An Analysis of a Practice-Based Research Network for Medical Cannabis Care 

Adverse Event Profile and Impact on Quality-of-Life Impact of Medical Cannabis in Chronic Pain Patient Population

Chronic pain is a prevalent condition that can affect people of all ages in all areas of the world. A recent estimate suggests that up to 34% of the population of England could suffer with chronic pain to some extent, across a variety of conditions. Common causes of chronic pain include conditions such as fibromyalgia and osteoarthritis, as well as traumatic injuries. Chronic pain is also the most common reason given for medical cannabis prescriptions globally.

Despite the high rate of prescriptions of medical cannabis in patients with chronic pain, clinical evidence remains relatively limited. A recent observational study in patients with refractory chronic pain in Australia aimed to collect evidence to capture the effectiveness, adverse event profile, and health-related quality of life (HRQoL) impact of oral medical cannabis formulations.

Design and Methods of the Study

A total of 151 patients with refractory chronic pain were recruited into this study. Each patient was prescribed an orally administered oil with equal parts CBD and THC for the treatment of pain as a symptom of a chronic pain condition. Researchers aimed to collect data on the efficacy of this formulation for the reduction of pain as well as reported adverse events and quality of life measures.

Adverse events were recorded by clinicians at regular patient monitoring visits and categorised as mild/moderate/severe. Patients were also asked to report any side effects of the medical cannabis preparation in questionnaires – the severity of which was then assessed by the clinicians.

Patient-Reported Outcomes Measurement Information System (PROMIS) analysis was also used to record impact to HRQoL measures. The PROMIS-29 tool consists of patient-reported outcomes across seven domains used to evaluate physical, mental, and social health and wellbeing in people with chronic illnesses. Patient data were included in the final analysis if patients had completed at least two PROMIS-29 questionnaires during the study period.

Results of the Study

A total of 151 patients were included for analysis relating to the adverse event profile of this medical cannabis formulation; 71 patients were included in PROMIS-29 (HRQoL) analysis. The most common chronic pain conditions included arthritis (n = 42; 27.8%), neuropathic pain (n = 34; 22.5%), and other musculoskeletal pain (n = 25; 16.6%).

The mean daily dose of cannabinoids for the adverse event analysis cohort was 22.4 ± 13.0 mg of tetrahydrocannabinol (THC) and 22.4 ± 13.0 mg cannabidiol (CBD) administered as a ∼2.25 mL volume of oral oil. The mean cannabinoid dose was significantly lower at the first time point compared with the last time point collected.

Adverse Events

Over half of patients (n = 91/151; 60.3%) experienced at least one adverse event during the observational period, as reported by their clinician. In comparison, 39.7% (n = 60/151) of patients experienced no adverse events. Some patients experienced more than one adverse event (196 adverse events were attributed to 91 patients).

The most commonly reported adverse event was somnolence (drowsiness) (n = 25), followed by dry mouth (n = 18). The severity analysis revealed that, while adverse events were common, the majority (n = 168/196; 85.7%) were mild, as opposed to moderate (n = 54/196; 27.6%; grade 2) or severe (n = 10/196; 5.1%; grade 3) in intensity. No serious adverse events were reported in this cohort.

Pain Intensity Scores

Patients who were included in PROMIS-29 analysis demonstrated a significant improvement in the impact of pain and an improvement nearing significance for pain intensity. Pain impact score was calculated based on responses to targeted pain impact items. Of those with a meaningful improvement a mean 9.6 ± 7.9-point decrease was observed. A majority of subjects experienced an improvement in pain impact (47.9%), suggesting that the reduction in pain intensity had an effect on patients’ quality of life that was not reflected in the pain intensity measurements.

Other Health-Related Quality of Life Measures

Sleep Disturbance and Fatigue

The majority of patients who reported changes to sleep and fatigue domains noted improvements (sleep disturbance 49.3% improved; fatigue 35.6% improved). An evaluation of measures that were improved sowed a significant improvement in sleep disturbance and fatigue scores between the first and last completed questionnaires.

Interestingly, within the sleep domain, participants appeared to either have experienced improved or worsened sleep, unlike in other domains where the majority were categorised as “not changed”.

Anxiety and Depression

The majority of patients reported no change in anxiety (50.7%) and depression (50.7%) domains. Analysis of this data revealed that the relative division between improvement, no change, and worsening in these two mental health domains was consistent with other domains, including physical functioning, pain interference, and social satisfaction.

Conclusions

The researchers note that the apparent positive impact of medical cannabis treatment on pain impact scores, which were significantly improved across the subset of patients. The improvements observed in sleep disturbance and fatigue are also relevant as these measures are known to be highly related to one’s ability to manage and cope with pain.

The results of this observational study were compared to existing published studies of nabiximols (Sativex) – a CBD:THC formulation produced by GW Pharma Ltd. The analgesic effects, changes to sleep disturbance and fatigue, and reported adverse events demonstrated by the medical cannabis preparation used in this study are consistent with existing clinical trials of nabiximols.

The data collected in this observational study demonstrated a “significantly positive effect of LGP Classic 10:10 oral medicinal cannabis oil on the impact of pain.” The researchers conclude that these findings are clinically relevant considering that this patient cohort had been unable to obtain relief with existing medicines, including opioids, NSAIDs, and steroids.

However, the researchers also note that medical cannabis is not efficacious for all patients – a finding consistent with other categories of drugs. Nonetheless, successful improvement of outcomes in one-third of patients with refractory chronic pain is a promising finding. Finally, this study highlights the need for continued research in this field, ideally in the form of randomised-controlled trials.