The horrific overdose deaths of two young men from the Hunter region after they were "cooked from the inside" have prompted fears about the possible re-emergence of killer synthetic drugs.

Both men died on Thursday following separate long and violent psychotic episodes during which their core temperatures rose to fatal levels, one to more than 42 degrees.

They were also known users of methamphetamine, and are believed to have used the drug in the days leading up to their deaths, but authorities believe toxicology tests and autopsies could show they succumbed to a substance other than ice.

"I know it's the old message, but this really shows that people have absolutely no idea what they are taking; and it could well be killing them," one senior detective told Fairfax Media.