This case highlights the complex and challenging management of chronic pancreatitis caused by recurrent acute pancreatitis and the potential role of medical cannabis as a novel therapeutic option. The patient's extensive medical history demonstrates the limitations of conventional treatments, which often provide limited and temporary relief. Despite multiple ERCPs, sphincterotomies, stent placements, and various pain management strategies, the patient continued to suffer from frequent and severe episodes of pancreatitis.

The introduction of the cannabis-based medication, resulted in significant symptom relief, suggesting a potential new avenue for managing chronic pancreatitis. According to a study by Barlowe et al (2019), medical cannabis has shown efficacy in reducing opioid use and hospital visits in patients with chronic pancreatitis, highlighting its potential as a pain management strategy (Barlowe et al. 2019). This aligns with the observed benefits in our patient, who experienced a complete cessation of pain flare-ups and acute pancreatitis attacks, eliminating the need for additional pain medications like Ketorolac, Paracetamol and Butylscopolamine. However, contrasting evidence has identified cannabis use as a potential risk factor for acute pancreatitis, particularly in young adults, underscoring the importance of careful patient selection and monitoring when considering cannabis-based therapies (Barkin et al. 2017).

A strength of this case is the demonstrated efficacy of medical cannabis in a treatment-resistant patient, highlighting its potential for managing chronic and refractory pancreatitis. The patient's remarkable response supports the hypothesis that cannabinoids may reduce the frequency and severity of pancreatitis episodes, possibly due to their anti-inflammatory properties. Studies suggest that cannabinoids may exert protective effects in certain contexts, such as alcohol-associated pancreatitis, further supporting their therapeutic potential (Adejumo et al. 2018). This protective effect may be due to the anti-inflammatory properties of cannabinoids, which modulate the body's inflammatory response. Our patient's positive response to cannabis treatment supports this hypothesis, indicating that cannabis may help reduce the frequency and severity of pancreatitis episodes. This is in line with various systematic review and meta-analyses, which concluded that cannabis may offer symptom relief, even if more high-quality, large-scale, and long-term studies are needed to clarify its therapeutic potential and risks (Volz et al. 2016; Martín-Sánchez et al. 2009). This is particularly relevant for chronic pancreatitis, where pain management is a significant challenge.

The form of choice for the cannabis treatment of chronic pain is the one based on oils prepared with standardized extracts, whose exact dosages of CBD and THC are guaranteed. Cannabis therapy is characterized by a cautious and personalized approach. It always starts from very low dosages, as in the clinical case presented here, gradually increasing the dose until the desired therapeutic effect is achieved, minimizing side effects. A doctor might start with a low concentration oil (for example, a 5% CBD/THC oil), initially prescribing 2 drops, 2–3 times a day, considering that each drop of a 5% oil corresponds to about 2.5 mg of active ingredient, and increase the dose by 1 drop every 3–7 days, depending on the patient's response and tolerability.

A crucial aspect of medical cannabis is that there is no "ceiling effect" for its analgesic potential, in the sense that there is no maximum established dose beyond which no benefit is observed. This means that titration can continue until the effective dose tolerated by the patient is found. Inhalation administration (through specific medical vaporizers) is generally reserved for conditions that require rapid and immediate action, such as severe neuropathic pain, sudden pain ("breakthrough pain") or acute spasticity. The advantage is the onset of the effect in a few minutes, but the duration is shorter than oral intake. On the contrary, in Italy, resins or edible products such as cannabis-based gummy candies are not reimbursed by the National Health Service (SSN) and are not commonly used in medical therapies due to their variability in dosage.

Despite the potential benefits, it is important to consider the adverse effects associated with cannabis use. It has been reported that cannabis-based medicines increased the incidence of nervous system and psychiatric disorders, emphasizing the need for careful patient selection and monitoring (Mücke et al. 2018). This is crucial in ensuring that the benefits of cannabis treatment outweigh the risks, especially in patients with chronic conditions. According to available literature, cannabis-based therapies are generally well-tolerated in patients without specific contraindications. Most adverse effects are mild, transient, and primarily associated with THC, with their occurrence being dose-dependent (Mick and Douek 2024). The extract prescribed to the patient contains a high concentration of CBD (5%) and a low concentration of THC (< 0.5%), administered at minimal dosages. Consequently, the absence of adverse drug reactions (ADRs) since the initiation of treatment was unsurprising to the medical team.

Regarding the potential mechanism of action, cannabinoids such as CBD and THC exert their therapeutic effects in pancreatitis through several mechanisms. CBD has been shown to have significant anti-inflammatory properties. According to Li et al. (2013), CBD reduces inflammation in experimental acute pancreatitis by improving the expression of GPR55 in pancreatic tissue and decreasing pro-inflammatory cytokines like IL-6 and TNF-α (Li et al. 2013). Additionally, CBD modulates oxidative stress, a key factor in the pathogenesis of chronic pancreatitis, by reducing the levels of oxidative markers and increasing the expression of cytoprotective factors such as (Yong-yu (n.d.)). CBD also interacts with the adenosine A2A receptor, which plays a crucial role in mediating its anti-inflammatory effects. CBD's inhibition of adenosine uptake enhances adenosine signaling, leading to reduced inflammation and tissue damage in models of acute lung injury, which can be extrapolated to pancreatic inflammation (Ribeiro et al. 2012). This suggests that CBD's anti-inflammatory effects in pancreatitis are partly mediated by its interaction with the adenosine system. Moreover, cannabinoids inhibit pain signaling by acting on central and peripheral receptors, providing an analgesic effect that is beneficial in chronic pain conditions like pancreatitis. Indeed, activation of cannabinoid receptors CB1 and CB2 reduced pain and inflammation in acute pancreatitis without producing central adverse effects (Michalski et al. 2007). This indicates that cannabinoids can effectively manage pain while also addressing inflammation. Nonetheless, the presented case has several limitations. First, it represents a single-patient report, and the observed benefits cannot be generalized without further evidence from larger, controlled studies; furthermore, the patient's long clinical history must be taken into consideration, as she visited many different hospitals and laboratories, even in different countries, which makes it more difficult to reconstruct in detail all the treatment attempts made. Second, while the absence of adverse drug reactions in this patient may be attributed to the high CBD-to-THC ratio and minimal dosages used, these findings should be interpreted cautiously. Further research is needed to validate the therapeutic potential of cannabinoids in chronic pancreatitis and to establish a clear risk–benefit profile.