Genetic ‘switch’ proves a breakthrough over side effects of cannabis drugs
RESEARCHERS have discovered a genetic “switch” which influences how people will respond to cannabis-based drugs.
The scientists at Aberdeen University believe the finding could be used to distinguish patients who would benefit from medicines containing cannabinoid compounds from those who would be likely to suffer adverse side effects, including depression and psychosis.
Although promising, the therapeutic potential of cannabinoids has been hampered by unpredictable side effects.
It is also hoped the research will pave the way to more genetically-tailored prescribing for other drugs, and a greater understanding of the mechanisms behind addiction, overeating or excess alcohol consumption.
The team, led by Dr Alasdair Mackenzie and including leading cannabis researcher Professor Roger Pertwee, used revolutionary DNA technology called CRISPR to pinpoint and then “knock out” the switches of a gene found to control cannabis receptors in the brain.
When they conducted the experiment in mice they found that alcohol intake and anxiety levels were reduced, as were the effects of cannabinoids. The switch is also associated with increased addiction to smoking.
Dr Mackenzie said: “We know there is a link between cannabis, food intake and addiction. It’s quite a complicated story but by identifying these switches we are hoping to burrow down and find out not only why people suffer side effects from cannabinoids but the mechanisms that control things like addiction and alcohol intake.”
Dr Mackenzie said the potential would be as a predictive tool and not a path to “genetically engineering people” to benefit from cannabinoids.
He said: “If we were able to use this as a prediction of those people who might suffer psychosis or depression as a result of taking cannabinoid drugs then we can start predicting who would most benefit, and winnow out the people who would suffer these adverse effects.
“Essentially we’re just trying to make these drugs safer and more effective by identifying the part of the gene required to switch it on.”
Professor Pertwee, a world expert in the therapeutic potential of cannabinoids, added: “By starting to look at the effects of genetic changes on the switches that turn genes on and off in specific cells and at specific times, instead of changes in the genes themselves, we can begin to understand how drug side effects arise in different patient groups and focus treatment using these drugs on those who would most benefit.”
Although it is unclear why, this genetic switch appears to have occurred millions of years ago in evolution and has remained almost identical ever since. It is found in animals from lizards to some fish, as well as mice and humans.
Dr Mackenzie added that the research could lead to better understanding the genetic basis for side effects in other drugs.
“I know there are people in the population who take two or three drugs but on top of that they take seven others to reduce the side effects of the first two.
“If we could make drugs more targeted for individuals then it would be good for those individuals, the economy, and the health service.”
The findings are published in the journals Psychoneuroendocrinology and Human Mutation.