While meds can definitely help, one month in is way too early to know if the change is long-term positive. This is especially true with stimulant medications.
Agree. It's important to remind people that the effects of the first few weeks aren't like the effects for the next 10-50 years.
It's especially concerning when people say the meds give them "more energy to do things" because that's more of a side effect that goes away after a while. The focus-enhancing effect is separate from the energizing/euphoric side effect that people experience in the first few weeks.
High-dose pyridoxine as an 'anti-stress' strategy
https://pubmed.ncbi.nlm.nih.gov/10859691/
Anxiolytic-like effect of pyridoxine in mice by elevated plus maze and light and dark box: Evidence for the involvement of GABAergic and NO-sGC-cGMP pathway
https://www.sciencedirect.com/science/article/abs/pii/S00913...
Your description perfectly matches my experience.
If I only get 80% of the stuff I need to get done before bedtime, there's no chance for me to do other. If I get the stuff I need to get done well before bedtime, there's time left for other things. Skewed self-assessment isn't really a factor in that.
And by the way, the effect on dopamine is secondary. ADHD meds work because they affect glutamate leveles. You all do not have low Dopamine, you have low glutamate.
https://www.nature.com/articles/nn0301_275
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966039/
https://www.brown.edu/news/2018-03-12/glutamate
And you all probably just need B6: https://pubmed.ncbi.nlm.nih.gov/24321736/
https://en.wikipedia.org/wiki/Aromatic_L-amino_acid_decarbox...
AADC is an enzyme in the path that converts amino acids into dopamine and PEA/NMPEA (see "biosynthetic pathways" in above link), the latter of which is an endogenous structural isomer of amphetamine.
You're not really making a strong case that this isn't about dopamine or that amphetamine is the wrong thing for it.
Moreover, B6 will make more of these things up until the point that it's no longer the rate limiter in their production, if it ever was. (The rate limiting step for dopamine is ordinarily AAAH converting Tyrosine into L-DOPA). And if you hit a different rate limiter before you have enough dopamine or PEA/NMPEA, what then?
Important note: This is also a thing:
https://en.wikipedia.org/wiki/Megavitamin-B6_syndrome
> Megavitamin-B6 syndrome has been reported in doses as low as 24 mg/day.
Meanwhile people sell 500mg B6 tablets and it has a half life of like a month. Ask your doctor etc etc.
https://www.uniprot.org/uniprotkb/Q99259/entry
https://www.researchgate.net/publication/340492849_The_Gluta...
I did not say it is not about dopamine, but it is, at a deeper level, about glutamate. Which is why coffee works so well for ADHD because the stimulant action from caffeine is produced by glutamate.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700297/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166758/
Regardless, here is so much evidence that B6 plays a large role in ADHD and what, you all just ignore it?
Caffeine also antagonizes adenosine receptors which modulate dopamine. (Caffeine is complicated. Nicotine too.)
> Regardless, here is so much evidence that B6 plays a large role in ADHD and what, you all just ignore it?
The problem is it's the same kind of thing as saying that eating more reduces nutrient deficiencies. It might be more effective than placebo. If you're deficient in one thing and you get more of everything, you get more of that. It might even be the right solution if your underlying problem is actually that you're not eating enough.
But you want the solution that solves the problem as effectively and as narrowly as possible. Unless your underlying problem is actually a B6 deficiency, it's completely plausible that B6 could be more effective than placebo and less effective than Adderall. At which point nobody wants to hear you telling them to give up their Adderall for B6.
The fact that I can read up on this as a civilian compared to your expert level knowledge is something I am deeply grateful for. Truly!
Energy still comes from food, and if you forget to eat on stimulants your body will eventually catch up with you.
Like coffee, stimulants let you better tap into that energy.
> The mechanism of action (norepinephrine and dopamine reputable inhibition) isn’t far from that of cocaine or methamphetamine.
Yep, they’re all stimulants. ADHD meds however, are manufactured in very controlled conditions, and taken in specific doses. Street drugs are more variable in quality, ratios, ingredients and strengths, and so not relevant to the treatment of ADHD.
Methamphetamine is a legitimate treatment for the most severe ADHD cases, it’s often a last resort. It’s sold as Desoxyn. It’s rarely used, but it _is used legally and successfully_.
> Let’s be real here. Amphetamine is known to skew one’s self assessment of their performance while on the drug.
If you don’t need it, stimulants are going to have a different effect.
People with ADHD are in my experience, going to be able to self-assess performance on their meds better than off them.
Don’t assume one experience is universal, especially when we’re talking about neurodiversity. Even among those with ADHD, experiences are not universal. We may rhyme, but we don’t always repeat.
Imagine doing the dishes. Unmedicated, thats 2 or 3 tasks. Each with a high failure rate, and high cognitive cost.
1. Stop what you’re currently doing. 2. Decide you next task will be to wash the dishes. 3. Wash dishes.
The spoon theory [0] covers this concept well, and can be a useful tool.
> The spoon theory[a] is a metaphor describing the amount of physical and/or mental energy that a person has available for daily activities and tasks, and how it can become limited.
Hard to see how this is "especially true" with stimulants, given they're the rare case of psychiatric meds you can get on and off safely at any time, and the bulk of the effects appear in hours to days after starting the treatment (and disappear just as fast after cessation). Contrast with e.g. depression treatment, where it takes a month or more before it's clear if the drug even works on you, and which of the bad side effects have a chance of eventually going away.
"Long-term positive" is impossible to know in individual, non-statistical sense, whether it's about stimulant medication, SSRIs, moving to another city, marrying, or starting a family - any of those is going to have cascading impacts on your entire life, and even if you think they're positive after a month/year, who knows, maybe few weeks from now you'll think they were negative. That (otherwise stupid) "Farmer's Son" story has a point here.
Maybe you can get off them safely, but not always easily. My alcohol/drug recovery group is filled with people who couldn't easily get off them, like my friend N., who rather than swallowing his medication (Ritalin?), he crushed it & snorted it like cocaine.
You're implying addiction, but in the more common case, people with ADHD can be apprehensive about getting off the meds for the same reason people with chronic pain can't easily get off painkillers, or people in general can't easily get off oxygen.
> like my friend N., who rather than swallowing his medication (Ritalin?), he crushed it & snorted it like cocaine
That's just drug use, not ADHD treatment. I wonder what your friend's dose was? Snorting instead of swallowing is massively increasing the absorption rate, but even then, I don't think you can get high like this, if you just do your regular regimen through the nose. But doing a week or month's worth of pills this way at once, I guess sure?
I don't have the data handy, but IIRC the difference in dose size between therapeutic effect and drug abuse that leads to addiction is ~100x.
There is no side-effect to glasses, you can put them on or off completely at-will any moment, and they make a very exact correction to one specific parameter (vision focusing ability).
ADHD meds are imprecise and affect many systems in different ways - some positive and some negative. You can only have them on/off daily. It might affect you differently depending on other factors. And treatment is not without risk.
It’s hard to understand how stopping will affect you due to the imprecision. It’s not as black-and-white as glasses.
But stimulant meds still don’t deserve any more stigma than glasses. For those who take it as part of treatment of a lifelong disability.
Edited to add: Btw, try playing squash or go swimming with kids. Suddenly your glasses aren’t the perfect solution that they may otherwise seem to be and they become yet another tool, like having the kids wearing bright swimming clothes so you can spot them in a crowd.
But you’re right, we’d love for ADHD meds to be as effective and universal as glasses, but they’re not. Probably because ADHD isn’t a single condition, but a spectrum of conditions with some overlap. So expecting a single treatment to take away all symptoms is a fantasy.
Anyways, I'm skeptical of that 100x number. Comparing 5mg of adderall to 50mg, I could easily imagine getting addicted to the euphoria from the latter and spiraling. I can't even imagine 500mg of adderall, that's just an absurd dose.
I could maaaybe imagine that the 50mg dose resulting in a sorta psychological addiction and 500mg being more physiological, but it doesn't really line up with the model I've built from my own experience. Of course, everyone's different
I’m sorry but this is just beyond silly.
You don't even need that much - a 10mg pill crushed and snorted (it will make a few lines) will fuck your shit up.
Its not a particularly fun high though, it comes with compulsive redosing, discomfort (skin crawling), and basically feels like the latter half of a cocaine bender - after the fun has ended but you are now just fiending.
Other fun ways to abuse methylphenidate at low doses include exploiting its synergy with alcohol and prozac to get, again, a rather cocaine like high, but much more enjoyable than just railing lines of the stuff, and lasts a few hours.
As for treatment of ADHD symptoms, personally I found dexamphetamine worked a lot better than methylphenidate for me, but its much harder to get prescribed.
I'm having a hard time pinning this on the meds honestly...
Having done exactly that (crushed and snorted Ritalin) in the past. I can't recommend it - its not a very good high.
They do not tell you that part for obvious reasons, but if you find the right doctor to explain the biochemistry of how they work it then becomes obvious.
Rhodiola is MAO inhibitors and so is Ginkgo, while 5-htp is the serotonin intermediate and corresponds to SSIs. Not to say that you need not to be careful, that still is required but with other cofactors consumed you can micro-dose.
Note, due to my understandings of what cofactors I need I do in fact micro dose L-DOPA as some recommend 500mg but I only consume 20mg daily.
Cofactors such as aromatic amino acids to increase tryptophan absorbtion across blood brain barrier including Macca extracts and fenugreek and Phenylanaline .
edit: feeling great only applies to some stimulant medications and seems to vary from person to person. Personally, I hated the pharmaceutical stimulant experience but they still helped me. I would be taking meds right now if I could afford it.
Sure, there’s also some risk for patients using them properly, but for them it does not compare to the sheer benefits provided by the meds.
Instead, look to nutrition.
However there's a general understanding of ADHD (and related disorders such as ASD) as a spectrum of conditions with multiple contributing factors. Depending on the person ADHD will manifest with more or less hyperactivity, distractability, working memory issues, and lacking emotional regulation (among other things). Different causes combine to give a somewhat amorphous disorder with a range of common symptoms.
So adding a new treatment with fewer downsides (because stimulants can have a few) is great, especially as it might treat aspects of the disorder that aren't treated by stimulants. But this doesn't mean stimulants won't still be relevant in the future.
There's there's also plenty of research showing specific dopamine receptor dysregulations as contributing to ADHD. See for example https://www.researchgate.net/publication/364120700_Dopamine_...
So unless the research also shows that this is caused by pyridoxine metabolism problems, these hypotheses can both hold at the same time.
Picking some paper that talks about different causes doesn't mean other causes aren't still relevant. It will probably be decades before we can definitively rule out contributing factors.
PS It's generalizations like yours that are very stigmatizing towards stimulant use. We already know many people benefit from them enormously and significant numbers are not getting or taking them due to stigma.
Just try taking high dose P5P.
And probably zinc:
https://www.nature.com/articles/s41598-021-94124-5
If you knew the metabolic pathways thus would be as clear as day. We need enzymes to make neurotransmitter and those enzymes need cofactors to work.
These are the cofactors.
Two, If you did, how much did you take? And what type? Pyridoxine or Pyridoxal-Phosphate? For how long? Were you tested for a B6 defieicny, high homocysteine?
Three, it is in NO WAY common for deficiencies to be tested for mood disorders and even less common for a doctor nevermind a psychiatrist to do anything about it.
And calling me an asshole when I am advocating for better health is making everyone's life worse. I do not mind if people choose to take stimulants, but they are not being advised that there are other options.
That makes you an asshole.
> Three, it is in NO WAY common for deficiencies to be tested for mood disorders and even less common for a doctor nevermind a psychiatrist to do anything about it.
Why do you believe this? It is easy and cheap to do a blood test for deficiencies, I have done that many time and they found I lacked nothing. Do you have any evidence it isn't common to check for deficiencies, because to me it seems like that is one of the first thing they check.
Because I have worked with health care professionals for 20 years and they do not test for nutritional deficiencies unless you ask/beg them to. This is even more true with psychiatrists. I am advocating right now for a woman with a serum B6 deficiency that her doctor will not address. She has an actual serum B6 deficiency and anemia and depression and her dopctor thinks it is not importnat. That is why.
> It is easy and cheap to do a blood test for deficiencies, I have done that many time and they found I lacked nothing.
There are deficiencies and functional deficiencies. Plus there is serum B6 and RBC B6. Have you had your RBC B6 tested? Nope.
And Homocysteine levels will reveal more than serum B6.
And I do not believe you because you did not answer "how much did you take? And what type? Pyridoxine or Pyridoxal-Phosphate? For how long? Were you tested for a B6 defieicny, high homocysteine?"
Then reason you are an asshole is that you are asking questions that takes a lot of work to answer since most wont know the answer to them on the spot. That is a very common tactic when you try to push your pet theory on others, but you should know that nobody thinks you won the argument when you do that they will just see you as an asshole. Even if you are doing it to be nice, you will be seen as an asshole, so please stop doing that.
Edit: Another part of the label says its this, didn't notice it at first:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyridoxine-hydroch...
People I know take 30 - 60mg of P5P to feel the effects.
You were not taking high dose B6, just the RDA, and that will not do anything. And it will not correct a deficiency.
You think it takes a lot of work to answer? What about all the work I do looking into this and asking? For who? For you. Instead of calling me an asshole understand that I am helping you, for free, unlike your doctors.
So you cannot say taking B6 did not work for you.
If a B6 deficiency cured your ADHD would you still want to take stimulants?
Assuming you mean “if treating a B6 deficiency”, and assuming I had strong expectations that I could expect a cure, I’d consider giving it a try. I’d be cautious about any transition, as it could mean either significant side effects while still taking stimulants, or significant regression without them if the B6 treatment doesn’t work as hoped.
But I don’t even have a strong expectation that I could expect equivalent or better management. The study you linked was conducted with children, and the conclusions based on observations of children’s behavior. Maybe that’s a good indicator that it’s helpful, but I have no clue. I wasn’t diagnosed as a child, my ADHD was noticeable to one adult in my adulthood enough to mention it, and my experienced symptoms are much closer to autism (again as experienced by adults, not as behavior observed in children, although those diverge much less for me). But the things mentioned improving in the study are very much not what I’ve struggled with having ADHD as an adult, nor things for which I sought diagnosis or treatment.
The way diagnosis and treatment saved my life was helping me manage crippling anxiety and helping me make chronic depression manageable. It’s possible that exploring a nutritional deficiency none of my doctors have found with supplements no one has studied for adult ADHD… it’s possible that would benefit me. It’s a very high risk proposition given I have meds which work for me and which present no side effects so negative I’d reconsider.
Moreover I haven’t had a single medical professional raise this possibility and with good reason. My treatment is working. Even if an alternative treatment might be promising… why would any responsible doctor propose disrupting a persistently successful treatment plan?
I don’t know why you’re so motivated to disabuse me of my effective medication, but you’ll have to do better than showing a study which made children more tolerable. I credit my life to the meds that I take now, and there’s very very little I could fault them for. Asking me to reconsider that is asking an AWFUL lot.
You go on and on about how you don’t think it would work, but have you ever had your B6 level tested never mind your red blood cell B6 levels?
I get it, you don’t care, you found a treatment that works, even though that treatment is not curing the underlying disorder. It’s just a treatment. I get it it works, until it doesn’t. I’ve been working with people with new disorders for 25 years and I’ve seen it over and over again.
So I’m not asking you to stop taking anything I’m asking you to keep an open mind which you seem to not be able to do. That’s OK.
> I mean you did not even bother to search for another paper.
I most certainly did. The search results I got were primarily ads, and few clinical studies I found were, like the one you linked, far less bold in the results they claimed than your claim of a “cure”.
> You make me assumption that I’m trying to disabuse you of taking your medication. I’m not. I don’t care, take it if you want. But by not being open to other methods of treatment, you aredisabusing people of that choice.
Excuse me, how?
> You go on and on about how you don’t think it would work
The studies themselves don’t support your claim of a cure.
> but have you ever had your B6 level tested never mind your red blood cell B6 levels?
No, I haven’t been to a doctor since some person on the internet mentioned this a few days ago. I did have a scheduled psychiatrist appointment in that time, but had to reschedule because il out of state for a family medical emergency.
> I get it, you don’t care
I don’t know where you got that impression. I took the time to reply thoughtfully and, despite your impressions otherwise, to look for other studies more pertinent to my own experience. In my thoughtful response I expressed caution and the reasons for that caution, which you completely ignored.
> you found a treatment that works, even though that treatment is not curing the underlying disorder
That’s right. And it’s important. It’s the reason I’m still alive. I’m cautious about upsetting treatment that works because I would very much like to remain alive.
> I’ve been working with people with new disorders for 25 years and I’ve seen it over and over again.
I don’t know if you mean the disorder is new in the world (it’s not) or in me (it’s also not).
> So I’m not asking you to stop taking anything I’m asking you to keep an open mind which you seem to not be able to do.
I don’t know where you got that impression. An open mind isn’t characterized by immediately accepting life changing “solutions” proposed by random people on the internet, regardless of whether they cite medical studies. I expressed an open mind, I said I’d consider giving it a try.
> That’s OK.
In your own words, I don’t believe you. You have talked past me and several others in this thread, and you don’t seem to want to accept anything other than a revelation that what I need is vitamins rather than the treatment that my doctor prescribes. You have even suggested that I’m preventing other people from treatment (or a “cure”) you think more appropriate simply because I haven’t dropped everything to try your preferred treatment. If this is how you “work with” other people who are hoping to treat their ADHD effectively, god help them. And it has nothing to do with the particular treatment, I felt the same way about my first psychiatrist who was just as zealous about stimulant treatment.
Maybe use PubMed and not google?
> you don’t seem to want to accept anything other than a revelation that what I need is vitamins rather than the treatment that my doctor prescribes.
I NEVER SAID THAT ONCE. Take stimulants if you want, but just because that is your choice do you need to be so outraged by the idea that B6 might work just as well?
>> But by not being open to other methods of treatment, you are disabusing people of that choice.
> Excuse me, how?
YOU: Moreover I haven’t had a single medical professional raise this possibility and with good reason.
You: But I don’t even have a strong expectation that I could expect equivalent or better management.
You: I don’t believe you.
This negative stance only feeds on this idea that medications are the only choice, the only answer, and that nutrition never works becasue "there are no studies" or "My doctor did not recommend it".
You are just shooting down the idea that this might be the root of the issue. And yet you have never even had you B6 levels tested. That is just willful ignorance. Have you worked in Nutritional Genomics? Do you even know why treating a B6 deficiency might be important not just for your behavior but your over all health? If you have a B6 deficiency and take stimulants to cover up the symptoms, what about all the other enzymes that need B6 to function?
Over and over they find B6 deficiency in ADHD. There will be no studies showing the efficacy of B6 because there is no funding for products that do not make a profit. You are on stimulants because they work and they are profitable.
Next thing they will get you to take will be Metadoxine. Ha!
https://pubmed.ncbi.nlm.nih.gov/25295645/
https://pubmed.ncbi.nlm.nih.gov/23290324/
Hmmmm...I wonder why they were trying out Metadoxine for ADHD, and wonder why it failed...oh....Metadoxine, also known as pyridoxine-pyrrolidone carboxylate. So they made a funked up version of B6? Why would all these smart science people want to make a funked up version of B6 if B6 was not linked to ADHD?
Do you think maybe they know something they do not want you to know? And maybe that is because ADHD meds brings in about $20 Billion for these companies?
Have you thought you do not want to hear anything but stimulants are the only answer for you? And that I am not talking past you but that there is no one there who wants to listen?
I normally hate to quote this but it fits: calmer than you are.
> You are just shooting down the idea that this might be the root of the issue. And yet you have never even had you B6 levels tested. That is just willful ignorance.
My gosh, you’re being a jerk. I haven’t had my B6 levels tested in the last few days because it’s in the last few days and my medical appointment was canceled because I’m out of state for a family medical emergency! Have you thought about the fact that I literally physically cannot meet your expectations of an open mind and that your expectations are totally unreasonable?
I was asking if you had your B6 levels tested ever, not in the last few days.
You’re reading what I wrote much more dramatically than it is implied. The fact you think I am really telling you to run out right now and get your B6 tested is distorted.
There was a decade between me first seriously suspecting it, and that.
Information about it is much easier to come by now, and more people talk openly about it. Without that, I probably would have struggled for much longer.
That is profound. Also says a lot about us as humans. Glad it's not raging anymore