This is, to our knowledge, the first study describing the GI manifestations of SCs use in the acute setting. Among symptomatic SCs users presenting to the ED, 38% had GI manifestations and abdominal pain was reported by of those with GI symptoms. Still, the clinical presentation, laboratory results, and imaging findings ranged in severity among these patients. Most patients had only mild abdominal pain, while others had severe elevations of serum lactate with one patient having an intestinal perforation. Nevertheless, the vast majority of patients (20/21) had complete resolution of abdominal pain and normalization of serum lactate levels within a few hours of presentation.
When comparing the differences between the patients with GI manifestations and those without GI manifestations, there were no statistically significant differences in their prognoses, clinical severity, or laboratory values. However, the patients with GI manifestations had higher lactate levels likely caused by the intestinal involvement and more patients with severe leukocytosis. Still, due to the relatively low number of patients the statistical difference was not significant. The mechanism causing the varied effects of SCs on the GI tract is unclear, but may be related to a previously reported effect of THC and cannbinoidiol on CBr1 and CBr2, which influence GI function, motility, and sensation [15, 17]. Our study suggests that SCs GI symptoms are unpredictable and can vary from minimal or no symptoms to intestinal perforation and death [16]. This varied GI response to SCs may be due to the varying potency of SCs, especially with the development of new ultra-potent SCs that may impact the GI tract more than regular cannabis [18]. Others have suggested that the variability of SCs on the GI tract may be due to adulterants (such as caffeine, nicotine, and tramadol), which can contribute to clinical effects and toxicity [19].
An additional mechanism of SCs induced GI symptoms may involve vascular spasm. SCs have been shown to rapidly alter neurotransmitter release from nerve terminals, thereby potently activating vascular smooth muscle cells, potentially resulting in vascular spasm. Rose et al. reported two cases of subarachnoid hemorrhage following SCs consumption and used digital subtraction angiography to confirm transient vasospasm [20]. Moreover, Mir et al. reported two patients with ST-elevation MI following SCs use with subsequent normal coronary angiography [21]. SCs impacting the GI tract and GI vasculature was also reported. Buyukbese Sarsu described a young patient who developed duodenal perforation as a complication of peptic ulcer disease following chronic SCs use [22]. Therefore, transient spasm occluding the mesenteric vessels might cause the severe abdominal pain that was present in some of our patients and also may explain the transiently elevated lactate levels. The low proportion of abnormal imaging in patients with severe abdominal pain, as in our study, supports the vasospasm theory as vasospasm is reversible, and no vascular pathological findings were demonstrated.
Currently, with the increasing prevalence of marijuana use by the public, there is extensive awareness of GI symptoms related to cannabis use, including abdominal pain and vomiting [23]. However, SCs related GI symptoms are less frequently reported. Furthermore, the lack of identifiable SCs in the toxicology screening in routine use make the diagnosis of SCs related GI symptoms difficult. With the increasing usage of SCs, it is important to recognize their potential to cause GI symptoms in the acute setting.
One limitation of our study is a lack of diagnostic serum and urine analytical studies to diagnose objective SCs use, a challenge noted in many SCs cohorts. As in many hospitals, the availability of gas chromatography and mass spectrometry testing in the acute setting is lacking, and similar to other studies in this field, we rely on patient and/or family reported history. A second limitation of our study is that patients presenting with SCs use often have concomitant drug intoxication, such as amphetamines and marijuana, which can also impact GI symptoms in a similar manner although not in the same rates of GI involvement compared to SCs. A third limitation is the lack of autopsy and post mortem imaging aside from one post mortem CT. Notwithstanding these limitations, we present the first cohort of patients presenting with various GI symptoms and SCs use in the acute setting. This can help to raise awareness and potentially guide future studies to evaluate the mechanisms of SCs GI involvement, including the hypothesis that transient arterial vasospasm causes the acute GI symptoms. GI consequences occurring with SCs use are often short-lived and resolve quickly though, in certain instances can be life-threatening (e.g. intestinal perforation; as demonstrated by one case in this cohort). Awareness of the breadth of clinical presentations and GI signs/symptoms common to SCs intoxication is important for providers treating these patients. Better analytic testing and drug confirmation is needed along with prevention of SCs use via counseling in at-risk populations is vital to reduce public health implications and morbidity from SCs use.