Medicinal cannabis is back in the news again after a planned trial to grow it in Norfolk Island was blocked by the federal government last week. The media is ablaze with political rumblings and tales of public woe, but what does science have to say on the subject?
Well, an article just published in the prestigious journal JAMA Internal Medicine provocatively suggests that US states with medical cannabis laws have dramatically reduced opioid mortality rates.
So the science is clearly every bit as alive and kicking as the political bluster, but rests on firmer, less emotive grounds. This is what we know: somewhere in that much-incinerated plant lies valuable medicine - perhaps a treatment for cancer or an antidote to obesity.
In fact, cannabis science is one of the fastest moving frontiers in pharmacology and has accelerated by the realisation that we're all already marinated in cannabis-like molecules (endocannabinoids) and their receptors.
Endocannabinoids help regulate many physiological processes: mood, memory, appetite, pain, immune function, metabolism and bone growth to name a few (there are even cannabinoid receptors in sperm).
Consuming cannabis modulates this endocannabinoid system in many ways. And the effects can be benevolent, although sometimes problematic.
Cannabis' changing fortunes
Humanity has used cannabis as medicine for thousands of years; the current era of prohibition is a historical aberration. But murky politics has seen a plant that has been widely utilised for clothing, fuel, food, fibre and medication ostracised - from nautical rope to killer dope.
Now, the pendulum is swinging back. Cannabis is legal in two of the United States of America, and a prescribed medicine in a further 23. Many other countries are also rapidly revising their attitudes.
But if we're going to rediscover the therapeutic value of cannabis - and we probably should - then there's much to be gained from examining recent developments in cannabinoid science.
Cannabis contains more than 120 different cannabinoid molecules. But, as far as we know, only one gets you stoned: THC. The plant contains a cornucopia of non-psychoactive, non-intoxicating THC cousins with emerging medicinal potential.
Their abbreviated names resemble a bad Scrabble hand: CBD, CBG, THC-V, CBC, and CBN to mention a few. These have the potential to heal without making you a paranoid, gormless grinner.
Cannabidiol (CBD) is perhaps the most interesting of the lot: a non-intoxicating cannabinoid that is present in variable amounts in different cannabis samples and moderates the actions of THC in the brain. Smoking high-cannabidiol weed appears less likely to cause psychosis, paranoia and cognitive impairment than low-CBD varieties.
Cannabidiol given alone has antipsychotic effects as efficacious as standard anti-psychotic drugs but with fewer side effects. It also has remarkable effects in treating intractable childhood epilepsy that cannot be treated with conventional anti-convulsants.
Cannabis plants appear genetically programmed to produce THC or CBD. But our recent analysis shows cannabidiol is bred out of street cannabis in Australia. Bringing it back may maximise cannabis' medicinal potential and lessen the adverse mental health consequences of smoking weed.
The cannabinoid molecule that causes the high from cannabis, THC, mostly exists in plants as non-psychoactive THC-A (more than 80% of plant THC is in the form of THC-A). Cannabis must be heated above 170 Celsius to transform THC-A into the psychoactive THC. This is why pleasure seekers smoke, bake or vaporise their weed.
THC-A is anti-inflammatory and neuroprotective, and if plant material is ingested without heating, for example by juicing, then non-psychoactive THC-A effects are maximised and intoxication minimised. This also reduces the long-term hazards involved in smoking.
THC-V is another non-psychoactive cannabinoid that may actually block cannabinoid receptors, reducing appetite and the tendency to store fat, and making it a potentially wonder treatment for obesity.
One cannabis-derived product is already approved in Australia; Sativex oral spray contains equal amounts of THC and CBD. Absorbed across the mucous membranes of the mouth, Sativex reduces muscle spasms in multiple sclerosis. The route of absorption gives low and steady levels of THC and CBD in blood, in contrast to the often-disorienting THC tsunami obtained with smoked cannabis.
In our recent study, cannabis users given high doses of Sativex in a Cannabis Replacement Therapy clinical trial could not discriminate it from placebo, and reported little intoxication.
We now know that the right cannabinoids, prepared and administered appropriately, might deliver medical benefits while minimising intoxication. So there's certainly no good scientific rationale for prosecuting those supplying high CBD strains, or preparations that maximise consumption of THC-A, THC-V or other non-psychoactive cannabinoids.
Indeed, blindly scheduling the bad-scrabble cannabinoids in the cannabis regulatory bracket limits future research.
Even THC is a legitimate target for ongoing medical research, particularly when dosed in forms that give slow and steady blood levels.
THC clearly has important therapeutic effects in multiple sclerosis and pain, in stimulating appetite in HIV or cancer patients, and even for anxiety disorders, such as post-traumatic stress disorder.
No medicine is perfect: opiates control pain but may be addictive and constipating; antidepressants lift mood but may numb you out and ruin your sex life; statins can lower your cholesterol but can cause muscle wastage. All drugs are poisons, it's just a matter of the dose you're taking.
Cannabis has its own positives and negatives, and the risks involved in its regular use, particularly during adolescence, continue to be well ventilated. But if we're clever about our use, then it can be a most valuable therapeutic: a voyage of rediscovery is long overdue.
We're currently recruiting participants for two cannabinoid research studies in Sydney. The first is looking at regular, non-treatment seeking cannabis users to help us understand the role of the endocannabinoid system in pain perception, while the other is recruiting people who need help with problematic cannabis use, examining the effects of daily exercise on endocannabinoid release and stored THC.
David J. Allsop is a Research Fellow in the Psychopharmacology Laboratory, and in the Discipline of Addiction Medicine at the University of Sydney. He receives funding from NHMRC. GW Pharmaceutical provided Sativex for our study.
Iain S. McGregor is Professor of Psychopharmacology, NHMRC Principal Research Fellow and Director of the Psychopharmacology Laboratory in the School of Psychology at the University of Sydney. He receives funding from NHMRC and ARC. GW Pharmaceutical provided Sativex for our study.