Certain substances make you high, or give you a buzz, but what does that mean, biologically and chemically?
Gabor Mate, MD explains it in his book In the Realm of Hungry Ghosts: Close Encounters with Addiction. This short article gives a very brief and simplified summary. I highly recommend reading the original, which gives a more in depth explanation of the topic.
The outer layer of any cell in your body is covered with many thousands of receptors - little organic loading docks, each shaped to receive a very specific messenger molecule.
One part of the brain will send a message to a cell. Eating or sex will trigger the part of the brain that says "this feels good." Your brain sends "this feels good" messengers (dopamine), which lock onto many cells throughout your body. The result: you feel good.
All commonly used and abused drugs temporarily increase dopamine functioning: alcohol, marijuana, heroin, morphine, nicotine, caffeine, cocaine, crystal meth. More dopamine = more good feelings.
After a neurotransmitter (dopamine, in this case) has delivered its message to a cell, it's released and returns to the neuron it came from, for later reuse. This is called "reuptake."
Cocaine inhibits dopamine reuptake. Cocaine molecules are just the right size and shape to fit into dopamine receptors on cells. They occupy. The more of them there are, the more dopamine remains in the space between cells, unable to return to their neurons of origin. They remain in play, delivering their chemical message ("feel good!") again and again. But cocaine molecules only occupy for a short time. Before long they wander off, leaving the user with the desire for another hit.
Nicotine doesn't block dopamine reuptake, but triggers dopamine release.
Crystal meth does both.
Food seeking can increase dopamine levels in some key brain centres by 50%.
Sexual arousal: 100%
Cocaine: more than 300%
And crystal meth takes the prize: 1200%
A person's brain is used to a certain amount of dopamine activity. When this amount increases, the brain compensates by reducing the number of dopamine receptors, in an attempt to restore dopamine activity to previous levels. A person pursuing her buzz then has to take more of her chosen substance (or engage in more of her favoured behaviour) to get the same effect from fewer receptors. This is how you build a tolerance.
If a long term addict kicks her habit, it'll take months or longer for her brain to recalibrate and increase the number of dopamine receptors to pre-drug use levels.
Some people have a reduced number of dopamine receptors in the first place.
Why? Chronic stress in early life.
Such a person would have a predisposition for the relief of a dopamine rush, in the way that someone with a lifelong parched throat would feel incredible relief drinking a tall glass of water. And very likely would keep drinking glass after glass, even if the water was polluted, expensive or illegal. And they'd keep on drinking, even as it unfortunately did a progressively less effective job of slaking their thirst.