Reference: JACC Adv. 2025 Mar 12 early online
Practice Point: Cannabis use has known adverse effects; we can add cardiovascular disease and risk of premature death in otherwise healthy young people to the list.
EBM Pearl: When considering if association may actually be causation, lifestyle factors like exercise, nutrition, and substance use usually require multiple observational studies from a wide variety of source material.
Two different studies approaching the same clinical question—Does cannabis use represent a risk for cardiovascular disease?—recently provided slightly different versions of "yes." Both studies examined population-based associations between cannabis exposure and cardiovascular outcomes in large populations of adults. The first study was a meta-analysis of observational data covering roughly 1.7 million people over the age 18, and the second study examined medical data claims for approximately 4.5 million people between the ages of 18 and 50.
In the first study mentioned, authors publishing in the Disease-a-Month journal in January examined the risk of adverse cardiac events in a diverse group of people with varied health conditions. For example, 1.2 million of the 1.7 million people included in the meta-analysis were from a single study of Canadians who were pregnant at the time of study entry. They were asked at study entry on whether or not they had ever used marijuana in the past (along with many other questions) and were followed for health outcomes for 30 years. This prospective observational study, combined with several much smaller studies, was used to calculate a relative risk (RR) of aggregated adverse cardiac outcomes for cannabis use versus non-use, which equaled 1.48, with a 95% CI of 1.2-1.9. However, the RR of specific events—myocardial infarction and stroke—were not significant.
The authors of the second paper, recently published in JACC: Advances, took a slightly more direct approach by accessing the privately-owned TriNetX retrospective cohort data set. TriNetX uses data sets of de-identified health information from hundreds of global health care organizations to conduct large-scale AI-assisted research projects. For this paper, researchers compared information on diagnosis codes between 2010 and 2018 for two groups of healthy-appearing adults between the ages of 18-50 who had no known cardiovascular risks (including family history or tobacco use) but were differentiated by marijuana use documented in their medical chart. This included people with cannabis use disorder and those who reported having used it. The data was limited in that it could not capture amount, route, or duration of use over time. Medical records of nearly 4.6 million people were examined to come up with two propensity-matched groups of 89,776 each, who essentially only differed in having a history of marijuana use. Once again, there were significantly higher absolute and relative risks for aggregated events, although this time the data set demonstrated additional risks for mortality, myocardial infarction, ischemic stroke, and heart failure. For example, for a composite of major adverse cardiac events the risk was 1.19% versus 0.37%, for an adjusted-odds ratio of 3.27, 95% confidence of 2.9-3.7. We felt that this study was particularly interesting because of its use of a commercially available privately held data set - and results showing that even younger people with no risk factors other than cannabis use in their medical history were at risk, consistent with previously reported information.
Proponents of cannabis use (a hugely profitable industry with immense marketing budgets) have often claimed that nobody has ever died from marijuana overdose. They tout medicinal benefits while simultaneously using legal loopholes to avoid the oversight given to standard pharmaceutical products. History buffs among us will know that similar claims were made in the past for the putative benefits and relative safety of alcohol, tobacco, cocaine, heroin, and other natural medicinal substances. These two studies add to the growing literature showing that while cannabis doesn’t cause respiratory depression-induced-overdose death, it can cause acute death and harm in other ways. There are caveats: observational data, even when propensity matched, can never control for confounders as effectively as randomization. Although there is an absolute mortality risk > zero for young otherwise healthy people, it's pretty low. This month, the ACP published a position paper that suggests that the benefits for cannabis use in chronic pain should be balanced against the risks in certain high-risk populations. These studies suggest that all cannabis consumers assume a risk, not just certain populations. Sure, the evidence is flawed and relatively weak. On the other hand (and for another edition of the Focus), the evidence of benefit is similarly weak. What will you tell your patients?
For more information, see the topic Adverse Effects of Cannabinoids in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, MPH, FACP, Senior Deputy Editor at DynaMed. Edited by Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; McKenzie Ferguson, PharmD, BCPS, Senior Clinical Writer at DynaMed; Rich Lamkin, MPH, MPAS, PA-C, Clinical Writer at DynaMed; Matthew Lavoie, BA, Senior Medical Copyeditor at DynaMed; Hannah Ekeh, MA, Senior Associate Editor II at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.