It is believed N-Bomb, linked to five deaths in the US, was among the substances taken by Antony Storrie, 25, who died after a party at his Paisley flat on Saturday.
It has emerged he was arrested over his "aggressive" behaviour. Police sources say he became out of control when he was unwell and officers took him to hospital. He was pronounced dead the next day.
The Crown Office has now asked the Police Investigations and Review Commissioner (PIRC) to investigate the circumstances.
A spokeswoman for the Police Investigations and Review Commissioner said: "The Commissioner will submit a report into the findings of the investigation to Crown Office and Procurator Fiscal in due course."
A post-mortem is taking place to establish the cause of death, but sources suggest Mr Storrie had taken "a whole array of stuff".
Police said they were not treating the death as suspicious.
One of the substances thought to have been taken is 25I-NBOMe, known as N-bomb, which mimics the psychoactive effects of LSD.
It was freely available on the internet until last month, when the Government issued a temporary class drug order.
Legal highs are synthetic substances which bear resemblance to illegal drugs.