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Response by Parekh and Desai to Letter Regarding Article, "Marijuana Use Among Young Adults (18-44 Years of Age) and Risk of Stroke: A Behavioral Risk Factor Surveillance System Survey Analysis".

In Response: Alipour Haris et al expressed their concerns on study findings stating that the Behavioral Risk Factor Surveillance System (BRFSS) Survey data are not fit to evaluate the effect of marijuana use on stroke, which is not true as many prior studies have used a similar methodology and end points. Assessing the direct effect requires causality and our study only aimed to examine the association between marijuana use and stroke with elucidated limitations. The authors stated that the study included a time-window bias in measuring marijuana use and stroke with a plausible reverse association, meaning having stroke increases the odds of using marijuana. We tend to disagree mainly for the following reasons. First, it is difficult to assume that all the respondents reporting frequent recent marijuana use have only started smoking very recently amid numerous reports revealing that frequent or everyday smoking habit develops over a period and not acutely. A national longitudinal study of nearly 10000 12th graders followed through the age of 50 and interviewed at every 5-years revealed that nearly 1 in 3 young respondents (18–50 years) were longer-term moderate/heavy users with greater negative health outcomes in mid-life. Second, with the uptrend in lower perceived risk of marijuana use among adolescents, studies have reported that even infrequent marijuana users have higher odds of chronic habitual use throughout adult-life with 4 to 7× higher likelihood of developing cannabis use disorder. Third, rising trends in Tetrahydrocannabinol potency with a consequent increase in emergency visits among marijuana users raise concerns for chronic marijuana users. Such findings support the notion that the significant proportion of respondents reporting recent frequent use could potentially be long-term users. We agree that the question “Ever had a stroke?” would capture remote or recent stroke events among marijuana users. Similarly, the question, “During the past 30-days, on how many days did you use marijuana/hashish?” would mainly discern young frequent and recent marijuana users but does not necessarily exclude long-term habitual users. Therefore, the possibility of this survey incorporating long-term young marijuana users experiencing stroke events remains strong. Also, the reported overall stroke prevalence in our study (≈1.0%) is consistent with national stroke prevalence in young adults, contradicting the authors’ assumption regarding the lower stroke reporting in the survey. Alipour Haris et al precisely stated that poststroke depression is a common consequence of stroke and could trigger substance use among young adults. However, the survey question, “Ever had a depressive disorder?,” could not be used to determine the association between ever diagnosed depression and recent frequent marijuana use owing to the same time-window bias proposed by authors and due to complex multifaceted association of depression, substance use, and stroke. Besides, it is difficult to consider that all respondents started using marijuana following the stroke-induced depression in the absence of any consensus regarding marijuana use benefitting depression. Furthermore, prior reports even suggested bidirectional relationship and marijuana use worsening depression with increasing severity. We appreciate authors’ comments and concur with possible limitations inherent to the survey-based data; however, we do not see enough merit in analyzing proposed reverse causality and any significant role of ever diagnosed depression in promoting very recent frequent marijuana use among young stroke survivors. The preliminary findings of our study can be used to design future prospective and longitudinal studies assessing the cardiovascular and cerebrovascular effects of frequent and habitual marijuana use with more precision on the dose-response relationship and impact of mental health disorders.