Things I learned that surprised me from a deep dive into how the medication I’ve been taking for years (Vyvanse) actually gets metabolized:
It says in the instructions that it works for 13 hours, and my psychiatrist informed me that it has a slow onset of about an hour. What that actually means is that after ~1h you reach 1⁄2 the peak concentration and after 13 hours you are at 1⁄2 the peak concentration again, because the half-life is 12h (and someone decided at some point 1⁄2 is where we decide the exponential starts and ends?). Importantly, this means 1⁄4 of the medication is still present the next day!
Here is some real data, which fit the simple exponential decay rather well (It’s from children though, which metabolize dextroamphetamine faster, which is why the half-life is only ~10h)
If you eat ~1-3 grams of baking soda, you can make the amount of medication you lose through urine (usually ~50%) go to 0[1] (don’t do this! Your body probably keeps its urine pH at the level it does for a reason! You could get kidney stones).
I thought the opposite effect (acidic urine gets rid of the medication quickly) explained why my ADHD psychologist had told me that the medication works less well combined with citric fruit, but no! Citric fruit actually increase your urine pH (or mostly don’t affect it much)? Probably because of the citric acid cycle which means there’s more acid leaving as co2 through your lungs? (I have this from gpt4 and a rough gloss over details checked out when checking Wikipedia, but this could be wrong, I barely remember my chemistry from school)
Instead, Grapefruit has some ingredients known to inhibit enzymes for several drugs, including dextroamphetamine (I don’t understand if this inhibitory effect is actually large enough to be a problem yet though)
Currently still learning more about basics about neurotransmitters from a textbook, and I might write another update once/if at the point where I feel comfortable writing about the effects of dextroamphetamine on signal transmission.
There is probably a lot of variation between people regarding that. In my family meds across the board improved people’s sleep (by making people less sleepy during the day, so more active and less naps). When I reduced my medication from 70mg to 50mg for a month to test whether I still needed the full dose, the thing that was annoying the most was my sleep (waking up at night and not falling asleep again increased. Falling asleep initially was maybe slightly easier). Taking it too late in the afternoon is really bad for my sleep, though.
That matches with what my psychiatrist told me. I find it surprising how large the variation between individuals can be with these meds.
I have met people who can drink an espresso before bed and it actually helps their sleep. But I find those people to be rare.
I see much more variance in amphetamines. My mental data set isn’t large enough to make any sold predictions. But I am unable to point to a clear “most people’s sleep is (X)ed by amphetamines”.
One confounder: depression/mania. Recently (the last ~two weeks) I have been having bad sleep (waking up 3-7 am and not feeling sleepy anymore (usually I sleep from midnight to 9). My current best guess is that the problem is that my life has been going too well recently, leading to a self-sustaining equilibrium where I have little sleep and mania. Reduced my medication today (~55mg instead of 70mg) which seems to have helped with the mania. I had another day with slight mania 1 month ago when sleeping little in order to travel to a conference, so in the future I’ll probably reduce my medication dose on such days. Took a friend describing his symptoms on too much medication for me to realize what is going on.
Things I learned that surprised me from a deep dive into how the medication I’ve been taking for years (Vyvanse) actually gets metabolized:
It says in the instructions that it works for 13 hours, and my psychiatrist informed me that it has a slow onset of about an hour. What that actually means is that after ~1h you reach 1⁄2 the peak concentration and after 13 hours you are at 1⁄2 the peak concentration again, because the half-life is 12h (and someone decided at some point 1⁄2 is where we decide the exponential starts and ends?). Importantly, this means 1⁄4 of the medication is still present the next day!
Here is some real data, which fit the simple exponential decay rather well (It’s from children though, which metabolize dextroamphetamine faster, which is why the half-life is only ~10h)
If you eat ~1-3 grams of baking soda, you can make the amount of medication you lose through urine (usually ~50%) go to 0[1] (don’t do this! Your body probably keeps its urine pH at the level it does for a reason! You could get kidney stones).
I thought the opposite effect (acidic urine gets rid of the medication quickly) explained why my ADHD psychologist had told me that the medication works less well combined with citric fruit, but no! Citric fruit actually increase your urine pH (or mostly don’t affect it much)? Probably because of the citric acid cycle which means there’s more acid leaving as co2 through your lungs? (I have this from gpt4 and a rough gloss over details checked out when checking Wikipedia, but this could be wrong, I barely remember my chemistry from school)
Instead, Grapefruit has some ingredients known to inhibit enzymes for several drugs, including dextroamphetamine (I don’t understand if this inhibitory effect is actually large enough to be a problem yet though)
This brings me to another observation: apparently each of these enzymes is used in >10-20% of drugs: (CYP3A4/5, CYP2D6, CYP2C9). Wow! Seems worth learning more about them! CYP2D6 gets actually used twice in the metabolism of dextroamphetamine, once for producing and once for degrading an active metabolite.
Currently still learning more about basics about neurotransmitters from a textbook, and I might write another update once/if at the point where I feel comfortable writing about the effects of dextroamphetamine on signal transmission.
Urinary excretion of methylamphetamine in man (scihub is your friend)
This seems like it will be useful for me in the future.
I’ve been wondering for a while how the long half life of ADHD meds impact sleep. Any data on that?
There is probably a lot of variation between people regarding that. In my family meds across the board improved people’s sleep (by making people less sleepy during the day, so more active and less naps). When I reduced my medication from 70mg to 50mg for a month to test whether I still needed the full dose, the thing that was annoying the most was my sleep (waking up at night and not falling asleep again increased. Falling asleep initially was maybe slightly easier). Taking it too late in the afternoon is really bad for my sleep, though.
That matches with what my psychiatrist told me. I find it surprising how large the variation between individuals can be with these meds.
I have met people who can drink an espresso before bed and it actually helps their sleep. But I find those people to be rare. I see much more variance in amphetamines. My mental data set isn’t large enough to make any sold predictions. But I am unable to point to a clear “most people’s sleep is (X)ed by amphetamines”.
One confounder: depression/mania. Recently (the last ~two weeks) I have been having bad sleep (waking up 3-7 am and not feeling sleepy anymore (usually I sleep from midnight to 9). My current best guess is that the problem is that my life has been going too well recently, leading to a self-sustaining equilibrium where I have little sleep and mania. Reduced my medication today (~55mg instead of 70mg) which seems to have helped with the mania. I had another day with slight mania 1 month ago when sleeping little in order to travel to a conference, so in the future I’ll probably reduce my medication dose on such days. Took a friend describing his symptoms on too much medication for me to realize what is going on.