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A French study provided support for an association between marijuana use and cardiovascular complications in younger adults, but didn't bring the field any closer to establishing a causal connection.

Over a 5-year period, 35 of 1,979 cannabis-related reports of serious adverse events (1.8%) received by a surveillance network in France involved cardiovascular complications, with an increase over time, according to , of the Centre Hospitalier Universitaire de Toulouse, and colleagues.

Most of the events (22) were cardiac, but there were also 10 peripheral and three cerebral events; about one-quarter (25.6%) resulted in death, the researchers reported online in the .

The findings are consistent with case reports of potential harm from marijuana use accumulating in the literature alongside the studies showing the benefits of cannabis for treating patients with conditions such as chronic neuropathic pain, glaucoma, multiple sclerosis, HIV, and other conditions related to chronic pain.

"Given that cannabis is perceived to be harmless by the general public and that legalization of its use is debated, data concerning its danger must be widely disseminated," Jouanjus and colleagues wrote. "Practitioners should be aware that cannabis may be a potential triggering factor for cardiovascular complications in young people."

Commenting on the study, , of Baylor Scott and White Health in Temple, Texas, said that "there seems to be a more than mere coincidental association between marijuana use in young people and cardiovascular events, although this study certainly cannot fully implicate causation."

"Marijuana use, in the form of smoking, is extremely difficult to study given lack of strong control groups with extreme variation in THC concentrations and the concomitant use of other drugs (including nicotine in the form of cigarette smoking)," Erwin told MedPage Today. "The authors are quite up front about this. The other limitations are the lack of understanding as to what the true denominator is and the under-reporting of the potential numerator."

The data from this and other studies published so far have not proven that marijuana increases cardiovascular risk, noted , of SUNY Downstate Medical Center in Brooklyn, "but they suggest that there is a relation ... in the people in the age groups that would be most likely to use marijuana. And that's a real concern.

"Even if there are relatively few events as there were in the study that was published, the fact that they could happen at all and that they're as devastating as they are, leads me to be concerned about increased use," Borer said.

The researchers acknowledged the need for future studies of the issue to more definitively nail down the potential connection.

"Our findings indicate that cannabis intoxication should be more systematically investigated in the medical management of cardiovascular complications observed in young adults," Jouanjus and colleagues wrote. "A prospective study with collection of all cardiovascular cases at hospital admission should complete the present findings, which add to the existing knowledge in the field of cannabis complications and must be considered as the starting point for further research."

The Study

The current data came from the French Addictovigilance Network, which collects information on serious cases of abuse of and dependence on psychoactive substances. The network relies on spontaneous reporting of events, and health professionals are legally obligated to report serious cases.

Of the 35 serious cardiovascular complications reported in users of cannabis from 2006 to 2010, most (85.7%) occurred in men. The average age of the patients was 34.

Nine had a personal history of cardiovascular disease and seven had a familial history. More than half (60%) also smoked tobacco.

The majority of the complications were cardiac, with 20 acute coronary syndromes and two heart rate disorders. Ten of the complications involved the peripheral vasculature, including lower limb or juvenile arteriopathies and Buerger-like diseases, and three involved the cerebral vasculature, including one case each of acute cerebral angiopathy, transient cortical blindness, and spasm of cerebral artery.

Eighteen of the patients were hospitalized and nine died; none of the deaths occurred in patients who were hospitalized.

The main shortcoming of the study, according to the authors, was the under-reporting of events, which resulted in a low number of events and the inability to determine whether the observed complications were actually related to cannabis use.

, of Yale University, hesitated to even call the cardiovascular events "complications" because the study was not able to establish that causal connection with cannabis use. He called the findings exploratory and urged caution in interpreting the results.

"It's not the kind of thing that should hit the front pages. It's not the kind of thing that should really worry people," he told MedPage Today. "It's the kind of thing that may make us look into other databases and try to understand this better."

Risk in the Context of Expanding Use

In an accompanying editorial in the journal, , of the Marshfield Clinic in Wisconsin, and , of the University of Southern California in Los Angeles, pointed out that several countries and 20 U.S. states and the District of Columbia have legalized the use of marijuana for medicinal purpose. In addition, Colorado and Washington have legalized the recreational use of marijuana, with other states preparing similar measures.

The potential for more widespread legalization raises the issue of safety, according to Rezkalla and Kloner, who recently published a review of reports of adverse vascular effects of marijuana. Events tied to marijuana use included myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and cannabis arteritis.

The French study "suggests that the plethora of single case reports describing temporal association between acute coronary syndromes and other cardiovascular events and marijuana use are more than just coincidence," they wrote.

"While the concomitant use of other products, such as tobacco and alcohol, may have contributed to some of these events," they wrote, "approximately half of the patients who presented with cardiac events had a record of exposure only to marijuana."

Despite the limitations of the study, it does highlight the need for further research into the potential safety concerns surrounding marijuana, they added.

Amid the growing push to legalize marijuana, Rezkalla and Kloner wrote, "we believe the time has come to stop and think about the best way to protect our communities from the potential danger of widespread marijuana use in the absence of safety studies."

To that end, they suggested a national system to capture potential marijuana-related complications, similar to that in France.

"It is the responsibility of the medical community to determine the safety of the drug before it is widely legalized for recreational use," they wrote.

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