Marijuana Use Impairs Verbal Memory

Liam Davenport

February 08, 2016

Individuals with long-term exposure to marijuana may experience significant impairment of verbal memory by the time they reach middle age, warn researchers, who found that other aspects of cognitive function were unaffected.

Investigators, led by Reto Auer, MD, of the Department of Ambulatory Care and Community Medicine, University of Lausanne, Switzerland, found that for each additional 5 years of exposure to marijuana, there was a significant decline in performance on a standard verbal memory test, although the researchers note that the clinical meaningfulness of the findings is open to question.

"Future studies with multiple assessments of cognition, brain imaging, and other functional outcomes should further explore these associations and their potential clinical and public health implications," they write.

"In the meantime, with recent changes in legislation and the potential for increasing marijuana use in the United States, continuing to warn potential users about the possible harm from exposure to marijuana seems reasonable."

The research was published online February 1 in JAMA Internal Medicine.

Worse Verbal Memory, Processing Speed

The investigators examined data from the Coronary Artery Risk Development in Young Adults (CARDIA) study on 5115 black and white men and women from four sites in the continental United States who were recruited between 1985 and 1986 and followed through August 2011.

Current and lifetime marijuana use was assessed at baseline and after 2, 5, 7, 10, 15, 20, and 25 years of follow-up. Cognitive function was assessed at the 25-year follow-up visit using the Rey Auditory Verbal Learning Test (RAVLT), the Digit Symbol Substitution Test, and the Stroop Interference Test.

Cumulative exposure to marijuana was calculated. Linear regression took into account demographic and cardiovascular risk factors, as well as tobacco smoking, alcohol and illicit drug use, physical activity, depression, and the results of the mirror star tracing test, which is a measure of cognitive function, at the 2-year assessment.

Cognitive function test results were available for 3385 participants, of whom 2852 reported lifetime marijuana use. Only 392 individuals were current users; 311 had more than 5 years of cumulative exposure to the drug; and 65 reported daily use.

The researchers found that current marijuana use was associated with worse verbal memory and processing speed. Cumulative exposure was associated with worse performance on all three cognitive tests.

Taking into account current users and potential confounding factors, there was a significant association between cumulative marijuana use and verbal memory, such that each additional 5 years of exposure was associated with 0.13 lower standardized units on the RAVLT (P = .02).

No other significant associations were identified. The findings were unaffected after adjustment for potential diagnoses of schizophrenia or the use of antidepressant medications.

Clinically Meaningful?

Dr Auer told Medscape Medical News that he had not anticipated that there would be an association between long-term marijuana use and worse verbal memory.

"To be honest, I was not expecting any effect, because of what I knew," he said, adding that because the study was long-term and there were many potential confounders, "we were not expecting much going on, so we were surprised that verbal memory was associated with this.

"We could throw anything at it, adjusting for as many confounders as we could, and this association did not go away. It was also a surprise that the other measures of cognition were not [associated], so this has to be confirmed in other studies," he added.

In the article, the authors put forward several possible explanations for the association between long-term marijuana use and worse verbal memory.

"We know marijuana has been associated with underlying measures that are linked in the hippocampus. Structural changes in the hippocampus could explain these associations, where you would find that people have a problem retaining words that would not impact on other domains of cognition," Dr Auer said.

The participants in the CARDIA study also underwent MRI, and the investigators are currently examining whether there are any correlations between the MRI data and the results on the different cognitive tests.

Dr Auer acknowledged that clinical meaningfulness of the findings is open to question. In a recent study by one of the study's coauthors, a 0.5–standard deviation (SD) cutoff was used to define a clinically meaningful decline in global cognition. In contrast, the point estimate for verbal memory for individuals with 5 years of marijuana exposure was 0.13 SD.

"To some people, this might be trivial," Dr Auer said. "I think the jury is out, and people have to decide by themselves if they find that this is significant or not.

"So while I think we find an association with verbal memory, I would also add that people should also question how important that is."

A Welcome Addition

Commenting on the findings for Medscape Medical News, Nadia Solowij, PhD, associate professor, School of Psychology, University of Wollongong, New South Wales, Australia, described the study as a "welcome addition to the literature."

She told Medscape Medical News that longitudinal studies of the use of cannabis are rare and that the current investigation confirms previous associations between use of the drug and poorer cognitive function.

Dr Solowij noted that although the participants were middle-aged, the impairment of memory function "does not appear to be age-related, rather, related to the cumulative exposure to cannabis, indicating that greater cannabis use at any age has the potential to impair cognitive functioning."

She added that the study indicates that on average, 1 in 2 people will recall one word less from a list of 15 words for every 5 years of cannabis use, which is in line with other studies.

"The clinical significance of this gradual and subtle loss of memory function remains questionable, but clearly there would be greater impact on daily functioning the longer that cannabis is used," she said.

"Wide-ranging individual differences and potential interactions with brain development at critical ages and in individuals compromised by neurological, psychiatric, socioeconomic, and other factors warrant the public health concerns regarding cannabis use in the community."

A remaining matter for debate is whether memory dysfunction associated with cannabis use can resolve following prolonged drug abstinence. "The evidence for recovery remains uncertain and mixed from the sparse literature addressing this important question," Dr Soliwij concluded.

The study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, the Kaiser Foundation Research Institute, and the Johns Hopkins University School of Medicine. It is also supported by the Intramural Research Program of the National Institute on Aging. The authors have disclosed no relevant financial relationships.

JAMA Intern Med. Published online February 1, 2016. Abstract

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