Researchers have discovered a genetic “switch” which may explain why some people are more susceptible to conditions such as obesity and addiction.
The “switch” may also play a role in chronic pain and psychosis and Aberdeen scientists believe that the findings, published in the Journal of Biological Chemistry, might help our understanding of these conditions and also be a step towards the development of personalised therapies to help treat them.
The team from Aberdeen University’s Kosterlitz Centre for Therapeutics studied genetic differences around the gene CNR1.
This gene produces what are known as cannabinoid receptors, which are found in the brain, and which activate parts of the brain involved in memory, mood, appetite and pain.
These receptors activate areas of the brain when they are triggered by chemicals produced naturally in our bodies called endocannabinoids.
Chemicals found in the drug cannabis mimic the action of these chemicals and there is growing evidence, according to researchers, that cannabis has pain relieving and anti-inflammatory properties which can help treat diseases such as multiple sclerosis and arthritis.
However, developing drugs from cannabis to treat these conditions is hampered by the fact that such drugs will have psychoactive side effects and smoked cannabis can cause addiction and psychosis in up to 12% of users.
In order to understand more about these side effects and the genetic factors which determine how people respond, scientists studied genetic differences around the gene.
Dr Alasdair MacKenzie, who helped lead the team, said: “We chose to look at one specific genetic difference in CNR1 because we know it is linked to obesity and addiction. What we found was a mutation that caused a change in the genetic switch for the gene itself – a switch that is very ancient and has remained relatively unchanged in over 300m years of evolution, since before the time of the dinosaurs.
“It is normally thought that mutations cause disease by reducing the function of the gene, or the switch that controls it. In this case however, the mutation actually increased the activity of the switch in parts of the brain that control appetite and pain, and also – and most especially – in the part of the brain called the hippocampus, which is affected in psychosis.
Dr Scott Davidson, who played a key role in the discovery of this genetic difference in the switch, added: “Further analysis of this mutation will help us to understand many of the side effects which are associated with cannabis use such as addiction and psychosis.”
Professor Ruth Ross, head of the Kosterlitz Centre and an internationally recognised expert in cannabis pharmacology, said: “Previously in drug research, attempts to detect the causes of adverse drug reactions have focused on the genes themselves.
“Our study is one of the first to explore the possibility that changes in gene switches are involved in causing side effects to drugs. We believe this approach will be crucially important in the future development of more effective personalised medicine, with fewer side effects.”
One question that is intriguing the research team is why this overactive genetic switch evolved in the first place.
Dr MacKenzie said the switch was rare in Europeans but common in the African population.
“We were all once African, so something must have decreased it in our early ancestors who left Africa and migrated through Central Asia towards Europe and the north.”
Hs said the one possibility was that migrants in Central Asia coming into contact with the cannabis plant could have decreased mutation across generations.
“This work is at a very early stage however, and there are likely to be more exciting discoveries – not only on how these differences came about, but also about the role of this genetic switch in health and disease,” he added.