I really hate it when I have to use gift cards to buy necessary things. It's annoying on a par with having to use dextromethorphan to treat an actual cough. Seems such a waste of potential fun.
This round was stupid sundries like vitamins, and a bottle of something that says Mucuna pruriens on the front, but is really just a bottle of low-dose capsules of L-DOPA.
Just to be clear: I am not to be used as a role model. Levodopa is a moderately dangerous thing to be fucking around with, about on a par with my benzos. Barring some kind of weird allergic reaction, taking a dose or two to see what happens shouldn't hurt, but if you start eating the things like candy over a long period of time, you run the risk of screwing up various chemical dependencies and receptor sensitivities on either a temporary or permanent basis. Knock back the bottle and win a trip to the ER. Do not do what I do. I'm just willing to risk it because so many of the standard medical treatments make me worse that I'm down to defending my self-medication choices with, "The internets will mail it to my house, so you can't really stop me."
The point of levodopa is to raise the levels of dopamine in the brain. Dopamine per se doesn't make it past the blood-brain barrier, so if you want this to work, you have to take a prodrug that does slip through, and can then be metabolized into dopamine in situ. You can take L-tyrosine and theoretically get the same effect, but L-tyrosine is one step farther away from dopamine on the metabolic chain; L-DOPA/levodopa is the direct precursor. It works better if you take it with a regulator like carbidopa, but damned if I can find that in the 'dodgy supplements' department on Amazon, so I'm apparently forging on without.
What does dopamine do, you ask? Loads of things. The two main functions that I'm concerned with here are that it regulates the reward pathways in the brain -- in other words, it mediates feelings of fun and accomplishment when you do stuff, thus informing whether you want to do any of it again -- and plays a pivotal role in initiating and controlling voluntary muscle movement.
I have long contended that some of the nastier problems I have when deeply stressed or depressed are related to a shortage of dopamine. I go profoundly anhedonic and have occasionally verged on catatonic. Anhedonia is difficult to distinguish from a lack of motivation, which can be indicative of a shortage of a lot of things, including epineprhine and serotonin, but catatonia tends to be a more fundamental disorder of movement initiation.
One of the more illustrative stories is the time, during a bad depressive fugue in college, where I walked outside on a really bad day and realized as soon as I closed my apartment door that I needed a better coat. It took me twenty minutes to get back inside and get one. It wasn't a matter of the rational voice in my brain going 'it's cold, this jacket is too thin' and some emotional troll impulse wailing 'nooooooo I'm a terrible person and I deserve to freeze'. The rational voice said 'I need a better coat' and the emotional voice said 'I concur, it's cold out here', and then I stared at my hand on the doorknob for a very long time, because I could not get it to move. No amount of wanting to would make it happen. It's puzzling and frustrating, mainly because it gums up my schedule a lot, and I have a feeling that outside observers think I'm being obstructionist or lazy.
I still have terrible trouble sometimes making myself stand up and do things. The literal start of movement is the hardest thing. At my worst, I even have difficulty initiating things like dance or hoop rehearsal; I start the music and get into position to begin, and then simply stand there for several songs, unable to overcome static friction. Once I've started, I'm fine. I've always found it easier to run pell-mell down uneven terrain than launch across smooth ground, a tendency which gets more pronounced the harder it is to initiate motion, and I wonder if part of why I like working with props like the hoops so much is that the inertia of the object keeps it in motion even if I'm still, and makes it easier for me to stay active.
The quintessential illustration of what happens when someone is out of dopamine is Parkinson's disease, which is caused by destruction of the substantia nigra, a little wad of dopamine-producing tissue deep in the brain. I am not Parkinsonian, thankfully; I have neither an essential nor an intentional tremor, and I lack the weird time-dilation effects that are common among those with dopamine-dependent movement disorders. (I also don't get any of the fun hallucinations. I'm more ambivalent on whether that's a good thing or a bad one.) My symptoms seem to me to be more logically the result of just not having enough dopamine to fucking run things sometimes, than a problem with transport or available receptors.
My working hypothesis at this point is simply that the resources dopamine is normally made from are being diverted to something else. The same basic stuff goes into producing other catecholamines like epinephrine and norepinephrine, which are prioritized in emergency situations, and I'm already well aware that my system has issues with keeping production of that to reasonable levels in times of stress. Probably the reaction is being rate-limited by either a precursor or a catalyst. I can't really do anything about my levels of DOPA decarboxylase, and my levels of B6 should be adequately covered by eating food, and by the multivitamin I mostly even remember to take. The closest intermediary I can dose down the dopamine metabolic pathway that isn't on the other catecholamine paths is L-DOPA.
Why isn't there a dopamine reuptake inhibitor, you ask? Serotonin reuptake inhibitors help people whose issue is a lack of serotonin. There are plenty of DRIs, as it turns out. They're mostly illegal, because they're extremely fun. Cocaine is an excellent one. So are the various branches of the amphetamine family. The problem is that, since dopagenic drugs hit up the raw reward/enjoyment pathways, they tend to be addictive, and huge amounts of dopamine flooding into your brain apropos of nothing starts to override everything else, like common sense. Or self-preservation. Or reality testing.
[ETA: With the recent resurgence of press coverage in re: ketamine as an antidepressant, there are some research papers starting to pop that suggest ketamine is a dopamine-reuptake inhibitor, directly via non-competitive binding, and indirectly via fooling with stuff like sigma ligands and NMDA receptor activity. Dextromethorphan has a substantially similar mechanism of action. I haven't sent a wheelbarrow of money to Elsevier and hence can't read anything but the abstracts, but I suppose that does explain why DXM hammers my brain temporarily back into shape.]
People who chronically take large doses of uppers can suffer what's called amphetamine (or cocaine) psychosis, which is essentially a chemical version of paranoid schizophrenia. What normally happens when you have one of those thoughts about what's going on in the world around you is that you compare the pattern you've come up with to reality. If it matches your brain goes 'yay! validation!' and you feed it back into the pattern detector for the next round of deductions. If on closer inspection it doesn't match, you get no good feels off it, and you throw it away. It's not perfect, but it works well enough for most people. When you're awash in crazy amounts of dopamine, everything feels 'yay!', so all of the bizarre brainstorming thoughts you normally only have in passing start to seem rational and become the scaffolding for further thinking. Eventually you get around to believing, in all sincerity, that there's a demon lurking at the bottom of your swimming pool. I am weird enough with my reality testing intact, thank you.
There are lesser critters that have proven helpful to me in the past. I find most stimulants incredibly unpleasant, because they boost norepinephrine as well, but caffeine, I can stand. Caffeine is unusual in that its main mechanism of action at cola/coffee doses is to block detection of a waste product of cellular metabolism that tells you that you're out of fuel -- it doesn't really wake you up, so much as it makes you oblivious to the fact that you're tired. It's also unusual in that, while it does impact dopamine and norepineprhine, the doses at which it does so are staggered. You get greater availability of D1 and D2 receptors at a dose higher than you normally get out of caffeinated beverages, but significantly lower than the dose that gives you an adrenaline charge. While my actual tolerance has gotten kind of ridiculous over the years -- I can take about a gram before I start to get the odor of burnt neuron hanging around in my sinuses -- my customary dose of the stuff is just off the high end of a decent espresso, 200-300mg.
No doctor on Earth would listen to me if I walked in and said, 'My brain is sad and I can't do anything, please give me a bottle of Sinemet,' and they'd be right. I suspect that I am not the only person who has these specific issues, but I've not seen them described in the literature in quite this way, so for all they know I'm an ignorant nutcase repeating something I've read on the website of one of those "quantum thought" gurus of questionable educational qualification.
Typical doses of levodopa for Parkinson's start at 300mg a day; typical doses for people taking it as a nootropic start slightly lower, at 100-300mg a day, and work up. Recreational doses (such as they are; Erowid suggests the acute abuse potential is pretty limited, since it takes a lot to get very little euphoria in the short term) are much higher. Assuming that the bottle markings are accurate -- and that is not always a good assumption to make about herbal supplements, but I'm going to roll with it -- the capsules I have contain 30mg L-DOPA per. I could empty them to precision-dose with the powder, but I'm not interested in finding out what velvet bean extract tastes like.
I'm starting out with 1-2 capsules in the morning. Supposedly this is beneath the effective dose, but I react weirdly to everything else, so I might as well play it safe. Neither levodopa nor dopamine proper go through the liver enzyme I appear to be deficient in, but it's a lot easier and more pleasant to take more drugs later, than to try to take less of them once you've already eaten a handful.
There's a bit of a body load which is not particularly obstructive, but also not necessarily pleasant; I should probably not try taking the stuff at night, since I think the goosebumps are probably annoying enough to stop me sleeping. I've been talking to myself a lot, which is a known side effect of being awash in dopamine -- see: every cokehead and tweaker ever -- but I talked to myself a lot before. It's where all the blog entries come from. Hard to tell if there are any other significant effects, but the dishes have been suspiciously oft-done lately.
This round was stupid sundries like vitamins, and a bottle of something that says Mucuna pruriens on the front, but is really just a bottle of low-dose capsules of L-DOPA.
Just to be clear: I am not to be used as a role model. Levodopa is a moderately dangerous thing to be fucking around with, about on a par with my benzos. Barring some kind of weird allergic reaction, taking a dose or two to see what happens shouldn't hurt, but if you start eating the things like candy over a long period of time, you run the risk of screwing up various chemical dependencies and receptor sensitivities on either a temporary or permanent basis. Knock back the bottle and win a trip to the ER. Do not do what I do. I'm just willing to risk it because so many of the standard medical treatments make me worse that I'm down to defending my self-medication choices with, "The internets will mail it to my house, so you can't really stop me."
The point of levodopa is to raise the levels of dopamine in the brain. Dopamine per se doesn't make it past the blood-brain barrier, so if you want this to work, you have to take a prodrug that does slip through, and can then be metabolized into dopamine in situ. You can take L-tyrosine and theoretically get the same effect, but L-tyrosine is one step farther away from dopamine on the metabolic chain; L-DOPA/levodopa is the direct precursor. It works better if you take it with a regulator like carbidopa, but damned if I can find that in the 'dodgy supplements' department on Amazon, so I'm apparently forging on without.
What does dopamine do, you ask? Loads of things. The two main functions that I'm concerned with here are that it regulates the reward pathways in the brain -- in other words, it mediates feelings of fun and accomplishment when you do stuff, thus informing whether you want to do any of it again -- and plays a pivotal role in initiating and controlling voluntary muscle movement.
I have long contended that some of the nastier problems I have when deeply stressed or depressed are related to a shortage of dopamine. I go profoundly anhedonic and have occasionally verged on catatonic. Anhedonia is difficult to distinguish from a lack of motivation, which can be indicative of a shortage of a lot of things, including epineprhine and serotonin, but catatonia tends to be a more fundamental disorder of movement initiation.
One of the more illustrative stories is the time, during a bad depressive fugue in college, where I walked outside on a really bad day and realized as soon as I closed my apartment door that I needed a better coat. It took me twenty minutes to get back inside and get one. It wasn't a matter of the rational voice in my brain going 'it's cold, this jacket is too thin' and some emotional troll impulse wailing 'nooooooo I'm a terrible person and I deserve to freeze'. The rational voice said 'I need a better coat' and the emotional voice said 'I concur, it's cold out here', and then I stared at my hand on the doorknob for a very long time, because I could not get it to move. No amount of wanting to would make it happen. It's puzzling and frustrating, mainly because it gums up my schedule a lot, and I have a feeling that outside observers think I'm being obstructionist or lazy.
I still have terrible trouble sometimes making myself stand up and do things. The literal start of movement is the hardest thing. At my worst, I even have difficulty initiating things like dance or hoop rehearsal; I start the music and get into position to begin, and then simply stand there for several songs, unable to overcome static friction. Once I've started, I'm fine. I've always found it easier to run pell-mell down uneven terrain than launch across smooth ground, a tendency which gets more pronounced the harder it is to initiate motion, and I wonder if part of why I like working with props like the hoops so much is that the inertia of the object keeps it in motion even if I'm still, and makes it easier for me to stay active.
The quintessential illustration of what happens when someone is out of dopamine is Parkinson's disease, which is caused by destruction of the substantia nigra, a little wad of dopamine-producing tissue deep in the brain. I am not Parkinsonian, thankfully; I have neither an essential nor an intentional tremor, and I lack the weird time-dilation effects that are common among those with dopamine-dependent movement disorders. (I also don't get any of the fun hallucinations. I'm more ambivalent on whether that's a good thing or a bad one.) My symptoms seem to me to be more logically the result of just not having enough dopamine to fucking run things sometimes, than a problem with transport or available receptors.
My working hypothesis at this point is simply that the resources dopamine is normally made from are being diverted to something else. The same basic stuff goes into producing other catecholamines like epinephrine and norepinephrine, which are prioritized in emergency situations, and I'm already well aware that my system has issues with keeping production of that to reasonable levels in times of stress. Probably the reaction is being rate-limited by either a precursor or a catalyst. I can't really do anything about my levels of DOPA decarboxylase, and my levels of B6 should be adequately covered by eating food, and by the multivitamin I mostly even remember to take. The closest intermediary I can dose down the dopamine metabolic pathway that isn't on the other catecholamine paths is L-DOPA.
Why isn't there a dopamine reuptake inhibitor, you ask? Serotonin reuptake inhibitors help people whose issue is a lack of serotonin. There are plenty of DRIs, as it turns out. They're mostly illegal, because they're extremely fun. Cocaine is an excellent one. So are the various branches of the amphetamine family. The problem is that, since dopagenic drugs hit up the raw reward/enjoyment pathways, they tend to be addictive, and huge amounts of dopamine flooding into your brain apropos of nothing starts to override everything else, like common sense. Or self-preservation. Or reality testing.
[ETA: With the recent resurgence of press coverage in re: ketamine as an antidepressant, there are some research papers starting to pop that suggest ketamine is a dopamine-reuptake inhibitor, directly via non-competitive binding, and indirectly via fooling with stuff like sigma ligands and NMDA receptor activity. Dextromethorphan has a substantially similar mechanism of action. I haven't sent a wheelbarrow of money to Elsevier and hence can't read anything but the abstracts, but I suppose that does explain why DXM hammers my brain temporarily back into shape.]
People who chronically take large doses of uppers can suffer what's called amphetamine (or cocaine) psychosis, which is essentially a chemical version of paranoid schizophrenia. What normally happens when you have one of those thoughts about what's going on in the world around you is that you compare the pattern you've come up with to reality. If it matches your brain goes 'yay! validation!' and you feed it back into the pattern detector for the next round of deductions. If on closer inspection it doesn't match, you get no good feels off it, and you throw it away. It's not perfect, but it works well enough for most people. When you're awash in crazy amounts of dopamine, everything feels 'yay!', so all of the bizarre brainstorming thoughts you normally only have in passing start to seem rational and become the scaffolding for further thinking. Eventually you get around to believing, in all sincerity, that there's a demon lurking at the bottom of your swimming pool. I am weird enough with my reality testing intact, thank you.
There are lesser critters that have proven helpful to me in the past. I find most stimulants incredibly unpleasant, because they boost norepinephrine as well, but caffeine, I can stand. Caffeine is unusual in that its main mechanism of action at cola/coffee doses is to block detection of a waste product of cellular metabolism that tells you that you're out of fuel -- it doesn't really wake you up, so much as it makes you oblivious to the fact that you're tired. It's also unusual in that, while it does impact dopamine and norepineprhine, the doses at which it does so are staggered. You get greater availability of D1 and D2 receptors at a dose higher than you normally get out of caffeinated beverages, but significantly lower than the dose that gives you an adrenaline charge. While my actual tolerance has gotten kind of ridiculous over the years -- I can take about a gram before I start to get the odor of burnt neuron hanging around in my sinuses -- my customary dose of the stuff is just off the high end of a decent espresso, 200-300mg.
No doctor on Earth would listen to me if I walked in and said, 'My brain is sad and I can't do anything, please give me a bottle of Sinemet,' and they'd be right. I suspect that I am not the only person who has these specific issues, but I've not seen them described in the literature in quite this way, so for all they know I'm an ignorant nutcase repeating something I've read on the website of one of those "quantum thought" gurus of questionable educational qualification.
Typical doses of levodopa for Parkinson's start at 300mg a day; typical doses for people taking it as a nootropic start slightly lower, at 100-300mg a day, and work up. Recreational doses (such as they are; Erowid suggests the acute abuse potential is pretty limited, since it takes a lot to get very little euphoria in the short term) are much higher. Assuming that the bottle markings are accurate -- and that is not always a good assumption to make about herbal supplements, but I'm going to roll with it -- the capsules I have contain 30mg L-DOPA per. I could empty them to precision-dose with the powder, but I'm not interested in finding out what velvet bean extract tastes like.
I'm starting out with 1-2 capsules in the morning. Supposedly this is beneath the effective dose, but I react weirdly to everything else, so I might as well play it safe. Neither levodopa nor dopamine proper go through the liver enzyme I appear to be deficient in, but it's a lot easier and more pleasant to take more drugs later, than to try to take less of them once you've already eaten a handful.
There's a bit of a body load which is not particularly obstructive, but also not necessarily pleasant; I should probably not try taking the stuff at night, since I think the goosebumps are probably annoying enough to stop me sleeping. I've been talking to myself a lot, which is a known side effect of being awash in dopamine -- see: every cokehead and tweaker ever -- but I talked to myself a lot before. It's where all the blog entries come from. Hard to tell if there are any other significant effects, but the dishes have been suspiciously oft-done lately.
Better living through chemistry!
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