Teen pot smokers run high risk of schizophrenia, Israeli researchers find

Greatest risk found when cannabis used by genetically-predisposed adolescents.

A marijuana leaf (photo credit: REUTERS)
A marijuana leaf
(photo credit: REUTERS)
Teenagers who are susceptible to schizophrenia may trigger that disorder by using marijuana, according to findings of Tel Aviv University researchers that were recently published in the journal Human Molecular Genetics.
Hallucinations, delusions and an inability to experience pleasure are just some of the afflictions experienced by victims of schizophrenia, a disorder of chemical reactions in the brain believed to be triggered by the interaction of genetic and environmental factors.
The research results are cause for concern, given the widespread and growing use of medical cannabis – with Health Ministry permission – by tens of thousands of patients who suffering from pain and other medical problems.
Medical marijuana in Israel , use of medical cannabis in Israel (credit: REUTERS)
The study by Dr. Ran Barzilay under the supervision of Prof. Dani Offen of Tel Aviv University’s Sackler School of Medicine found that smoking or using cannabis in other ways during adolescence may serve as the catalyst for schizophrenia in individuals already susceptible to the illness.
“We showed in a controlled paradigm that cannabis has a differential risk on susceptible versus non-susceptible individuals,” said Barzilay, a child-and-adolescent psychiatrist and the study’s principal investigator. “In other words, young people with a genetic susceptibility – who have psychiatric diseases in the family – should bear in mind that they are ‘playing with fire’ if they smoke pot during adolescence.”
Researchers exposed mice with a genetic susceptibility to schizophrenia – the mutant DISC-1 gene – to THC, the most significant psychoactive compound in cannabis. During a specific time period – equal to that of human adolescence – the susceptible mice were found to be at a far higher risk for lasting brain defects related to the onset of schizophrenia.
Four groups of mice were used in the experiment: genetically susceptible and exposed to cannabis; genetically susceptible and not exposed to cannabis; genetically intact and exposed to cannabis; and genetically intact and not exposed to cannabis.
The results of various behavioral tests and neurological biochemical analyses found that only the genetically susceptible mice developed behavioral and biochemical brain pathologies relevant to schizophrenia after being exposed to cannabis.
“The study was conducted on mice but it mimics a clinical picture of ‘first episode’ schizophrenia, which presents during adolescence in proximity to robust cannabis use,” said Barzilay.
The research team, which included Prof. Inna Slutsky and Hadar Segal-Gavish of Sackler; Prof. Abraham Weizman of Geha Medical Health Center; and Prof. Akira Sawa of Johns Hopkins Medical Center – also discovered the mechanism by which cannabis and the specific gene interact.
“A protective mechanism was observed in the non-susceptible mice,” explained Offen. “This mechanism involves the upregulation of a protective [brain-derived] neurotrophic [relating to the growth of nervous tissue] factor, BDNF, in the hippocampus. We showed in the study that if we artificially deliver BDNF to the genetically susceptible mice, they could be protected from the deleterious effect of THC during adolescence.
“This research clearly has implications in terms of public health – the differential risk of cannabis use in vulnerable adolescents and in future drug development – the molecules that induce BDNF function and protect the adolescent brain from the deleterious effect of cannabis.”