Recent marijuana use linked to risk for complication from subarachnoid hemorrhage
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Among patients with aneurysmal subarachnoid hemorrhage, those with recent cannabis use were more likely to have delayed cerebral ischemia than those without recent use, researchers reported.
“We’re all vulnerable to a bleeding stroke or a ruptured aneurysm; however, if you’re a routine marijuana user, you may be predisposed to a worse outcome from a stroke after the rupture of that aneurysm,” Michael T. Lawton, MD, president and CEO of Barrow Neurological Institute in Phoenix, said in a press release.
Lawton and colleagues analyzed 1,014 patients treated for aneurysmal subarachnoid hemorrhage from August 2007 to July 2019, of whom 4.5% tested positive for cannabis on routine urine toxicology screening (users: mean age, 47 years; 41% women; nonusers: mean age, 56 years; 71% women).
Among the cohort, 36.2% developed delayed cerebral ischemia; 50.2% had a poor functional outcome, defined as modified Rankin Scale score of greater than 2; and 13.5% died.
Cannabis and delayed cerebral ischemia
Delayed cerebral ischemia was more common in patients who tested positive for cannabis than in those who did not (52.2% vs. 35.4%; P = .03), but there was no relationship between delayed cerebral ischemia and testing positive for cocaine, methamphetamine or tobacco (P .29), Lawton and colleagues found.
Radiographic vasospasm was also more common in patients who tested positive for cannabis than in those who did not (88.9% vs. 70.5%; P = .008), and among those with radiographic vasospasm, 50% of cannabis users had delayed cerebral ischemia compared with 39% of nonusers (P = .17), according to the researchers.
In a propensity score-adjusted analysis, cannabis use was associated with delayed cerebral ischemia in the patient population (OR = 2.7; 95% CI, 1.4-5.2; P = .003).
“When people come in with ruptured aneurysms, and they have a history of cannabis use or are positive on a toxicology screen, it should raise a red flag to the treating team that they are at higher risk of vasospasm and ischemic complication,” Lawton said in the release. “Of all the substances detected in the toxicology screen, only cannabis raised the risk of delayed cerebral ischemia. Cocaine and meth are hypertensive drugs, so they are likely related to the actual rupture but not expected to have an impact on vasospasm.”
‘An open question’
In a related editorial, Feras Akbik, MD, PhD, and Ofer Sadan, MD, PhD, both assistant professors of neurology and neurosurgery at Emory University School of Medicine, wrote: “Ultimately, given the prior mixed results regarding the association of marijuana with cardiovascular complications, ischemic stroke or hemorrhagic stroke, it remains an open
question whether cannabis precipitates cerebral ischemia via cerebral vasospasm and delayed cerebral ischemia. Future studies should attempt to better quantify the cannabis exposure in terms of chronicity, dose and temporal relationship between the cannabis use and the aneurysm rupture event, in order to better understand whether indeed marijuana can precipitate cerebral ischemia.”
References:
- Akbik F, et al. Stroke. 2022;doi:10.1161/STROKEAHA.121.037791.
- Marijuana users’ risk of deadly complication doubles after rare type of bleeding stroke. newsroom.heart.org/news/marijuana-users-risk-of-deadly-complication-doubles-after-rare-type-of-bleeding-stroke?preview=3591. Published Jan. 6, 2022. Accessed Jan. 6, 2022.
Perspective
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Robert L. Page II, PharmD, MSPH, FAHA
These data add to the current evidence that, as with any psychotropic medication, there can be neurologic side effects from cannabis. While this is a retrospective observational study that cannot prove causation, it represents a red flag for neurologists and other providers. Of note, the study population was young adults, which is the population we see using cannabis. While this population may not have a very high comorbidity burden, cannabis use may present issues for them.
A larger, prospective study would need to be done to truly show causation. At this point, we only have data suggesting an association. But there are now three studies addressing neurologic issues with cannabis. I think it is not just coincidental and it needs to be taken seriously.
A major area of interest is the different types of cannabinoid receptors and their distribution through the body. The authors highlight the CBD1 and CBD2 receptors. Interestingly, in certain areas of the body, CBD1 is more of an anti-inflammatory and antioxidant. But in other areas, such as, potentially, the central nervous system, it has various effects upon our vasculature. In some cases, it can constrict, and in others, it can vasodilate. The potential mechanism is there, but we are still trying to understand what those receptors can do.
There are some issues with the study. No. 1, it covers a very large time period. There is a difference between first-generation cannabis, in which the plants were grown, and second-generation “designer” cannabis, which has a much higher concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) and is sold within dispensaries. One may be more neurotoxic than the other, and we do not know what the patients in this study used. No. 2 is chronicity. Cannabis use was determined based on urine tests. Cannabis can stick around for a much longer period, depending on how long one has been consuming cannabis. We don’t know if this association is seen only in acute use or chronic use. A retrospective observational study cannot answer that. In addition, cannabis side effects vary with acute use vs. chronic use. No. 3, there is no information about how the cannabis was consumed. Edibles and vaping came on the market around 2014 to 2016 as states changed their laws and allowed dispensaries for recreational use. Knowing whether cannabis was smoked, eaten or vaped can be very important. Vaping gives the user a limitless amount of other neurotoxins compared with combustible or edible forms.
Patients need to be transparent about their use and providers need to be nonjudgmental so that we can accurately document cannabis use and patients can be better educated. Just because something is natural does not always make it safe; we have seen that in the herbal supplement market as well. We have to discuss side effects, including CV and neurologic, with patients. And we need to perform prospective studies with cannabis.
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