The nature of the relationship between cannabis and psychiatric disorders has been hotly debated for decades. A new study, using genetically modified mice, adds more fuel to an already blistering blaze.
Cannabis is, by far, the most commonly used illicit drug both across the United States and globally.
According to the 2015 National Survey on Drug Use and Health, 22.2 million people had used the drug in the previous month.
Furthermore, according to the Monitoring the Future Study of 2016, almost half of 12th graders have tried marijuana at least once in their life.
Because of its prevalence and the new legislation affecting its legality in the U.S., research into its pros and cons is at an all-time high.
Over the years, the question of whether cannabis is linked to psychiatric conditions has been investigated many times. Research has produced mixed results.
What seems clear is that, if there is a relationship, it is a complex one. A range of factors appears to play a part, such as the age at which marijuana is first used, how much and how often it is consumed, and genetic vulnerabilities.
The psychosis-cannabis question
To date, the consensus is that cannabis use increases the risk of psychosis but, across the population, the effect is relatively small. However, the effect seems to be stronger in individuals who are already at risk, such as people with a family history of psychotic disorders or those who have experienced childhood abuse.
The latest researchers to throw their hat into the ring of fire hail from Tel Aviv University (TAU) in Israel. Their results are published this week in the journal Human Molecular Genetics. A mouse model was used in this particular study - more specifically, a strain of mice with a mutant DISC-1 gene. These mice have a genetic susceptibility to developing schizophrenia and were split into four experimental groups:
- susceptible mice exposed to tetrahydrocannabinol (THC), which is the psychoactive compound found in cannabis
- susceptible mice not exposed to THC
- normal mice exposed to THC
- normal mice not exposed to THC
The exposure to THC came at a point in their life equivalent to human adolescence.
Neurological biochemical analysis and behavioral tests carried out on the animals showed that only the genetically susceptible mice developed schizophrenia-related changes after being exposed to cannabis.
Dr. Ran Barzilay, a child and adolescent psychiatrist at TAU's Sackler School of Medicine, explains that: "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."
The study confirms the conclusions of earlier research: that cannabis is most likely to produce long-term psychiatric effects in individuals who are most susceptible.
"Our research demonstrates that cannabis has a differential risk on susceptible versus non-susceptible individuals. In other words, young people with a genetic susceptibility to schizophrenia - those who have psychiatric disorders in their families - should bear in mind that they're playing with fire if they smoke pot during adolescence."
The role of BDNF and the hippocampus
Alongside the original study, the scientists investigated potential pathways that might explain the increased schizophrenia risk with cannabis use. One of the lead researchers, Prof. Dani Offen, explains their theory: "A protective mechanism was observed in the non-susceptible mice. This mechanism involves the upregulation of a protective neurotrophic factor, BDNF [brain-derived neurotrophic factor], in the hippocampus."
The hippocampus is a region of the brain heavily involved in emotion and memory. Scientists have found a range of anatomical and functional differences in the hippocampus of individuals with schizophrenia.
To test their theory, the researchers gave BDNF to the schizophrenia-susceptible mice. They found that THC exposure no longer produced psychiatric symptoms. The introduction of BDNF prevented the development of schizophrenia. Normally, BDNF supports existing neurons and encourages the growth of new synapses and neurons.
Overall, the study's findings have clear implications for public health. The authors warn that young people who have a family history of psychiatric conditions or have responded strongly to drugs previously should be particularly cautious around marijuana during their adolescence.
Additionally, the relationship between cannabis, schizophrenia, and BDNF can now be explored to help design drugs that could reduce the negative consequences of cannabis on psychiatric health.
Because this study was conducted on mice, it will not finalize the debate around cannabis and psychiatric conditions, and more work will need to be done. However, it adds further weight to the theory that cannabis increases the risk of developing schizophrenia in individuals who are particularly susceptible.