They took what they thought was MDMA at separate gatherings across Melbourne between July 2016 and January 2017.

But it was actually a rare and lethal combination of a synthetic hallucinogenic, 25C-NBOMe, and a stimulant known as 4 Fluoroamphetamine.

One of the men, 22-year-old Jordan, was pronounced brain dead on Christmas morning, three days after losing consciousness at a friend's house.

The following month, 23-year-old James jumped off his CBD Melbourne balcony after taking the drugs and telling his friends "f*** this". He died at the scene.

Coroner Paresa Spanos is investigating the lead-up to their deaths, alongside those of 17-year-old Anson, Ilker, 32, and 30-year-old Jason.

Anson suffered seizures after taking the drugs with friends in July 2016 and died in hospital. Ilker died in similar circumstances about five months later.

Jason stopped breathing when he took drugs with his girlfriend in January 2017.

A toxicologist told Wednesday's inquest he rarely saw those particular drugs combined.

"And for good reason because they often lead to fatal outcomes," Dimitri Gerostamoulos, from the Victorian Institute of Forensic Medicine, said.

Ms Spanos will hand down her inquest findings at a later date.

Australian Associated Press