Recent research supports the theory that cannabis can increase the risk of schizophrenia symptoms in users, but only those with a genetic predisposition to the condition. This may imply that there is no increased risk of schizophrenia for those who lack this predisposition. However, further research must be done before firm conclusions on the precise relationship between cannabis use and schizophrenia can be drawn.
The AKT1 gene, linked to several genetic conditions
The gene in question is AKT1, which is responsible for production of the AKT1 kinase protein. This protein plays several key functions within various types of cell, where it regulates proliferation (growth and division of new cells), differentiation (maturation to different cell types) and apoptosis (programmed cell death).
Significantly, AKT1 kinase also plays an important role in neuronal signalling, where information is passed along cells in the central nervous system to control movement, speech and thought. It is believed to be particularly important in the formation of new memories.
As well as schizophrenia, variation or mutation of the AKT1 gene is also thought to be linked to Proteus syndrome (the most famous sufferer was Joseph Merrick, the “Elephant Man”), and several cancers including breast, ovarian and colorectal. A particular mutation of the gene, Glu17Lys, causes over-production of AKT1 kinase protein, which leads to abnormal proliferation of cells. This mutation is linked to Proteus syndrome, explaining the overgrowth of bone and tissue linked to the disease, and is also linked to the aforementioned cancers.
Mutations of the AKT1 gene are often somatic in origin
Due to this link between the AKT1 gene and these cancers, it is considered an oncogene – a gene that has the potential to cause cancer. These genes are usually over-expressed or mutated in tumour cells, but may express normally in other parts of the body. It is important to note that in cancer, the mutation of the AKT1 gene is somatic, meaning that it occurs within the individual’s lifetime rather than being inherited from a parent.
With Proteus syndrome too, the gene mutation is not inherited, but occurs randomly during development. Affected cells proliferate simultaneously with other, normal cells, leading to a condition known as mosaicism, where normal cells are mixed with mutated versions.
Therefore, it could be possible that a similar somatic mutation, perhaps arising as a result of an external or environmental factor, could be responsible for the increased risk of schizophrenia. Conversely, the specific mutation may arise from an as-yet-unknown abnormality during otherwise-normal cell division.
Further research to determine the cause of the mutation is definitely needed, as an environmental factor could arguably be cannabis itself. Until it is clear that cannabis use itself is not a factor, it is erroneous to believe that simply not having the mutation means that it is safe to use cannabis without moderation. In addition, cannabis users should be aware that – short of genetic testing – there is no way of knowing whether the mutation is present within an individual, or not.
How variation of the AKT1 gene may affect predisposition to schizophrenia
The variant of the AKT1 gene linked to an increased risk of schizophrenia is known as the rs2494732 genotype. In a recent study, cannabis users with this mutation were found to have a twofold increase in probability of a psychotic disorder, rising to seven-fold if the individual used cannabis every day. Ironically, carriers of the rs2494732 mutation were also more likely to use cannabis frequently.
Researchers focused on the AKT1 gene as it is known to affect dopamine signalling in the brain, which is often abnormal in patients with neuropsychiatric conditions such as schizophrenia. However, it is not yet clear if the disease can be fully explained by genetically-caused dopamine overabundance, as there are various other significant factors at work.
This result supports a wealth of anecdotal information suggesting that while many people can smoke cannabis regularly without fear of a psychotic episode, there is a minority that is greatly affected by the potent cannabinoids contained within it. For these susceptible individuals, cannabis use during adolescence (while the neuronal pathways are still developing) may greatly increase the risk of psychotic illness.
However, even a positive test for the presence of the rs2494732 variant is not a reliable indicator of the likelihood of an individual being negatively affected by consuming cannabis. There are countless chemical interactions occurring during cannabis use which have yet to be fully explored, and until more is understood about the processes at work, firm conclusions cannot be drawn.