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I think another likely reason why disulfiram might not work is that the hypothesis is wrong, and the gene variant is only correlated with alcoholism, but might

I think another likely reason why disulfiram might not work is that the hypothesis is wrong, and the gene variant is only correlated with alcoholism, but might not be the cause of why there are lower rate of alcoholism in people with it.

vintermann 5y ago
Well, we know that 1. People with the gene variant drink slightly less than people without it, but otherwise their drinking patterns follows everyone else's. 2. alcoholism does not cause the gene variant in individuals (obviously). 3. The gene variant is invisible. Within a reasonable population group, it seems basically random who carries it or not (I.e, you can predict that Koreans are more likely to carry it than Americans, but within a group of Americans, or a group of Koreans, it's basically impossible to guess who carries it or not). It's even been used for Mendelian randomization studies, because as far as we can tell, it affects nothing else than alcohol digestion. A better explanation for the relative lack of success of disulfiram is that you don't take it from birth without choosing to. You have to want to take it to gain the benefit of it, but if you need it, you don't really want to take it. You want to drink. It's the big problem of addiction, you want things that contradict each other, and you want the bad things more. The drug researcher and philosopher Ole-Jørgen Skog wrote a lot of interesting things on this topic, on "The weakness of will" and time preferences: "If the consumer's sole motive for changing his level of patience is to escape an allocation that is dictated by his first order preference (including time preference), but that contradicts his second order preferences, he will not be able to achieve this by rational means. This is to put the cart before the horse." (But he thought that if you sought patience for its own sake, rather for the sake of not wanting to be an alcoholic, there was maybe a way. Since deciding to value patience for its own sake is not strictly speaking a rational decision.)
- didibus 5y ago
  > A better explanation for the relative lack of success of disulfiram is that you don't take it from birth without choosing to. You have to want to take it to gain the benefit of it, but if you need it, you don't really want to take it. You want to drink. It's the big problem of addiction, you want things that contradict each other, and you want the bad things more. I don't see what supports this being a better explanation, I feel at this point all explanation that fits the data are equally likely, otherwise it's just bias. In fact, I would say the proposed model failed the first test, which is that a good model should be good at predicting outcomes. In this case, the model failed to predict the outcome, as causing the condition in people did not reduce their alcohol consumption as we expected from the model. Sure, it could be that only some details of the model are wrong, like that the condition only works if established prior to a history of alcohol consumption, or that it only works if having no choice on the matter of the condition, etc. But at this point it seems just as likely that the condition might not be the cause, but only correlated in possibly another way. For example, we might have it backwards, and it is the lower drive to consume alcohol which caused the gene variant in the fist place.

vintermann 5y ago

Well, we know that 1. People with the gene variant drink slightly less than people without it, but otherwise their drinking patterns follows everyone else's. 2. alcoholism does not cause the gene variant in individuals (obviously). 3. The gene variant is invisible. Within a reasonable population group, it seems basically random who carries it or not (I.e, you can predict that Koreans are more likely to carry it than Americans, but within a group of Americans, or a group of Koreans, it's basically impossible to guess who carries it or not). It's even been used for Mendelian randomization studies, because as far as we can tell, it affects nothing else than alcohol digestion. A better explanation for the relative lack of success of disulfiram is that you don't take it from birth without choosing to. You have to want to take it to gain the benefit of it, but if you need it, you don't really want to take it. You want to drink. It's the big problem of addiction, you want things that contradict each other, and you want the bad things more. The drug researcher and philosopher Ole-Jørgen Skog wrote a lot of interesting things on this topic, on "The weakness of will" and time preferences: "If the consumer's sole motive for changing his level of patience is to escape an allocation that is dictated by his first order preference (including time preference), but that contradicts his second order preferences, he will not be able to achieve this by rational means. This is to put the cart before the horse." (But he thought that if you sought patience for its own sake, rather for the sake of not wanting to be an alcoholic, there was maybe a way. Since deciding to value patience for its own sake is not strictly speaking a rational decision.)

didibus 5y ago
> A better explanation for the relative lack of success of disulfiram is that you don't take it from birth without choosing to. You have to want to take it to gain the benefit of it, but if you need it, you don't really want to take it. You want to drink. It's the big problem of addiction, you want things that contradict each other, and you want the bad things more. I don't see what supports this being a better explanation, I feel at this point all explanation that fits the data are equally likely, otherwise it's just bias. In fact, I would say the proposed model failed the first test, which is that a good model should be good at predicting outcomes. In this case, the model failed to predict the outcome, as causing the condition in people did not reduce their alcohol consumption as we expected from the model. Sure, it could be that only some details of the model are wrong, like that the condition only works if established prior to a history of alcohol consumption, or that it only works if having no choice on the matter of the condition, etc. But at this point it seems just as likely that the condition might not be the cause, but only correlated in possibly another way. For example, we might have it backwards, and it is the lower drive to consume alcohol which caused the gene variant in the fist place.