Table 2. Showing the observational studies, clinical trials, and case series conducted on the use of cannabis for the treatment of fibromyalgia.

THC, tetrahydrocannabinol; CBD, cannabidiol; FM, fibromyalgia; FIQ, Fibromyalgia Impact Questionnaire; NRS, Numerical Rating Scale; ODI, Oswestry Disability Index; WPI, Wide Pain Index; SyS, severity score.

Author and year of publication	Purpose of study	No. of patients	Type of study	Results	Conclusion
Yassin et al. (2019) [20]	Effect of adding cannabis to analgesic treatment in FM patients with low back pain.	31	Observational cross-over single-center study.	Medical cannabis showed a significant improvement in three months after initiation of therapy and the improvement was maintained at six months.	This observational crossover study showed improvement of back pain in FM patients treated with medical cannabis. Further randomized clinical trial studies are suggested for assessment.
Van de Donk et al. (2019) [19]	The analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia.	20	Randomized placebo-controlled crossover trial.	This experimental trial showed the complex behavior of different inhaled cannabinoids compounds in chronic pain patients with just small analgesic responses after a single inhalation.	Further studies are needed to determine long-term treatment effects on spontaneous pain scores, THC–CBD interactions, and their role in pain relief.
Sagy et al. (2019) [21]	Safety and efficacy of medical cannabis in fibromyalgia.	367	A prospective observational study.	Pain intensity (scale 0–10) reduced from a median of 9.0 at baseline to 5.0 (p < 0.001), and 81.1% of patients achieved treatment response. Mild adverse effects were dizziness, dry mouth, and gastrointestinal symptoms.	Medical cannabis appears to be a safe and effective alternative for the treatment of fibromyalgia symptoms. Standardization of treatment regimens is required.
Giorgi et al. (2020) [22]	Adding medical cannabis to standard analgesic treatment for fibromyalgia.	102	A prospective observational study.	After six months, 50% showed a moderate improvement in the anxiety and depression scales. One-third experienced mild adverse events but did not cause any significant treatment modifications.	There is a possible clinical advantage of medical cannabis in FM patients, especially in those with sleep dysfunctions; further studies are needed to confirm these data.
Chaves et al. (2020) [23]	Ingestion of THC-rich cannabis oil in people with fibromyalgia.	17	A randomized, double-blind, placebo-controlled clinical trial.	Cannabis showed a decrease in Fibromyalgia Impact Questionnaire (FIQ) score in comparison with the placebo group (p = 0.005). There were no intolerable adverse effects.	Cannabinoids can be used to reduce symptoms and increase the quality of life of patients with fibromyalgia. Future studies are still needed to assess long-term benefits.
Safakish et al. (2020) [14]	Medical cannabis for pain management and quality of life improvement.	751	A longitudinal, prospective, observational study.	Medical cannabis was associated with improvements in pain severity and interference (p < 0.001) observed at one month and maintained over 12 months.	The results were promising but the percentage of patients with fibromyalgia included in this study is 17.6%, which is very low to make any conclusion.
Mazza et al. (2021) [24]	Medical cannabis for the treatment of fibromyalgia syndrome.	38	A retrospective, open-label case series.	Significant improvements (p < 0.01) were observed in NRS, ODI, WPI, and SyS for 12 months.	Cannabinoids may be used as an alternative treatment for patients with FM who are unresponsive to conventional therapy. However, it is limited by the incidence of non-serious adverse effects.