The research, funded by the nation's top health authority, will put licensed drivers to the test in a hi-tech simulator after they have consumed alcohol, codeine and the anti-anxiety drug oxazepam.
Lead researcher Dr Stefanie Leung said the rationale behind the research was the alarming number of road accidents in which the driver was found to test positive to everyday prescription medicines.
"People generally believe that it is safe to drive after taking medicines, simply because they have been prescribed by a doctor and are being used responsibly," said Dr Leung from the University of Sydney and the Research on Alcohol Drugs and Driving (RoADD) group.
"While it is widely accepted that recreational drug use impairs driving, it now appears that taking prescribed medicines could also compromise safety on the road."
Benzodiazepines - which have a relaxing effect - and painkilling opioids are thought to play a role in around 15 per cent and four per cent of serious road crashes respectively.
Dr Leung said the research would be held over several medically supervised sessions, and participants will be given "therapeutic" doses of the drugs.
The volunteers would then be asked to complete a series of driving tests in an advanced driving simulator.
They would also do the same after consuming enough alcohol to raise their blood alcohol level to 0.05, placing them on the cusp of illegal drink driving.
Dr Leung said the research, funded by the National Health and Medical Research Council, would improve understanding of how the common medicines affected driving ability.
"We want to improve that understanding and raise awareness of the risks of driving while taking medication, and hopefully help to reduce the senseless road toll," she said.
"This is not about marginalising people that have to take medicines. This is about ensuring everyone's safety on the road."
Volunteers must have a medical assessment prior to starting.
They must be aged 25 to 50, hold a current driver's licence and be willing to attend Sydney's Royal Prince Alfred Hospital for the experimental sessions over a period of several weeks.
RoADD is a national collaborative group comprising researchers from the University of Sydney, Monash University Accident Research Centre and the University of Tasmania.
To register call (02) 9515 7210 or email drivingmed.usyd.edu.au.