Yes that is a key difference with modafinil. I think there's a bit of a stigma about the perceived overprescription of stims like ritalin and others that are more addictive. Modafinil is in a different camp but even its mechanism of action isn't fully understood.
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Need help with stimulants
- Thread starter redaxe
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Yes that is a key difference with modafinil. I think there's a bit of a stigma about the perceived overprescription of stims like ritalin and others that are more addictive. Modafinil is in a different camp but even its mechanism of action isn't fully understood.
A.B.
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I'm more concerned about falling into a deep exhaustion caused by taking a stimulant that reduces the sensation of fatigue without affecting the underlying cause.
heapsreal
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Modafinil might not be like whipping a dead horse as many seem to think but may work through replacing low neurotransmitters such dopamine and noradrenaline .
Its called a stimulant but i dont think its stimulating as such but more a trigger that flicks the button on and allows our brain to work normally not hypernormally???
Its called a stimulant but i dont think its stimulating as such but more a trigger that flicks the button on and allows our brain to work normally not hypernormally???
If you have doubts or caution you can always trial at a low dose under the supervision of a physician. I've been using at 200mg which is pretty standard but there's no reason why you couldn't start at 50mg.
For the matter I also experimented with nicotine patches and I find the effect from both quite similar though that said nicotine is generally regarded as being a stronger mental stimulant/cognitive enhancer but it also carries more risks than modafinil.
For the matter I also experimented with nicotine patches and I find the effect from both quite similar though that said nicotine is generally regarded as being a stronger mental stimulant/cognitive enhancer but it also carries more risks than modafinil.
knackers323
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I'm also at the same point. I'm looking for something to give me an occasional boost. Its not a cure and I don't plan on doing it every day but if anyone can help me find Ritalin or something similar on the net I would really appreciate it. Thanks
minkeygirl
But I Look So Good.
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I don't think anyone will ship to the US. I tried to get midifinal and was specifically told they can't ship to the US because of the class of drug.
Have you looked at the racetams? Check out powder city.
Have you looked at the racetams? Check out powder city.
knackers323
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I'm in oz. Yes I have, they were not much good. The one Ritalin I tried made a huge difference. It would be nice to have something that was useful there when I needed it
@redaxe @barbc56 - Provigil or Nuvigil is definitely a better choice than ritalin. It's not habit forming, its effects don't wear off over time requiring increasing dosage, and it's not as tightly regulated by governments so it's much easier to get. The main downside is it costs a lot more.
Provigil is a racemic mixture of 2 enantiomers - r and s (hence the ARmodafinil, just as there is citalopram and EScitalopram). The 2 enantiomers are mirror images, as you said above, but they are thus chemically very different and function entirely differently in the body. For example, the mirror image of glucose has no calories in people - we cannot break it down, our enzymes are chiral too, so they work differently with enantiomers or diastereomers (like enantiomers, but not all the chiral centers are opposite each other, so they aren't mirror images, even if some chiral centers may be).
One of the two enantiomers in provigil has a long half life, and the other has a short half life. Nuvigil does away with the shorter acting one, so it lasts longer throughout the day. Provigil gives a bigger boost in the morning, but then tapers off more quickly as the shorter acting enantiomer is removed. So if you have more trouble early in the morning, provigil is probably better. If you want it to last longer and be more even all day, nuvigil is probably better. Often, people take more provigil than nuvigil though, which means you get more boost early on, but then less as the day progresses. At an equivalent dose, the nuvigil will last longer (same number of milligrams).
Chirality is something the pharma companies are doing now to re-patent blockbuster drugs. In some cases, they may even be less effective (effexor is a racemic mixture, but probably works better than pristiq, which is just one enantiomer). Zyrtec has a chiral version too - and it's probably not any better (most likely, about the same). It's true that sometimes removing one of the two enantiomers gets rid of side effects - the chemicals can act very differently.
One example would be thalidomide. One enantiomer of thalidomide causes birth defects. The problem with thalidomide though is that the chiral center is a nitrogen with a lone pair in one of the 4 sp3 hybridized orbitals (tetrahedral per VSEPR model). The lone pair on a nitrogen doesn't lock it in place as with a carbon, so it spontaneously interconverts (think an umbrella on a windy day - it can flip inside out if there is enough force), so unless you make it very carefully and store it at absolute zero or something similar, it's going to be a racemic mixture (half and half) by the time the patient takes it (and it's not made to be one or the other anyways). I give it as an example of how important chirality can be in side effects (or beneficial effects). A lot of the time though, pharma companies just do it to make more money by adding a new patent - so in these cases, it's not worth paying extra. Look for studies that actually do head to head comparisons and see if it's worth the difference. With pro/nuvigil, I think there is a difference, although neither is clearly better.
Provigil is a racemic mixture of 2 enantiomers - r and s (hence the ARmodafinil, just as there is citalopram and EScitalopram). The 2 enantiomers are mirror images, as you said above, but they are thus chemically very different and function entirely differently in the body. For example, the mirror image of glucose has no calories in people - we cannot break it down, our enzymes are chiral too, so they work differently with enantiomers or diastereomers (like enantiomers, but not all the chiral centers are opposite each other, so they aren't mirror images, even if some chiral centers may be).
One of the two enantiomers in provigil has a long half life, and the other has a short half life. Nuvigil does away with the shorter acting one, so it lasts longer throughout the day. Provigil gives a bigger boost in the morning, but then tapers off more quickly as the shorter acting enantiomer is removed. So if you have more trouble early in the morning, provigil is probably better. If you want it to last longer and be more even all day, nuvigil is probably better. Often, people take more provigil than nuvigil though, which means you get more boost early on, but then less as the day progresses. At an equivalent dose, the nuvigil will last longer (same number of milligrams).
Chirality is something the pharma companies are doing now to re-patent blockbuster drugs. In some cases, they may even be less effective (effexor is a racemic mixture, but probably works better than pristiq, which is just one enantiomer). Zyrtec has a chiral version too - and it's probably not any better (most likely, about the same). It's true that sometimes removing one of the two enantiomers gets rid of side effects - the chemicals can act very differently.
One example would be thalidomide. One enantiomer of thalidomide causes birth defects. The problem with thalidomide though is that the chiral center is a nitrogen with a lone pair in one of the 4 sp3 hybridized orbitals (tetrahedral per VSEPR model). The lone pair on a nitrogen doesn't lock it in place as with a carbon, so it spontaneously interconverts (think an umbrella on a windy day - it can flip inside out if there is enough force), so unless you make it very carefully and store it at absolute zero or something similar, it's going to be a racemic mixture (half and half) by the time the patient takes it (and it's not made to be one or the other anyways). I give it as an example of how important chirality can be in side effects (or beneficial effects). A lot of the time though, pharma companies just do it to make more money by adding a new patent - so in these cases, it's not worth paying extra. Look for studies that actually do head to head comparisons and see if it's worth the difference. With pro/nuvigil, I think there is a difference, although neither is clearly better.
A bit late reply but caffeine pills helped me alot when I was at the worst parts of my issues.
I also found amino acid mitochondrial support supplements help, they are usually used by body builders but help with fatigue and pain issues.
Right now I use a mixture of L-aspartic acid, L-citruline and the branch chain amino acids all in bulk powder form, I mix it all with an orange fiber supplement for taste and take before and after a hard day as needed.
In my experience it helped with energy during the day but taking it at the end of a rough day kept me from crashing the next.
There are other similar supplements that may also help (creatine comes to mind) and realize the basic body needs like vitamins and nutrition have an effect.
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panckage
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For you maybe. For me it made me scared of everything including going out in public lol. I found it helped my body energy but ritalin is superior for my brain fog
Nicotine is a cholinergic drug. There are 2 types of acetycholine receptors (and subtypes of those as well) - nicotinic (an ion channel, named because nicotine activates it) and muscarinic (a 7-pass G-protein coupled receptor, named because muscarine activates it). Essentially, you're taking a cholinergic if you are taking nicotine, and there are actually a number of cholinergics available as prescriptions and even some as supplements. Their labeled use is for dementia (Aricept, Razadyne) and Myasthenia (Mestinon). There are studies of Mestinon (aka pyridostigmine) in fibro patients - it was found that taking it restored the normal production of growth hormone in response to exercise. I don't know of any studies testing the others. Weirdly, you can buy Razadyne as an expensive prescription drug or as an OTC supplement. They aren't completely harmless, so I'd go the prescription route - plus you get better quality control. Huperzine A is another cholinergic - but it's not approved for anything so there's little data on safety, although I think it's used a a Chinese herbal remedy (it's OTC too). Cholinergics are drugs you should probably talk to your doctor about - they aren't completely harmless - but pyridostigmine is used frequently by docs who specialize in the treatment of POTS and autonomic dysfunction, so it's an interesting and potentially important pathway.
There is a test you can get for antibodies to the particular subunits that form the nicotinic acetylcholine receptor, and in some patients with POTS they are positive (<10% I think). If you are positive, this is probably the cause of the disease. This is different from myasthenia gravis, where the antibodies are to the nicotinic receptors in skeletal muscle (which is why myasthenia causes weakness). The nicotinic receptor is 5 subunits of varying types that can be assembled in different combinations in different tissue types. I think the antibodies are to the alpha-3 subunit in dysautonomias and to the alpha-1 subunit in the neuromuscular junction in myasthenia - and the symptoms produced are quite different (generally no weakness in dysautonomia, and no dysautonomia in myasthenia).
There is a test you can get for antibodies to the particular subunits that form the nicotinic acetylcholine receptor, and in some patients with POTS they are positive (<10% I think). If you are positive, this is probably the cause of the disease. This is different from myasthenia gravis, where the antibodies are to the nicotinic receptors in skeletal muscle (which is why myasthenia causes weakness). The nicotinic receptor is 5 subunits of varying types that can be assembled in different combinations in different tissue types. I think the antibodies are to the alpha-3 subunit in dysautonomias and to the alpha-1 subunit in the neuromuscular junction in myasthenia - and the symptoms produced are quite different (generally no weakness in dysautonomia, and no dysautonomia in myasthenia).
lansbergen
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The immune modulator I use is a positive a7nAchR allosteric modulator.
A cardiologist prescribed me Pyridostigmine - it seemed to resolve some OI issues I had. But after a few weeks I felt no more effect from it so I discontinued use - even though the OI improvement continued. The doctor said it was safe but I was a little nervous after reading about the 'supposed' link to Gulf War Syndrome - but I don't think there's any evidence that Pyridostigmine is associated with that. I think Dr Goldstein was using it too in his instant remission treatments.
I wouldn't bother if you aren't getting benefit, but cholinergics in general have been found to help a lot of people with autonomic dysfunction, especially in POTS. It can help with many autonomic issues.
There was a study done on this in fibromyalgia patients. (The brand name, referred to in the study, is Mestinon.) It found that normal subjects had an increase in human growth hormone after exercise, but fibro patients did not. After treatment with Mestinon, the HGH response to exercise was restored to normal. Patients reported subjectively improved exercise tolerance. It wasn't a huge study, but I think it's interesting, and I do know that many neuros treat with pyridostigmine in POTS patients, and I have yet to hear of a patient report significant worsening of symptoms.
I suspect if there is any link at all it might have to do with concommitant exposure to other AChEI's (acetylcholinesterase inhibitors). There are 2 major classes of these - reversible and irreversible. The first are used medically in many conditions. The latter are not used medically and are quite dangerous - examples are VX nerve agent used in the gulf wars, organochlorine and organophosphate pesticides, etc. The latter cause nerve damage by overexciting the nerves (they completely inactivate acetylcholinesterase) - so ACh just builds up indefinitely. This kills bugs, among other things.
The reversible inhibitors are quite different and do not exhibit the same toxicity. However, I wonder if GWI patients were exposed to both. It seems that in some cases, the reversible inhibitors may even be protective, as they block the binding sites of the irreversibles, so as the latter are cleared, there is still functional enzyme that doesn't have to be made, and it naturally dissociates. This has all probably been studied in great detail by the military - I would bet there is a lot of well funded research on it.
I think there is very likely to be therapeutic potential for cholinergics in POTS/OI patients or in general in patients with dysautonomia. These agents are used extensively and serious side effects have not generally been found to be a major issue. Most of these are peripherally acting drugs - the main exception is physostigmine which does cross the BBB. The main application of these drugs is actually in myasthenia gravis, an autoimmune disease where autoantibodies to the nicotinic acetylcholine receptors at the neuromuscular junction cause motor weakness. They enhance the conduction of nerve signals for cholinergic neurons. Pyridostimine does not appreciably penetrate the BBB.
There was a study done on this in fibromyalgia patients. (The brand name, referred to in the study, is Mestinon.) It found that normal subjects had an increase in human growth hormone after exercise, but fibro patients did not. After treatment with Mestinon, the HGH response to exercise was restored to normal. Patients reported subjectively improved exercise tolerance. It wasn't a huge study, but I think it's interesting, and I do know that many neuros treat with pyridostigmine in POTS patients, and I have yet to hear of a patient report significant worsening of symptoms.
I suspect if there is any link at all it might have to do with concommitant exposure to other AChEI's (acetylcholinesterase inhibitors). There are 2 major classes of these - reversible and irreversible. The first are used medically in many conditions. The latter are not used medically and are quite dangerous - examples are VX nerve agent used in the gulf wars, organochlorine and organophosphate pesticides, etc. The latter cause nerve damage by overexciting the nerves (they completely inactivate acetylcholinesterase) - so ACh just builds up indefinitely. This kills bugs, among other things.
The reversible inhibitors are quite different and do not exhibit the same toxicity. However, I wonder if GWI patients were exposed to both. It seems that in some cases, the reversible inhibitors may even be protective, as they block the binding sites of the irreversibles, so as the latter are cleared, there is still functional enzyme that doesn't have to be made, and it naturally dissociates. This has all probably been studied in great detail by the military - I would bet there is a lot of well funded research on it.
I think there is very likely to be therapeutic potential for cholinergics in POTS/OI patients or in general in patients with dysautonomia. These agents are used extensively and serious side effects have not generally been found to be a major issue. Most of these are peripherally acting drugs - the main exception is physostigmine which does cross the BBB. The main application of these drugs is actually in myasthenia gravis, an autoimmune disease where autoantibodies to the nicotinic acetylcholine receptors at the neuromuscular junction cause motor weakness. They enhance the conduction of nerve signals for cholinergic neurons. Pyridostimine does not appreciably penetrate the BBB.
I know of at least one ME + POTS patient who had an extremely severe negative reaction.
When we can find just one drug that doesn't cause just one person with ME to have a severe reaction I think we should all go out and buy a lottery ticket.
Stretched
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(I posted below recently but not checked out on how to hot link it. Here's an edited version for this thread.)
What about a Pregnelonone protocol (OTC, precursor to and mother of all systemic steroids) with or w/o DHEA for feel better in general?
I just finished a ton of research on Preg and switched to it this past week after trying Prednisone for 10 days, which was too much even at low doses, eg 10mgs. Too soon to know real effects but anecdotally, initial week (at 50-100mg, daily) seems to help with burning feet (neuropathy), osteoarthritis and other symptoms but makes me irascible.
I know it's not studied much in pharm due to Merck's 1949 patenting of Cortisol, but this stuff looks promising as for use as an OTC. Any insights, experience on dose, frequency, known problems, gold standard or anecdotal?
@Eeyore, @Heapsreal
Do you have any thoughts on Wellbutrin? It's classed with antidepressants but it's mode of action is actually quite a bit different - it's more said to treat atypical depression (which is very different from major depression in that the main symptoms are oversleeping and muscle weakness/low energy rather than constant sadness). That said the label atypical depression obviously reveals our poor understanding of what the underlying pathology is - but there is some symptom overlap between this and ME/CFS (again - oversleeping, insomnia, muscle weakness - obviously without the exertion induced crashes).
There is evidence that bupropion induces the release of norepinephrine and dopamine in addition to inhibiting their reuptake, similarly to other cathinoneslike amfepramone (diethylpropion).[16][17] Chemically, bupropion belongs to the class of aminoketones and is similar in structure to stimulants such as cathinone and amfepramone, and to phenethylamines in general
This drug appears to get the brain to release more norepinephrine and dopamine as well as inhibiting reuptake but it also shares characteristics with stimulants.
Wellbutrin is popular because it is said to cause less side-effects than other drugs - notably no sexual dysfunction.
In the brain norepinephrine increases arousal and alertness, promotes vigilance, enhances formation and retrieval of memory, and focuses attention; it also increases restlessness and anxiety. In the rest of the body, norepinephrine increases heart rate and blood pressure, triggers the release of glucose from energy stores, increases blood flow toskeletal muscle, reduces blood flow to the gastrointestinal system, and promotes voiding of the bladder and large intestines.
Do you have any thoughts on Wellbutrin? It's classed with antidepressants but it's mode of action is actually quite a bit different - it's more said to treat atypical depression (which is very different from major depression in that the main symptoms are oversleeping and muscle weakness/low energy rather than constant sadness). That said the label atypical depression obviously reveals our poor understanding of what the underlying pathology is - but there is some symptom overlap between this and ME/CFS (again - oversleeping, insomnia, muscle weakness - obviously without the exertion induced crashes).
There is evidence that bupropion induces the release of norepinephrine and dopamine in addition to inhibiting their reuptake, similarly to other cathinoneslike amfepramone (diethylpropion).[16][17] Chemically, bupropion belongs to the class of aminoketones and is similar in structure to stimulants such as cathinone and amfepramone, and to phenethylamines in general
This drug appears to get the brain to release more norepinephrine and dopamine as well as inhibiting reuptake but it also shares characteristics with stimulants.
Wellbutrin is popular because it is said to cause less side-effects than other drugs - notably no sexual dysfunction.
In the brain norepinephrine increases arousal and alertness, promotes vigilance, enhances formation and retrieval of memory, and focuses attention; it also increases restlessness and anxiety. In the rest of the body, norepinephrine increases heart rate and blood pressure, triggers the release of glucose from energy stores, increases blood flow toskeletal muscle, reduces blood flow to the gastrointestinal system, and promotes voiding of the bladder and large intestines.