The spray called Sativex is being trialled as evidence mounts for medicinal use of cannabis in people with cancer and multiple sclerosis.
Dr Brian Le, a palliative care specialist at the Royal Melbourne Hospital, said four Australian hospitals were participating in the study which involves about 300 patients in 20 locations around the world.
The trial is the last of several studies required for manufacturer GW Pharmaceuticals to try to license the drug in Australia, the Sydney Morning Herald reported.
A spokeswoman for Novartis, the company employed by GW Pharmaceuticals to commercialise the drug in Australia, said it was also working with the Therapeutic Goods Administration to make Sativex available to patients with multiple sclerosis who suffer from uncontrolled muscle spasticity.
No pharmaceutical drugs based on cannabis are currently licensed for use in Australia. Since 2004, health authorities in the UK, Canada and Spain have licensed Sativex for patients with MS, a neurological condition that causes painful muscle stiffness in about 90 per cent of sufferers.
While cannabis has been strongly associated with mental illness, Le said phase one and two trials of Sativex in more than 400 cancer patients found it relieved pain with few side effects, the most common being nausea.
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He said psychiatric side effects were very rare in the doses used and that patients did not report feeling "stoned".
"Our experience is that pain improves and the patients actually feel better. They're more able to do daily activities, sleep better through the night without pain and think clearly, so instances of feeling confused or 'out of it' are low," he said.
"They don't feel better because they're stoned, they feel better because their pain is well controlled," he said.
The drug works by targeting cannabinoid receptors in the brain.
"Cannabinoid receptors are like morphine receptors in the body, they mediate how the pain is sensed and how that pain message is transmitted to the brain and therefore perceived, so it reduces the conduction of that message to say there is pain occurring," he said.
Director of the National Cannabis Prevention & Information Centre Professor Jan Copeland said low doses of Sativex was unlikely to have the same effect on people as illicit cannabis.
Copeland said it was made of almost equal parts of the drug's two psychoactive properties: tetrahydrocannabinol (THC), the psychoactive part of cannabis that most recreational users look for, and cannabidiol (CBD), the "good cannabis" which typically lowers anxiety and psychotic symptoms.