OBJECTIVE: The study aims to evaluate the clinical outcomes in patients with hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) with chronic pain following treatment with cannabis-based medicinal products (CBMPs). METHODS: This was a case series conducted with the UK Medical Cannabis Registry. The primary outcomes were changes in the following validated patient-reported outcome measures at 1, 3, 6, 12, and 18 months compared with baseline: Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2), pain visual analog scale score (Pain-VAS), Brief Pain Inventory (BPI), five-level EQ-5D (EQ-5D-5L), Single-Item Sleep Quality Scale (SQS), General Anxiety Disorder Seven-Item Scale (GAD-7), and Patient Global Impression of Change. The incidence of adverse events was analyzed as secondary outcomes. Statistical significance was defined as P <
0.050. RESULTS: A total of 161 patients met inclusion criteria. Improvements were observed in BPI severity and interference subscales, SF-MPQ-2, and Pain-VAS (P <
0.001). Changes were also seen in the EQ-5D-5L index value, SQS, and GAD-7 (P <
0.001). A total of 50 patients (31.06%) reported one or more adverse event with a total incidence of 601 (373.29%). The most frequent rating for adverse events was moderate (n = 258
160.25%), with headache being the most common (n = 44
27.33%). CONCLUSION: An association was identified between patients with HSD/hEDS with chronic pain and improvements in pain-specific and general health-related quality of life following the commencement of CBMPs. CBMPs were also well tolerated at 18 months. These findings must be interpreted within the context of the limitations of study design but add further weight to calls for randomized controlled trials.