Cannabis-Stroke Link: First Case-Control Study

February 06, 2013

Honolulu, Hawaii — More evidence that smoking cannabis is associated with an increased risk for stroke has come from a New Zealand study.

The first case-control study to investigate this association, presented at the American Stroke Association's International Stroke Conference (ISC) 2013, found that patients with ischemic stroke/transient ischemic attack (TIA) were twice as likely to have recently used cannabis as age-, sex-, and ethnicity-matched controls.

"Cannabis is generally perceived as having few serious adverse effects, but this study suggests that this may not be the case," lead author Alan Barber, PhD, MD, from University of Auckland, New Zealand, concluded.

For the study, Dr. Barber and colleagues tested urine for cannabis within 72 hours of hospital admission in 160 patients with ischemic stroke/TIA aged 18 to 55 years and 160 controls (patients admitted with nonstroke diagnoses, matched for age, sex, and ethnicity).

Dr. Alan Barber

The cannabis screen was positive in 25 (16%) of the stroke/TIA group vs 13 of 160 (8%) control participants. Logistic regression analysis found an odds ratio of 2.30 (95% confidence interval, 1.07 - 4.95).

Dr. Barber said the 16% rate of cannabis use in the stroke patients "took us by surprise." Cannabis users were more likely to be male, tobacco smokers, and Maori. No other illicit drugs were detected.

He explained that he and his colleagues conducted the study after a young woman presented to their emergency department with a stroke after smoking cannabis. "We looked in the literature and found several other case reports, and so decided to do a study."

Dr. Barber said a causal association between cannabis and stroke is plausible, given that cannabis use has been shown to increase sympathetic and decrease parasympathetic activity and to increase heart rate; it is also associated with supine hypertension and postural hypotension, as well as increased cardiac output. It also reduces the oxygen-carrying capacity of blood and may lead to accelerated atherosclerosis, along with cerebral vasoconstriction.

He noted that cannabis use has been associated with a 5-fold increased risk for myocardial infarction in the 60 minutes after use and with atrial fibrillation and sudden unexplained cardiovascular death.

Tobacco Confounding

A problem with the study, Dr. Barber said, was that tobacco use confounded the result; 24 of the 25 stroke patients who tested positive for cannabis were also smokers. "We couldn't tease apart the confounding effect of tobacco, but what we can say is that a lifestyle that includes cannabis use appears to double your risk of stroke."

Dr. Barber explained that the ethics committee of this study did not give permission for any more information other than age, sex, and ethnicity to be revealed about the control patents, given that cannabis was an illicit drug. "That made controlling for confounding factors impossible. We are going to ask them again if we can go through the control patients' notes for this additional information so we might be able to establish a causal effect."

Nevertheless, Dr. Barber believes cannabis has an effect on stroke over and above that of tobacco. He referred to a study conducted in 1974. That study randomly assigned patients with angina to placebo, nicotine, or cannabis cigarettes; time to angina on exercise was reduced by 8% with placebo, 23% with nicotine, and 50% with cannabis.

He concluded, "Future research should determine if the association we found is independent of tobacco." But he warned that even though this may prove difficult given ethical strictures and risk of bias with studying an illicit drug, "the high prevalence of cannabis use in this cohort, as well as moves to decriminalize cannabis makes this research imperative."

Dr. Kyra Becker

Surprising Finding

Asked for comment on these findings, Kyra Becker, MD, professor of neurology and neurological surgery at the University of Washington School of Medicine and co-director of the University of Washington Stroke Center at Harborview, Seattle, said that to her, the findings were not anticipated.

"To me it's actually quite surprising," she told Medscape Medical News. "It's something that I didn't anticipate, and certainly it's something that we don't screen for in our young stroke patients. I'm very intrigued and I'd like to see the follow up studies to actually prove the causation, and why cannabis would actually increase the risk of stroke."

She pointed out that, ironically, some data suggest cannabis is actually neuroprotective in the acute phase of stroke, the difference between the effect on the vessels and the effect on the neurons. "So at the time of stroke, if you get cannabis in your system it actually protects and limits the amount of brain injury," she said, similar to the observed effects with estrogen.

Larry Goldstein, MD, professor of neurology at Duke University Medical Center and director of the Duke Stroke Center, Durham, North Carolina, was cautious. "The thing to keep in mind is that there are very limited data on these patients," he said. "It was done retrospectively so there is undoubtedly residual confounding and factors that weren't measured that might be important."

Dr. Larry Goldstein

In addition, a high relative risk doesn't mean a high absolute risk, and the absolute risk is not clear from this kind of observation.

"It raises a signal that might need to be paid attention to, but I think more work needs to be done before we understand what that risk is, and whether it's real or not after you fully control for other factors," he concluded.

The authors have disclosed no relevant financial relationships.

International Stroke Conference 2013. Abstract 147. Presented February 6, 2013.