Scientists have identified a mechanism in the brain that seems to explain how long-term marijuana use in the teenage years might lead to schizophrenia and other similar psychiatric diseases in adulthood. They also showed how drugs might be able to reverse the schizophrenia-like symptoms.
In a paper published in the journal Scientific Reports, researchers from the University of Western Ontario in Canada report how they showed this effect in laboratory rats.
Marijuana refers to the dried parts - that is, the flowers, leaves, stems, and seeds - of the Cannabis sativa or Cannabis indica plants.
The plants contain a number of psychoactive (mind-altering) compounds, or cannabinoids, with the main one being delta-9-tetrahydrocannabinol (THC).
In the United States, marijuana is the "most commonly used illicit drug," and use is widespread among adolescents and young adults.
Last year, around 9.4 percent of 8th graders and 23.9 percent of 10th graders in the U.S. said that they had used marijuana at least once in the previous year.
However, the highest use was among 12th graders, with 35.6 percent of them saying that they had used it at least once in the previous year, and 6 percent saying that they used it every day or nearly every day.
Focus on GABA
In their study paper, senior author Steven Laviolette - a professor at the University of Western Ontario's Schulich School of Medicine and Dentistry - and colleagues explain that while it is "still a matter of debate," some studies have suggested that long-term exposure to THC raises the long-term risk of schizophrenia and other psychiatric diseases.
In fact, in some of their own previous work with animal models, the team had found that long-term exposure to THC leads to "persistent abnormalities in adulthood resembling schizophrenia."
They had also found that these abnormalities are accompanied by changes in the prefrontal cortex region of the brain and increased activity in the region's dopamine system.
Dopamine is a chemical messenger, or neurotransmitter, that plays a number of roles - such as helping to regulate brain centers involved with reward, pleasure, movement, and emotion. Insufficient dopamine is a hallmark of Parkinson's disease.
However, the researchers note that the underlying mechanism linking the brain changes to the schizophrenia-like symptoms has remained somewhat of a mystery, and so they devised the new study to investigate it further, focusing on another chemical messenger called GABA.
"GABA is an inhibitory neurotransmitter and plays a crucial role in regulating the excitatory activity in the frontal cortex, so if you have less GABA, your neuronal systems become hyperactive leading to behavioural changes consistent with schizophrenia," explains study co-author Justine Renard, a postdoctoral fellow.
'Hyperactive dopamine system'
After exposing adolescent rats to THC, the team found that it reduced GABA and caused neurons in the animals' frontal cortex to become hyperactive in adulthood. The rats also developed schizophrenia-like symptoms such as higher levels of anxiety and lower social motivation.
As well as becoming hyperactive, the frontal cortex neurons also became "out of synch with each other," as evidenced by disruptions in a type of brain wave called gamma waves.
Moreover, the reduction in GABA resulted in a "hyperactive dopamine system," which is commonly seen in the brains of people with schizophrenia.
Finally, the researchers found that they could reverse these effects in the brain and in the rats' behavior by using drugs that activate GABA.
Prof. Laviolette says that the discovery that they could reverse the effects with drugs is particularly well timed for Canada, where marijuana is about to become legal.
He explains that this could mean that people might be able to combine use of marijuana - either for recreational or medicinal purposes - with compounds that increase GABA to protect against the potentially adverse effects of THC exposure.
The team now plans to investigate the safety and effectiveness of combinations of cannabinoids and GABA-boosting drugs in the treatment of depression, addiction, anxiety, and other mental health conditions.
"What is important about this study is that not only have we identified a specific mechanism in the prefrontal cortex for some of the mental health risks associated with adolescent marijuana use, but we have also identified a mechanism to reverse those risks."
Prof. Steven Laviolette