ARTICLE IN BRIEF
Investigators reported that in the study of 320 patients admitted to a hospital, cannabis was detected in the urine of 16 percent of those who had had an ischemic stroke or transient ischemic attack (TIA).
HONOLULU—In a retrospective review of case reports involving stroke patients, ages 18-55, investigators reported evidence that cannabis is associated with a doubling of stroke risk.
“As the largest case-controlled study to date to show a possible association, this provides the strongest evidence [yet of] an association between cannabis and stroke,” said lead author P. Alan Barber, MD, PhD, a professor of clinical neurology at the University of Auckland.
“Cannabis is not the benign drug many patients perceive it to be,” he said here at the American Stroke Association (ASA) International Stroke Conference in February.
In the study of 320 patients, cannabis was detected in the urine of 16 percent of those who had had an ischemic stroke or transient ischemic attack (TIA), compared with 8 percent of age-, gender-, and ethnicity-matched controls admitted to the hospital for other reasons.
A major limitation of the study is that the investigators were unable to control for other confounding factors, including tobacco use and cannabis dose.
This had neurologists entering the presentation room shaking their heads, “asking a lot of questions about study design,” said Daniel T. Lackland, DrPH, professor in the department of neurosciences at the Medical University of South Carolina College of Medicine in Charleston, who moderated the scientific platform session and was not involved with the study.
While “Dr. Barber went on to carefully address the study limitations during his talk, the general feeling afterward was that the findings were hypothesis-generating,” rather than strong evidence of a link between cannabis and stroke, he told Neurology Today.
Dr. Barber said he undertook the study after a young stroke patient with none of the traditional risk factors such as hypertension or diabetes presented to their emergency room. “The woman admitted smoking cannabis when the symptoms began,” he said.
A search of the literature revealed “a sprinkling of case reports of one to three patients with no typical risk factors who were smoking cannabis at or around the time of their stroke. Among them was a patient who recovered and then had a second stroke when again smoking cannabis,” he said.
For their study, Dr. Barber and his colleagues tested urine for cannabis within 72 hours of hospital admission in 160 patients with stroke or TIA aged 18 to 55 years.
One hundred of the patients were men. Ninety-four percent (150) had an ischemic stroke and 6 percent (10) had a TIA. As controls, the researchers used 160 age-, sex- and ethnicity-matched patients admitted to their hospital with diagnoses other than stroke or TIA. “We also avoided internal medicine patients who had broken bones or head injuries because they are more likely to have used cannabis,” Dr. Barber said.
Twenty-five (15.6 percent) stroke/TIA patients tested positive for cannabis, compared with 13 (8.1 percent) of controls. In a logistic regression analysis adjusted for age, sex, and ethnicity, only cannabis use was associated with a significantly increased risk of ischemic stroke (odds ratio 2.30, 95 percent confidence interval 1.07-4.95).
Among the group of stroke/TIA patients, those who were male and tobacco users were more likely to have positive cannabis drug screens. There were no differences in age, stroke mechanism, or most vascular risk factors between those with and without positive cannabis tests. The test was not positive for any other illicit drugs.
“We were fairly surprised that one in six stroke patients had recently used cannabis recreationally,” Dr. Barber said. “Given the findings, we strongly advise that young stroke patients are tested for cannabis, especially when no other risk factors are apparent,” he said.
“Only about 10 percent to 15 percent of all stroke victims fall into the 18- to 55-year-old age category, so it is easy to miss the association,” he added.
The regional ethics committee did not give permission to gather information on anything other than age, sex, and ethnicity on the control patients, given that cannabis is illegal. As a result, controlling for other confounders was impossible.
That proved particularly problematic when it came to tobacco use, as all but one of the stroke patients who used cannabis also used tobacco.
“We couldn't tease apart the confounding effect of tobacco. But we can say that a lifestyle that includes cannabis use is clearly associated with a doubling in risk of stroke,” Dr. Barber said.
WHY THE INCREASED STROKE RISK?
There are several reasons to believe that the increased stroke risk is due to use of cannabis and not tobacco, he said. “We think causality is plausible, given that cannabis can cause changes in blood pressure and heart rate and can lead to palpitations such as atrial fibrillation, which is very strongly associated with stroke,” he said.
Cannabis use has been linked to increased sympathetic and decreased parasympathetic activity, supine hypertension, postural hypotension, and increased cardiac output, Dr. Barber continued. It may also accelerate the atherosclerotic process and can cause cerebral vasoconstriction, he said.
Dr. Barber pointed to studies linking cannabis to a five-fold increased risk for myocardial infarction in the hour after use, sudden unexplained cardiovascular death, and atrial fibrillation.
He added: “This is a young age group to be having strokes, and many didn't have any of the traditional risk factors. And some patients had a stroke while actually smoking cannabis,” Dr. Barber said.
The findings are especially important given that patients generally consider marijuana to be relatively harmless for their health — “safer than drinking alcohol or using other drugs,” he said.
Add to that the fact that states in the US and Australia have legalized its use in one form or another, “and it's imperative to know the risks,” Dr. Barber said.
EXPERTS WEIGH IN
As Dr. Lakeland observed, other neurologists were generally cautious when commenting on the findings. Larry B. Goldstein, MD, professor of neurology at Duke University Medical Center and director of the Duke Stroke Center in Durham, NC, said: “There are several methodological issues. There are very limited data on these patients and it was done retrospectively, so there is likely residual confounding and other factors that weren't measured that might be important.”
Additionally, this type of study precludes making conclusions about absolute risks, he said. “It offers an interesting and potentially important observation that needs to be looked at further before we understand what the risk actually is and whether it's real after fully controlling for other factors,” Dr. Goldstein said.
Lee H. Schwamm, MD, director of stroke services at Massachusetts General Hospital and professor of neurology at Harvard Medical School, echoed each of his remarks.
“The real question,” he said, “is whether there is a direct association or whether cannabis is [a marker for another] risk factor. The impact of cigarette smoking may or may not be relevant; we simply don't know,” he said.
“It is also possible that cigarette smoke and cannabis smoke may cause a similar pattern of lung injury and clotting disturbance,” Dr. Schwamm said.
Dr. Barber said future studies need to determine if the association is independent of tobacco and other confounders. Ethical constraints when studying an illicit drug may make such studies difficult, he acknowledged. But the high prevalence of cannabis use, its perception of being harmless, and the continued movement to decriminalizing marijuana make this research imperative, Dr. Barber concluded.