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Neurology Today:
doi: 10.1097/01.NT.0000393327.64884.bd
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Adolescent Marijuana Use May Cause Lasting Cognitive Deficits

Samson, Kurt

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ARTICLE IN BRIEF

Chronicle marijuana users who started smoking before age 16 scored consistently lower on cognitive tests than those who started smoking later in life and in healthy individuals who had never used the drug.

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Chronic marijuana users who start smoking regularly prior to the age of 16 show impairments in executive function and concentration compared to those who began smoking later, according to research that was presented at the annual meeting of the Society for Neuroscience in November.

Staci Ann Gruber, PhD, assistant professor of psychiatry at Harvard Medical School, and the director of the Cognitive and Clinical Neuroimaging Core at Mclean Hospital in Belmont, MA, described results of a study in which younger chronic users were tested for cognitive flexibility and the ability to inhibit inappropriate responses, elements of what neuropsychologists term “executive functions.”

Users who started before age 16 scored consistently lower than those who started smoking later in life and in healthy individuals who had never used the drug, they found.

The researchers used the Wisconsin Card Sorting Task, comparing responses of 35 chronic heavy users with those of 29 healthy individuals, matched for age and other characteristics. During the task, subjects are presented with four stimulus cards that vary on the basis of color, shape, and quantity and are asked to match a deck of cards to the corresponding stimulus card. Subjects are not told how to sort the cards, only whether their responses are correct or not. Over the course of the test, researchers change the sorting rule without warning, and the ability of the subjects to adjust to this feedback is used to gauge their cognitive flexibility, ability to maintain set, and control impulsive responses.

Compared to control subjects, marijuana users made more repeated errors when the rules were changed, even when told that their responses were wrong, and had significantly greater difficulty sorting the cards as per instructions than did their healthy counterparts. The team then compared responses in those individuals who began using before and after age 16 and found the younger group consistently scored lower, completing fewer total correct categories (7.7 versus 9.0) and making significantly more repetitive errors (14.2 versus 6.4).

Moreover, scores fell proportionally as the amounts of marijuana young subjects used increased. Those who started smoking before age 16 also smoked more than twice as often per week and nearly three times as many grams of marijuana per week relative to their later onset smoking counterparts.

“This study provides further evidence that early marijuana use is associated with poorer executive functioning, and that the younger a person starts, as well as the quantities used, may play a significant role in this impairment,” Dr. Gruber told Neurology Today.

“Animal studies have shown the same thing: the brain is quite vulnerable at this stage of development,” she said in a telephone interview. “This is something to be mindful of, because these tasks are on par with those encountered in everyday life, abstract thinking, the ability to change one's behavior relative to changing demands, and inhibition of inappropriate responses.”

She noted that a 2008 study in the journal European Psychopharmacology linked marijuana use to changes in blood flow in the brain, even after one month of abstinence. Another 2005 study in Neurology found similar evidence.

Whether or not these and cognitive deficits are reversible in younger users remains to be seen, Dr. Gruber told Neurology Today. “The frontal cortex is largely responsible for executive functions and it is the last to fully develop but the first to take a hit from chronic marijuana or other drug and alcohol use. The bottom line is that we have to be very careful during this critical phase of brain development”.

She said this is especially important given the growing number of states who are approving medical use of marijuana.

“We need to be very clear about establishing guidelines for use, in much the same way we've done for alcohol and tobacco,” she said.

In October 2010, Gil Kerlikowske, director of the Office of National Drug Control Policy, reported that the number of persons over age 12 using marijuana jumped by 9 percent between 2008 and 2009.

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MOUNTING EVIDENCE

Frances E. Jensen, MD, professor of neurology at Harvard Medical School, and senior associate in neurology at Children's Hospital in Boston, told Neurology Today in a telephone interview that the study adds to a growing body of research indicating that heavy marijuana use by adolescents may have long-term consequences on cognitive development.

Dr. Jensen, who moderated the session during which Dr. Gruber presented and discussed her findings, said: “This should be a public service announcement. Dr. Gruber's data are robust and consistent with other studies showing that teens are especially vulnerable because this is a critical stage of development for one of the most sophisticated parts of the brain — the frontal and pre-frontal cortex. Interrupting this development has implications far beyond their early years.”

“What we are learning is that if the [brain development] system is manipulated at this early age, it affects the entire trajectory of development, and these deficits may not appear until later in life,” she said.

The message, she said, is that teens are not as resilient as adults to the effects of marijuana, and researchers are learning more and more about the subtleties of its effects on executive function in this population as they grow older.

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PERSISTENT DEFICITS?

DR. KAREN I. BOLLA T...
DR. KAREN I. BOLLA T...
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“This study is important because it replicates and validates findings from earlier studies done in the early 2000s,” said Karen I. Bolla, PhD, associate professor of neurology at Johns Hopkins Bayview Medical Center in Baltimore, in a telephone interview with Neurology Today.

In a study published in Neurology in 2002, Dr. Bolla and her associates reported that as the amount of marijuana smoked increased, performance decreased on tests of executive functioning, memory, psychomotor speed, and manual dexterity, even after 28 days of abstinence.

Dr. Bolla also noted that marijuana has become far more potent in recent years, which makes the risk among adolescents even greater.

But could other factors in adolescents’ lives be contributing to the deficits reported in neuropsychological testing and imaging studies?

“It always comes down to the chicken or the egg dilemma,” Dr. Bolla said. “Does a bad brain cause drug use or does drug use cause a bad brain? My guess is that it is a little bit of both.”

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REFERENCES:

Jager J, Ramsey NF. Long-term consequences of adolescent cannabis exposure on the development of cognition, brain structure and function: an overview of animal and human research. Curr Drug Abuse Rev 2008;1:114-123.
Pope HG, Gruber AJ, Hudson JI, et al. Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug Alcohol Depend 2003;69:301-310.
Tapert SF, Schweinsburg AD, Medina KL, et al. The influence of recency of use on fMRI response during spatial working memory in adolescent marijuana users. J Psychoactive Drugs 2010:42:4010412.
Sneider JT, Pope HG, Gruber SA, et al. Differences in regional blood volume during a 28-day period of abstinence in chronic cannabis smokers. Euro Psychopharmacol 2008;18:612-619.
Medina KL, Nagel BJ, Tapert SF. Abnormal cerebellar morphometry in abstinent adolescent marijuana users. Psychiatry Res 2010;182:152-159.
Bolla KI, Brown K, Tate K, Cadet JL. Dose-related neurocognitive effects of marijuana use. Neurology 2002;59:1337-1343.
Herning RI, Better WE, Tate K, Cadet JL. Cerebrovascular perfusion in marijuana users during a month of monitored abstinence. Neurology 2005;64:488-493.

©2010 American Academy of Neurology

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