This is kind of a ELI5, not because you guys are dumb, but because I just enjoy explaining things this way. I think that, even though a lot of people in this sub know a lot of this, there's take away for most people on this sub in the following write up.

We often want to take medications to change the way our neurotransmitters are flowing in our brain. All recreational drugs do this. So do anti depressants and anti anxiety medications. Even many over the counter supplements do the same (st John's wort, kava, 5htp, etc).

Over time, sustained use of these substances can weaken our brains ability to produce these neurotransmitters.

Let's use the example of dopamine. Dopamine is primarily produced in the ventral tegmental area (or VTA). Let's call the VTA "Vinnie". Vinnie is healthy and strong and produces dopamine regularly for his human, producing more when needed and vice versa. He sends the dopamine NTs out to the brain and body, they create a (hopefully) positive effect on the human. After a while, some of the dopamine NTs degrade while they're out doing their thing, but a lot of them actually come back home to Vinnie. They come home once they've done their job, they don't want to overdo it as that can cause problems. This is great because Vinnie can reuse them later instead of having to produce even more. Regardless, he is always in the process of producing dopamine as, naturally, they'll all eventually degrade and more will be needed.

One day Vinnie's human decides to take a drug. Specifically, a dopamine reuptake inhibitor (caffeine, nicotine, cocaine, wellbutrin, Adderall, Effexor, you name it). So Vinnie is waiting up for the dopamine NTs to come home, but they don't. They're out working still. In fact, many of them work so long that they degrade when, under normal circumstances, they would have been able to come back home to be reused. So now they're gone and Vinnie is going to have to work harder later to make more. Except, human keeps taking the substance, so the dopamine NTs keep working overtime. Vinnie keeps making more, but he actually doesn't have to make that much because the dopamine NTs keep working overtime.

So Vinnie actually ends up getting lazy. The time he would have spent laboring and staying strong is instead spent lying around doing nothing. The time he would have spent helping the dopamine NTs come home is spent being a couch potato. Vinnie loses his strength and capacity to care for the dopamine NTs. In fact, when some of them want to come home now, he doesn't even have the capacity to take them back in. He's basically a fraction as useful as he was before the human started taking the drug.

This continues until human stops taking the drug. Now, suddenly, Vinne has a lot of work to do, but he can't. He's literally physically incapable of the work needed to keep the human feeling motivated and happy. He can't produce enough dopamine NTs to do the work that needs to be done in the brain and body. When they're done with their work and want to come home, he can't let as many of them in because he isn't used to letting them back in, so it's a major adjustment.

So the human feels like crap, and this can last for a whole because Vinnie has to start working out again and hard. Human can do somethings to aid in this process (work out, eat healthy, cognitive work, all the basic health things) but it's still a slow process to get back to normal.

Anyways that's the gist of it. If you think that's bad, opiates are even scarier.

There's more to this story but I wanted to start here. If people like this I can write more about other things that happen when we take substances and how they affect our brains' neurotransmitter regulation.