Univ. of MD finds that marijuana use in adolescence may cause permanent brain abnormalities

Regular marijuana use in adolescence, but not adulthood, may permanently impair brain function and cognition, and may increase the risk of developing serious psychiatric disorders such as schizophrenia, according to a recent study from the University of Maryland School of Medicine. Researchers hope that the study, published in Neuropsychopharmacology - a publication of the journal Nature – will help to shed light on the potential long-term effects of marijuana use, particularly as lawmakers in Maryland and elsewhere contemplate legalizing the drug.

“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,” says the study’s senior author Asaf Keller, Ph.D., Professor of Anatomy and Neurobiology at the University of Maryland School of Medicine. “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 the Program in Neuroscience in the Department of Anatomy and Neurobiology 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.”

The scientists - including co-author Sarah Paige Haughwout, a research technician in Dr. Keller’s laboratory - 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 Ms. 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.”

MArijuana use in adolescence may cause permanent brain abnormalities The scientists 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 Dr. 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.”

Dr. Keller’s team believes that the results have indications for humans as well. They 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 Dr. 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.”

Regular use of marijuana during adolescence can lead to irreversible IQ loss, findings from a long-range study suggest.

The report, published in Proceedings of the National Academy of Sciences, relies on data from a series of interviews conducted with over 1,000 residents of Dunedin, New Zealand, who were tracked from birth until the age of 38.

Those in the study group who reported using marijuana more than once a week during their teen years scored, on average, 8 points lower in IQ tests at age 38 than at age 13. Furthermore, friends and relatives of persistent users were more likely to note attention and memory problems than those of non-users.

“Adolescent-onset cannabis users showed significant I.Q. declines, and more persistent use was associated with greater declines,” said lead author Madeline H. Meier of Duke University.

MArijuana use in adolescence may cause permanent brain abnormalities “This study is an example of how the basic science research taking place in our state-of-the-art laboratories can impact human health and inform health policy,” says E. Albert Reece, M.D., Ph.D., M.B.A., Vice President for Medical Affairs at the University of Maryland and John Z. and Akiko K. Bowers Distinguished Professor and Dean of the University of Maryland School of Medicine. “We are proud of this groundbreaking discovery and look forward to watching this research develop further.”

Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study
Using cannabis in adolescence increases the likelihood of experiencing symptoms of schizophrenia in adulthood. Our findings agree with those of the Swedish study and add three new pieces of evidence. Firstly, cannabis use is associated with an increased risk of experiencing schizophrenia symptoms, even after psychotic symptoms preceding the onset of cannabis use are controlled for, indicating that cannabis use is not secondary to a pre-existing psychosis. Secondly, early cannabis use (by age 15) confers greater risk for schizophrenia outcomes than later cannabis use (by age 18). The youngest cannabis users may be most at risk because their cannabis use becomes longstanding. Thirdly, risk was specific to cannabis use, as opposed to use of other drugs, and early cannabis use did not predict later depression. Our findings now require replication in large population studies with detailed measures of cannabis use and schizophrenia.

Although most young people use cannabis in adolescence without harm, a vulnerable minority experience harmful outcomes. A tenth of the cannabis users by age 15 in our sample (3/29) developed schizophreniform disorder by age 26 compared with 3% of the remaining cohort (22/730). Our findings suggest that cannabis use among psychologically vulnerable adolescents should be strongly discouraged by parents, teachers, and health practitioners. Policy makers and law makers should concentrate on delaying onset of cannabis use.

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BMJ 2002; 325 doi: http://dx.doi.org/10.1136/bmj.325.7374.1212 (Published 23 November 2002)

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Karen Robinson
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410-706-7590
University of Maryland Medical Center

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