By “transmission mechanism”, do you mean “mechanism of action”? If so, when you say “with no plausible transmission mechanism”, do you mean “whose mechanism of action has not yet been discovered” or “I believe it is implausible that a mechanism of action for this could exist”?
’Cause if you mean the former, the fact that we don’t understand it shouldn’t be a barrier to using it (you might be surprised how many medications we have no idea how they work), and if you mean the latter, well, as the old saying goes, “If it happens, it’s possible”.
This is doubly true for lithium, where even if you want to reject every single one of the studies I cited, we already know it works in higher dose as a treatment for bipolar disorder.
(and I hate to follow up an interesting rationality point with a boring discussion of pharmacology, but many of the effects of lithium are known or plausibly speculated upon, including protecting neurons against glutamate excitotoxicity; I am no neuroscientist, but I know excitotoxicity has a role in dementia, probably some psychiatric disorders, and in a bunch of common neurological causes of death.)
Literally no idea how they work? Not super common, although a paper on drug targets in Nature gives this list of drugs where they can’t even begin to classify what sort of entity they act on.
But many other drugs are still incompletely understood, or only have very speculative mechanisms of actions. For example, we know that SSRI antidepressants increase levels of serotonin in the brain, but we’re not really sure why that should treat depression (the hypothesis that depression is an imbalance of neurotransmitters was originally an ad hoc hypothesis explaining why these sorts of drugs seemed to treat it, although we’ve learned a lot since then).
Paracetamol (aka acetaminophen aka Tylenol) is actually pretty mysterious and still the subject of a lot of study, as are anaesthetics (which is too bad, because if we understood how anaesthetics worked, we’d have a promising lead in figuring out what consciousness is). Most psychiatric medications range somewhere from “incompletely understood” to “might as well be witchcraft”, and lot of neurologic ones like some of the antiepileptics aren’t much better.
I was surprised to learn recently that a lot of drug discovery is now being done by brute force. For example, they discovered new cystic fibrosis drug ivacaftor by dosing lung cells in solution with more or less every known organic chemical until one of them caused the chlorine concentration of the solution to change, which indicated that it had somehow solved the error in cellular chlorine transport that causes CF.
By transmission mechanism I mean something more general. X has a non-negligible effect on Y, Y on Z etc.
An example of implausible transmission mechanism:
This or that food contains antioxidants, antioxidants protect from molecular damage, less molecular damage means you’ll live longer—it has 2 totally broken links since entirely insignificant amount of antioxidants from food get anywhere in the body, and putting more antioxidants in the cells doesn’t actually do much at all (even if reducing their amount increases damage considerably).
An example of plausible transmission mechanism:
Having dogs improve people’s moods, people in better mood have lower blood pressure, lower blood pressure decreases risk of major cardiovascular disease—we don’t have much hard data here (funnily enough they did a randomized study once, and found such effects), but every link in the chain is plausible and effect is within realistic order of magnitude.
With sufficiently overwhelming evidence it might be reasonable to ignore lack of any plausible transmission mechanism, but evidence is anything but, and I’m more inclined to think that it went from “I need to publish X papers a year” to “finshing for statistical correlations involving lithium” to “publishing a paper about that”.
By “transmission mechanism”, do you mean “mechanism of action”? If so, when you say “with no plausible transmission mechanism”, do you mean “whose mechanism of action has not yet been discovered” or “I believe it is implausible that a mechanism of action for this could exist”?
’Cause if you mean the former, the fact that we don’t understand it shouldn’t be a barrier to using it (you might be surprised how many medications we have no idea how they work), and if you mean the latter, well, as the old saying goes, “If it happens, it’s possible”.
This is doubly true for lithium, where even if you want to reject every single one of the studies I cited, we already know it works in higher dose as a treatment for bipolar disorder.
(and I hate to follow up an interesting rationality point with a boring discussion of pharmacology, but many of the effects of lithium are known or plausibly speculated upon, including protecting neurons against glutamate excitotoxicity; I am no neuroscientist, but I know excitotoxicity has a role in dementia, probably some psychiatric disorders, and in a bunch of common neurological causes of death.)
How common are such medicines, in your experience?
Literally no idea how they work? Not super common, although a paper on drug targets in Nature gives this list of drugs where they can’t even begin to classify what sort of entity they act on.
But many other drugs are still incompletely understood, or only have very speculative mechanisms of actions. For example, we know that SSRI antidepressants increase levels of serotonin in the brain, but we’re not really sure why that should treat depression (the hypothesis that depression is an imbalance of neurotransmitters was originally an ad hoc hypothesis explaining why these sorts of drugs seemed to treat it, although we’ve learned a lot since then).
Paracetamol (aka acetaminophen aka Tylenol) is actually pretty mysterious and still the subject of a lot of study, as are anaesthetics (which is too bad, because if we understood how anaesthetics worked, we’d have a promising lead in figuring out what consciousness is). Most psychiatric medications range somewhere from “incompletely understood” to “might as well be witchcraft”, and lot of neurologic ones like some of the antiepileptics aren’t much better.
I was surprised to learn recently that a lot of drug discovery is now being done by brute force. For example, they discovered new cystic fibrosis drug ivacaftor by dosing lung cells in solution with more or less every known organic chemical until one of them caused the chlorine concentration of the solution to change, which indicated that it had somehow solved the error in cellular chlorine transport that causes CF.
By transmission mechanism I mean something more general. X has a non-negligible effect on Y, Y on Z etc.
An example of implausible transmission mechanism:
This or that food contains antioxidants, antioxidants protect from molecular damage, less molecular damage means you’ll live longer—it has 2 totally broken links since entirely insignificant amount of antioxidants from food get anywhere in the body, and putting more antioxidants in the cells doesn’t actually do much at all (even if reducing their amount increases damage considerably).
An example of plausible transmission mechanism:
Having dogs improve people’s moods, people in better mood have lower blood pressure, lower blood pressure decreases risk of major cardiovascular disease—we don’t have much hard data here (funnily enough they did a randomized study once, and found such effects), but every link in the chain is plausible and effect is within realistic order of magnitude.
With sufficiently overwhelming evidence it might be reasonable to ignore lack of any plausible transmission mechanism, but evidence is anything but, and I’m more inclined to think that it went from “I need to publish X papers a year” to “finshing for statistical correlations involving lithium” to “publishing a paper about that”.