Cannabis Extract in Fibromyalgia Syndrome - the SUNRISE Study

Fibromyalgia (FM) is a chronic condition characterized by widespread pain, mechanical hyperalgesia, fatigue, sleep disturbances, psychological and cognitive impairments, mood changes, headaches, migraines, and gastrointestinal symptoms. Despite its recognition as a medical condition with diagnostic criteria and severity scales, its exact causes and effective treatment remain unclear. FM significantly impacts patients' quality of life and poses a societal burden due to high direct and indirect costs.

Cannabis-based treatments have gained attention for FM symptom management. In Italy, therapeutic cannabis has been legal since 2013 and may be prescribed when conventional treatments fail or cause intolerable side effects. Its primary components, tetrahydrocannabinol (THC) and cannabidiol (CBD), interact with cannabinoid receptors to potentially provide pain relief, anti-inflammatory effects, and mood stabilization.

The study aims to evaluate the efficacy of the standardized cannabis extract Avextra 10/10 (10 mg/mL THC and 10 mg/mL CBD) for FM treatment.

Objectives Primary objective: -Assess the extract's impact on pain after 12 weeks.

Secondary objective:

* Evaluate the clinical effect of cannabis extract Avextra 10/10 solution on fatigue, sleep, anxiety and depression after 4, 8 and 12 weeks among patients affected by FM * Evaluate the clinical effect of cannabis extract Avextra 10/10 solution on pain after 4 and 8 weeks among patients affected by FM. * Evaluate the effect of cannabis extract Avextra 10/10 solution on the quality of life at 4, 8 and 12 weeks among patients affected by FM. * Describe any adverse events or the principal reasons of drug discontinuation.

Design and Methods This is a monocentric observational prospective study in which patients with FM who undertake cannabis therapy with cannabis extract Avextra 10/10 solution will consecutively be recruited.

Population: The inclusion criteria are:

* Patients with a diagnosis of FM according to 2016 American College of Rheumatology Criteria \[2\]. * Patients with FM prescribed cannabis extract Avextra 10/10 solution after failure and/or intolerance of first- or second-line treatment. * Aged 18 years and older. * Able to fully understand and fill questionnaires. * Able to provide informed consent, according to requirements of local IRB/ethics committee.

The exclusion criteria are:

* Known history of pain not due to FM. * Patients who have not received stable therapy for pain, sleep disorders, or any psychiatric condition for at least 2 weeks. * Patients who are taking other types of medical cannabis besides Avextra 10/10 solution. * Concomitant diagnosis of other pathologies that could interfere with clinical judgment. * Psychiatric diagnosis according to DSM-V-TR

All patients with FM will undergo a standard clinical assessment, at baseline and at the follow-up visits, as part of the routine clinical practice. After the baseline visit, corresponding to the appointment where medical cannabis is prescribed within two weeks before the undertake of cannabis extract, follow-up visits will be scheduled according to routine clinical practice as follow:

* 15 days after the undertake of cannabis extract (T15) * 30 days after the undertake of cannabis extract (T30) * 60 days after the undertake of cannabis extract (T60) * 90 days after the undertake of cannabis extract (T90) * 6 months after the undertake of cannabis extract. All patients with FM will undergo a standard clinical assessment, at baseline and at the follow-up visits, as part of the routine clinical practice.

Data collected from participants during clinical evaluations at baseline visit will include:

* Demographic data: age, gender, BMI, residence * Educational qualification * Occupational status * Age at menopause (if applicable) * Current medication * Comorbidities * Symptom duration * Age at FM diagnosis * Number of sure tender point * Smoke status * Physical activity

Data collected from participants during clinical evaluations at follow-up visit will include:

* Number of sure tender point * Smoke status * Physical activity * Efficacy or side effects of cannabis extract * Discontinuation of cannabis extract

Conclusion The study seeks to establish the feasibility and clinical effects of a standardized cannabis extract for FM, addressing a critical gap in treatment strategies. Further research is needed to validate its efficacy and optimize FM management.

• Evaluate the clinical effect of cannabis extract Avextra 10/10 solution on sleep quality among patients affected by FM using Pittsburgh sleep quality index (PSQI) [Time frame: 4, 8 and 12 weeks]
• Evaluate the clinical effect of cannabis extract Avextra 10/10 solution on pain using Widespread pain indexWPI [Time frame: 4, 8 and 12 weeks]
• Evaluate the effect of cannabis extract Avextra 10/10 solution on the quality of life using The Italian versions of the Revised Fibromyalgia Impact Questionnaire (FIQR) [Time frame: 4, 8 and 12 weeks]
• Describe any adverse events or the principal reasons of drug discontinuation. [Time frame: 4,8,12 weeks]
• 1. Evaluate the clinical effect of cannabis extract Avextra 10/10 solution on pain after 12 weeks among patients affected by FM [Time frame: 4, 8 weeks]
• Evaluate the clinical effect of cannabis extract Avextra 10/10 solution on Functional Appreciation Scale (FAS) [Time frame: 4, 8, 12 weeks]
• Evaluate the clinical effect of cannabis extract Avextra 10/10 solution on Symptom Severity Scale (SSS) [Time frame: 4, 8, 12 weeks]