Fibromyalgia

This is a guideline/position paper, not a clinical study with measurable treatment outcomes. Recommendations for the use of cannabis-based medicines in chronic pain are given, but no specific effect measures are reported.

EFIC position paper on the appropriate use of cannabis-based medicines in chronic pain; recommends cautious use in fibromyalgia due to limited evidence (weak recommendation).

Duloxetine, milnacipran and pregabalin showed moderate to good evidence for pain relief of at least 50% in about 1 of 10 adults with moderate or severe fibromyalgia pain over 4-12 weeks; other medications showed limited, insufficient or no evidence.

Umbrella review of k=21 Cochrane Reviews on pharmacological fibromyalgia therapy (87 trials, n=17.631). For cannabinoids: limited and inadequate data situation identified — no sufficient evidence for efficacy. Duloxetine, milnacipran and pregabalin showed moderate/good evidence for substantial pain reduction (≥50%) in about 1 of 10 adults over 4-12 weeks.

No convincing, unbiased, high-quality evidence that nabilone is effective in fibromyalgia; tolerability was low.

Cochrane SR of 2 RCTs (n=72) on cannabinoids for fibromyalgia; nabilone vs. placebo showed no statistically significant pain reduction or improvement in quality of life; very small sample size and short study duration limit interpretability; insufficient evidence for efficacy.

Moderate evidence for chronic pain and spasticity, low evidence for nausea/vomiting, weight gain and sleep disorders; increased risk of side effects.

Comprehensive SR across 79 RCTs (n=6.462) on medical cannabis; moderate evidence for chronic pain (incl. neuropathic), MS spasticity; fibromyalgia mentioned within the pain subgroup (limited separate data). Pooled OR for pain reduction ≥30%: 1,41 (95%-CI 0,99–2,00).

Cannabis use was associated with a decrease in pain intensity (VAS pain baseline 8,2 vs 5,6 mm over time; pooled effect -1,75).

Systematic review + meta-analysis on cannabis in rheumatic diseases (k=11, n=10.873); fibromyalgia subgroup (k=4, n=611) with cannabis use rate 68,2% (95% CI: 0,41–0,90). Pain reduction VAS 8,2 (SD 2,9) at baseline vs. 5,6 (SD 3,5) mm over time; pooled effect size -1,75 (95% CI: -2,75, -0,76). Cannabis users younger (58,4 vs. 63,6 years, p<0,001), more often smokers (OR 2,91) and unemployed (OR 2,40).

Cannabinoids show only minimal pain reduction (3 mm on a 100-mm scale) compared with placebo with a high rate of harm; benefit-harm ratio unfavourable (NNT 24 vs. NNH 6).

Comprehensive SR+MA on cannabinoids in chronic non-cancer pain; k=104 studies (47 RCTs, 57 observational studies), n=9.958 participants. Fibromyalgia subgroup: k=7 studies. Pooled RCT data: 30% pain reduction 29,0% (cannabinoids) vs. 25,9% (placebo), significant, NNTB=24 (95% CI 15-61); 50% pain reduction 18,2% vs. 14,4%, not significant. Pain intensity reduction SMD=-0,14 (95% CI -0,20 to -0,08), corresponds to 3 mm on 100-mm VAS. Adverse events 81,2% vs. 66,2%, NNTH=6 (95% CI 5-8). No significant effect on physical/emotional function; weak evidence for improvement in sleep. Authors' conclusion: limited efficacy, high NNTB, low NNTH.

Cannabinoids show a small but statistically significant reduction in pain intensity of 0,70 points on a 0-10 scale; the effect is small and GRADE evidence is low to moderate.

SR + MA across 32 RCTs (n=5.174) on cannabinoids for chronic non-cancer pain; significant pain reduction vs. placebo (SMD=-0.14, 95%CI -0.20 to -0.08, p0.001); subgroup analysis shows benefit in neuropathic pain and MS-associated pain, fibromyalgia data included but limited.

Cannabis-based medicines showed positive effects on pain, sleep and mood in some chronic pain patients with very low quality of evidence, without achieving large clinically relevant effect sizes.

Systematic review of long-term observational studies (n6 months) on cannabis-based medicines in chronic non-cancer pain; includes fibromyalgia patients, shows moderate pain reduction (NRS -1 to -2) and high dropout rates (30–50%).

Cannabinoids offer overall only limited benefit in chronic primary pain, at most a significant but clinically small pain reduction with longer treatment duration.

SR + meta-analysis, k=8 RCTs (n=240) on cannabinoids in chronic primary pain (CPP, incl. fibromyalgia); primary endpoint VAS pain reduction not significant vs. placebo (MD=-0,64; 95% CI -1,30 bis 0,02); with treatment duration >4 weeks significant pain reduction (MD=-1,28; 95% CI -2,33 bis -0,22). FIQ fibromyalgia questionnaire: MD=-21,69 (95% CI -46,20 bis 2,82), not significant. Generally low evidence quality (GRADE) due to imprecision and risk of bias.

Cannabinoids showed statistically significant effects on pain in 2 of 4 studies and on sleep in 2 studies, but with frequent side effects (dizziness, cognitive problems, drowsiness, nausea in about half of patients) and overall insufficient evidence for a recommendation.

Systematic review on cannabinoid treatments in rheumatic diseases incl. fibromyalgia; moderate evidence for pain reduction in fibromyalgia patients, tolerability variable.

Cannabinoids show safe and modest analgesic efficacy in neuropathic pain, with preliminary indications of efficacy in fibromyalgia and rheumatoid arthritis.

Systematic review on cannabinoids in chronic non-cancer pain; k=18 RCTs included (neuropathic pain, fibromyalgia, rheumatoid arthritis, mixed pain syndromes). 15 of 18 studies showed significant analgesia vs. placebo; significant sleep improvement reported. No serious adverse effects; mild to moderate AEs well tolerated, low discontinuation rate. Evidence for moderate efficacy in neuropathic pain, preliminary evidence for fibromyalgia and rheumatoid arthritis.

Seven of eleven studies showed significant analgesic effects; cannabinoids were assessed as safe, moderately effective analgesics with good tolerability.

Systematic review of RCTs on cannabinoids in chronic non-cancer pain (update); moderate evidence for neuropathic pain, limited data for fibromyalgia; cannabinoids show moderate analgesic effects with acceptable side effect profile.

Moderate efficacy of cannabinoid-based medications in chronic pain and comorbidities such as sleep problems, anxiety and selected chronic conditions.

Clinical practice guideline on cannabis-based medicine in chronic pain and comorbidities; based on SR of k=70 studies (19 SRs + 51 original papers, PROSPERO 135886). Moderate pain reduction in chronic pain; positive evidence for comorbidities (sleep, anxiety, appetite) as well as symptomatic effect in MS, fibromyalgia, arthritis. GRADE-based recommendations on dosage, titration and risk management.

CBPMs and CBMs show potential efficacy for pain, quality of life and sleep in FMS, but the evidence base is limited and methodologically heterogeneous.

Systematic review of cannabis-based products (CBPMs) and medicines (CBMs) in fibromyalgia; k=19 publications included (up to April 2024). General improvement in pain, quality of life and sleep; no serious adverse events. Evidence limited, need for high-quality studies.

The findings on superiority of cannabinoids over controls (placebo, amitriptyline) were inconsistent; currently insufficient evidence for a recommendation.

Systematic review on cannabinoids for rheumatic pain conditions; k=2 RCTs with nabilone in fibromyalgia (n=71, study duration 2 and 4 weeks). Superiority of cannabinoids over controls (placebo, amitriptyline) not consistently demonstrable. High risk of bias in 3 of 4 included studies. Conclusion: insufficient evidence for a recommendation of cannabinoid preparations in chronic rheumatic pain.

Inconsistent findings on the efficacy of cannabis-based medicines for neuropathic pain and muscle spasms in MS; insufficient evidence for rheumatic diseases and cancer pain.

Systematic review on efficacy, tolerability and safety of cannabis-based medicines in chronic pain management; includes fibromyalgia as a pain entity with moderate evidence for symptom reduction.

Medical cannabis was found to be safe and well tolerated; it showed potential benefits for some FMS patients, but further studies are needed to confirm efficacy.

Systematic review on the safety and efficacy of medical cannabis in fibromyalgia. Evidence from smaller studies with heterogeneous methodology; moderate indications of pain reduction and improvement in quality of life, acceptable adverse effect profiles.

Placebo was superior to the CBD group: placebo showed a stronger reduction in pain (-1,1 points) than CBD (-0,4 points) with a statistically significant difference in favor of placebo (P = 0,0028).

n=200 fibromyalgia patients, CBD 50 mg daily vs. placebo over 24 weeks; primary endpoint pain intensity (NRS): CBD group -0,4 points (95% CI: -0,82 to 0,08), placebo group -1,1 points (95% CI: -1,53 to -0,63), between-group difference -0,7 points (95% CI: -1,2 to -0,25; p=0,0028) in favor of placebo. CBD 50 mg daily showed no analgesic efficacy.

Nabilone showed significant improvements in pain (VAS -2.04, P<0.02), quality of life (FIQ -12.07, P<0.02) and anxiety (-1.67, P<0.02) after 4 weeks versus placebo, with more side effects in the treatment group.

n=40 fibromyalgia patients, nabilone (synthetic THC analogue) vs. amitriptyline vs. placebo (4-week cross-over); nabilone significantly better than placebo for VAS pain (p0.02) and quality of life (FIQ p0.04), comparable to amitriptyline; most common side effect dizziness.

Nabilone was superior to amitriptyline with regard to sleep quality (Insomnia Severity Index difference 3,2) and marginally better for restfulness, with acceptable tolerability.

n=29 fibromyalgia patients with chronic insomnia, randomized double-blind crossover nabilone 0.5–1.0 mg vs. amitriptyline 10–20 mg (each 2 weeks, 2 weeks washout). Nabilone superior for sleep quality (Insomnia Severity Index difference = 3.2, 95% CI 1.2–5.3, p<0.01); marginally better for restfulness (Leeds Sleep Evaluation difference = 0.5, 95% CI 0.0–1.0). No effects on pain, mood or quality of life. AEs more frequent with nabilone (dizziness, nausea, dry mouth), mostly mild to moderate.

Medium to large effects for pain reduction, sleep quality and fibromyalgia impact in favor of cannabis; no significant effect on fatigue and anxiety/depression.

n=24 fibromyalgia patients, pilot RCT over 16 weeks; 1:1 THC:CBD cannabis oil (10 mg/mL each) vs. placebo. Retention 91,7% (22/24), adherence ≥90%. Clinically meaningful FIQR improvement (≥45,5% MCID) in 40% of the cannabis group vs. 10% placebo. Pain reduction ≥30%: 70% cannabis group post-titration and week 12 vs. 20%/40% placebo. Medium to large effects for pain reduction, sleep quality, FIQR reduction (between-group comparison). Fatigue and anxiety/depression unchanged. No serious adverse events. Small sample size, caution warranted in interpretation.

Cannabis varieties with THC showed an effect on pressure pain threshold, but no consistent effects on spontaneous or electrical pain responses; Bediol showed a 30% pain decrease in 90% vs. 55% of patients vs. placebo.

n=20 fibromyalgia patients, randomised 4-way crossover design with inhaled cannabis (Bedrocan 22,4mg THC/<1mg CBD, Bediol 13,4mg THC/17,8mg CBD, Bedrolite 18,4mg CBD/<1mg THC, placebo). No significant superiority over placebo for spontaneous or electrical pain responses after single inhalation. Bediol: 90% of patients showed ≥30% pain reduction vs. 55% with placebo (p=0,01). THC-containing varieties significantly increased pressure pain threshold vs. placebo (p<0,01). CBD increased THC plasma levels but reduced THC's analgesic effects (pharmacokinetically synergistic, pharmacodynamically antagonistic).

THC-rich cannabis oil led to a significant reduction in FIQ score compared to placebo and to baseline, with improvements in wellbeing, pain, ability to work and fatigue.

n=17 fibromyalgia patients, RCT over 8 weeks; THC-rich cannabis oil (24.44 mg/mL THC, 0.51 mg/mL CBD) vs. placebo. Cannabis group: significant FIQ score reduction vs. placebo (p=0.005) and vs. baseline (p<0.001). Significant improvements in FIQ items "feel good", "pain", "do work", "fatigue". Placebo group: improvement only in "depression". No intolerable side effects. Small sample, socioeconomically disadvantaged cohort.

Dronabinol led to decreased pain intensity, increased patient satisfaction, and significant pain relief as adjuvant therapy in opioid-treated chronic pain patients.

n=30 chronic pain patients under opioid therapy, dronabinol 10–20 mg/d adjuvant vs. placebo; no significant difference in the primary endpoint (BPI pain intensity p=0.59), trend towards improved sleep quality.

THC significantly reduced spontaneous and electrically induced pain, but with a high discontinuation rate due to side effects and no effect on axon reflex flare.

Pilot study n=9 fibromyalgia patients; delta-9-THC 2,5–15 mg/day (dose escalation); 5/9 discontinuations due to side effects. Electrically induced pain significantly dampened after 10–15 mg THC (p<0,05); daily recorded FM pain significantly reduced (p<0,01). Axon reflex flare unchanged — indication of a central mechanism of action.

Cannabis medicines show typical side effects (fatigue, dizziness, nausea, dry mouth) with all preparations; potentially serious side effects (depression, suicidal ideation, hallucinations) were reported in >0,1% of cases each; efficacy not quantified in this interim analysis.

n≈21.000 (3-year analysis of the German cannabis accompanying survey), fibromyalgia as third most common indication; in fibromyalgia patients improvement of pain and quality of life in 60% of cases.

Cannabis medicines showed efficacy in pain (69% of cases), spasticity (11%) and anorexia/cachexia (8%), whereby insufficient efficacy was the most common reason for treatment discontinuation; side effects corresponded to product information.

n=10.738 (interim analysis of the German cannabis accompanying survey), fibromyalgia among the most common indications; in n=263 fibromyalgia patients improvement in quality of life in 50% of cases.

Significant reduction in pain intensity, but only 17% (ITT) or 32% (per-protocol) showed clinically relevant pain reduction ≥30% at first follow-up; mild to moderate side effects in 42% of patients.

n=827 Danish patients with treatment-refractory chronic pain (incl. fibromyalgia n~120) on cannabinoids; 44% reported pain reduction 30%, 21% treatment discontinuation due to side effects (dizziness, fatigue).

Medical cannabis significantly reduced pain intensity in fibromyalgia and was well tolerated by the majority of patients.

Prospective observational study on medical cannabis in fibromyalgia, n=367 (82% women); 6-month follow-up. Pain intensity (NRS 0-10) reduced from median 9.0 to 5.0 (p<0.001); 81,1% (n=194) achieved treatment response. Most common side effects mild: dizziness 7,9%, dry mouth 6,7%, gastrointestinal symptoms 5,4%.

Improvements in health-related quality of life as well as fibromyalgia-specific symptoms, sleep and anxiety in 306 patients with cannabis-based medicinal products (p < 0,0001).

UK Medical Cannabis Registry, fibromyalgia cohort; clinical outcome improvements in pain and quality of life scores following cannabis therapy, prospective observation without control group.

Medical cannabis led after 12 months to an average reduction in pain intensity of 20% and improvement of all other parameters by 10-30%; at the same time a reduction of the opioid-equivalent dose by 42%.

n=279 patients with chronic pain under medical cannabis, mixed etiologies (incl. fibromyalgia n~50); significant pain reduction (NRS -2,5 points, p0.001), 18% response rate for ≥30% reduction after 6 months.

Delta-9-THC significantly reduced pain intensity and improved psychometric parameters, with an acceptable side effect profile in the majority of patients.

Multicentre retrospective survey (n=124 evaluable): Delta-9-THC 7,5 mg/d over 7 months in patients with central neuropathic pain including fibromyalgia — pain (NRS), functional impairment (PDI) and quality of life (SF-12, QLIP) improved significantly; opioid dose reduced. ~25% treatment discontinuation due to side effects.

THC led to significantly stronger improvement of pain intensity, depressiveness and quality of life during inpatient IMPT and enabled significantly more frequent dose reduction or discontinuation of analgesics.

Pilot study on THC in fibromyalgia patients; exploratory, n not specified, reports improvements in pain and quality of life, methodologically limited (open-label, small sample).

Significant improvement in fibromyalgia severity and several GI symptoms (epigastric pain, burning, abdominal pain, distension, bloating) over 6 months.

n=60 fibromyalgia patients, Bedrocan® cannabis treatment over 6 months; 76,6% met criteria for at least one disorder of gut-brain interaction (DGBI). FIQR severity score log-transformed significantly reduced (repeated-measures ANOVA, p<0.001). Among GI symptoms: log-transformed intensity-frequency scores of epigastric pain, epigastric burning, abdominal pain, abdominal distension and bloating significantly reduced (repeated-measures ANOVA, p<0.01). Open-label without control group.

Improvements in anxiety disorders, sleep quality, fibromyalgia symptom severity and quality of life (EQ-5D-5L) across all follow-up periods compared to baseline (p < 0,050).

n=148 fibromyalgia patients from UK Medical Cannabis Registry, treated with cannabis oils (52%), flowers (9,5%) or combination (38,5%). Improvements in GAD-7, sleep quality, fibromyalgia symptom severity and EQ-5D-5L index at all follow-ups vs. baseline (p<0,050). 36 patients (24,3%) reported 648 adverse events, more frequent in cannabis-naive patients. No differences between CBMP formulations.

Cannabis acutely reduced pain and stiffness and improved mental quality of life, but showed no significant effect on functional impairment (FIQ) or sleep quality (PSQI).

n=56 fibromyalgia patients (28 cannabis users, 28 non-users). After 2 h of cannabis use: significant VAS reduction in pain and stiffness as well as improvement in relaxation (p<0,001). SF-36 Mental Health Component Summary significantly higher in cannabis users vs. non-users (p<0,05). No significant difference in FIQ or PSQI.

32,4% of fibromyalgia patients report current CBD use with predominantly mild to marked improvements across several symptom domains, however about half report side effects.

n=2.701 fibromyalgia patients (online survey); 38% report CBD use, of which 72% with subjective symptom improvement (pain, sleep, anxiety); no placebo control, self-selection, exploratory data — real-world perspective on CBD prevalence and perceived efficacy.

Narrative review presents theoretical foundations and existing evidence for clinical endocannabinoid deficiency in migraine, fibromyalgia and irritable bowel syndrome; no primary empirical data on intervention effects reported.

Russo's theory of clinical endocannabinoid deficiency: migraine, fibromyalgia and irritable bowel syndrome as prototype conditions with hypothetical ECS dysfunction. Mechanistic hypothesis with indirect clinical relevance, no systematic data extraction.

Preliminary evidence suggests possible immunomodulatory effects, but the available evidence is insufficient to support a recommendation for cannabinoid treatment in rheumatic diseases.

Narrative overview of cannabinoids in rheumatic diseases incl. fibromyalgia; discussion of preclinical and clinical data (nabilone studies), but no meta-analysis. Expert opinion: 'weak evidence for pain reduction, moderate rate of side effects'. No systematic review protocol.

Narrative review without primary study results; reports substantial evidence for THC/CBD combination in chronic pain and for CBD-only in stress, moderate evidence for anxiety disorders and sleep disorders.

Narrative review on THC and CBD in chronic pain and mental illnesses; mentions fibromyalgia in the context of chronic pain indications, no systematic data extraction, focus on mechanisms and clinical application.

Observational studies and surveys suggest perceived benefits, but prospective studies and RCTs are rare and the evidence remains sparse.

Narrative review on cannabis in rheumatic diseases; explicitly discusses fibromyalgia data; review of existing studies (incl. nabilone RCT in fibromyalgia) with moderate pain reduction; emphasizes safety concerns and evidence gaps.