Cannabis Medicinal Products For Fibromyalgia Pain
Overview
This study aimed to assess the impact of cannabis-based medicinal products (CBMPs) on individuals with fibromyalgia, considering changes in health-related quality of life and adverse events. The research, conducted on 306 patients identified from the UK Medical Cannabis Registry, revealed significant improvements in overall health-related quality of life at 1, 3, 6, and 12 months (p < .0001). Common adverse events included fatigue (24.51%), dry mouth (22.55%), concentration impairment (21.57%), and lethargy (21.24%). The study concluded that CBMP treatment led to enhancements in fibromyalgia-specific symptoms, sleep, anxiety, and overall quality of life. Notably, individuals with prior cannabis use exhibited a more robust response, and CBMPs were generally well-tolerated. It is essential to interpret these results considering the study’s inherent limitations.
Introduction
Fibromyalgia, characterized by chronic widespread musculoskeletal pain and associated symptoms like sleep disturbance and cognitive dysfunction, poses significant challenges to patients’ daily lives. With a prevalence of 4% in American and European populations, it predominantly affects females. Current treatment approaches, following a biopsychosocial model, involve nonpharmacological methods such as psychological therapies and exercise. However, pharmacological interventions, including opioids and tricyclic antidepressants, show limited efficacy and carry notable risks.
The study underscores the increasing trend of self-administered cannabis use for symptom relief in fibromyalgia. Cannabis, containing over 140 active cannabinoids, interacts with the endocannabinoid system, implicated in central nervous system function and inflammatory response. The study hypothesizes a potential role of cannabinoids in addressing fibromyalgia symptoms, given their influence on pain perception and inflammatory processes.
The two primary cannabinoids in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), exhibit diverse pharmacological actions. CBD, for instance, inhibits fatty acid binding ligands, demonstrating analgesic and anti-inflammatory properties. THC, while also influencing pain pathways, carries psychoactive effects. Clinical evidence on cannabis-based medicinal products (CBMPs) remains limited, but studies suggest potential benefits for pain, sleep, and mood in chronic pain patients.
The study aims to contribute to the understanding of CBMPs’ impact on fibromyalgia-specific symptoms, health-related quality of life, anxiety, and sleep. Additionally, it seeks to explore changes in opioid consumption during CBMP treatment and assess adverse events. The motivation stems from the need for novel therapeutic options addressing the multifaceted nature of fibromyalgia symptoms, considering the reported minimal adverse event profile associated with cannabinoids. The study acknowledges the existing gaps in the literature, emphasizing the importance of investigating broader outcomes beyond pain relief in fibromyalgia research.
Method
This uncontrolled case series focuses on patients with fibromyalgia treated with cannabis-based medicinal products (CBMPs) for at least one month, sourced from the UK Medical Cannabis Registry (UKMCR). The study adheres to STROBE guidelines for reporting. The UKMCR, established in 2019, collects pseudonymized data from patients prescribed CBMPs at Sapphire Medical Clinics in the United Kingdom and Channel Islands.
Participants in the study provided informed consent upon registry enrollment, and ethical approval was not deemed necessary. The research includes individuals with fibromyalgia as their primary indication for CBMP treatment, excluding those without baseline assessments or prescriptions exceeding one month.
Data collection encompasses patient demographics, comorbidities, Charlson comorbidity index, drug, alcohol, and cannabis history. Concurrent medications, CBMP prescriptions (including formulation details), and patient-reported outcome measures (PROMs) assessing health-related quality of life were recorded at baseline, 1, 3, 6, and 12 months.
The PROMs cover various aspects, such as Fibromyalgia Symptom Severity, Single-Item Sleep Quality Scale, Patients’ Global Impression of Change, General Anxiety Disorder Scale, Visual Analogue Scale-Pain, and EQ-5D-5L, providing a comprehensive evaluation of patients’ experiences.
Opioid consumption analysis involved calculating daily oral morphine equivalents for patients with opioid prescriptions. Adverse events, reported electronically or during clinician follow-ups, were classified using the Common Terminology Criteria for Adverse Events version 4.0.
Overall, this study contributes valuable insights into the impact of CBMPs on fibromyalgia, utilizing a robust data collection approach aligned with established guidelines, providing a thorough analysis of patient outcomes and safety considerations.
Statistical Analysis
The patient-reported outcome measures (PROMs) data were systematically analyzed at 1, 3, 6, and 12 months in comparison to the baseline assessment. Subgroup analysis based on participants’ previous cannabis usage was conducted only up to 6 months due to limitations in participant numbers at the 12-month mark. Changes in the consumption of prescribed opiates per 24 hours were assessed at 1 month, 3 months, and the end of the follow-up period.
Shapiro–Wilk test was used to determine the data normality. Non-parametric data were expressed as median with interquartile range (IQR), while parametric data were presented as mean ± standard deviation (SD). Paired statistical analysis utilized either a paired t-test or Wilcoxon rank-sum test, depending on the parametric or nonparametric nature of the data, respectively. Significance was set at a p-value of <.050, and a Bonferroni correction was applied to mitigate the risk of Type I error.
To gauge the magnitude of the effect, the r (effect size) was computed for the Wilcoxon rank-sum test by dividing the Z-value by the square root of the number of participants. The data analysis was executed using IBM Statistical Package for Social Sciences (version: 27.0.0.0 SPSS Inc., Armonk, NY, USA), and GraphPad Prism (version 9.0.0; San Diego, CA, USA) was employed for visualization. This rigorous analytical approach ensures robust and reliable interpretation of the outcomes while maintaining statistical integrity.
Result
As of February 15, 2022, the UK Medical Cannabis Registry (UKMCR) comprised 3546 patients, with 3240 (91.37%) excluded based on criteria such as incomplete baseline PROMs, enrollment less than one month, and fibromyalgia not being the primary indication. The analysis focused on 306 patients with fibromyalgia, with demographics including a median Charlson comorbidity index of 1.00 and comorbidities like anxiety/depression, arthritis, and hypertension.
Baseline characteristics revealed 37.91% ex-smokers, 32.03% non-smokers, and 29.74% current smokers. Approximately half were current cannabis users, 37.91% were cannabis-naïve, and 13.40% were ex-users. Median lifetime cannabis consumption was 5.00 gram years.
Cannabis-based medicinal products (CBMPs) data indicated that 94.77% of patients received maximally titrated prescriptions, with various formulations and median THC and CBD doses. The most common CBMP oils and dried flower preparations were specified.
Patient-reported outcome measures (PROMs) analysis demonstrated consistent improvements across various domains, including EQ-5D-5L index values, Fibromyalgia Symptom Severity, Single-Item Sleep Quality Scale, and Visual Analogue Scale-Pain. Notably, the EQ-5D-5L index value significantly improved at all follow-up periods.
Subgroup analysis based on previous cannabis use revealed significant improvements in PROMs for those with a history of cannabis consumption. Similarly, cannabis-naïve patients showed improvements in EQ-5D-5L index values and Fibromyalgia Symptom Severity at different follow-up points.
The median oral morphine equivalent dose for opioid prescriptions remained stable at 1 month but showed a decrease at 3 months and the end of follow-up, with no new opioid prescriptions initiated during the study.
Adverse events were reported by 23.53% of participants, with fatigue, dry mouth, concentration impairment, and lethargy being the most common. Most adverse events were moderate or mild, and none were life-threatening or disabling. Subgroup analysis based on cannabis status and administration method revealed variations in reported adverse events.
This comprehensive analysis provides valuable insights into the efficacy and safety of CBMPs in fibromyalgia treatment, highlighting improvements in PROMs and a favorable adverse event profile.
Conclusion
This case series from the UK Medical Cannabis Registry (UKMCR) presents findings suggesting a potential link between the initiation of Cannabis-Based Medicinal Products (CBMP) treatment and positive outcomes in fibromyalgia patients over 12 months. Statistically significant improvements were noted in fibromyalgia-specific metrics, pain, sleep, anxiety, and health-related quality of life. Notably, there was a significant reduction in opioid consumption by the end of the follow-up period.
Among the 306 fibromyalgia patients analyzed, 23.53% reported 979 adverse events, mostly mild or moderate, with none being life-threatening or disabling. The incidence of adverse events, although higher than typical for the UKMCR, was in line with fibromyalgia’s tendency to elicit stronger responses to medications. Fibromyalgia Symptom Severity scores decreased up to 6 months, aligning with similar studies and indicating a consistent positive trend.
Improvements in overall health-related quality of life, measured by EQ-5D-5L index values, were observed at every follow-up compared to baseline. This aligns with previous studies indicating the positive impact of CBMPs on chronic pain patients, including those with fibromyalgia.
Pain reduction, evidenced by EQ5D-5L-Pain and Discomfort scores and VAS-Pain scores, displayed statistically significant improvements at 1-, 3-, and 6-month intervals. This aligns with short-term improvements seen in trials using THC-rich cannabis oil and synthetic THC analogues, supporting the notion that CBMP treatments can effectively alleviate fibromyalgia-related pain.
Improvements were also noted in sleep quality (Single-Item Sleep Quality Scale scores) up to 6 months. The complex role of the endocannabinoid system in sleep regulation warrants further investigation to understand the dose–response relationship of CBMPs and sleep quality.
Anxiety and depression metrics, including GAD-7 and EQ-5D-5L-Anxiety and Depression, improved at various follow-up points. The potential of CBMPs to address multiple domains of burden in fibromyalgia, as seen in this study, is a promising avenue for future research.
The study suggested an association between CBMPs and reduced opioid consumption, with a statistically significant decrease observed at 3 months and extraction dates compared to baseline. While unable to imply clinical significance, these findings contribute to the growing body of evidence supporting the role of CBMPs as an adjunct or alternative to opioids in fibromyalgia management.
Despite these positive indications, the study’s limitations, such as the lack of a control group, self-reporting bias, and potential selection bias, underscore the need for randomized controlled trials to establish causation definitively. Nevertheless, this case series contributes valuable insights to inform future trials and current clinical practices in fibromyalgia treatment.
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