Genetic Variant Could Identify Cannabis Users at Risk for Psychosis

Young, otherwise healthy people with a variation in the ‘AKT1′ gene are more susceptible to the mind-altering effects of smoking marijuana, according to research published in Translational Psychiatry.

While previous research has shown a link between the AKT1 gene and cannabis smokers who go on to develop psychosis, this study by researchers at the University of Exeter and University College London is the first to examine healthy people’s acute response to marijuana in the context of the AKT1 gene.

“The current study is the largest ever to be conducted on the acute response to cannabis. Our finding that psychotic-like symptoms when young people are ‘stoned’ are predicted by AKT1 variants is an exciting breakthrough, as this acute reaction is thought to be a marker of a person’s risk of developing psychosis from smoking the drug,” said Val Curran, PhD, from the University College London in a statement.

In order to study the relationship between the effects of cannabis and AKT1 variants, the researchers recruited 442 participants (308 men, 114 women, aged between 16 and 23 years) and measured their symptoms of intoxication and memory loss while they were under the influence of their own cannabis, and again 7 days later when they were drug free. The researchers had the cannabis samples analyzed for their make-up and strength by the forensic science service.

The researchers found that those with variation at the rs2494732 locus of the AKT1 gene predicted acute psychotic response to cannabis, along with dependence on the drug and baseline schizotypal symptoms.

“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 Celia Morgan, PhD, from the University of Exeter in a statement. “To find that having this gene variant means that you are more prone to mind-altering affects of cannabis when you don’t have psychosis gives us a clue as to how it increases risk in healthy people. 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. Although cannabis-induced psychosis is very rare, when it happens it can have a terrible impact on the lives of young people.”

The researchers also found that women were more vulnerable than men to short-term memory impairment after smoking marijuana.

“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,” added Dr 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 the findings from this study could help identify those most at risk for negative effects of cannabis smoking, and may aid in developing genotype-targeted medication.


Morgan CJA, Freeman TP, Powell J, Curran HV. AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers. Transl Psychiatry. 2016; doi:10.1038/tp.2015.219.