US researchers have uncovered part of what's happening, on a cellular level, to make cocaine addicts going cold turkey feel so awful.
The results provide a better understanding of what's creating that crashing low of withdrawal - and may offer a clue for researchers looking to mitigate the symptoms and keep the user from relapsing.
Studying genetically-engineered mice, the researchers focused on a molecule - called cannabinoid receptor 1, or CB1 - that slows communication between nerve cells.
The molecule is particularly important in what is called the nucleus accumbens region of the brain, which governs emotion and motivation.
It was already well-known that cocaine produces strong effects on that part of the brain. But this is the first study of cocaine's impact on CR1 production, and what that means for the nucleus accumbens during and after a cocaine high.
When a person is high on cocaine, "it speeds everything up, pushing you to a highly rewarding emotional state," said lead author Bradley Winters.
The cocaine caused the mice to produce an excess of CB1, effectively slamming the brakes on the brain's hyper-activity in the nucleus accumbens.
"It is kind of like going down a steep hill so you have to start riding that brake really hard," Winters explained in a statement.
The problem is that the brain doesn't seem to know to let up on the brakes, after the cocaine high wears off.
"You're still riding that brake just as hard. Now you're going down a regular, low-grade hill but you're going two miles per hour because your foot is still jammed on the brake," he said.
"The state is like, 'I feel terrible and I don't want to do anything," he continued, adding that's "what brings you back to the drug because you want to feel better and the drug is the only thing you feel motivation for."
The study was published on Monday in the Proceedings of the National Academy of Sciences.