Today, chronic pain is one of the most common reasons for the medicinal use of cannabis, globally. Yet, the mechanisms through which medical cannabis and its derivatives may be useful for these indications remain incompletely understood. Furthermore, evidence of the effectiveness of medical cannabis for the treatment of pain is underdeveloped. As such, there is a clear need for the collection of high-quality clinical and real-world data in this area.
In Australia, medical cannabis was made legally available in 2016, giving patients with a number of indications access to cannabis-based medicinal products (CBMPs). The Australian Therapeutic Goods Administration (TGA) figures for prescriptions in 2021 demonstrate chronic pain to be the most common indication for which they approved applications for medical cannabis. The TGA’s guidance on the use of medical cannabis for chronic non-cancer pain concluded that there is evidence that medical cannabis can reduce pain scores and pain intensity ratings compared with placebo, based on the findings of 49 randomised controlled trials (RCTs). However, other reviews, including a 2018 review by Stockings et al., concluded that evidence was still limited.
RCTs and systematic reviews have long been considered the gold standard of evidence in medicine and are important in improving our knowledge of the effects of medical cannabis for specific conditions. However, whilst these are awaited real-world evidence can help guide current practice. Moreover, they can be useful in informing future trials. To this end, a number of patient registries have been developed to examine the health outcomes of people prescribed medical cannabis.
What is Project Twenty21?
Project Twenty21 (T21) Australia is an observational study that follows patients prescribed medical cannabis for chronic pain, anxiety, PTSD, and multiple sclerosis for up to 12 months. In a recent study, researchers assessed the data collected from a cohort of patients prescribed medical cannabis products for chronic pain at three-month intervals over the study period.
Methods of the Study
Once recruited into the study, each patient completed a condition-specific questionnaire alongside six general questionnaires which address secondary outcome variables. The pain questionnaire (Brief Pain Inventory – Short Form [BPI-SF]) and three questionnaires measuring health-related quality of life (EQ-5D-5L Summary Index), Depression and mood (Patient Health Questionnaire [PHQ-9]), sleep (Pittsburgh Sleep Quality Index), were conducted at baseline and every three months up to a maximum of 12 months.
Three more questionnaires, measuring patient global impression of change (PGIC), symptoms, adverse effects, and behavioural changes (cannabis-based medicines questionnaire and symptoms questionnaire), were conducted at follow-ups only.
Results of the Study
As of 30 October 2022, a total of 55 patients had been recruited into the study with a primary indication of chronic pain and had completed the three-month follow-up. Almost three-quarters (73.2%) of these patients reported at least one additional comorbid or secondary condition. The most commonly reported secondary conditions were: back and/or neck pain (28.6%), stress (28.6%) and generalised anxiety disorder (23.2%).
The majority of medical cannabis products prescribed were oils (68/1%), of which the majority were high cannabidiol (CBD) oils (89.4%) and the remainder balanced CBD/tetrahydrocannabinol(THC) oils (10.6%). Less than a third (31.9%) of products prescribed were flower, all of which were high THC.
Measures of pain severity and interference changed following three months of medical cannabis. Specifically, the mean rating across the four severity items from the BPI-SF went from 5.54 at baseline to 4.33 at three months. The mean rating across the seven pain interference items was 6.24 at baseline and 4.98 at three months.
Quality of Life and General Health
Both general health and quality of life scores were seen to change between baseline and three-month follow-up. General health was assessed using the visual analog scale (VAS) of the EQ-5D-5L. The mean general health score went from 52.79 at baseline to 64.25 after three months.
Depression and Mood
Depression often occurs comorbidly alongside chronic pain. In this patient cohort, 17.9% and 44.6% of participants were classified as having moderately severe or severe depression, respectively. At baseline, the average PHQ-9 score was 12.35. The researchers note a significant change in the severity of depression symptoms.
Sub-optimal sleep quality was common across the patient cohort, which is consistent with the finding that insomnia is often co-morbid with chronic pain, anxiety, and depression.
Reported Adverse Events
Only one patient was considered by their treating doctor to have experienced an adverse reaction, defined by the Australian National Health and Medical Research Council as ‘any untoward and unintended response to an investigational medicinal product related to any dose administered’. The patient reported dry eyes and feeling cold, both of which were resolved on the same day.
These findings, whilst promising must be interpreted within the limitations of study design. This was a limited evaluation of 55 patients in an observational study, which is subject to selection bias and the rate of attrition is not known as the participant number was limited to only those who had completed 3-month follow-up. Data from Project T21, alongside data from the UK Medical Cannabis Registry and other sources of real-world data will be important in shaping the future of medical cannabis care globally.