Is Medical Cannabis a Solution for Controlling Fibromyalgia Symptoms?

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Fibromyalgia syndrome (FMS) represents a complex chronic pain disorder primarily characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive impairment. Because of the complexities it entails, FMS is also manifested with significant challenges in diagnosis and management. Despite numerous approved pharmacologic and nonpharmacologic interventions, the clinical outcomes of patients with FMS remain suboptimal, prompting exploration into new therapeutic modalities.

Recent research has highlighted the potential of medical cannabis (MC) in alleviating chronic pain and improving sleep quality. The cannabis is consumed by smoking, vaporization, or sublingual application of cannabis-containing oil drops. The MC products are sorted by the concentrations of the active constituents, tetrahydrocannabinol (THC) and cannabidiol (CBD), exerting analgesic effects through binding to CB1 and CB2 receptors, inhibiting presynaptic γ-aminobutyric acid and glutamatergic transmission, and thus reducing neuronal excitability.

THC affects pain, appetite, and mood, whereas CBD is believed to confer anti-inflammatory and analgesic effects.

The therapeutic effects of cannabis products are influenced by the ratio of THC to CBD, which should be tailored to the individual patient’s needs and treatment goals. A cohort study by Aviram et al

reported durable long-term efficacy of MC in reducing pain intensity and opioid consumption in patients with chronic pain, providing compelling evidence for its therapeutic utility.

Given that chronic pain constitutes the primary characteristic of FMS and recognizing the potential effectiveness of MC in pain management, cannabis is increasingly emerging as a viable treatment option for fibromyalgia. Systematic evaluations, including the comprehensive review by Khurshid et al,

have corroborated these findings—synthesizing evidence from more than 22 studies, including mostly reviews but also some observational studies and randomized clinical trials—and suggest that MC is a safe and effective adjunctive therapy for the management FMS.

In this issue, the study by Singla et al

offers valuable insights into patients’ perspectives and experiences with cannabis use, shedding light on the widespread use of cannabis by patients with fibromyalgia and its favorable impact on pain, stress, and sleep disturbances. Their exploration of a cohort of 1336 patients with fibromyalgia at Mayo Clinic underscores the multifaceted nature of patients’ responses to MC, emphasizing the need for personalized treatment approaches. They found that nearly half of the participants reported cannabis use since their diagnosis of fibromyalgia. Cannabis users generally correlated with a younger age and higher disability rates. Most patients (82%) reported improvement in pain symptoms with cannabis use, and most of them also noticed improvement in terms of stress/anxiety/depression and sleep disturbances, yet not all reported symptoms improved, including sweating, sexual disinterest, and fatigue, thereby indicating variability in response. Around 35% of patients consumed cannabis containing mainly THC and 34% a THC-CBD mixture, and daily dosing was not constant in 62% of the patients. Because of the potential recall bias and lack of data concerning cannabis use before the diagnosis of FMS and the use of different dosages and compositions of MC, larger clinical studies are needed to validate these findings.

Previous studies support the findings of Singla et al.

Other observational studies have reported an improvement in pain and quality of life of patients with FMS, also in the long term, even 1 year after starting treatment with MC.

Habib and Artul

reported that the effect was so beneficial that half of the patients stopped taking other fibromyalgia medications. In a prospective observational study conducted by Giorgi et al,

102 FMS patients experiencing persistent pain despite standard treatment were enrolled to assess the potential clinical advantages of incorporating MC during a 6-month period. Patients received prescriptions for 2 combinations of cannabis oil extracts, namely, Bedrocan (containing 22% THC and <1% CBD) and Bediol (with 6% THC and 8% CBD). The study revealed notable clinical improvements measured by the Revised Fibromyalgia Impact Questionnaire scores for 44% of patients and improvements in the Pittsburgh Sleep Quality Index for 33% of participants. In addition, approximately half of the patients had amelioration in symptoms related to anxiety and depression. Nearly half of the participants witnessed a reduction or cessation of concomitant analgesic therapy. Notably, the degree of improvement had an inverse correlation with body mass index.

Because of numerous legal and logistical constraints, there are a limited number of randomized clinical trials in the literature, mostly with small cohorts. For example, Chaves et al

investigated the efficacy of THC-rich cannabis oil (containing 24.44 mg/mL of THC and 0.51 mg/mL of CBD) in alleviating symptoms and enhancing quality of life for 17 women diagnosed with FMS, finding significant reduction in Revised Fibromyalgia Impact Questionnaire scores compared with both the placebo group (P=.005) and baseline (P<.001), with no reported intolerable adverse effects. In addition to sublingual administration, the inhalation of cannabis has demonstrated positive effects on pain management. Investigating this, van de Donk et al

conducted a randomized placebo-controlled 4-way crossover trial, evaluating the impact of cannabis inhalation. Their study examined 4 cannabis products, each with specific THC and CBD levels: Bedrocan, Bediol, Bedrolite (containing 9% CBD and <1% THC), and a placebo variant devoid of THC or CBD. Whereas no statistically significant differences were detected between the placebo group and various cannabis inhalation formulations concerning their effectiveness in alleviating spontaneous or electrical pain responses, Bediol stood out for its efficacy in reducing pain scores by 30% compared with placebo (with 90% of patients experiencing relief vs 55%; P=.01). Notably, combinations with a higher THC proportion significantly enhanced pressure pain thresholds relative to the placebo (P<.01).

However, despite growing excitement about using MC to treat FMS, it is important to be cautious. The systematic review of Strand et al

pointed out that there is not enough high-quality evidence, especially from controlled trials, to fully understand how well MC works for FMS. This means more research is needed to determine the best doses and composition for each symptom, long-term safety, and whether people might become dependent on MC when using it to manage FMS.

The evolution of the clinical use of MC goes along with the shifts that have occurred in the social, political, and medical opinions toward this issue; this spectrum ranges from “legalization” to “medicalization.” There are many overlaps between these processes, with some countries regarded as “progressive” or “permissive” in their social view concerning recreational cannabis use, whereas others (eg, Israel), although relatively advanced in integrating cannabis use as part of the pharmacologic armamentarium in various medical conditions such as fibromyalgia, nonetheless have no clear perspective about legalization. Regardless of the formal view of the Ministries of Health worldwide, MC seems to penetrate many patients’ communities based on the “wisdom of the crowds” and its high availability despite the formal legal status. This is notable as the use of “approved” medications for fibromyalgia in “real-world” studies is extremely disappointing.

In summary, whereas using MC alongside other treatments of fibromyalgia seems to be a promising and available option in difficult-to-treat disease at least in some countries, it is crucial to be careful. More solid evidence from larger studies is required to ensure the safe use of MC.