Melatonin is not regulated as a drug in the U.S., but the long-term adaptations of the body to exogenous melatonin are not fully understood.

“So that's a very tricky question because melatonin is not regulated in the U.S., but in other countries it is regulated. And the reason why it's not regulated in the U.S. is you can feed a lot of melatonin to a mouse and the mouse will never die. In that sense, when you give various drugs or chemicals to an animal, then there is LD 50 or lethal dose 50 at which some animals would die. So based on that, we think that melatonin is safe and, of course, there is not much adverse effect of melatonin shown in any major experiments. But having said that, we don't know what are the long-term adaptation of our body to melatonin, whether you start with a milligram of melatonin and your body will slowly become resistant to that milligram and we'll need more and more.”