Cannabis is increasingly becoming one of the most commonly used recreational substances and according to a survey by WHO, its use in the United States (US) and New Zealand are higher than other countries. ⁴ The prevalence of cannabis use has doubled within a span of 10 years between 2001 and 2012. ⁵ Changing regulations and ease of access have increased the prevalence of complications associated with cannabis use.

Cannabis induced pancreatitis is a rare cause of AP and the diagnosis is difficult because a clear diagnostic criteria is lacking. Cannabis was first reported as a possible cause of AP in 2004 and since then only 26 total cases have been reported. A systematic review by Barkin et al in 2017 describes a temporal relationship between the use of cannabis and recurrent pancreatitis in 15 of these 26 cases. Furthermore, the study showed that there were 13 reports of no further pancreatitis episodes after cannabis cessation. ⁶ Although cannabis use has been associated with an increased incidence of AP, typically patients present earlier between 3 and 5 days after recent cannabis use. ⁷ Manifestations of AP after prolonged use is rare but not entirely uncommon. In order to better understand the association between cannabis use and AP, a more detailed analysis of the underlying pathogenesis is important and required.

The pathogenesis of pancreatitis is proposed to be due to a “Three Hit mechanism” involving genetic, environmental, and an acute trigger leading to trypsinogen activation and, in turn, pancreatic injury. The genetic factors leading to pancreatitis have been studied extensively and several genes such as SPINK1, CFTR, HLA‐DRB*0401, and PRSS1 have been attributed with the increase in predisposition to develop pancreatitis. ⁸ , ⁹ These factors when combined with acute triggers such as pancreatic hyperstimulation, biliary disease, alcohol, medications, and recreational drugs lead to unregulated trypsin activity, rise in intra acinar calcium levels, zymogen activation, pancreatic autodigestion, and pancreatic inflammation. ¹⁰ , ¹¹ However, the specific mechanisms involving the pathogenesis of CIP are poorly defined and understood. Currently, it is known that cannabis acts via two cannabinoid receptors CB I and CB II, which are both extensively prevalent in pancreatic tissue. ¹² , ¹³ Dembinski et al demonstrated the physiological effects of CB I receptor with the help of anandamide, an endocannabinoid that caused significant increases in pancreatic amylase, lipase, ribonuclease, and IL‐1β secretions. It is thought that this interaction creates a physiological milieu similar to that which is noted in AP. Some other studies have also hypothesized that the activation of the CB I receptor leads to an impaired relaxation of the sphincter of oddi, which can further act as an acute trigger for CIP. ¹³ , ¹⁴

These cannabinoid receptors have also been noted to decrease gastric acid secretions, intestinal secretions, and delay gastric emptying. ¹³ The relationship between cannabinoid receptors and the exocrine activity of the pancreas is well defined; however, its association with the endocrine functions remains unknown. Some suggest that the activation of CB1 receptors leads to a decrease in insulin secretion. ¹⁵ Michalscki et al ¹⁶ showed in a study that the activation of CB I and CB II receptors abolished the abdominal pain associated with pancreatitis. It is postulated that continued and prolonged use of cannabis will eventually lead to a compounding effect in the body triggering CIP in patients. As there can also be several other possible triggers to potentiate AP, establishing a strong causal link between cannabis use and AP is difficult. Further in‐depth molecular studies are needed to better define the roles of cannabinoid receptors and its physiological mechanisms regarding the pathophysiology involving CIP.