While marijuana has not been definitively shown to cause cancer or heart disease, its harmful cognitive and psychological effects will take time to capture in studies. The underlying biochemistry at work suggests deeply pathologic consequences. Tetrahydrocannabinol (THC) in marijuana attaches to receptors in the brain that subtly modulate systems ordinarily involved in healthy behaviors like eating, learning, and forming relationships. But THC — which has been increasing in potency in legal products being sold in places like Colorado — throws the finely tuned system off balance.

“Smoking pot turns the volume on this system way, way up,” says Jonathan Long, a research fellow at the Dana-Farber Cancer Institute.

Each hit of THC rewires the function of this critical cognitive system: Early evidence in mice has shown that repeated exposure to THC causes these receptors to disappear altogether, blunting the natural response to positive behaviors and requiring higher doses to achieve the same effect. Marijuana exploits essential pathways we’ve evolved to retrieve a memory, to delicately regulate our metabolism, and to derive happiness from everyday life.