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In a very general way, why is the brain a system that responds euphorically in response to certain stimulants yet over time that substance may be addictive and have negative health effects?

What is it about the brain’s in-built mechanisms as well as evolution that did not cause the brain to respond positively to that which is good for health, aversively to that which is bad?

Why is there an initial positive incentive to use addictive drugs?

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Short answer
The brain with its reward centers did not evolve with purified plant-based stimulants (nicotine, cocaine) or synthetic variants ((meth)amphetamine and other designer drugs) around.

Background
Cocaine leaves have been chewed on for ages, but the trick is that the 'high' comes gradually and it is hardly addictive at all. The reward centers may be stimulated, but mildly. It wasn't until folks started to chemically isolate and purify the active ingredients in the leaves that the trouble began. These purified compounds flush the reward centers in the brain with dopamine, resulting in nearly instant longing for more (craving) when the high is over. After a while dependence to the drug can develop and consumption may become habitual. Note that tobacco is heavily processed to ensure a 'pleasant' taste and readily release of the addictive nicotine. The same can be said for the 'downers' (opiates and synthetic relatives like fentanyl).

Ethanol (stimulant and neuro-suppressant all in one) is another example; it occurs in nature in fermented fruit (you know the funny movies); yet fermented fruit with enough alcohol in it to become intoxicated wasn't available all-year round and the conditions have to be pretty perfect for it to happen in the first place. Only when people started to brew beer and purify ethanol to increase alcohol content through distillation the trouble (addiction and development of diseases associated with chronic alcohol abuse) started.

The reward centers in the brain (responsible for addiction) haven't evolved in the presence of all these purified and synthetic compounds. It evolved in eras where sugars, fat and salt were scarce. Now things are different, and people get addicted to drugs, get overweight because of the excess carbohydrates and fat they consume (also driven by the reward centers making them feel good) and develop kidney failure because of high salt intake.

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    $\begingroup$ I might add to this that for the most part, commonly abused drugs act directly on the reward machinery. There's no cognitive "check" there or anything evolved to like those things, they're going directly to the spot in the brain that says "keep doing the thing that made this happen". $\endgroup$
    – Bryan Krause
    Sep 13, 2022 at 17:28

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