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Adults with ADHD show decreased function in brain dopamine reward pathway (2010)

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Re: Adults with ADHD show decreased function in brain dopamine reward pathway (2010)

#221

Post by smileybarry »

jiofih wrote: post #193
olyjohn wrote: post #163

Earlier quoted context omitted.

None of those drinks have anywhere near the caffeine of coffee, though. An energy drink of some kind probably does though.

That’s not true. ~100mg in a cup of coffee, 40mg in an espresso shot, the same 40mg in a can of Coca-Cola (and ~60mg in Diet Coke).

Caffeine in an espresso shot (and conversely one cappuccino) is ~63-77mg[1], and one can of Coca-Cola & Diet is 32mg & 42mg[2].

[1] Nespresso is 63mg (5g of coffee), "average" espresso is 77mg (7g of coffee) https://www.caffeineinformer.com/caffeine-content/espresso

[2] https://www.coca-cola.co.uk/ingredients/caffeine/the-caffein...

Re: Adults with ADHD show decreased function in brain dopamine reward pathway (2010)

#222

Post by jjeaff »

acituan wrote: post #189
jjeaff wrote: post #168

Earlier quoted context omitted.

I'm not sure that the affects of stimulants for ADD are across the board, as you describe. That is, for lots of people, me included, add meds seem to boost my executive functions. Without them, I actually have no problem focusing on certain things, but it's usually some unimportant problem or project that I become distracted by. With meds, I find it much easier to step back and get a clear picture of not just my work…

I might have over-emphasized the worker drone persona. But I think the potential for self-deception and long term foolishness is still there across the board. > With meds, I find it much easier to step back and get a clear picture of not just my work, but my whole life. Executive function boost is non-negligible for sure, but it is still bound to operate in the short term. Think your bioeconomics as a ledger, your en…

I think you are probably right that "conforming" may not always be the best way to handle things. But most people that end up being diagnosed with ADD are already very non-conforming and they want to just be nudged closer to average.

Now, if your goal is to swing for the fences and try to hit a home run, get to the top of your field, make a grand discovery, then ya, most of those kind of people are very non-coforming. But many are/were also very unhappy personally. In fact, many of the greatest outliers in our history suffered from manic depression or ADD or other mental issues.

Personally, I'm not swinging for the fences. I'm going to bunt if it means I have a much better chance of getting on base. Steve Jobs was very non-conforming. He was always very irritated and unpleasant with everyone around him. And sure, it seems to have had results. But I have no interest in becoming the next Steve Jobs if it means having what appears to have been an unhappy life with an early death.

Re: Adults with ADHD show decreased function in brain dopamine reward pathway (2010)

#223

Post by AnthonBerg »

gavinray wrote: post #210
AnthonBerg wrote: post #187

Earlier quoted context omitted.

> Once your stomach cleaves the l-Lysine, it yields free-floating D-Amp. This is incorrect. – With all due respect! The action is enzymatic, and the enzyme is in red blood cells. It is slow. This is not the same as other “mechanical” time-release mechanisms. https://en.m.wikipedia.org/wiki/Lisdexamfetamine

Sure, technically, but read the FDA paper on it's pharmacokinetics. Smoking, shooting, or squirting it up your ass won't do the trick. But injecting it would put it in direct contact with red blood cells, and so would rectal administration via absorption through rectal mucosa. Lisdexamfetamine needs to pass through the GI tract where there's proper enzymatic activity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805…

Ah - I understand these passages such that they describe the passage of the intact LDX molecule into the bloodstream, and I don't see mention of the lysine-amphetamine cleavage action. This describes what part of the intestine is able to pull the whole LDX molecule into the blood. Note the distinction between absorption and metabolism. Later passages:

LDX was not metabolized in vitro by SGF, SIF, or trypsin, [so] any conversion of LDX to d-amphetamine in the GI tract in vivo is likely to be minimal. [...,] consistent with a model of absorption of predominantly intact LDX with subsequent enzymatic conversion to active d-amphetamine and l-lysine.

LDX was metabolized to d-amphetamine in rat and human whole blood but not in plasma. [Red blood cells] are responsible for the presystemic conversion of LDX to d-amphetamine.

LDX was metabolized to d-amphetamine by human RBCs but not by other blood fractions, such as white blood cells or platelets. Moreover, RBCs had a very high capacity for the metabolism of LDX. The rate of metabolism was not substantially reduced until concentrations of RBCs were reduced to 10% of normal hematocrit. Lysis of the RBCs also had little impact on the rate of metabolism of LDX, and nor did EDTA (a calcium chelator that inhibits the activity of calcium-dependent enzymes).

In conclusion, LDX is absorbed as the intact prodrug and converted to inactive l-lysine and active d-amphetamine primarily in the blood by RBCs.

It's fascinating isn't it? :)

I find the effect to be very very different.

Here's a graph of plasma concentration of free dextroamphetamine, time release capsules, and molecular-braked lisdexamfetamine: https://farm1.staticflickr.com/727/23028958560_2ae3ddc5bd_o....

Re: Adults with ADHD show decreased function in brain dopamine reward pathway (2010)

#224

Post by bobloblaw45 »

stevefan1999 wrote: post #136

I'm an ADD adult and this especially hits me when I'm participating competitions, be it leetcode coding competition or examination. I just hate to do it and every other bits of attention source will got me seeked on, like a notification from my phone, or someone dropped a pen to the ground. That's how fast I lost focus. But on the other hand sometimes I can be extra-focused, with a prerequisite it's something I enjoy…

I also have ADD. I'm untreated since it's kinda expensive and my job is easy enough to not need to be.

I'm glad that ADD/ADHD is more accepted now because I remember when the idea some people have problems focusing was immediately dismissed as laziness or a fault in character. I didn't even consider getting tested until far into adulthood because of the stigma.

Re: Adults with ADHD show decreased function in brain dopamine reward pathway (2010)

#225

Post by robswc »

fnord123 wrote: post #198
smnplk wrote: post #192

In my country you can't get diagnosed and treated for adult ADHD if you weren't diagnosed as a child. Which is a complete bullshit. One can only buy meds on a black market and hope for the best...

>In my country Why not just say the country?

I'm curious too.

I would think that would also imply that access in other ways might be a bit "easier" as well...

Re: Adults with ADHD show decreased function in brain dopamine reward pathway (2010)

#226

Post by SummerlyMars »

PragmaticPulp wrote: post #46
_dibly wrote: post #25

Earlier quoted context omitted.

I'm not a parent, so I don't really have any grounds to argue how someone should raise their children. The only anecdote I'll add is that I would be reluctant to hold someone back from an opportunity to have the normalcy that I couldn't have in school. When I got to high school it was like my ADHD kicked into full gear, I started performing significantly worse and outright failing classes. My classmates, friends, and…

> All this is to say that medication can help when you need to feel normal, but it can't replace the skills you should have been developing. Exactly. These articles about ADHD and dopamine are often misinterpreted by people who assume that ADHD is a purely chemical imbalance with only chemical solutions. It's similar to the situation with depression, where decades of misleading ads and pop-neuroscience articles led p…

>Many people take medication as a gateway to develop those skills and go on to do quite well in life.

This is important. When I went on anti-depressants (for pure-o OCD), my intent was to get some breathing room and learn to manage my symptoms better.

I've definitely been able to do that, but it's lead to a few cases of thinking 'hey, I should be able to stop taking these now', which have all gone poorly for me. I think I'm better able to cope now if I don't have access to medication, but I won't be stopping again any time soon, it's too risky for me.

Re: Adults with ADHD show decreased function in brain dopamine reward pathway (2010)

#227

Post by robertely »

heimatau wrote: post #218
sibeliuss wrote: post #213

Earlier quoted context omitted.

> withdrawing from them isn't bad either Perhaps for you, but for others its a nightmare.

> but for others its a nightmare. I can only assume one of two reasons: 1. They were on XR. 2. Abuse. If it's another reason, maybe the formulation isn't the best for them because it's highly unlikely to have a 'nightmare' problem with getting off.

+1 on the XR makes it worse, but -1 on the only other reason being abuse. These drugs are not one-size-fits-all. Different people have different reactions.

Re: Adults with ADHD show decreased function in brain dopamine reward pathway (2010)

#228

Post by popinman322 »

fnord77 wrote: post #172
GABeech wrote: post #153

Earlier quoted context omitted.

> The only thing I had to deal with it slightly is my Ritalin...only so slightly I can "normally" focus for an hour. I just hope things go right in the rest of my life. Talk to your doctor, there have been many advances in ADHD meds and they all work differently on different people. Some people respond well to Ritalin, Some respond well to the generic. Some respond well the Adderal, or Vyvanse. For some people only t…

> there have been many advances in ADHD meds respectfully, I disagree with this. The last new therapy was atomoxetine, which is almost 20 years old now and not seen as terribly efficacious. Everything else new has been some variation on mixed dextroamphetamine/amphetamine salts or methylphenidate. Vyvanse is just a pro-drug for dextroamphetamine. The only novel thing in the pipeline is SPN-812, which may work similar…

There was also some work on repurposing fasoracetam for individuals with glutamate receptor issues, though I think they started with teens instead of adults. [0]

For a 2019 review of novel molecules, see [1].

[0]: https://www.nature.com/articles/s41467-017-02244-2 [1]: https://doi.org/10.1080/14737175.2019.1628640

Re: Adults with ADHD show decreased function in brain dopamine reward pathway (2010)

#229

Post by nxc18 »

robswc wrote: post #225
fnord123 wrote: post #198

Earlier quoted context omitted.

>In my country Why not just say the country?

I'm curious too. I would think that would also imply that access in other ways might be a bit "easier" as well...

Not OP but this is functionally true in the US.

I was diagnosed when I was younger, made the mistake of letting my prescription lapse (because I give myself breaks and therefore end up accumulating excess), and now can’t get the medication I need to function.

Fun fact, when you’re ADHD-PI, trying SSRIs isn’t just a harmless fun little exercise, it could have potentially life ruining consequences, which the psychiatrist will not tell you about.

If any psychiatrists are reading this, please know that the ‘harms’ of giving your patients the medication that is proven to work absolutely do not outweigh the harms of all the alternative coping mechanisms needed to avoid losing employment: black market pills, smoking/nicotine, caffeine by the gram, etc.

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