The links between cannabis use and psychosis has long been of interest to scientists, with studies in recent times indicating that a gene called AKT1 affects the likelihood of cannabis users developing a psychotic disorder.
Now, for the first time, researchers in the UK have shown that this gene also mediates the acute response to cannabis in healthy individuals. This means AKT1 can be used to predict how susceptible people are to the mind-altering effects of the drug, and the gene pathway might be a target for the prevention and treatment of cannabis psychosis.
"These findings are the first to demonstrate that people with this AKT1 genotype are far more likely to experience strong effects from smoking cannabis, even if they are otherwise healthy," said psychopharmacologist Celia Morgan from the University of Exeter. "To find that having this gene variant means that you are more prone to [the] mind-altering affects of cannabis when you don't have psychosis gives us a clue as to how it increases risk in healthy people."
According to the researchers, about 1 percent of cannabis users end up developing psychosis, with those who smoke the drug daily doubling their risk of experiencing a psychotic disorder. While previous research has found a high prevalence of a particular variant of the AKT1 genotype in cannabis users with psychosis, it wasn't known how the gene and the effects of smoking cannabis tied together.
To figure this out, the scientists enlisted the help of 442 healthy young cannabis users who were tested both under the influence of the drug and while sober. The extent of symptoms of intoxication and the effects of memory loss were measured when the participants were under the influence, then compared with the results of new tests 7 days later, when the users were drug-free.
The researchers found that those with the AKT1 gene variation were more likely to experience a psychotic response. This is important to know, because it's thought that frequent psychotic responses could be linked to a heightened risk of developing a psychotic disorder.
Also, when it comes to short-term memory impairment, women were more susceptible than men.
"Animal studies have found that males have more of the receptors that cannabis works on in parts of the brain important in short term memory, such as the prefrontal cortex," said Morgan. "We need further research in this area, but our findings indicate that men could be less sensitive to the memory impairing effects of cannabis than females."
The researchers hope that their findings, which are reported in Translational Psychiatry, could help identify those who might be most at risk of the negative effects of cannabis, and envision a genotype-targeted medication that could prevent people from developing a psychotic disorder through recreational use.
"Putting yourself repeatedly in a psychotic or paranoid state might be one reason why these people could go on to develop psychosis when they might not have done otherwise," said Morgan. "Although cannabis-induced psychosis is very rare, when it happens it can have a terrible impact on the lives of young people. This research could help pave the way towards the prevention and treatment of cannabis psychosis."