–300 mg standardized extract. Benefits: Mental energy, reduced fatigue, improved mood. Caution: Can cause overstimulation in some with sensitive nervous systems.

7. Low-Dose Hydrocortisone (under medical supervision) – Typical onset: Hours to 1 day.
Dose: 2.5–10 mg in the morning. Benefits: Temporary adrenal support, reduction in fatigue. Risks: Suppression of HPA axis if overused.

8. Ketamine (oral or nasal, off-label) – Typical onset: Minutes to hours.
Used for: Refractory fatigue, depression, sensory overload. Caveats: Requires medical supervision; experimental in ME/CFS.

9. Intranasal Insulin (off-label) – Typical onset: 30 minutes to a few hours.
Effect: Improved cognition and alertness. Mechanism: CNS insulin signaling, neurotrophic effects.

10. D-Ribose – Typical onset: Hours to a couple days.
Dose: 5 g 1–3x/day. Effect: Increased energy production in some, especially if mitochondrial dysfunction is involved. Evidence: Some small studies and strong anecdotal support.

 

[heapsreal]

Modafinil Low dose 50mg but only use it a couple of times a week if needed.

Caffeine, but works well if one has been off caffeine for several weeks and then use 100mg a couple of times per week. Good to have a couple of weeks every so often where you have no Caffeine.

AlphaGPC, milder than Caffeine. Also limit it to a couple of times a week to avoid tolerance.

Tramadol, although a pain killer, it also works through serotonin and noradrenaline which can help with feeling better and giving energy.

Pregnenolone and dhea especially if testing shows your low. But start low and go slow.

Tryptophan 3000mg before bed, improved sleep and in a good mood the next day. Another supp to use every so often.

Korean Ginseng for energy, again use 2-3 times a week when needed.

Tyrosine 1000-2000mg on its own or with caffeine if caffeine has lost its edge. Tyrosine is the raw material for adrenaline/noradrenaline.

A short list of things I personally find helpful. It's really a trial and error thing for everyone including doses. Really they are band aid approaches for those days when you need a lift or someone works 2-3 days a week and is struggling and has no real options, which was me for many years.

But when in a crash, these band aid fixes don't work for me, then i know it's time to rest and stop trying to push.

 

[cfs since 1998]

Huperzine A is an herb that has a similar mechanism of action as Mestinon/pyridostigmine. I took 1/4 of a 200 microgram tablet and was barely able to sit down. I got my entire apartment cleaned in one day but it was overly stimulating.

Unfortunately I haven't been able to repeat that as I haven't been able to get the dose right. I am afraid to take too much (causes GI upset, muscle twitching, restlessness) and if I take too little it doesn't make a difference.

 

[Wayne]

Piracetam — this supplement at 600 to 2000 mg daily is usually effective for reducing brain fog within two hours for most patients. Piracetam is not a stimulant; it is classed as nootropic supplement (cognitive enhancer). One common side effect is increased emotional blunting, but this can be minimised by taking low doses of only 600 mg daily.

I experimented with piracetam, and initially thought I'd really discovered something that would make a difference for me. I started out at the lowest dose, and felt quite stimulated by it. It was great to think clearer and have more energy. But the initial low dose was too intense. I experimented with using lower doses, but couldn't avoid that overstimulation effect.

I went down to as much as 50 mg., and even less--down to a "speck". Still felt overstimulated, so I finally gave up. Just a word of caution for those considering taking it. It might work really well for you (apparently balances the two hemispheres of the brain), but you could have the same reaction I did. Also, there are other "cetams" that are purported to be less stimulating. Worth checking out, which has been on my back burner for quite some time.

 

[hapl808]

There's also Goldstein's drugs, which I think he had listed a bit in the order of effect onset? Vaguely remember naphazoline, nitro, etc.

 

[Wayne]

There's also Goldstein's drugs,

Hi @hapl808 -- Great addition. Below is a list of the top drugs Goldstein used.

Spoiler: Dr. Jay Goldstein's Fast Acting ME/CFS Treatments

---

Dr. Jay Goldstein's Fast-Acting ME/CFS Treatments​

Core Idea: ME/CFS is a disorder of dysfunctional neuronal signal transduction, especially in the limbic system. Drugs that modulate CNS signaling can sometimes trigger remission or dramatic symptom improvement within minutes to days.

Drug	Mechanism	Effect Onset	Notes
Ketamine	NMDA receptor antagonist	Minutes	Rapid reset of glutamate signaling; improves fatigue, pain, cognition. Low-dose oral or IV/intranasal.
Nimodipine	Calcium channel blocker	Hours–days	Enhances cerebral blood flow; may reduce brain fog and neuroinflammation.
Ondansetron (Zofran)	5-HT3 serotonin antagonist	Minutes–hours	Reduces sensory overload, nausea, brain fog; low dose (e.g. 4 mg).
Naloxone / Naltrexone	Opioid receptor antagonists	Minutes–hours	Restores endogenous opioid balance; sometimes used at higher doses than LDN.
Amantadine	Dopaminergic + NMDA modulator	Hours–days	Increases mental energy and alertness; also has antiviral properties.
Dextromethorphan	NMDA antagonist + sigma-1 agonist	Minutes–hours	Improves fatigue, pain; often used in combo with quinidine (Nuedexta).
Baclofen	GABA-B receptor agonist	Hours	Reduces CNS hyperexcitability and pain sensitization.
Ranitidine / Cimetidine	H2 receptor antagonists	Hours	Affects CNS histamine and possibly immune modulation. Ranitidine now restricted.
Oxytocin (intranasal)	Neuropeptide / social hormone	Minutes	May reduce stress, improve social function, modulate HPA axis.
Phenytoin (Dilantin)	Sodium channel blocker	Hours–days	Stabilizes overactive brain circuits; anti-seizure agent with sedating effect.
Tianeptine	Atypical antidepressant, glutamate modulator	Hours–days	Enhances neuroplasticity; can improve mood, cognition, energy.
Lamotrigine	Glutamate release inhibitor	Days	May reduce neuroinflammation and sensory overload; mood-stabilizing.
Lidocaine (IV or patch)	Sodium channel blocker	Minutes (IV)	IV can blunt pain and CNS irritability rapidly; topical forms milder.
Clonazepam (Klonopin)	GABA-A modulator	Minutes	Reduces sensory overload, anxiety, sleep disruption; caution with dependence.
Prazosin	Alpha-1 blocker	Hours	Lowers sympathetic tone, may improve sleep and PTSD-like symptoms.
Guanfacine	Alpha-2A adrenergic agonist	Hours–days	Calms hyperaroused CNS, improves executive function.
Cyclobenzaprine	Central muscle relaxant, TCA-related	Hours	Sedating; improves sleep and reduces sensory amplification in some.

---

Usage: Goldstein used these in a trial-and-error format, starting with low doses, observing for rapid response, and switching quickly if ineffective.
Legacy: His treatments often acted in minutes to days and sometimes led to full or near-remission. Though lacking clinical trials, many patient reports support their efficacy.

More About Dr. Jay Goldstein and His Theories

Dr. Jay A. Goldstein was a pioneering but unconventional physician who specialized in treating ME/CFS and related neuroimmune disorders during the 1980s and 1990s. His approach was radically different from mainstream medicine: he believed ME/CFS was primarily a disorder of central nervous system (CNS) signaling and information processing, and he treated it by “rebooting” the brain using fast-acting medications that targeted neurotransmitter receptors or neural pathways. His most dramatic claim was that some patients could experience full or near-remission within minutes to hours of taking the right drug.

---

Core Theory​

Goldstein believed ME/CFS resulted from dysfunctional neuronal signal transduction, especially in limbic system structures like the hypothalamus and amygdala. He hypothesized that:

• ME/CFS symptoms stem from altered brain signal amplification, affecting how the CNS responds to stimuli (pain, fatigue, effort, etc.).
• The condition could be reversible if brain signaling was "reset" using neuroactive agents.
• Individual responses were highly idiosyncratic; trial-and-error was essential.

He wrote three detailed books on his theories and treatments:

• Betrayal by the Brain (1994)
• The Limbic Hypothesis (1996)
• Tuning the Brain (2001) — his magnum opus, listing over 100 drugs with detailed usage notes

 

[hazylinn41]

I want to add to this list and to what others have already said, from my many years of experience with Nootropics and from talking to other ME patients about their experiences. In addition to my own experience with trying these, I have had SEVERE ME/ CFS since 2023. *SCROLL DOWN FOR MY RECOMMENDATIONS FOR ANY ME/CFS PATIENTS* And not just for a few.

- PIRACETAM is one of the least used racetams, it was the first that developed. Nootropicsexpert.com has a good guidance for which racetam would work best for you.

My favorite racetam is ANIRACETAM, it has anxiolytic effects and works less like a stimulant than the others. PHENYLPIRACETAM is my least favorite, it's extremely stimulating for me. There are individual, genomic differences to why some racetams work for some people and others don't, I used ANIRACETAM together with CDP CHOLINE -VERY IMPORTANT- for years, before I had to switch to antipsychotic medicine.

- OXALOACETATE is, as far as I understood, only effective for those who have a deficiency somewhere in their Krebs cycle. For me who has an abundance, the parts working too well to compensate for chronic inflammation, will not benefit from Oxaloacetate. I tried it before knowing, to no results.

- HIGH DOSAGE B1 works for a minority of ME patients. I know at least 20 ME patients who have tried it extensively (it's a huge topic in the Norwegian ME fb group) and it didn't work for any. It might possibly work for people on the milder range and for those neurotypical. In my (and friends') experience it certainly doesn't work for neurodivergents or those with significant gut microbiome dysbiosis.

- A better suggestion than MESTINON is HUPERZINE-A which already has been mentioned. It increases acetylcholine (like CDP CHOLINE for racetams) which is an important neurotransmitter for memory and cognitive ability. Many ME patients lack ACh and Huperzine is a supplement that has less side effects and is easier attainable than Mestinon.

- LOW DOSE NALTREXONE has a much higher success rate than LOW DOSE ABILIFY. Both are good to try, but try Naltrexone first, it has less side effects as well.

- B12 TRANSDERMAL OILS has extrememly low absorbtion rate unless you use DMSO (at your own risk) for better solubility. It's much better to try either SUBLINGUAL B12 (good absorbtion) or B12 INJECTIONS (great absorbtion)
----------------------------------
Now, for my recommendations, that helps most people in one way or another, either by supporting general health or treating important looked over symptoms:

1) PRUCALOPRIDE or DOMPERIDONE motility medicine. Estimated 88% of ME patients have SIBO. SIBO is caused by slow motility. My gut symptoms got SO much better after I started this. No side effects, cheap, easily accessible medicine. Try it if you have gut issues.

2) MAGNESIUM (HIGH DOSAGE), the dosage varies from person to person. Start at 100 mg and work yourself up. I have taken 1100 mg for two years consistently. Magnesium is an absolute must as a supplement, no discussion. The type of magnesium matters, check out Fb group "Nutrient teams" for great advice about the good and bad absorbtion types. Take magnesium every day.

3) OMEGA 3 (HIGH DOSAGE), Omega 3-6-9 fatty acids are needed for the brain among many other processes in our body. I have looked at many many Organic Acids tests of ME patients. Everybody lacks Omega 3 and 6 usually. High dosage Omega 3 is anti-inflammatory and a safe supplement that really makes a huge difference long term. Any amount helps, everyone's different. Like Magnesium, take it every day. I take 10.000 mg every day for my brain fog.

4) DHEA, this is a hormone so thread cautiously. If you have tested your hormones and have too much DHEA, this advice is not for you. However, most ME patients have too little DHEA. It's a common feature of adrenal fatigue. This supplement helps my brain fog more than any other. More than any ADHD medicine or antidepressant etc. Dosage is from 10 mg to 50 mg. It has few side effects.

5) ADRENAL CORTEX, this is bovine extract from pig or cow brains (sorry for explicit description). In addition to alleviate MCAS histamine intolerance which many ME patients have comorbid, it supplies energy for anyone with adrenal fatigue (which all of us obvsly have). You can supplement endlessly with this, it's very safe. PORCINE is similar.

What I have recommended here are safe and cheap supplements and medicine.
To end this list, what's more important than any tips about supplements or medicine, is TO FIGURE OUT YOUR INDIVIDUAL CAUSES TO YOUR ILLNESS. EVERY ME/CFS PATIENT IS DIFFERENT, WHAT WORKS FOR ONE WILL NOT NECESSARILY WORK FOR ANOTHER. Thank you for reading my essay. Hope this helps someone, stay strong lovely bedbound people<3

 

[hazylinn41]

I want to add to this list and to what others have already said, from my many years of experience with Nootropics and from talking to other ME patients about their experiences. In addition to my own experience with trying these, I have had SEVERE ME/ CFS since 2023. *SCROLL DOWN FOR MY RECOMMENDATIONS FOR ANY ME/CFS PATIENTS* And not just for a few.

- PIRACETAM is one of the least used racetams, it was the first that developed. Nootropicsexpert.com has a good guidance for which racetam would work best for you.

My favorite racetam is ANIRACETAM, it has anxiolytic effects and works less like a stimulant than the others. PHENYLPIRACETAM is my least favorite, it's extremely stimulating for me. There are individual, genomic differences to why some racetams work for some people and others don't, I used ANIRACETAM together with CDP CHOLINE -VERY IMPORTANT- for years, before I had to switch to antipsychotic medicine.

- OXALOACETATE is, as far as I understood, only effective for those who have a deficiency somewhere in their Krebs cycle. For me who has an abundance, the parts working too well to compensate for chronic inflammation, will not benefit from Oxaloacetate. I tried it before knowing, to no results.

- HIGH DOSAGE B1 works for a minority of ME patients. I know at least 20 ME patients who have tried it extensively (it's a huge topic in the Norwegian ME fb group) and it didn't work for any. It might possibly work for people on the milder range and for those neurotypical. In my (and friends') experience it certainly doesn't work for neurodivergents or those with significant gut microbiome dysbiosis.

- A better suggestion than MESTINON is HUPERZINE-A which already has been mentioned. It increases acetylcholine (like CDP CHOLINE for racetams) which is an important neurotransmitter for memory and cognitive ability. Many ME patients lack ACh and Huperzine is a supplement that has less side effects and is easier attainable than Mestinon.

- LOW DOSE NALTREXONE has a much higher success rate than LOW DOSE ABILIFY. Both are good to try, but try Naltrexone first, it has less side effects as well.

- B12 TRANSDERMAL OILS has extrememly low absorbtion rate unless you use DMSO (at your own risk) for better solubility. It's much better to try either SUBLINGUAL B12 (good absorbtion) or B12 INJECTIONS (great absorbtion)
----------------------------------
Now, for my recommendations, that helps most people in one way or another, either by supporting general health or treating important looked over symptoms:

1) PRUCALOPRIDE or DOMPERIDONE motility medicine. Estimated 88% of ME patients have SIBO. SIBO is caused by slow motility. My gut symptoms got SO much better after I started this. No side effects, cheap, easily accessible medicine. Try it if you have gut issues.

2) MAGNESIUM (HIGH DOSAGE), the dosage varies from person to person. Start at 100 mg and work yourself up. I have taken 1100 mg for two years consistently. Magnesium is an absolute must as a supplement, no discussion. The type of magnesium matters, check out Fb group "Nutrient teams" for great advice about the good and bad absorbtion types. Take magnesium every day.

3) OMEGA 3 (HIGH DOSAGE), Omega 3-6-9 fatty acids are needed for the brain among many other processes in our body. I have looked at many many Organic Acids tests of ME patients. Everybody lacks Omega 3 and 6 usually. High dosage Omega 3 is anti-inflammatory and a safe supplement that really makes a huge difference long term. Any amount helps, everyone's different. Like Magnesium, take it every day. I take 10.000 mg every day for my brain fog.

4) DHEA, this is a hormone so thread cautiously. If you have tested your hormones and have too much DHEA, this advice is not for you. However, most ME patients have too little DHEA. It's a common feature of adrenal fatigue. This supplement helps my brain fog more than any other. More than any ADHD medicine or antidepressant etc. Dosage is from 10 mg to 50 mg. It has few side effects.

5) ADRENAL CORTEX, this is bovine extract from pig or cow brains (sorry for explicit description). In addition to alleviate MCAS histamine intolerance which many ME patients have comorbid, it supplies energy for anyone with adrenal fatigue (which all of us obvsly have). You can supplement endlessly with this, it's very safe. PORCINE is similar.

What I have recommended here are safe and cheap supplements and medicine.
To end this list, what's more important than any tips about supplements or medicine, is TO FIGURE OUT YOUR INDIVIDUAL CAUSES TO YOUR ILLNESS. EVERY ME/CFS PATIENT IS DIFFERENT, WHAT WORKS FOR ONE WILL NOT NECESSARILY WORK FOR ANOTHER. Thank you for reading my essay. Hope this helps someone, stay strong lovely bedbound people<3

Don't know how to edit my own comment. Here are some corrections:
- Adrenal cortex comes from bovine or pig kidneys, not brains haha sorry that was a brain fart from my side. It helps the DAO enzyme which is what causes histamine buildup when it doesn't function well
- Alternative supplements to motility meds for increased motility and improving stomach acid issues are: GINGER, ARTICHOKE, FENNEL, LEMON.
- If you have eating / esophagus (gastritis) issues (like me) try BUTYRATE and TAURINE supplements. I couldn't eat before supplementing these, they made me able to eat within a day of supplementing them and I went from VERY SEVERE for a month without eating anything at all, to eating normally, right away.

Forgot to add: OFC ALWAYS DO YOUR OWN RESEARCH BEFORE TRYING ANYTHING ANYONE SUGGESTS TO YOU. IT WILL MOST LIKELY NOT WORK FOR YOU AS WELL SADLY (Except for my recs hehe). UNTIL YOU HAVE FIGURED OUT YOUR INDIVIDUAL CAUSES YOU*RE THROWING RANDOM S*** AT THE WALL AND NOTHING WILL STICK.

Do testing, examples of great tests to figure out your causes are: Organic acids / Metabolomix, IgG and IgM antibody tests (Vibrant), inflammatory cytokines antibody tests, hair mineral tests (Doctor's data), gut microbiome tests (Biomesight), the list goes on. GENOMIC TESTING is the best of all, but requires lots of personal research. E.g. I have a common HLA-DR gene mutation combination that causes my immune system to not detect toxins and to detoxify them at less than normal rate, causing buildup of toxins over time. Lmk if anyone is interested in the topic<3

(And pls everybody, rule out hypermobile Ehlers Danlos syndrome (or HSD) and Craniocervical instability first before testing anything, thx)

 

[hazylinn41]

I get almost immediate results from being inside an mHBOT chamber. I usually detect a notable shift within minutes, and often a more profound shift after 20 minutes. Sometimes I will continue to feel better and better the whole time I'm in, which can be 1-2 hours. The increased energy I experience usually lasts for several hours afterwards. I attribute at least part of the profound relaxation I feel afterwards to being able to shift into parasympathetic mode.

I also get almost immediate results from doing a coffee enema, to which I add approximately 10 grams of sodium ascorbate. I used to think I would feel immensely better because of the purported detoxification effect, but I've come to believe it's a combination of that, plus the fact that enemas stimulate the vagus nerve. Which for me, seems to balance out the entire neurological system, and like mHBOT, allows it to go into parasympathetic mode.

AI had some suggestions--in the link below.

Spoiler: AI Suggested Fast Acting Treatments

Additional Fast-Acting Treatments for ME/CFS​

1. Low-Dose Naltrexone (LDN) – Typical onset: 1 day to 1 week (some report within hours).
Dose: 0.5 to 4.5 mg at night. Benefits: Immune modulation, reduced pain, better sleep, improved cognition. Mechanism: Microglial inhibition, endorphin upregulation, TLR4 modulation.

2. Methylene Blue – Typical onset: Within hours.
Dose: 0.5 to 4 mg/kg/day (start very low). Benefits: Mitochondrial support, cognitive boost, antimicrobial. Notes: Can worsen symptoms in some due to MAOI effects or serotonin syndrome risk with SSRIs.

3. Caffeine + L-Theanine – Typical onset: Within 30 minutes.
Dose: 50–100 mg caffeine + 100–200 mg L-theanine. Benefits: Quick boost to cognition and alertness with reduced jitteriness. Note: Some ME/CFS patients are paradoxically worsened by caffeine.

4. CoQ10 (Ubiquinol Form) – Typical onset: Within a day or two for some.
Dose: 100–300 mg. Benefits: Mitochondrial support, energy. Notes: Best absorbed with fat; often used in combo with carnitine or NADH.

5. NADH (e.g., Enada) – Typical onset: Within a few hours to 1 day.
Dose: 5–10 mg sublingual. Benefits: Energy production, reduced fatigue. Study: Shown to improve symptoms in a subset of ME/CFS patients.

6. Rhodiola Rosea – Typical onset: 30–90 minutes.
Dose: 100–300 mg standardized extract. Benefits: Mental energy, reduced fatigue, improved mood. Caution: Can cause overstimulation in some with sensitive nervous systems.

7. Low-Dose Hydrocortisone (under medical supervision) – Typical onset: Hours to 1 day.
Dose: 2.5–10 mg in the morning. Benefits: Temporary adrenal support, reduction in fatigue. Risks: Suppression of HPA axis if overused.

8. Ketamine (oral or nasal, off-label) – Typical onset: Minutes to hours.
Used for: Refractory fatigue, depression, sensory overload. Caveats: Requires medical supervision; experimental in ME/CFS.

9. Intranasal Insulin (off-label) – Typical onset: 30 minutes to a few hours.
Effect: Improved cognition and alertness. Mechanism: CNS insulin signaling, neurotrophic effects.

10. D-Ribose – Typical onset: Hours to a couple days.
Dose: 5 g 1–3x/day. Effect: Increased energy production in some, especially if mitochondrial dysfunction is involved. Evidence: Some small studies and strong anecdotal support.

I agree, I get effects from HBOT as well. Everybody should try it.

I also take coffee enemas, they are good for emptying bowels if anyone has issues with that. They give good temporary energy like coffee.

Sodium Ascorbate is Vitamin C so it makes sense that it works for you. I prefer Ascorbic Acid form as this lasts longer and is just more researched as THE form of Vit C.

The AI list was not too bad! Damm I spent hours on my reply and AI isn't half off in its recommendations, with zero spoons spent haha.

PLS PLS PLS everybody though: DO NOT TAKE METHYLENE BLUE. It's a synthetic textile dye. It's not for sensitive ME/CFS bodies. The whole MB thing is a huge gimmick IMO.

Everything else it lists is good to try though. I have tried everything except Ket and none of these worked for me, even at higher dosages than recommended Which again, comes to show that we need to research our own causes

 

[hazylinn41]

Modafinil Low dose 50mg but only use it a couple of times a week if needed.

Caffeine, but works well if one has been off caffeine for several weeks and then use 100mg a couple of times per week. Good to have a couple of weeks every so often where you have no Caffeine.

AlphaGPC, milder than Caffeine. Also limit it to a couple of times a week to avoid tolerance.

Tramadol, although a pain killer, it also works through serotonin and noradrenaline which can help with feeling better and giving energy.

Pregnenolone and dhea especially if testing shows your low. But start low and go slow.

Tryptophan 3000mg before bed, improved sleep and in a good mood the next day. Another supp to use every so often.

Korean Ginseng for energy, again use 2-3 times a week when needed.

Tyrosine 1000-2000mg on its own or with caffeine if caffeine has lost its edge. Tyrosine is the raw material for adrenaline/noradrenaline.

A short list of things I personally find helpful. It's really a trial and error thing for everyone including doses. Really they are band aid approaches for those days when you need a lift or someone works 2-3 days a week and is struggling and has no real options, which was me for many years.

But when in a crash, these band aid fixes don't work for me, then i know it's time to rest and stop trying to push.

This is a good list for anyone mild and those who tolerate stimulants. I don't tolerate any of those mentioned personally.

Pretty much all of these supplements are stimulating, which is not great for most ME/CFS patients, as it creates false energy, an indication to our bodies that the energy reserves to spend are greater than they are.

Stimulants and stimulant-like substances can be harmful to some people in the way that it can indirectly cause PEM.

Thread with caution

 

[Hip]

LOW DOSE NALTREXONE has a much higher success rate than LOW DOSE ABILIFY. Both are good to try, but try Naltrexone first, it has less side effects as well.

LDN normally takes months to start working, so is not a treatment which can work within hours or days.

The ME/CFS patient I was speaking to asked me for treatments that work within hours, hence this thread which details fast-acting ME/CFS treatments with a track record of helping ME/CFS patients (rather than speculative treatments which may have just worked for one patient).

B12 TRANSDERMAL OILS has extrememly low absorbtion rate unless you use DMSO

Dr Greg Russell-Jones B12 transdermal oils are unique, they contain a microemulsion permeation enhancer, which pulls the B12 through the skin. Greg is an expert in microemulsion and nanoemulsion permeation enhancers.

Without this microemulsion technology, the B12 would not cross the skin.

Magnesium is an absolute must as a supplement, no discussion.

Never seen any stories of ME/CFS patients improving from oral magnesium.

Dr Myhill is big on magnesium injections for ME/CFS patients, but I have not come across any stories of this helping ME/CFS patients.

A good alternative to injections is applying saturated magnesium sulphate solution to your body skin from head to toe. You can absorb more magnesium this way that orally, as bowel flushing limits oral doses. I sometimes use this transdermal magnesium for treating anxiety (high doses of magnesium help block NMDA receptors, which calms anxiety). But I have not noticed much benefit from transdermal magnesium on ME/CFS symptoms.

most ME patients have too little DHEA. It's a common feature of adrenal fatigue. This supplement helps my brain fog more than any other.

I have never come across any stories of DHEA helping ME/CFS patients. When I tried it, it made me aggressive, a known side effect, but it had no other benefits that I noticed.

 

[hazylinn41]

LDN normally takes months to start working, so is not a treatment which can work within hours or days.

The ME/CFS patient I was speaking to asked me for treatments that work within hours, hence this thread which details fast-acting ME/CFS treatments with a track record of helping ME/CFS patients (rather than speculative treatments which may have just worked for one patient).

That's true, I missed that detail. There aren't gonna be many helpful supplements that will work within hours or days. Meds sure, but most supplements take time to work in general. All vitamins and minerals take time. I think it's unrealistic for any ME patient to expect that much from supplements. The exception is ofc Butyrate and Taurine which I already mentioned in the reddit sub.

Dr Greg Russell-Jones B12 transdermal oils are unique, they contain a microemulsion permeation enhancer, which pulls the B12 through the skin. Greg is an expert in microemulsion and nanoemulsion permeation enhancers.

Without this microemulsion technology, the B12 would not cross the skin.

Never seen any stories of ME/CFS patients improving from oral magnesium.

Dr Myhill is big on magnesium injections for ME/CFS patients, but I have not come across any stories of this helping ME/CFS patients.

A good alternative to injections is applying saturated magnesium sulphate solution to your body skin from head to toe. You can absorb more magnesium this way that orally, as bowel flushing limits oral doses. I sometimes use this transdermal magnesium for treating anxiety (high doses of magnesium help block NMDA receptors, which calms anxiety). But I have not noticed much benefit from transdermal magnesium on ME/CFS symptoms.

Yeah that's bc transdermal B12 has terrible absorbtion rates. Literally nobody else than this guy ships this method, for a reason. It's a scam:

https://www.reddit.com/r/ScienceBasedParenting/comments/1cg00jx

I'm sorry but all due respect, you need to widen your horizons. Oral magnesium is effective but the form matters. If you're by any chance Norwegian /Scandi, I could link you to all the threads about magnesium in those ME forums. "Nutrient teams" on fb is a great place to start, I advocate for this group's magnesium and Vit D recommendations all the time, bc it works. Magnesium is, however, a topic in every chronically ill sub or forum on any platform. ME/CFS platforms are no exception. I think it makes zero sense to advocate for random weird supplements like NADH and CoQ10 when those aren't well absorbed and nobody feels a diffrence from taking these. It makes much more sense to supplement smth we know works, like basic vitamins and minerals that most people are deficient in, even "healthy" people.

Magnesium injections make no sense when oral magnesium works well. Magnesium transdermally is also not an efficient way of supplementing Magnesium. There's just no way I'll be able to apply enough Magnesium sulphate to cover my daily 1100mg. As an autist that would make me itch like crazy as well and I'd writhe in agony for hours, not great for treating anxiety I reckon hehe.

Whoever sold you that magnesium is well absorbed transdermally, needs a checkup, seriously. I have taken transdermal magnesium to compare and it's inefficient. It's however a good source of sulphate, which is highly absorbable. If you lack sulphate for the important detoxification process sulfation, that might be what's good for you You can try to take the best absorbable oral magnesium to exist to compare if you feel any better: Sucrosomial Magnesium https://nootropicsdepot.com/micromag-capsules-optimized-magnesium/
That's the only known oral magnesium to give people this extreme improvement in all symptoms, also ME/CFS symptoms. I think just about every Norwegian ME patient uses this now, standing for all shipments to Europe from the US I'm sure haha. It's extremely effective for unknown reasons ( we have tried to figure it out but couldn't )

I have never come across any stories of DHEA helping ME/CFS patients. When I tried it, it made me aggressive, a known side effect, but it had no other benefits that I noticed.

Well there's an easy explanation to that, you might be high in DHEA, unlike most other ME patients. My sister is also high in DHEA and she has the same effects, it's ineffective on her. It's similar mechanism to Oxaloacetate to Krebs cycle actually, which I already mentioned in my first comment. DHEA is the hormone that works as a precursor to all the other hormones. If you have too little, DHEA supplementation will benefit you by delegating the DHEA to the deficient hormones in your cycle and your neurotransmitters.

Similarly, Oxaloacetate is a precursor to the gluconeogenesis that can be delegated into each of the components of the Krebs cycle. Which mechanism only works if there's already too little of each of these. In my experience oxaloacetate didn't work bc I'm not deficient in any part of the Krebs Cycle. However I have had lots of benefits supplementing pyruvate, another precursor to the Krebs cycle, but for unknown reasons. I could go more into detail but this is enough for today

 

[Wayne]

AI isn't half off in its recommendations, with zero spoons spent haha. -- I could go more into detail but this is enough for today

Yes, preserve your spoons! We don't have zillions upon zillions of them like AI does. lol. Thanks for the wealth of information you've shared on this thread today. Lots of actionable suggestions!

 

[Wayne]

LDN normally takes months to start working, so is not a treatment which can work within hours or days.

I think you're correct that it "normally takes months" for LDN to start working, but that's not always the case. I thought I'd check with AI, and ask it about more immediate results. It confirmed there are a minority of people who do notice benefits quite quickly. Below is the summary--if you're interested.

Spoiler: LDN Onset Time Is Highly Variable

LDN onset time is highly variable. While most ME/CFS patients who benefit from low-dose naltrexone (LDN) report improvements over several weeks to a few months, a notable minority experience effects within hours to days—sometimes even after a single low dose. These fast responses can include reduced pain, better sleep, improved sensory tolerance, and mental clarity. Because of this, LDN is often included in community-curated and clinician-supported lists of potentially fast-acting treatments for ME/CFS.

Mechanistically, this makes sense: LDN modulates microglia and the endogenous opioid system, both of which can quickly affect perception, inflammation, and mood in some individuals. While not everyone responds quickly—or at all—its safety profile, affordability, and wide range of anecdotal success make it a popular early candidate for patient trials.

LDN (low-dose naltrexone) has highly variable onset time in ME/CFS patients.

• While most report improvements after weeks to months, a notable minority feel benefits within hours to days, sometimes after just 1–3 doses.
• Fast improvements include: reduced pain, better sleep, less sensory overload, mental clarity, and calmer mood.
• These rapid effects are likely due to LDN’s ability to modulate microglia, reduce neuroinflammation, and boost endogenous endorphins.
• Some patients respond better to very low doses (e.g. 0.25–1.0 mg) than the typical 4.5 mg.
• LDN appears regularly on patient-curated “fast-acting treatment” lists
• Practitioners who’ve noted or used LDN for potential rapid reliefinclude:
  • Dr. Jared Younger (UAB) – notes fast symptom modulation via microglia in some patients.
  • Dr. David Kaufman and Dr. Bela Chheda (Center for Complex Diseases) – often trial LDN early in protocols, observe quick effects in some cases.
  • Dr. Teitelbaum, Dr. Bredesen, and other integrative doctors – include LDN in early-stage symptom protocols across fatigue, pain, and neuroinflammatory conditions.
• Though not universally effective, LDN’s safety, affordability, and occasional rapid impact make it a strong early option for ME/CFS trials.

 

[Wishful]

I second the variability of LDN, both for delay and effects. Maybe multiple mechanisms for one drug? For me, I took one dose the first afternoon, and the next day my ME-aches were gone. I went from painful trudges to a multi-km hike up a steep hill, and only stopped my hike because I worried about overdoing it.

Most other reports about LDN here sounded like a different drug response.

If you want "worked only for me" rapid effect treatments, I'll offer iodine or T2, and cumin. Prednisone abruptly started working (full remission) on the fifth day the first time I tried it, and the second day the second trial (and never again). Gut microbiome alteration (probiotics as well as food poisoning) also had next-day full effects.


That brings up another question: what percentage of treatments that did work, had an abrupt improvement vs a gradual one? Maybe it depends totally on the treatment, but it could also mean that ME's mechanism is on/off rather than a continuous function.

Further distinction: maybe treatments that provide gradual improvements are for single symptoms, which might be far downstream from ME's core mechanism, while abrupt reductions of many symptoms might involve the core mechanism.

 

[Wishful]

Another thought about treatments: My ME symptoms are strongly affected by my digestive system--and pertinent to this thread, tend to have next-day effects. A food I'm intolerant of will typically make my general ME symptoms significantly worse the next day, and fade the day after avoiding it, although a few foods take a couple of days of eating them before the effects show up, and a couple of days before the effects fade. Likewise, flushing out the gut by food poisoning, or taking a probiotic, had dramatic next-day improvements.

So, some treatments for ME might work via modulating gut microbiome or function (permeability, immune cells, etc). Just something to think about.

 

[hazylinn41]

Can someone help me how to edit posted comments on this forum? My ADHD goes rampant when I write and I know my statements can be polarizing, so I like to go back and smooth the edges a bit to conform. I'd like to edit my lists bc I have gotten some pepper for it in the reddit cfs sub. They called the advice "misinformation, we do not allow the promotion of anti-scientific propaganda", (which is wrong) and they took it down. I have a feather to pluck with that sub.

I'm not exaggerating when I say some of my suggestions have saved lives. Very severe ME patients being unable to eat, who have regained the ability. Too bad they are not active in that sub, for good reason, there's not much else help to get from the vast majority of ME patients, and I wish it was better everywhere, not just the cfs sub. Don't get me wrong, I'm glad the mods work hard to keep the psych lobby away etc.

If the list is taken down from this sub as well or if you have questions, feel free to message me (I have the same profile name on all platforms, but I can't promise I'll reply sorry, AuDHD brain). I usually just help chronically ill people who reach out to me, bc only a minority seem to understand what I'm talking about. Whenever I post a list of what works/ helps, even with citations and citing researchers I have personally talked to etc, It usually still gets reported in the reddit sub by some random ME patient getting offended by the slightest suggestion.

Thanks to the mods in this sub for keeping my list up so far Sorry Hip if I was too direct to you, it's nothing personal! I'd love to talk more about these things. Especially to share the Butyrate and Taurine recommendation which is really sensational (and safe) and I can't believe not more people know of it. I'll edit all of my comments if necessary.

I'm not gaining any personal agenda from sharing this, I literally just wanna help ME patients get better on their own without spending money they don't have. Being severe myself I'm very limited, otherwise I'd like make a fb group for this hehe.

 

[hazylinn41]

At the BOTTOM LEFT of each post are 3 options: 1) Report; 2) Edit; 3) Delete. Just click on "Edit".

Thank you very much