Cannabis edibles led to a higher percentage of acute psychiatric events and cardiovascular symptoms among emergency department (ED) patients than inhaled marijuana, according to a Colorado hospital chart review.
While inhalable cannabis accounted for more ED visits overall, edibles led to more ED visits than expected, accounting for 10.7% of cannabis-attributable ED visits but only 0.3% of tetrahydrocannabinol (THC) in cannabis dispensary sales from 2014 to 2016, reported Andrew Monte, MD, PhD, of the University of Colorado School of Medicine in Aurora, and co-authors in Annals of Internal Medicine.
This research is "the first study to systematically demonstrate that edible cannabis products are more dangerous than inhaled cannabis," Monte told MedPage Today.
"In this time of cannabis policy liberalization, this can help guide us in educating cannabis users and physicians," he added. "It can also help guide us in the development of public health policy to mitigate patient illness."
Colorado laws allowed for medical marijuana in 2009 and recreational cannabis in 2014. In Colorado, cannabis is purchased most often in flower form for smoking; edible cannabis accounts for 0.3% of the weight of THC in total cannabis product sales. A Colorado Behavioral Risk Factor Surveillance System survey showed that 40.4% of users smoke cannabis and 3.6% use edible products only; the rest use a combination of the two. Poison center reports, focus groups, and anecdotal reports suggest that edibles frequently account for adverse events.
For the retrospective study by Monte and co-authors, the team looked at 9,973 charts at the University of Colorado Health ED from 2012 through 2016 with ICD-9-CM or ICD-10-CM codes consistent with cannabis exposure. Of these, 2,567 ED visits were deemed at least partially attributable to cannabis.
The frequency of cannabis-attributable visits increased each year from 2012 to 2016, with the total number more than tripling during that period. Nearly 82% of patients were white and 90% were Colorado residents.
Overall, edibles accounted for 238 visits (9.3%). Edible cannabis patients were similar in age (about 30) to those who inhaled marijuana, but were more likely to be female and to live outside Colorado.
Gastrointestinal (GI) symptoms were the most frequent cause of ED visits (30.7%). Cannabinoid hyperemesis syndrome was the most common GI adverse event and the reason for most hospital admissions, occurring twice as frequently in patients who smoked cannabis versus those who consumed edibles.
Patients who used edibles more commonly had acute psychiatric symptoms (18.0% vs 10.9%), cardiovascular symptoms (8.0% vs 3.1%), and intoxication (48.3% vs 27.8%) than patients who inhaled (all P<0.001). Severe adverse cardiovascular events, including myocardial infarction and ventricular dysrhythmia, occurred in both groups.
The researchers compared their data against cannabis product sales in Colorado, assuming a THC content of 20% per kilogram of flower sold for inhalable cannabis and 10 mg of THC for each unit sold for edible cannabis. Based on the calculations, 309 times more THC was sold in flower (inhalable) form than edible products from 2014 through 2016. During the same period, 1,819 University of Colorado Health ED visits were attributable to inhaled exposure and 219 (10.7% of total) to edibles.
"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," the researchers noted. "The observed proportion of cannabis-attributable visits with edible exposure was about 33 times higher than expected (10.7% vs 0.32%) if both routes of exposure were equally toxic."
This higher-than-expected number of adverse events "is consistent with prior findings, including a 2017 poison control center report in which edible products accounted for 17% of cannabis-related visits to health care facilities among adults," observed Nora Volkow, MD, director of the National Institute on Drug Abuse (NIDA) in Bethesda, Maryland, and Ruben Baler, PhD, of NIDA's Office of Science Policy and Communications, in an accompanying editorial.
"The slow rate of absorption of orally ingested THC (peak blood levels achieved in 3 hours) compared with inhalable THC (peak blood levels achieved within 30 minutes) makes it harder for users of edible cannabis to titrate the doses required to achieve the desired drug effects," Volkow and Baler wrote. "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."
Personal variability in oral THC absorption can contribute to adverse outcomes, the editorialists added; with edibles, the fat content of food ingested with THC also may be a factor.
The increased number of edible-attributable ED visits among non-residents of Colorado suggests that naive users or tourists may be at greater risk, Monte and colleagues noted. "At the very least, users must be educated about the delayed kinetic profile and the increased risk for acute psychiatric and adverse cardiovascular events associated with edible ingestion."
The authors noted several limitations to their study: They used state-level sales data to infer ED visit rates for a single hospital and made assumptions about the THC content of flower and edible products based on average known concentrations. They could not account for marijuana obtained outside dispensaries, and exposures were self-reported.
Doses could not be verified; it's possible edibles contained more THC than inhaled cannabis, the researchers added. However, among documented doses in 80 edible-cannabis ED visits, only 19 had 50 mg of THC or higher. A typical joint in Colorado contains approximately 100 mg of THC, they noted.
The study was supported by the National Institutes of Health and the Colorado Department of Public Health and Environment.
The researchers reported relationships with the Colorado Department of Public Health and Environment and the Colorado Retail Marijuana Public Health Advisory Committee.
Volkow and Baler reported having no conflicts of interest.
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