Over the last four years, the UK Medical Cannabis Registry has collected real-world data from patients who have been prescribed medical cannabis for the treatment of a range of conditions, including chronic pain. As one of the most commonly reported reasons for medical cannabis use, it is essential that we are able to understand the potential of cannabis-based medicines in this setting. While randomised controlled trials remain few and far between, real-world evidence can help to provide an important insight these products.
Chronic pain is believed to have a high prevalence in the UK, with estimates suggesting that between one-third and one-half of the population may be affected. Characterised by physical pain persisting for longer than three months, chronic pain represents a significant personal and economic burden. However, current treatment options have been found to be of questionable efficacy and are often associated with serious side effects. Such treatments include non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and gabapentinoids. As such, the identification of alternative treatment options has become an important area of focus.
Growing evidence has implicated the role of the endocannabinoid system in pain sensation and perception pathways. CB1 receptors, found in the nervous system, have been found to inhibit ascending nociceptive transmission from the dorsal horn in the spinal column and stimulate descending analgesic pathways. In contrast, CB2 receptors may play a neuroprotective role in neurological disorders and mediate neuronal sensitisation in chronic pain conditions, among other processes.
The widespread use of medical cannabis makes the continued evaluation of cannabis-based medicines in such settings particularly important.
Data Collection for the UK Medical Cannabis Registry
The UK Medical Cannabis Registry (UKMCR), which has been managed by Sapphire Medical Clinics since 2019, is the first UK patient registry to collect data regarding CBMP prescription formulations, patient demographics, patient-reported outcome measures (PROMs) and adverse events (AEs). The current analysis assessed data from patients who had received a medical cannabis prescription for chronic pain.
Patient-Reported Outcome Measures (PROMs)
The data assessed in this study were reported electronically by patients or contemporaneously by clinicians during initial clinical consultations. Primary outcome measures were changes in PROMs from baseline to 1-, 3-, and 6-month follow-up. Secondary outcomes were the incidence and severity of AEs. The researchers identified 812 patients who were prescribed CBMPs for chronic pain conditions. Of those, 761 (93.7%) completed baseline PROMs and were included in the analysis.
PROMs were measured using the Pain Visual Analog Scale (P-VAS), Brief Pain Inventory Short-Form (BPI), Short-Form McGill Pain Questionnaire-2 (MPQ2), Single-Item Sleep Quality Scale (SQS), Generalized Anxiety Disorder-7 (GAD-7), EQ-5D-5L, and Patient Global Impression of Change (PGIC).
The P-VAS questionnaire records patient-reported pain scores from 0-10. The BPI allows patients to score their worst, strongest, current, and average pain intensity and scores are combined to create a ‘pain severity score’ from 0-10. The BPI also records the patient-reported impact of pain on daily activities, such as sleep, socialising, and work to create a ‘pain interference score.
The EQ-5D-5L is the HRQoL measure recommended by the National Institute for Health and Care Excellence (NICE). The SQS utilises a numerical rating scale rating from 0 (terrible) to 10 (excellent) to assess sleep quality over the past 7 days. GAD-7 evaluates seven aspects of generalized anxiety by the number of days they were experienced in the past fortnight. The PGIC assesses perceived change since starting treatment in terms of activity limitations, symptoms, emotions, and overall quality of life, through two parts.
Results of Analysis
For patients prescribed oil products, statistically significant changes in P-VAS, BPI, and MPQ2 were recorded at 1, 3, and 6 months compared to baseline. Statistically significant changes were also observed in patients prescribed only dried flower in P-VAS, BPI Severity Score, and MPQ2 after 1 and 3 months.
Changes in BPI Interference Scores were also seen after 1 month and patients prescribed both dried flower and oils demonstrated improvements in P-VAS, BPI Interference Score, and MPQ2 after 1, 3, and 6 months, respectively. Finally, changes were seen in the BPI Severity Score after 3 and 6 months.
Health-Related Quality of Life (HRQoL)
For non-pain-specific HRQoL measures, patients prescribed oils reported changes in SQS scores and the EQ-5D-5L index, usual activities, and pain and discomfort subscales after 1, 3, and 6 months. Furthermore, changes in GAD-7 and the EQ-5D-5L anxiety and depression subscales were found at 1 and 3 months compared to baseline. The median PGIC remained constant at 5.00.
Patients prescribed dried flower reported changes for SQS, and the EQ-5D-5L index, as well as the pain and discomfort subscales after 1 and 3 months. Dried flower users also reported changes for the EQ-5D-5L usual activities domain after 1 month.
Patients prescribed both oils and dried flower reported changes in SQS, GAD-7, as well as the EQ-5D-5L index, mobility, usual activities and pain and discomfort subscales after 1,3, and 6 months, respectively. Changes were also reported in the EQ-5D-5L self-care and anxiety and depression subscales and the median PGIC increased from 5.00 at 1 month to 6.00 at 3 months.
Adverse Events could be recorded by patients as they occurred, in combination with PROMs or during clinical consultations. For patients prescribed oils, 857 total adverse events were reported, the most common being fatigue (n = 114; 14.0%), somnolence (n = 88; 10.8%), and dry mouth (n = 84; 10.3%). Most adverse events were categorised as mild (n =387) or moderate (n = 360); however, 109 adverse events were categorised as severe and 1 as life–threatening.
An increased adverse event incidence was identified for females, cannabis naïve and ex-users. Patients who were prescribed dried flower were not included in adverse event analysis due to low numbers of adverse events (n = 1).
The researchers conclude that future studies should “consider the impact of gender and prior cannabis use when prescribing CBMPs… [and] whether these factors influence the extent of HRQoL [changes] should be investigated in active comparator trials.”