In a compelling new study, researchers at Johns Hopkins Medicine have established a fascinating hypothesis attempting to explain how marijuana use in some teenagers can result in cognitive impairment in adulthood. The research also suggests anti-inflammatory therapies may be able to prevent the marijuana-induced brain damage.
"Now that marijuana is moving toward widespread legalization and recreational use, it's important to learn more about why it's not harmless to everyone," says co-senior author of the new research, Atsushi Kamiya. "There's still a lot that we don't know about how pot specifically affects the brain."
Several studies have confidently linked adolescent marijuana use to certain cognitive impairments in later life. However, the connection has not been consistent across all research leading many scientists to suspect there must be an underlying genetic component that amplifies the adverse effects of the drug. This would explain why some people can smoke marijuana as a teenager with no adverse effects in later life while others may develop memory impairments or suffer from metal health issues.
To try and better understand how marijuana can trigger cognitive problems the researchers began by focusing on a specific mouse model genetically engineered to have a mutation in a gene called DISC1. The effects of a mutation in DISC1 were first discovered in a family found to have a major heritable history of schizophrenia, bipolar disorder and major depression. So, for this new research the mutated gene acts as a good bellwether for studying whether THC amplifies its effects.
The first stage of the research revealed that when the DISC1 mice were administered THC in their adolescent stages, they went on to display enhanced cognitive deficits in later life, compared to animals not administered THC. The next step was to home in on what specific brain cells and genes were activated after THC exposure that could be associated with the worsened cognitive effects.
It was discovered that cognitive problems in the mice only developed when THC exposure triggered the mutated DISC1 gene in astrocyte cells in the brain. Astrocytes are important star-shaped glial cells that surround, and protect, neurons in the brain. Alongside this revelation the researchers discovered that 56 genes specifically related to inflammation were seemingly catalyzing the cognitive problems in relation to THC exposure.
What all this fundamentally means is that exposure to THC seems to be increasing inflammation in astrocyte brain cells, and in the presence of a specific genetic mutation, this ultimately results in brain damage and cognitive dysfunction.
"The inflammation we saw in our mice is probably activated in many people who smoke marijuana, but our results may help explain why and how some mice – and some people – are genetically predisposed to experience an enhanced inflammatory response and brain damage," says Mikhail Pletnikov, a researcher working on the project.
To test this hypothesis further the researchers restaged their experiment, but this time administered the DISC1 mice with an anti-inflammatory drug before the animals were treated with THC. The results were incredibly compelling, with the mice tested for memory or cognitive impairments later in life and displaying absolutely no signs of brain damage. The anti-inflammatory agent essentially protected the animal's brain from THC-mediated damage in adolescence.
"If our results turn out to be applicable to people, they suggest we could develop safer anti-inflammatory treatments to prevent long-term consequences of marijuana use," notes Pletnikov.
Developing a drug that protects against the potential negative effects of adolescent marijuana use isn't the primary goal of this research, though, the more pressing outcome is to better understand and identify those young people that are most at risk from the harmful effects of marijuana. The next step for this research is to further investigate the different genetic vulnerabilities that amplify marijuana's harmful cognitive effects, and hopefully be able to better target the teenagers that are most susceptible to these effects.
The new study was published in the journal Biological Psychiatry.
Source: Johns Hopkins Medicine
