This is the fifth in a series of blog posts on new research in emergency toxicology. The last post was about pain relief in opioid dependence, and can be found here. We deal with all sorts of poisons here in Virchester, so be prepared for anything.
Cannabis has been legalised in over ten countries, including regions of the United States and Canada. It is likely to be legalised elsewhere in the near future, although probably not in the United Kingdom. In some jurisdictions, possession of cannabis has been de-criminalised, but supply remains illegal.
As the law has changed, so has the market. Traditionally, cannabis leaf has been smoked — either on its own, or in a “joint” with tobacco. But smoking is less appealing than it used to be, and demand has increased for other ways to get high. The main alternatives on offer are liquid for vaporisation (“weed pens”) and edibles. The latter can take any form, although we mostly see brownies, gummies, and lollipops here in Virchester. The common ingredient is oil or butter infused with delta-9-tetrahydrocannabinol (THC), the psychoactive ingredient in cannabis leaf. Some also contain cannabidiol (CBD) which has only mild effects and is legal in most countries.
The problem with edibles lies in dosing. It is quite difficult to accidentally smoke too much cannabis, although users may, of course, under-estimate the effects of what they are taking. But with edibles, surprisingly high THC doses can be packed into small volumes, and the effects are delayed. Cannabis gummies seized in England have been high potency, with inconsistent labelling. It is easy to see how an inexperienced user could overdo it.
Edibles have, for this reason, raised questions for us at St Emlyn’s. In our department we regularly see the effects of chronic cannabis use, which include increased risk of psychosis and the ever-challenging ‘cannabis hyperemesis syndrome.’ But it is rare that we see acute problems with this drug in the same way we do with alcohol, cocaine, and opioids. In fact, outside of case reports, it is not clear that cannabis toxicity actually exists.
Is this because our patients have, up until recently, been exposed to relatively low doses of THC? Have high-dose cannabis edibles changed the game?
Helpfully, a study on this topic was recently published in Medical Toxicology. This study analysed three years’ data on edible-related presentations to an emergency department in Florida, USA.
Abstract
Introduction: Cannabinoid-related emergency department (ED) visits are increasing, yet little has been published about how the route of cannabinoid use (inhaled versus oral) affects ED presentations. We sought to compare ED visits from inhaled versus oral cannabinoid use.
Zitek T, Raciti C, Nguyen A, Roa V, Lopez E, Oliva G, Farcy DA. Emergency Department Patients Presenting after Oral versus Inhaled Cannabinoid use: A Retrospective Analysis. Journal of Medical Toxicology. 2024 Nov 29:1-0.
Research design and methods: We performed a retrospective cohort study using ED patients with a cannabinoid related diagnosis from January 1, 2020 and May 31, 2023 from a single hospital system in Florida. We performed manual chart review to categorize visits into “unlikely”, “possibly”, or “highly likely” to be due to acute cannabinoid use. For our primary analysis, we used the “highly likely” group to compare the presentations and outcomes of patients who had used oral cannabinoids versus inhaled. Our primary outcome was hospital admission.
Results: We deemed 303 patient visits “highly likely” to be from acute cannabinoids: 59 (19.5%) inhaled and 244 (80.5%) oral. Zero patients in the inhaled group were admitted compared to 15 (6.2%) in the oral group, a difference of 6.2% (95% CI 3.1–9.2%), p = 0.05. Additionally, 65 (26.7%) of the oral group reported using cannabinoids unintentionally including 8 housekeepers who ate food products left by hotel guests. Comparatively, 4 (6.8%) of the inhaled group unintentionally used cannabinoids (difference 19.9% [95% CI 11.4–28.3]).
Conclusions: Most patients who presented to the ED for the effects of acute cannabinoids had used them orally. Compared to patients who had inhaled cannabinoids, those who used them orally required more ED diagnostic resources and were more likely to be admitted to the hospital for additional evaluation or treatment. From a public health perspective, increased regulation of edible cannabinoid products may be needed.
What was the study design?
This was a retrospective chart review conducted by researchers at Florida International University using electronic data (2020-2023) from three local emergency departments.
During data collection, the legal situation for cannabis use in Florida was complex. Possession for recreational use was, and still is, a criminal offence. However, consumption of cannabis (smoked or eaten) for medical purposes was legal. I had a quick look through some of the indications for medical cannabis in Florida. They included back pain, anxiety, and migraines — so I suspect these licenses are not overly difficult to obtain.
Can you tell me about the patients?
The study involved data from 303 visits to the ED that were deemed “highly likely” to be related to acute cannabis intoxication.
Their criteria were fairly broad. Patients had to have at least one of a long list of symptoms, which included psychiatric (agitation, anxiety, paranoia, dysphoria, euphoria, lethargy, altered mental status), mucosal (conjunctival injection, dry mouth), gastrointestinal (nausea, vomiting), neurological (seizures, tremors, dizziness, loss of consciousness) and cardiorespiratory (dyspnoea, chest pain) complaints. They could not have a prior psychiatric diagnosis that explained their symptoms. Co-ingestion of other illicit drugs was not allowed, but some co-ingestion of alcohol was fine. Patients with symptoms attributable to chronic cannabis use (e.g. hyperemesis) were excluded.
For all cases labelled as “highly likely” a second data reviewer was brought in to provide a second opinion. I was pleased to see that the researchers calculated kappa values for this consensus process. They achieved a score of 0.82, indicating very good agreement between reviewers.
The majority of patients used edibles (n=244; 80.5%) and the remainder (n=59; 19.5%) smoked cannabis. Most were young, although unexpectedly, the smokers were significantly younger, with a mean age of 26.9 as opposed to 36.5. There was a female predominance in the edibles group.
The presenting symptoms were fairly typical for stoned patients: lots of anxiety, light-headedness, nausea, and palpitations. Differences between groups were minimal. Edibles were more associated with lethargy (26.2% vs 11.9%) but less associated with syncope (4.9% vs. 17%). The latter finding does not surprise me. Over-enthusiastic inhalation can cause a transient rise in vagal tone, leading to collapse.
Tachycardia and hypertension were common in both groups. Curiously, there is no mention of hypotension in the published manuscript.
What outcome measures were used?
A bit of everything. The researchers were interested in cardiovascular abnormalities, hypokalaemia, and patient disposition. They were also interested in resource usage, and documented median length of stay in ED as well as any investigations ordered in the department.
What were the main results?
Despite the high prevalence of palpitations and light-headedness, arrythmia was only found in a single patient. QT prolongation (>500ms) was absent in the smokers, but was seen in six patients (3.8%) who had used edibles. Roughly half the patients in each group were hypokalaemic, although it is not clear to what extent.
Most patients received blood tests and an ECG. A CT head was ordered in a minority of cases, but significantly more in the edibles group (9.8% vs. 3.4%).
Edibles were associated with a prolonged length of stay in ED (261 vs. 174 minutes) and unlike the smokers, who were all discharged home, fifteen (6.2%) were admitted to hospital.
What should we take away from this study?
Edibles have theoretical potential to cause greater harm than smoking cannabis, and this study provides some actual data to test whether this is the case in the ED. The authors conclude that their findings ‘suggest more acute morbidity and more resource utilization’ with these patients. I am not sure that I agree.
To begin with: it is not clear to me that these patients actually incurred any harm. One patient had an arrythmia and six had a prolonged QT interval. It would have been useful to know whether the patients with QT-prolongation were one of the twenty-six with a history of mental illness, as we know many psychiatric drugs influence the QT. But either way: I am not sure that a handful of abnormal ECGs demonstrates ‘morbidity.’ Neither does admission, without further information on why hospitalisation was necessary. Were they brought in for observation or for treatment?
A similar point can be made about resource utilisation. It may be that the additional investigations requested in the edibles group (e.g. CT head) were a response to doctors’ fears about these drugs, and not clinical signs. There was no masking used in this study, and so all management decisions were made with the edibles in mind.
None of this is to say that the study demonstrates edibles to be safe. Data was only extracted from cases where it was “highly likely” that cannabis caused the patient’s symptoms. This is likely to have been from self-report — which implies an awake, relatively cogent patient. It may be that there were cases of life-threatening toxicity during the recruitment period, but they were missed because the patient was too sick to describe their drugs. Alternatively, it may be that the worst overdoses are found outside of Florida, where there is less access to legal, regulated edibles.
Should this study change our practice?
Not really. I disagree with the authors’ conclusions about their findings.
I am also uneasy about their recommendations, which include a call for ‘increased regulation of edible cannabinoid products.’ What exactly does this mean? Regulation of the way edibles are produced, marketed, or packaged? Would any of this be supported by the study?
I will keep an open mind, but it seems to me from the evidence we have that THC is just not a significant problem for us in emergency medicine.
Greg Yates
References
- Zitek, T., Raciti, C., Nguyen, A. et al. Emergency Department Patients Presenting after Oral versus Inhaled Cannabinoid use: A Retrospective Analysis. J. Med. Toxicol. (2024). https://doi-org.manchester.idm.oclc.org/10.1007/s13181-024-01048-3
- RCEM: Cannabinoid Hyperemesis Syndrome (CHS). https://www.rcemlearning.co.uk/foamed/cannabinoid-hyperemesis-syndrome/
