. 2024 Oct 11;16:100524. doi: 10.1016/j.rcsop.2024.100524

Table 2.

Key information regarding observational clinical studies assessing the efficacy/effectiveness of CBPMs in patients with fibromyalgia syndrome.

Reference	Objective	Cannabis-based medicinal products (route of administration)	Dose	Efficacy/effectiveness measure	Efficacy/effectiveness results
²⁷	To assess any clinical improvement with the addition of CBPMs to standard analgesic treatment in patients with FMS	Bedrocan, (22 % THC and less than 1 % CBD), and Bediol, (6.3 % THC and 8 % CBD), prepared in olive oil (1 g cannabis, 10 g of olive oil) (Oral)	Bedrocan at night, Bediol at the morning 10–30 drops, not exceeding 120 drops/day	• The Fibromyalgia Assessment Status (FAS) • The Pittsburgh Sleep Quality Index (PSQI) • The Italian version of the Revised Fibromyalgia Impact Questionnaire (FIQR) • The Zung Self-Rating Depression Scale (ZSR-D) • The Zung Self-Rating Anxiety Scale (ZSR-A) • Self-Administered Pain Scale (SAPS) • The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale	• The improvement in FAS scores was not significant, the PSQI and FIQR scores showed a significant improvement (>30 %); the ZRS-A and ZRS-D scores showed a moderate improvement • FAS: Baseline mean = 7.698 SD = 1.939, and at 6 months mean = 7.030 SD = 2.100 • PSQI: Baseline mean = 10.554 SD = 3.206, and at 6 months Mean = 9.001 SD = 3.641 • FIQR: Baseline mean = 69.003 SD = 19.181, and at 6 months mean = 62.252 SD = 22.751 • ZSR-A: Baseline mean = 64.754 SD = 12.585, and at 6 months Mean = 61.924 SD = 13.193 • ZSR-D: Baseline mean = 52.758 SD = 10.728 and at 6 months mean = 50.815 SD = 11.777 • (FACIT)-Fatigue Scale: Baseline mean = 18.379 SD = 9.939, and at 6 months mean = 288 SD = 11.558
²⁸	To evaluate the possible role of CBPMs as add-on therapy in the management of Low back pain in FMS patients.	The recommended one was 1:4 THC to CBD, with THC levels less than 5 % (Smoked or vaporized)	20 g of cannabis for a month. It could be increased to 30 g/month	• Pain in Visual Analogue Scale (VAS) • Oswestry Disability Index (ODI) • Revised Fibromyalgia Impact Questionnaire (FIQR) • Physical examination: The modified-modified Schober test to assess lumbar flexion • Patient's Global Impression of Change (PGIC) Scale • Decrease, increase, or maintenance of standard analgesic treatment	• The later addition of CBPMs allowed a significantly greater decrease in pain and significant improvement in the modified-modified Schober test • The spine range of motion was not affected by the use of standard analgesic therapy but improved when patients used medical cannabis for 3 months • VAS: Baseline mean:8.1 ± 1.4, and at 6 months 3.3 ± 2.2, p < 0.0001 • ODI: Baseline mean: 77.5 ± 10.6, and at 6 months 30.7 ± 13.6, p < 0.0001 • FIQR: Baseline mean: 45.3 ± 10.2, and at 6 months 80.5 ± 12.2, p < 0.0001 • Modified-modified Schober test (cm): Baseline mean: 3.5 ± 1.8, and at 6 months 5.3 ± 1.5, p < 0.0001 • PGIC scale: Mean difference at baseline and 6 months 3.3 CI 95 % =2.5–4.1, p < 0.0001
⁴⁶	To evaluate the efficacy of Cannabis flos 19 % on pain, fatigue, sleep disturbances, anxiety, and depression in FMS patients.	Cannabis flowering tops marketed as Cannabis flos 19 % for oral decoction (Oral)	30 mg twice a day for the first month, 60 mg twice a day for the second month	• The Fibromyalgia Impact Questionnaire Revised (FIQR) • Pain in Visual Analogue Scale (VAS) • The Fibromyalgia Activity Score (FAS) • The Functional Assessment of Chronic Illness Therapy (FACIT) • The Pittsburgh Sleep Quality Index (PSQI) • The Zung Self-Rating Anxiety Scale (ZS-RA) • The Zung Self-Rating Depression Scale (ZS-RD)	• Cannabis flos 19 % is effective in improving pain, fatigue, anxiety and depression in patients with FMS • FIQR: Baseline 74.4 ± 17.2 vs 60.3 ± 24.3, p = 0.0615 NS* • VAS pain: Baseline 8.2 ± 1, and at 6 months 6.2 ± 2.4, p = 0.0273 • FAS: Baseline 7.8 ± 1.7, and at 6 months 6.2 ± 2.1, p = 0.0494 • FACIT: Baseline 13.5 ± 7.4 and at 6 months 22.9 ± 10.5, p = 0.0042 • PSQI: Baseline 11 ± 2.8, and at 6 months 10.5 ± 3.8, p = 0.5435 NS* • ZR-SA: Baseline 66.2 ± 14, and at 6 months 57.6 ± 13.3, p = 0,0172 • ZS-RD: Baseline 58 ± 10.3, and at 6 months 48.7 ± 11.5, p = 0.0491
⁴⁸	To describe the patterns of CBPMs use and the associated benefits reported by patients with FMS	The cannabis derivative used in every case was cannabis whole plant (Smoked and oral)	The most frequent doses were between 1 and 2 cigarettes each time when patients smoked and 1 full spoonful each time when eating	• Range of symptoms by patients (pain, stiffness, relaxation, drowsiness, well-being) using 100-mm Visual Analogue Scale (VAS) • The 36-item Short Form Health Survey (SF-36) • The Fibromyalgia Impact Questionnaire (FIQ) • The Pittsburg Sleep Quality Index (PSQI)	• Cannabis alleviates pain and almost all the symptoms associated with FMS, and no one reported worsening of symptoms following cannabis use • The proportion of patients who reported strong relief ranged from 81 % for sleep disorders to 14 % for headaches • All symptoms assessed by VAS showed statistically significant improvement following 2 h of cannabis self-administration • Pain scale by VAS: mean reduction of 37.1 mm, p < 0.001 • Stiffness scale by VAS: Mean reduction of 40.7 mm, p < 0.001 • Relaxation scale by VAS: mean reduction of 27.6 mm, p < 0.05 and 20.0 mm, p < 0.05 • Somnolence scale by VAS: mean reduction 20.0 mm, p < 0.05 • Perception of well-being by VAS: mean increase of 40.0 mm, p < 0.001 • SF-36-mental health component: mean 29.6 SD = 8.2 in users, compared to 24.96 SD = 8.9, p < 0.05 in non-users • FIQ: Mean 65.56 SD = 11.9 in users, compared to = 65.56 SD = 12.8 in non-users, p = 0.36 NS* • PSQI: Mean 14.1 SD = 3.2 in users, compared to = 14.4 SD = 3.3 in non-users (p = 0.73) NS*
⁴⁹	To investigate the safety and effectiveness of FMS patients receiving CBPMs	Not specified: product contains CBD/THC	The median cannabis approved dosage was 670 mg/day at initiation and 1000 mg/day at 6 months. The median of THC was 140 mg/day and for CBD was 39 mg/day at 6 months	• Perception of the general effect of cannabis—global assessment by using the Likert scale • Sleep disturbances • Depression-related symptoms • Pain intensity—assessment by the Numeric Rating Scale (NRS) with an 11-point scale • Quality of life (QOL)—global assessment by the patient using the Likert scale	• The overall treatment success (patients reporting at least moderate improvement, without serious adverse events) was achieved in 81.1 % of the patients (proportion of patients reporting at least moderate improvement in their condition with no serious adverse events) • The sleep disturbances reported by 92.9 % of the patients (196 patients) at baseline improved in 73.4 % (144 patients), and disappeared in 13.2 % of them (26 patients), p < 0.001 • Depression-related symptoms reported by 59.2 % of the patients at the baseline improved in 80.8 % of them, p < 0.001 • Pain by NRS scale: At baseline, 52.5 % of the patients reported 8–10 on the Likert scale, and at 6 months, just 7.9 % of the patients reported pain of the same intensity. Mean pain at baseline 9, interquartile 8–10, and after 6 months was 5, interquartile 4–6, p < 0.001 • QOL: At baseline, 2.7 % of the patients reported good or very good, and at 6 months it increased to 61.9 %, p < 0.001
⁵⁰	To examine the effects of CBPMs on patients with FMS	Not specified: product contains whole cannabis plant (Smoked or inhaled)	The mean cannabis dose was 26 g/month	• Revised Fibromyalgia Impact Questionnaire (FIQR)	• FIQR: Statistically significant improvement in outcomes in every item evaluated. In some cases, the impact of the illness decreased making the patients stopped the previously drug-therapy • Results of some items: “Fibromyalgia prevented me from accomplishing goals for the week”: mean value at baseline 9.17 ± 1.06, and after 2 months 3.77 ± 1.87, p = 0.000, and “Please rate your level of pain”: mean 9.21 ± 0.95, and at 2 months 3.35 ± 1.64, p = 0.000
⁵¹	To assess the effects of CBPMs on pain intensity, disability, widespread pain, disease severity, and mood disorders	Cannabis with the same proportion of THC and CBD as the first option, or THC-dominant (Oral as decoction, vaporized as oil, and sublingual as oil)	The starting dose of the milled flowers in the sachet was 50 or 100 mg twice per day. In the case of cannabis olive oil extract, one drop every 3–4 days and a subsequent increase	• Pain relief by Numeric Rating Scale (NRS) • Analgesic effects were considered when there was a reduction in pain intensity by at least 30 %. • Oswestry Disability Index (ODI) • Mood disorders were evaluated with the Hospital Anxiety and Depression Scale (HADS-anxiety or HADS- depression, respectively) • Widespread Pain Index (WPI) • Severity score (SS) • Interruption of conventional drug-therapy for FMS (e.g. analgesics) during CBPM treatment	• Pain relief by NRS: MC therapy significantly reduced pain intensity at 1, 3, and 12 months by at least 30 %. At baseline mean NRS was 8.5 SD = 1.2 and at 12 months was 4 SD = 2.1, p < 0.01 • ODI: Mean at baseline 61 % SD = 18.3, and at 12 months was 47 % SD = 22.2, p < 0.01 • HADS-anxiety: Mean at baseline 9 SD = 4.7, and at 12 months was 7 SD = 6.3, p > 0.01 NS* • HADS-depression: Mean at baseline 11 SD = 3.9, and at 12 months was 7 SD = 5.7, p > 0.01 NS* • WPI: Mean at baseline 15 SD = 4.2, and at 3 months was 7 SD = 7.1, p < 0.01 • SS: Mean at baseline 10.5 SD = 1.3, and at 12 months was 6.5 SD = 3.3, p < 0.01 • Before CBPM therapy, all patients were taking one or more usual drugs for FMS. After 12 months of CBPM, 66.7 % of the patients were taking only CBPM, p < 0.01
⁵²	To explore the efficacy of THC on electrically induced pain, axon reflex flare, and psychometric variables	THC (Oral)	FMS patients received a daily dose of 2.5–15 mg of THC. The dosage was increased weekly by 2.5 mg THC, as long as no severe side effects were reported	• Hypersensitive responses to touch (allodynia) and pinprick (hyperalgesia) • Axon reflex flare • Threshold perception to electrical stimulation • Induced pain • Pain in Visual Analogue Scale (VAS) and numeric pain scale • Pain Disability Index (PDI) • Fibromyalgia Impact Questionnaire (FIQ) • Medical outcome survey short form (MOS SF-36)	• Assessed touch-evoked allodynia and pinprick-induced hyperalgesia were not significantly affected by delta-9-THC medication • Axon reflex flare: THC did not attenuate the development of the flare reaction, p = 0.9 NS* • Threshold to electrical stimulation: The detection limit for electrical stimulation did not alter significantly during delta-9-THC medication, p = 0.1 • Induced pain: THC attenuated experimentally induced pain significantly, p < 0.05 • Pain by VAS: The mean value at baseline was 8.1 ± 7.0 and at long term 2.8 ± 5.0, p < 0.01 • PDI: Mean value at baseline was 34 ± 10.0 and in the long term was 23 ± 11.0 NS* • FIQ: Mean value at baseline was 52 ± 20.0, and at long term was 35 ± 15.0, NS* • MOS SF-36: the only domain that had statically significance was “General healthy”, with a mean value of at baseline 30 ± 5.0, and at long term was 45 ± 6.0, p < 0.01
⁵³	To assess the effects of CBPMs on pain intensity, disability, widespread pain, disease severity, and mood disorders”	Dronabinol THC in liquid or capsules (Oral)	The mean dose administered of THC concentration was 7.5 mg/day (interquartile range 5–12.5 mg). It could increase by 2.5 mg of THC weakly as long as no adverse effects were reported	• 6-point Verbal Rating Scale (VRS-6) for pain intensity • Numeric rating scale (NRS) for pain intensity • Medical Outcomes Short-Form (MO SF-12) • Pain Disability Index (PDI) • Quality-of-Life Impairment by Pain (QLIP) • Hospital Anxiety and Depression Scale (HADS-anxiety or HADS- depression, respectively)	• VRS-6: median value of 6 “very severe” at baseline, and median value of 4 “moderate” after THC, p < 0.001 • NRS: mean of 7.9 ± 1.5 at baseline, and 4.4 ± 1.5 during/after THC, p < 0.001 • NRS: NRS < 6 in 3 % of the patients before THC and NRS < 6 in 44 % of the patients after THC • PDI: mean value of 36.4 ± 10.7 before THC to 22.8 ± 10.8 after THC, p < 0.001 • MO SF-12: mean value of 23.1 ± 6.3 before THC to 33.4 ± 9.7 after THC, p < 0.001). • QLIP: mean value of 9.7 ± 6.6 before THC to 24.7 ± 6.9 after THC • HADS-anxiety: from 10 ± 6.1 before THC to 5.2 ± 3.6 after THC; and HADS-depression from 13.3 ± 5.5 before THC to 7.3 ± 4.1 after THC, p < 0.001
⁵⁴	To assess the outcomes of patients prescribed with CBPMs on fibromyalgia-specific symptoms, health-related quality of life, anxiety, and sleep	CBD or THC (Oral, sublingual, or vaporized)	The median dose of THC was 100.00 (IQR: 20.00–195.00) mg/day and the median dose of CBD was 20.00 (IQR: 20.00–35.00) mg/day.	• Fibromyalgia Symptom Severity, which combines widespread pain index (WPI) and Symptom severity score (SSS) • Single-Item Sleep Quality Scale (SQS) • Patients' Global Impression of Change (PGIC) • General Anxiety Disorder Scale (GAD-7) • Pain in Visual Analogue Scale (VAS) • Health-Related Quality of Life Measure with EuroQol 5 Dimension – 5 levels (EQ-5D-5L)	• Fibromyalgia Symptom Severity: median score of 20.00 (IQR: 16.25–25.00) at baseline, to 17.00 (IQR: 14.00–24.00) at 6 months, p < 0.001 • SQS: median score of 4.00 (IQR: 3.00–6.00) at baseline to 6.00 (IQR: 4.00–8.00) at 6 months, p < 0.001 • GAD-7: median Score of 7.00 (IQR: 3.00–12.00) at baseline to 6.00 (IQR: 2.25–9.00) at 3 months, p < 0.001 • VAS: median score of 7.00 (IQR: 5.00–8.00) at baseline to 6.00 (IQR: 4.00–7.00) at 6 months, p < 0.001 • EQ-5D-5L: median score of 0.36 (IQR: 0.21–0.61) at baseline, and at 6 months the score was 0.55 (IQR: 0.40–0.67), p < 0.001

NS* Not significant; CBD: Cannabidiol; THC: Tetrahydrocannabinol; CBPMs: cannabis-based products for medicinal use; FMS: Fibromyalgia syndrome; SD: standard deviation; CI95 %: Confidence interval 95 %; IQR: interquartile range.