Regular marijuana use in adolescence may permanently impair brain function, cognition and increase the risk of developing serious psychiatric disorders such as schizophrenia, according to a recent study in Neuropsychopharmacology.

Lawmakers in Maryland and elsewhere are contemplating legalizing the drug and the study's senior author Asaf Keller, Ph.D., Professor of Anatomy and Neurobiology at the University of Maryland School of Medicine, and colleagues have weighed in. "Over the past 20 years, there has been a major controversy about the long-term effects of marijuana, with some evidence that use in adolescence could be damaging. Previous research has shown that children who started using marijuana before the age of 16 are at greater risk of permanent cognitive deficits, and have a significantly higher incidence of psychiatric disorders such as schizophrenia. There likely is a genetic susceptibility, and then you add marijuana during adolescence and it becomes the trigger."

"Adolescence is the critical period during which marijuana use can be damaging," says the study's lead author, Sylvina Mullins Raver, a Ph.D. candidate in neuroscience at the University of Maryland School of Medicine. "We wanted to identify the biological underpinnings and determine whether there is a real, permanent health risk to marijuana use."

So adults who begin using it are not found to be at similar risk.

The research began by examining cortical oscillations in mice. Cortical oscillations are patterns of the activity of neurons in the brain and are believed to underlie the brain's various functions. These oscillations are very abnormal in schizophrenia and in other psychiatric disorders. The scientists exposed young mice to very low doses of the active ingredient in marijuana for 20 days, and then allowed them to return to their siblings and develop normally.

"In the adult mice exposed to marijuana ingredients in adolescence, we found that cortical oscillations were grossly altered, and they exhibited impaired cognitive abilities," says Raver. "We also found impaired cognitive behavioral performance in those mice. The striking finding is that, even though the mice were exposed to very low drug doses, and only for a brief period during adolescence, their brain abnormalities persisted into adulthood." 

They repeated the experiment, this time administering marijuana ingredients to adult mice that had never been exposed to the drug before. Their cortical oscillations and ability to perform cognitive behavioral tasks remained normal, indicating that it was only drug exposure during the critical period of adolescence that impaired cognition through this mechanism. The researchers took the next step in their studies, trying to pinpoint the mechanisms underlying these changes and the time period in which they occur. 

"We looked at the different regions of the brain," says Keller. "The back of the brain develops first, and the frontal parts of the brain develop during adolescence. We found that the frontal cortex is much more affected by the drugs during adolescence. This is the area of the brain controls executive functions such as planning and impulse control. It is also the area most affected in schizophrenia."

They believe that the results have indications for humans as well and will continue to study the underlying mechanisms that cause these changes in cortical oscillations. "The purpose of studying these mechanisms is to see whether we can reverse these effects," says Keller. "We are hoping we will learn more about schizophrenia and other psychiatric disorders, which are complicated conditions. These cognitive symptoms are not affected by medication, but they might be affected by controlling these cortical oscillations."

Citation: Sylvina M Raver, Sarah P Haughwout and Asaf Keller, 'Adolescent Cannabinoid Exposure Permanently Suppresses Cortical Oscillations in Adult Mice', Neuropsychopharmacology July 4th 2013, doi:10.1038/npp.2013.164