Inhaling versus ingesting cannabis leads to very different health outcomes. A study in the Annals of Internal Medicine that examined cannabis-related emergency department (ED) visits in Colorado since legalization revealed a much higher than anticipated rate of visits due to edible cannabis, linking the ingested product to psychiatric and cardiovascular problems.

Colorado has seen a sharp rise in cannabis-related ED visits since its legalization of marijuana in 2014. However, the harms of ingested and inhaled cannabis haven’t been studied extensively. Making up just a small proportion of overall cannabis products, edible cannabis has contributed to adverse events reported to poison control centers and ED visits, and might even be more toxic than inhalable cannabis. “In Colorado, the only deaths definitively associated with cannabis use involved edible products,” wrote the investigators.

To compare adult ED visits associated with inhaled and edible products, the researchers conducted a health record review of patients presenting to the University of Colorado Health Emergency Department from 2012 to 2016. Overall, they looked at nearly 10,000 visits with a cannabis-related ICD-9-CM or ICD-10-CM code.

Looking at factors such as patient demographic characteristics, route of exposure, dose, symptoms, length of stay, disposition, discharge diagnoses, and attribution of visit to cannabis, they found a more than threefold increase in cannabis-associated ED visits over this four-year period.

Cases involving inhaled cannabis, which accounted for most of the visits, had longer ED stays and higher hospitalization rates. However, the proportion of cannabis-attributable visits ED visits due to edible exposure was 33 times higher than expected. Edibles represented just 0.32% of total cannabis sales (in kilograms of tetrahydrocannabinol [THC]) in Colorado, yet they accounted for 10.7% of all ED visits between 2014 and 2016. “If inhalable and edible cannabis were equally toxic and resulted in the same number of ED visits, we would expect that 0.3% of cannabis-attributable visits would be due to use of edible products,” according to the investigators.

Cannabinoid hyperemesis syndrome was the chief complaint in patients visiting for inhaled cannabis. In comparison, patients visiting for ingesting cannabis were more likely to have acute psychiatric symptoms or present with intoxication and cardiovascular symptoms.

“Future studies that examine cannabis-attributable ED visits should be stratified by route of exposure and should account for population exposure to inhalable and edible products,” the researchers recommended.

The study underscores the fact that edible cannabis may be more of a problem than previously thought. “The higher-than-expected number of adverse events associated with edible cannabis products, considering the frequency of their sale, is consistent with prior findings, including a 2017 poison control center report in which edible products accounted for 17% of cannabis-related visits to healthcare facilities among adults,” observed Nora D. Volkow, MD and Ruben Baler, PhD of the National Institute on Drug Abuse, in a related editorial.

Users of edible cannabis may find it harder to titrate the doses due to its slow absorption rate. “Further, the slower clearance of oral (12 hours) versus inhalable (4 hours) THC can lead to drug accumulation if users take additional doses when they do not experience the desired effects as quickly as expected,” the Volkow and Baler observed. In addition, edible cannabis in its various incarnations can appear harmless, leading to overconsumption.

Cannabis exposure is increasing, especially with regard to medical uses, yet much is still unknown about this substance and its impact on human health, the editorialists continued.

“Research is needed not only to rigorously ascertain evidence about potential beneficial effects of cannabis but also to carefully characterize its potential negative effects. These must be studied as a function of THC and [cannabidiol] CBD content, route of administration, doses consumed, sex, age, body mass index, and the medical conditions for which cannabis might be prescribed,” Volkow and Baler recommended.