Study: Cannabis use during adolescence significantly increases the risk of schizophrenia among genetically predisposed adolescents

A study conducted at Tel Aviv University found that using cannabis during adolescence significantly increases the risk of schizophrenia among genetically predisposed adolescents. The researchers identified the biological mechanism that contributes to the outbreak of the disease when using cannabis.

The use of cannabis (marijuana, hashish and cannabis substitutes such as "Nice Guy") significantly increases the risk of schizophrenia among genetically predisposed teenagers - according to a new study published this month (April 2017) in the prestigious journal Human Molecular Genetics.

The study was conducted by a team of researchers from Tel Aviv University led by Dr. Ran Barzilai, Prof. Daniel Ofen and research student Hadar Segal Gabish, in collaboration with Prof. Ina Slutsky from Tel Aviv University, Prof. Avraham Weizman from the Gaha Mental Health Center and Prof. Akira Sawa from G University Vince Hopkins in Baltimore.

"Schizophrenia is a serious disease that erupts in adolescence, probably due to genetics and environmental damage," says Prof. Ofen. "Unfortunately, the set of genes that may trigger the disease of schizophrenia is still not clear, but it is known about a number of genes that a mutation in them may increase the risk level of the onset of the disease. One of those genes is called DISC-1. In our current study, we examined whether the use of THC, the active substance in cannabis, may advance the onset of the disease or make it worse."

The researchers used young mice with the defective DISC-1 gene. The mice were treated for several days with THC, and then underwent several behavioral and biochemical tests. In the control group, the researchers followed healthy mice that were also treated with THC. "Basically, we tested whether the mice with the defective gene, which represent the population with the genetic predisposition to the disease, would react differently to THC treatment," explains Prof. Ofen.

"Among those young mice with the defective gene that were exposed to THC, we saw a significant increase in the behavioral signs associated with schizophrenia, including damage to brain functions," says Hadar Segal Gabish, who performed the research as part of her doctoral thesis. "From other studies done on patients, we know that adolescence is the critical period for the onset of the disease. In the new study, we found that at a young age, the combination of a genetic predisposition to schizophrenia and the use of THC worsens the signs of the disease."

The researchers even identified the biological mechanism responsible for combining the explosive. Healthy mice treated with THC increased the level of the protein BDNF in the brain, which apparently counteracts the effects of THC, while the mice with the genetic damage failed to increase the level of the protein. In the second phase of the study, the researchers injected the BDNF protein into the hippocampus region of the brain, and showed that the protein prevents the damage of cannabis.

Confirmation of the clinical observations

According to Dr. Barzilai, who also serves as a physician and a child and youth psychiatrist in Gaha, the new study confirms clinical observations. "As someone who works with teenagers, I see a lot of young people between the ages of 15-25 whose disease broke out around the time of using cannabis or synthetic cannabis. Our study tried to mimic in a murine model the clinical picture we see in patients. In the research, we clearly showed that the disease does not break out only as a result of genetic predisposition, but our behavior and life circumstances have a decisive contribution. There are young people with a certain genetic profile who can live up to 120 in peace, but if those young people are exposed to marijuana, hashish or 'Nice Guy', the chance that they will develop schizophrenia is very high. This is a warning light regarding the uncontrolled use of cannabis against the backdrop of legalization trends in Israel and the world. Without diminishing at all the positive aspects of cannabis - for example, in the treatment of chronic pain in adults - we must be careful with the exposure of seemingly healthy young people to THC."

Although the biological mechanism identified by the researchers can be used in the future to prevent the harms of cannabis among teenagers who are genetically predisposed to schizophrenia, Dr. Barzilai estimates that it will take some time before the findings of this study lead to treatment.

"It may be possible to increase the level of the BDNF protein to prevent the outbreak of the disease among teenagers who use cannabis, and perhaps in the future such preparations will be developed. But until that happens, I suggest, as a psychiatrist, to both young people and the authorities, to exercise extra caution. Young people who have a family history of psychiatric illnesses, or young people who have previously reacted in a severe and unusual way to drugs, are playing with fire when they use cannabis."