Mary-Ann Fitzcharles’s research while affiliated with McGill University Health Centre and other places

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Publications (253)


Change in medication use since starting medical cannabis. DMARD, disease‐modifying antirheumatic drug; NSAID, nonsteroidal anti‐inflammatory drug; SNRI, serotonin norepinephrine uptake inhibitor; SSRI, selective serotonin reuptake inhibitor.
Substituting Medical Cannabis for Medications Among Patients with Rheumatic Conditions in the United States and Canada
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September 2024

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Mary‐Ann Fitzcharles

Objective There are numerous reports of people substituting medical cannabis (MC) for medications. Our obejctive was to investigate the degree to which this substitution occurs among people with rheumatic conditions. Methods In a secondary analysis from a cross‐sectional survey conducted with patient advocacy groups in the US and Canada, we investigated MC use and medication substitution among people with rheumatic conditions. We subgrouped by whether participants substituted MC for medications and investigated differences in perceived symptom changes and use patterns, including methods of ingestion, cannabinoid content (cannabidiol vs delta‐9‐tetrahydrocannabinol [THC]), and use frequency. Results Among 763 participants, 62.5% reported substituting MC products for medications, including nonsteroidal anti‐inflammatory drugs (54.7%), opioids (48.6%), sleep aids (29.6%), and muscle relaxants (25.2%). Following substitution, most participants reported decreases or cessation in medication use. The primary reasons for substitution were fewer adverse effects, better symptom management, and concerns about withdrawal symptoms. Substitution was associated with THC use and significantly higher symptom improvements (including pain, sleep, anxiety, and joint stiffness) than nonsubstitution, and a higher proportion of substitutors used inhalation routes than those who did not. Conclusion Although the determination of causality is limited by our cross‐sectional design, these findings suggest that an appreciable number of people with rheumatic diseases substitute medications with MC for symptom management. Inhalation of MC products containing some THC was most commonly identified among those substituting, and disease characteristics did not differ by substitution status. Further study is needed to better understand the role of MC for symptom management in rheumatic conditions.

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The Elusive Truth of Cannabinoids for Rheumatic Pain

Current Rheumatology Reports

Purpose of Review Medical cannabis (MC) has entered mainstream medicine by a unique route. Regulatory acceptance as a medical product in many jurisdictions has bypassed the traditional evidence-based pathway required for therapies. Easier access to MC, especially related to recreational legalization of cannabis, has led to widespread use by patients for symptom relief of a variety of medical conditions and often without medical oversight. Musculoskeletal pain remains the most common reason for MC use. This review examines real-world issues pertaining to MC and offers some guidance for clinical care of patients with rheumatic diseases being treated with MC. Recent Findings Controlled clinical studies of cannabis products in patients with rheumatic diseases have been small and tested a range of compounds, routes of administration, and clinical populations, limiting our ability to generate conclusions on MC’s effectiveness in this population. Observational cohort studies and surveys suggest that use of MC and related products in patients with rheumatic diseases improves pain and associated symptoms but is commonly accompanied by mild to moderate side effects. Conflicting evidence contributes to practitioner and patient uncertainty regarding the use of MC for rheumatic disease-related pain. Summary Despite promising preclinical and observational evidence that MC and cannabis-derived compounds are useful in the management of rheumatic disease-related pain, there remains limited high-quality clinical evidence to substantiate these findings. There are a significant number of clinical trials on this topic currently planned or underway, however, suggesting the next decade may yield more clarity. Nevertheless, given that many people with rheumatic diseases are using cannabis products, healthcare professionals must remain apprised of the evidence pertaining to cannabinoids, communicate such evidence to patients in a meaningful way that is free from personal bias and stigma, and maintain strong collaborative clinical care pertaining to MC.


Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.
Figure 2. Pooled proportion of respondents endorsing fibromyalgia as a distinct clinical entity. CI = confidence interval; *rheumatologists; **general practitioners.
Figure 3. Subgroup analysis of rheumatologists' versus GPs'/other physicians' endorsement of comprehensive knowledge of the American College of Rheumatology diagnostic criteria (moderate credibility [27] ; test of interaction, P = .04). CI = confidence interval; *rheumatologists; **general practitioners.
Physicians' knowledge, attitudes, and practices regarding fibromyalgia: A systematic review and meta-analysis of cross-sectional studies

August 2024

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70 Reads

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1 Citation

Medicine

Background The diagnosis, etiology, and optimal management of fibromyalgia remains contentious. This uncertainty may result in variability in clinical management. We conducted a systematic review and meta-analysis of cross-sectional studies examining physicians’ knowledge, attitudes, and practices regarding fibromyalgia. Methods We searched MEDLINE, Embase, and PubMed from inception to February 2023 for cross-sectional surveys evaluating physicians’ attitudes toward, and management of, fibromyalgia. Pairs of independent reviewers conducted article screening, data extraction, and risk of bias assessment in duplicate. We used random-effects meta-analysis to pool proportions for items reported by more than one study and the Grading of Recommendations Assessment, Development, and Evaluation approach to summarize the certainty of evidence. Results Of 864 citations, 21 studies (8904 participants) were eligible for review. Most physicians endorsed fibromyalgia as a distinct clinical entity (84%; 95% confidence interval [CI], 74–92), and half (51%; 95% CI, 40–62) considered fibromyalgia a psychosocial condition. Knowledge of formal diagnostic criteria for fibromyalgia was more likely among rheumatologists (69%, 95% CI, 45–89) versus general practitioners (38%, 95% CI, 24–54) ( P = .04). Symptom relief was endorsed as the primary management goal by most physicians (73%, 95% CI, 52–90). Exercise, physiotherapy, antidepressants, nonsteroidal anti-inflammatory drugs, and non-opioid analgesics were most endorsed for management of fibromyalgia, but with wide variability between surveys. Opioids and most complementary and alternative interventions (e.g., homeopathy, chiropractic, and massage) received limited endorsement. Conclusion There is moderate certainty evidence to suggest that physicians are divided regarding whether fibromyalgia is a biomedical or psychosocial disorder. Physicians typically prioritize symptom relief as the primary goal of management, and often endorse management with exercise, non-opioid analgesics, nonsteroidal anti-inflammatory drugs, antidepressants, and physiotherapy (moderate to high certainty evidence); however, important practice variation exists.


The State of Synthetic Cannabinoid Medications for the Treatment of Pain

July 2024

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73 Reads

CNS Drugs

Synthetic cannabinoids are compounds made in the laboratory to structurally and functionally mimic phytocannabinoids from the Cannabis sativa L. plant, including delta-9-tetrahydrocannabinol (THC). Synthetic cannabinoids (SCs) can signal via the classical endogenous cannabinoid system (ECS) and the greater endocannabidiome network, highlighting their signalling complexity and far-reaching effects. Dronabinol and nabilone, which mimic THC signalling, have been approved by the Food and Drug Administration (FDA) for treating nausea associated with cancer chemotherapy and/or acquired immunodeficiency syndrome (AIDS). However, there is ongoing interest in these two drugs as potential analgesics for a variety of other clinical conditions, including neuropathic pain, spasticity-related pain, and nociplastic pain syndromes including fibromyalgia, osteoarthritis, and postoperative pain, among others. In this review, we highlight the signalling mechanisms of FDA-approved synthetic cannabinoids, discuss key clinical trials that investigate their analgesic potential, and illustrate challenges faced when bringing synthetic cannabinoids to the clinic.


Are Electronic Health Records Sufficiently Accurate to Phenotype Rheumatology Patients With Chronic Pain?

January 2024

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11 Reads

The Journal of Rheumatology

Chronic pain in rheumatic diseases (RDs), a symptom often neglected, is prevalent and an important contributor to poor health and reduced quality of life. Various studies report that up to a third of patients with inflammatory RDs have persistent pain, often attributed to pain sensitization, even when the underlying disease is controlled.




Figure 2 Self-reported solicited adverse events to mRNA-1273 SARS-CoV-2 vaccine by diagnosis and vaccine dose. HC, healthy controls; RA, rheumatoid arthritis; SLE, systemic lupus erythematous; AE, adverse event; D1, first dose of the Moderna Spikevax vaccine; D2, second dose of the Moderna Spikevax vaccine; D3, third dose of the Moderna Spikevax vaccine; MSK, musculoskeletal.
COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series

November 2023

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47 Reads

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7 Citations

Objective To assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease. Methods We conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed. Results Frequency of solicited self-reported AEs following vaccination was similar across groups (HC 90%, RA 86%, SLE 90%); among them, musculoskeletal AEs were more frequent in RA (HC 48% vs RA 66% (Δ95% CI CI 3 to 32.6)). Disease activity scores did not increase postvaccination. No vaccine-related serious AEs were reported. Postvaccination immunogenicity was reduced in RA and SLE (RA 90.2%, SLE 86.4%; for both, ΔCIs compared with HC excluded the null). Similarly, NAbs were reduced among patients (RA 82.6%, SLE 81.8%). In RA, age >65 (OR 0.3, 95% CI 0.1 to 0.8) and rituximab treatment (OR 0.003, 95% CI 0.001 to 0.02) were negative predictors of immunogenicity. ELISpot was positive in 16/52 tested RA and 17/26 HC (ΔCI 11.2–53.3). During the study, 11 HC, 19 RA and 3 SLE patients self-reported COVID-infection. Conclusion In COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases, the Moderna Spikevax primary series was safe. MMF, RA age >65 and rituximab were associated with reduced vaccine-induced protection.




Citations (70)


... Samples from Hamilton, Quebec City, Calgary and some samples from Winnipeg were processed locally, as per Table 1. All labs (Toronto, Hamilton [3], Quebec City [4], Calgary [5], and Winnipeg [6]) performed neutralization for the ancestral strain; four of these labs (those in Winnipeg, Quebec City, Toronto, and Hamilton) also assessed Omicron BA1, and three (in Winnipeg, Quebec City, and Toronto) also assessed Omicron BA5. Two serum samples from each participant collected between 2022 and 2023 were assessed. ...

Reference:

Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study
COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series

... Fibromyalgia is a condition with no currently validated biomarker, [52,53] pathognomonic imaging, or consistent examination findings, and diagnosis is subjective and dependent on patients' reporting of symptoms. [54] This uncertainty likely contributes to the high variability in treatment that we found. One of the only interventions that was endorsed by most respondents across different surveys of physicians was "physical therapy"; however, this is a profession and not a distinct modality. ...

Adherence to Clinical Guidelines for Fibromyalgia: Help or Hindrance?

... This potential change in federal policy may have broad effects on the cannabis marketplace, how cannabis is used clinically, and public health outcomes related to changed cannabis legality. We have conducted large online surveys of naturalistic cannabis and cannabidiol (CBD) use showing that many individuals initiate cannabis use due to inadequate symptom relief, and that more individuals report that their rationale for use is personal research or a friend's recommendation rather than recommendations from a healthcare professional [4,5]. Further, a nationally representative survey conducted in 2017 showed that nearly half of the US population believe unsubstantiated claims about cannabis, such as that it is not at all addictive or that secondhand cannabis smoke is completely or somewhat safe [6]. ...

Medicinal Cannabis Use for Rheumatic Conditions in the US Versus Canada: Rationale for Use and Patient-Health Care Provider Interactions

... In these cases, the degree of damage is far out of proportion with the severity of the pain. In other conditions such as chronic back pain (Hartvigsen et al., 2018), fibromyalgia (Pinto et al., 2023), or chronic regional pain syndrome (Marinus et al., 2011), severe pain may occur without any identifiable structural pathology. On the other hand, athletes injured on the field may only notice the injury after the game is over. ...

Neurophysiological and Psychosocial Mechanisms of Fibromyalgia: A Comprehensive Review and Call for An Integrative Model
  • Citing Article
  • May 2023

Neuroscience & Biobehavioral Reviews

... Investigating the experiences of clinicians can provide new data on its usage and risk, particularly in subpopulations, such as women vs. men or <65 vs. ≥ 65 years old clinicians. Indeed, these professionals are at the forefront of patient care when they encounter adverse effects (Clarke & Fitzcharles, 2023), and can provide relevant information to guide clinical research on the risk associated with cannabis use in pain management. Thus, educational interventions could be conceptualized for the different clinicians to increase their knowledge about medical cannabis and prescribed cannabinoids for pain management (mode of action, indication, effects, risk of adverse effects). ...

The evolving culture of medical cannabis in Canada for the management of chronic pain

... The global economy has suffered due to the pandemic, leading to governments implementing measures to mitigate the spread of the virus and revitalize their economies. The pandemic has also affected individuals' physical and mental health, with healthcare workers experiencing psychological distress and individuals with pre-existing conditions like fibromyalgia experiencing worsened symptoms [2]. The socioeconomic implications of the pandemic have been far-reaching, affecting various aspects of the world economy [3]. ...

Effects of the COVID-19 Pandemic on Individuals with Fibromyalgia - a Systematic Scoping Review Protocol

... 2,16 Some studies exist that address this issue from a quantitative perspective but in order to identify potential diagnostic misunderstandings, a qualitative design was chosen for this investigation. 13,17,18 This study aims to examine which questions based on the DSM-5 criteria show problematic overlaps (false positives or false negatives) in this context. It was verified whether patients affirmed a criterion due to dependent behavior or because their pain was not being adequately treated. ...

Face validity of the ICD ‐10 criteria of substance abuse and dependence for patients prescribed cannabis‐based medicines for chronic pain—A survey of pain medicine physicians in Canada, Germany and Israel

European journal of pain (London, England)

... 41,42 This evidence highlights that fibromyalgia-related pain depends on not only attentional and emotional impairments but also sensory-motor alterations due to nociplastic changes (i.e., related to altered nociception without evidence of nociceptor activation or lesion of the somatosensory system) frequently observed in these patients. [78][79][80] Importantly, this evidence is consistent with other findings in the literature suggesting that neuromodulation techniques may be pivotal in normalizing specific neurophysiological mechanisms that are characteristically altered in fibromyalgia patients, who experience widespread chronic pain and central sensitization. 81 Consistently, in addition to regulating the excitability of brain areas most involved in processing various aspects of pain, as previously suggested, tDCS may also influence neuroplasticity mechanisms in the CNS to reduce the amplification of pain signals. ...

Emotion regulation and the salience network: a hypothetical integrative model of fibromyalgia
  • Citing Article
  • December 2022

Nature Reviews Rheumatology

... 12 In order to operationalize the use of the diagnostic criteria, standardized manuals based on the DSM-5 criteria, such as DIPS Open Accesses (German version) and the Composite International Diagnostic Interview (CIDI) as well as simple questions or self-questionnaires based on the DSM-5 criteria are commonly utilized in epidemiological studies. 7,[13][14][15] This practice is scientifically logical, as it allows for standardized procurement and increases interrater reliability. On the other hand, it increases the risk of omitting individual clarification of potential misunderstandings. ...

Cannabis use disorder in chronic pain patients: over- and underestimation in a cross-sectional observational study in three German pain management centres
  • Citing Article
  • November 2022

Pain

... Mindfulness is recognized as a primary treatment for depression and a supplementary treatment for other symptoms. Additionally, various interventions, such as music therapy, relaxation techniques, warm baths, and localized heat, are suggested as supplementary treatments, depending on the symptoms [14]. Nonsteroidal anti-inflammatory drugs like ibuprofen and diclofenac have not proved their effectiveness as standalone treatments [15]. ...

International, multidisciplinary Delphi consensus recommendations on non-pharmacological interventions for fibromyalgia
  • Citing Article
  • September 2022

Seminars in Arthritis and Rheumatism