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New Data Show No Link Between Cannabis and Stroke

A new study that used admission urine toxicology tests to ascertain drug use found no independent association between recent cannabis use and the incidence of acute ischemic stroke.

“Previous studies have shown conflicting data on cannabis use and stroke. Our study is a step forward in that we had quite a large population and we had an objective measure of marijuana use with the urine screen, whereas some previous studies have just relied on asking the patient about marijuana use,” senior author Shreyas Gangadhara, MD, University of Mississippi Medical Center, Jackson, told Medscape Medical News.

This latest study was published online in Neurology on June 3.

The researchers, led by Carmela V. San Luis, MD, also from the University of Mississippi Medical Center, note that the question as to whether cannabis use is linked to acute ischemic stroke was raised after several case reports suggested such a correlation. A few population-based analyses of hospitalized patients have also shown a positive association.

A previous study showed no association between cannabis use and stroke after controlling for diabetes mellitus, hypertension, alcohol consumption, migraine, cigarette smoking, and age, but that study relied on patients’ reports for marijuana use, and no objective tests were performed. There is also evidence of neuroprotectant effects of cannabidiol in the central nervous system, and animal studies have suggested it could be protective against ischemic stroke, so the evidence is conflicting.

“We conducted the current study because we have seen in clinical practice many younger patients with an ischemic stroke but no traditional stroke risk factors who had a positive urine test for cannabis. As there is no consensus on this in the literature so far, we wanted to look at this further,” Gangadhara said.

For the retrospective observational study, the researchers analyzed the medical records database for all patients aged 18 years and older who were admitted to the University of Mississippi Medical Center from 2015 to 2017 and who underwent urine toxicology testing on admission.

Owing to difficulty in differentiating true transient ischemic attack (TIA) from mimics, such as migraine with aura, patients who were diagnosed with TIAs were excluded. Those with intracranial hemorrhage whose results of urine drug screening were positive for amphetamine or cocaine were also excluded.

Results showed that of 9350 patients who underwent urine drug screening during admission, 18% had a positive result on urine cannabis testing.

Unadjusted risk ratio showed a 50% decrease in risk for acute ischemic stroke among cannabis users (risk ratio, 0.50; 95% confidence interval [CI], 0.42 – 0.60), but this effect was lost after adjusting for possible confounders, including age, race, ethnicity, sickle cell disease, dyslipidemia, hypertension, obesity, diabetes mellitus, cigarette smoking, atrial fibrillation, and other cardiac conditions (odds ratio, 1.04; 95% CI, 0.77 – 1.39).

Conflicting Data

The authors note that this result is not in line with previous studies that included persons with polysubstance use but not persons who only used cannabis, which may explain the difference.

They also point out that a previous study found an association between reported heavy marijuana use and history of stroke, but there was no association for those who used marijuana less than once a week. The current study did not evaluate for dose, chronicity, and frequency of cannabis exposure.

The researchers note that cannabinoids have both harmful and protective effects in the nervous systems, which may account for the conflicting results in various studies and the overall neutral effects found in the current study. However, the conflicting results could also be due to small sample size.

“I would not say that this is the end of the story. We don’t have all the answers,” Gangadhara said. “This was a retrospective study, and we couldn’t quantify the use of marijuana. We couldn’t look at how frequently or how much was used. It was more of a yes-or-no question.”

They also report that urine drug screening does not test for synthetic cannabinoids; therefore, synthetic cannabis use was not assessed.

The researchers conclude: “Further prospective studies should be done with a larger sample size and looking into dose-related effects.”

Commenting for Medscape Medical News, Tarang Parekh, MBBS, a health policy researcher at George Mason University, Fairfax, Virginia, said the study is important considering recent legalization and decriminalization of cannabis use in the United States. “With increasing popularity, rigorous data on any associated link between marijuana and stroke remains vital,” he commented.

Parekh, who has also been involved in research in this area, listed strengths of the current analysis as sample size, use of medical records data, and control for potential risk factors and confounders. But he points out that in this study, three control variables that are already known to be associated with stroke ― smoking, obesity, and diabetes ― were found to be nonsignificant.

“The key problem with that is we cannot interpret the findings of this study that there is no association between any of these three risk factors and ischemic stroke. The same is applied for recent cannabis use,” he said.

Parekh maintains that the unadjusted risk ratio indicating a 50% decrease in risk should be disregarded because of the “stark difference” between cannabis users and nonusers with respect to demographics and risk factors. Users were much younger, and nearly all comorbid conditions were less prevalent among users than nonusers.

“As the authors suggested, it would be worth conducting longitudinal studies exploring the temporal relationship between the duration and dose-dependent relationship with stroke using a larger sample size. Until then, it would unwise to neglect the health concern evidenced and raised by multiple case reports and studies,” he concluded.

Neurology. Published online June 3, 2020. Abstract

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However, because findings from multiple other studies are conflicting, further research on this issue is required, the authors say.