In November 2018, the UK government introduced the rescheduling of cannabis, from Schedule 1 to Schedule 2 of the Misuse of Drugs Act 1971. This move officially recognised the medicinal value of cannabis allowing it to be prescribed under certain restrictions for conditions where patients had not seen benefit from first line treatments. However, access to cannabis-based medical products (CBMPs) remains relatively limited due to strict recommendations of use and a lack of clinical evidence.
Medical cannabis utilisation is also on the rise outside of the UK, with the most common reason for use being chronic pain. CBMPs target the role of the endocannabinoid system – a receptor system within our bodies – in modulating central and peripheral pain processes. They also have several other pharmacological targets which are implicated in the sensation of pain. CBMPs are increasingly being explored as a potential alternative to opioid medications, due to the increasing evidence of their associated harms and lack of data to support their effectiveness in chronic pain conditions.
Despite promising pre-clinical data in this area, there remains a relative lack of high-quality evidence to support the routine use of CBMPs in chronic pain. A recent study, however, assessed the outcomes of chronic pain patients who were treated with cannabis-based medicinal oils.
Design and Methods of the Study
This study is an uncontrolled case series of patients identified using the UK Medical Cannabis Registry, developed by Sapphire Medical Clinics. The UK Medical Cannabis Registry captures real-world data on prescribing outcomes and adverse events and aims to present this data transparently to help inform clinical practice, licensing decisions and decisions regarding cost-effectiveness.
The research team assessed patient-reported outcome measures (PROMs): EQ-5D-5L, General Anxiety Disorder-7 (GAD-7) and Single-Item Sleep Quality Scale (SQS). Fibromyalgia patients were also assessed using the Fibromyalgia Severity Scale (FSS), while all other chronic pain aetiologies were administered the Pain Visual Analogue Scale (VAS), Brief Pain Inventory Short Form (BPI) and Short-form McGill Pain Questionnaire-2 (SF-MPQ-2).
These PROMs were administered to patients alongside adverse event questionnaires electronically at baseline, and again at one month, three months, six months, and six-monthly intervals thereafter. Only patients who were prescribed exclusively Adven® CBMPs, manufactured by Curaleaf International, in the form of oil preparation and no other CBMPs and modes of administration were included in this analysis.
Results of the Study
Out of a cohort of 831 patients who had been registered on the UK Medical Cannabis Registry, 257 patients were identified who had prescribed only Adven® oil preparations for the treatment of chronic pain. Of these, 148 had completed the baseline PROM data and 110 of those had completed at least one follow-up data point: 100 patients had recorded PROMs at one month, 54 at three months and 20 at six months.
The most common primary diagnosis was chronic non-cancer pain (n=53; 48.2%), followed by neuropathic pain (n=26; 23.6%) and fibromyalgia (n=18; 16.3%). Fifty-two (47.3%) and fourteen (12.7%) patients, respectively, also had a secondary or tertiary indication for CBMP therapy.
Results of Patient-Reported Outcome Measures
Researchers identified statistically significant improvements in health-related quality of life (HRQoL) at months 1, 3, and 6 months in results from the Sleep Quality Scale (SQS), EQ-5D-5L pain and discomfort subscale, and Brief Pain Inventory Interference Subscale. Statistically significant improvements were also demonstrated at 1 and 3 months only in the EQ-5D-5L Index, Pain Visual Analog Scale, and EQ-5D-5L Visual Analog Scale.
There were no notable differences between cannabis naïve and previous cannabis users in terms of quality-of-life outcomes. In addition, there was no detectable improvement in the EQ-5D-5L domains of mobility, self-care and usual activities which, the researchers speculate, may suggest that CBMPs oils may be associated with improved perception of pain without resulting in functional change.
The results relating to pain perception and quality of life in this study are supportive of previous findings from the German pain e-Registry in 2017, which investigated the effectiveness and safety of THC/CBD spray for chronic pain management in a cohort of 800 patients. This analysis found that 56% of patients have had >50% improvement in pain intensity (67.5%) depression (66.5%), overall well-being (61.3%), anxiety (57.6%), disabilities in daily life (56.3%), sleep (47.0%), physical (42.1%), and mental quality-of-life (17.4%).
Adverse events (n=63) were reported by 33 patients (30%). Most of these events were mild or moderate (n=58; 92.1%), including nausea and dizziness. Only 2 events were described as severe and 1 disabling.
The researchers noted that, interestingly, all but one adverse event was reported by patients who self-reported never having used cannabis before. This suggests that a potential initial adjustment period in which dosing regimens are being optimised may result in the largest incidence of adverse events. After patients have developed a degree of tolerance, as suggested by prior cannabis use, this may reduce the incidence and/or severity of adverse events.
The authors of this study conclude that the present analysis demonstrates “a statistically significant improvement in health-related quality of life in a range of pain-related metrics.” These findings are consistent with the results of a prospective observational study of 751 patients in Canada, who were prescribed CBMPs for chronic pain conditions. They are also consistent with the initial analyses of patients from the UK Medical Cannabis Registry, which also revealed an improvement in health-related quality of life across all conditions and prescribed CBMPs.
The researchers concede that the results of this study are limited due to the small sample size of patients who completed multiple follow-up analyses. Moreover, a lack of a comparator arm or control group also may also limit the researchers’ ability to make any statements regarding causation for the associations found.
The authors conclude that the treatment of chronic pain with selected prescription regiments of sublingual CBMP oils is associated with an improvement in pain-specific outcomes in health-related quality of life and self-reported sleep quality. These results also demonstrate the incidence profile of adverse events, particularly highlighting how severe or disabling side effects are rare over medium-term treatment.
While the researchers note that the present study has some notable limitations, as the UK Medical Cannabis Registry increases in the number of participants and follow up available, further product-specific analyses are planned across conditions, to gain a clearer understanding of the potential of medical cannabis therapy.