Chronic pain is an unpleasant sensory or emotional experience associated with or resembling actual or potential damage, lasting longer than 3 months. This can result in a spectrum of physical pain, disability, emotional disturbance, and social impacts. Chronic pain is believed to affect between 15% and 30% of adults worldwide and so, represents a significant socioeconomic burden on the global community.
Treatment options for chronic pain usually involve a multimodal analgesic (including nonsteroidal anti-inflammatory drugs and opioids) and adjunctive therapies (anxiolytics and muscle relaxants; however, there is a paucity of evidence that demonstrates their effectiveness and they can often carry significant side effects and risks. Opioid-based medications have questionable efficacy and have a high serious side-effect profile. This means that many patients and their practitioners are seeking alternative options to address chronic pain and its impact on quality of life.
Cannabis has been used medicinally for thousands of years, particularly as an analgesic. In recent years, many studies have aimed to understand the link between the endocannabinoid system and pain perception and quality-of-life measures, including sleep quality, mobility, and anxiety. One recent cross-sectional analysis aimed to evaluate effectiveness, reported adverse events, and health-related quality of life in individuals administered medical cannabis for chronic pain in Australia.
Design and Methods of the Study
Patients in Australia may be prescribed medical cannabis products for various refractory chronic pain conditions. However, there remains a perceived lack of evidence on the safety and effectiveness of different cannabinoids. In response, researchers used an observational study design to measure outcomes of medical cannabis in this population.
This multi-centre, prospective, open-label, observational study was conducted within cannabis access clinics – a network of practice clinics throughout Australia that specialise in prescribing cannabinoid-based medicines. Participating patients were prescribed an orally administered oil formulation containing equal parts of THC and CBD (10 mg/mL THC; 10 mg/ mL CBD) for pain.
Patients were eligible if they had reported symptoms of pain for at least three months, had tried, unsuccessfully, other pain killers, and were seeking medical cannabis therapy at a cannabis access clinic. Data were collected from 151 participants between December 2018 and May 2020.
Clinician-reported adverse events (AEs) and serious adverse events (SAEs) were collected at regular patient monitoring visits conducted as part of routine standard of care. Patients were also advised to visit their clinician once monthly for the first three months of medical cannabis and once every three months thereafter. Clinicians reported the severity (mild/moderate/severe) and relatedness (unlikely/ possibly/probably) of AEs within the clinical notes.
Patients were also sent a weekly online questionnaire during the period in which they were prescribed medical cannabis that included the question “Have you been experiencing any side effects from your medicinal cannabis prescribed by Cannabis Access Clinics?”. Participants were given a list of possible side effects and were able to choose “Other” or “None”. Patients who reported an AE in this questionnaire were contacted by their Cannabis Access Clinics clinician to assess the type and severity of the AE(s).
Quality of Life
Patients also completed PROMIS-29 questionnaires, “a validated, generic (disease non-specific) health-related quality of life (HRQoL) tool consisting of patient-reported outcome measures across seven domains used to evaluate physical, mental, and social health and wellbeing in people with chronic illnesses”.
Patient data were included in the analysis if they had completed at least two PROMIS-29 questionnaires during the study period. Of the 151 participants who submitted AE analysis, a subset of 71 participants were also included in PROMIS-29 analysis.
Results of the Study
The most common chronic pain conditions reported in this cohort included arthritis (n = 42; 27.8%), neuropathic pain (n = 34; 22.5%), and other musculoskeletal pain (n = 25; 16.6%). The majority (n = 134) of participants presented with a single chronic pain condition, while the remainder presented with two or more conditions. The cannabinoid dose increased significantly from the first time point to the last time point collected.
Over half of the AE analysis cohort (n = 91/151; 60.3%) experienced at least one AE during the observational period, while 39.7% (n = 60/151) of patients had no AEs. A total of 196 AEs were attributed to 91 patients, indicating that some patients experienced multiple AEs. The majority of adverse events (85.7%) were, however, reported to be mild. In comparison, 27.6% and 5.1% were reported to be moderate or severe, respectively. Somnolence (11.7%) and dry mouth/throat (7.1%) were the most common AEs experienced.
No serious adverse events were reported within the observational period for this cohort of patients.
Pain Intensity and Pain Impact
PROMIS –29 analysis showed a 9% decrease in overall pain intensity scores, indicating an improvement verging on significance for pain intensity across the observational period. Almost a third (32.9%) of the cohort was improved compared with 45.2% unchanged and 21.9% worsened.
Impact scores, as measured by PROMIS-29 questionnaires, were also significantly reduced across the study population. Most participants experienced an improvement in pain impact (47.9%), suggesting that the reduction in pain intensity influenced patients’ quality of life that was not reflected in the pain intensity measurements.
Sleep Disturbance and Fatigue
While no statistically significant improvements were observed across other PROMIS-29 domains, the majority of subjects who reported changes to fatigue and sleep disturbance domains noted improvements. This included improvements in sleep disturbance (49.3%) and fatigue (35.6%).
The researchers note that, while the majority of patients reported at least one adverse event, results concerning pain impact were encouraging, with scores reduced significantly across the cohort. Additionally, improvements in sleep disturbance and fatigue, both known to be highly related to one’s quality of life as well as their ability to manage and cope with pain, were also promising.
It is also noted that the analgesic effects and adverse events associated with medical cannabis in this observational study are consistent with existing clinical trials of Nabiximols (a CBD:THC medical cannabis formulation).
The researchers also suggest that the up-titrating of medical cannabis doses demonstrated between the first time point and the last time point may indicate, in addition to the nature of medical cannabis prescribing, that patients develop some level of tolerance throughout the study period. However, more analyses exploring this topic are needed to address this question.
It is concluded that, in the absence of randomised controlled trials, studies like this observational analysis can be used to yield important information regarding the potential of medical cannabis for chronic pain conditions. Nonetheless, it is recommended that more clinical trials be developed to continue to fill the gap in knowledge in this area.