Every four hours an Australian is dying of a drug overdose, prompting a renewed call for urgent action to combat the long-term crisis.

An annual report by public health research group Penington Institute shows there were 2231 drug-induced deaths reported in Australia in 2021.

Of those, 1675 were unintentional.

"The annual number of unintentional drug-induced deaths surpassed the road toll in 2014," reads the 244-page report published on Sunday.

"The gap between the two has continued to widen ever since."

Seven out of 10 unintentional drug overdose deaths in 2021 were men and Indigenous Australians were almost four times more likely to die under those circumstances than non-Indigenous Australians.

The most common drug found in people's systems was opioids, contributing to 45.7 per cent of overdose deaths in 2021.

Opioids, which are prescribed as pain relief but are often linked to addiction and abuse, were found in 81 per cent of deaths involving multiple substances.

Deaths linked to the synthetic opioid fentanyl were cited by the report as a major cause for concern after skyrocketing by more than 800 per cent since 2001.

The global opioids crisis has coincided with drug overdose death rates increasing across all Australian age brackets above 30 over the past 20 years, especially among 50 to 59-year-olds (298 per cent).

Despite Australia's population only growing by 33 per cent in that time span, unintentional drug deaths have risen by 71 per cent.

The institute started producing the annual overdose report eight years ago to drive change, but its chief executive John Ryan said the response has been wholly inadequate compared to the scale of the problem.

"The time to address this national crisis is now," he said.

"We already have the tools and know-how to reduce overdose deaths - we just need to do it by implementing evidence-based solutions, supporting access to treatment, and closing the gap in overdose death rates between Indigenous and non-Indigenous Australians."

Drug overdose death numbers from 2021 are likely to rise further as the data is revised and finalised in coming years.

UNINTENTIONAL DRUG-INDUCED DEATHS BY DRUG TYPE IN 2021:

* Opioids - 765

* Benzodiazepines - 544

* Stimulants - 461

* Anti-depressants - 324

* Alcohol - 313

* Anti-convulsants - 206

* Anti-psychotics - 187

* Cannabinoids - 165

* Cocaine - 87