The objective of this protocol is to evaluate if Dextromethorphan (DXM) reduces Fibromyalgia (FM) pain. DXM is a drug found in several over-the-counter products, including cough suppressants. The drug may reduce FM pain by suppressing inflammation in the central nervous system. The investigators will be observing the effects of DXM on daily self-reported pain measures in people with FM. If DXM reduces FM pain, it will provide important information about the nature of FM pathophysiology.

Fibromyalgia (FM) is a chronic, widespread pain syndrome. Individuals with FM frequently report body pain, fatigue, sleep issues, cognitive impairment, headaches, and other symptoms. The disease affects approximately 5% of women in the United States. Many of those patients suffer with decreased quality of life and loss of employment.

The precise pathological mechanism of FM is not yet understood, and there is no targeted treatment for the condition. One hypothesis of FM with prior scientific support is that pain is caused by abnormal inflammation of the brain. When microglia cells in the brain adopt an inflammatory state, they release chemicals that can cause neurons to increase the transmission of pain signals.

DXM has been used in previous research and demonstrated to suppress pain symptoms. When given at higher dosages (above 200mg), the medication acts as a dissociative agent. This dosage can reduce pain, but produces side-effects that can limit daily functioning. At lower dosages, however, DXM may reduce inflammatory aspects of chronic pain while not causing dissociative side effects.

In animal models, central inflammation can be reduced with intraperitoneal dosages of DXM of 0.1mg/kg. In an average U.S. woman, this dosage would translate to approximately 8mg. Because an oral versus intraperitoneal dosing route will be used, the dose will be raised to 10mg, administered twice a day (once in the morning and once at night). The investigator will examine the impact of 20mg total daily DXM on self-reported FM pain.

Inclusion Criteria:

1. Severe chronic fatigue ≥6 consecutive months not due to ongoing exertion or other medical condition associated with fatigue;
2. Daily self-reported pain of at least 4 out of 10;

3. Meets American College of Rheumatology 2016 case definition criteria for FM;

4. Able to attend UAB for all scheduled appointments;

5. Can complete daily self-reports of pain and other symptoms for duration of project.

Exclusion Criteria:

1. Blood draw contraindicated or otherwise not able to be performed;
2. High-sensitivity C-reactive protein (HS-CRP) ≥ 10 mg/L;
3. Erythrocyte sedimentation rate (ESR) >60 mm/hr;
4. Positive rheumatoid factor;
5. Positive anti-nuclear antibody (ANA);
6. Abnormal thyroid stimulating hormone or free thyroxine;
7. Diagnosed rheumatologic or auto-immune condition;
8. Blood or clotting disorder;
9. Use of blood thinning medication;
10. Current use of MAOI
11. Daily consumption of grapefruit juice
12. Oral temperature >100˚F at baseline;
13. Febrile illness or use of antibiotics in the 4 weeks before study commencement;
14. Planned surgery or procedures during the study period, or operated on in the 4 weeks before study commencement;
15. Pregnant or planning on becoming pregnant within 6 months, or currently breastfeeding
16. Regular use of any anti-inflammatory medication (such as aspirin, ibuprofen, naproxen);
17. Baseline HADS (Hospital Anxiety and Depression Scale) depression subscale score of ≥16;
18. Current litigation or worker's compensation claim;
19. Current participation in another treatment trial;
20. Planned vaccination during the study period, or vaccinated in the 4 weeks before study commencement.

Throughout participants' study completion, 19 weeks.

Medication was tested in a small number of fibromyalgia (FM) patients, limiting generalizability. Length of DXM treatment was only 10 weeks, so it is unclear if the results are durable. We used a single-blind design that could have led to experimenter bias. We relied only on self-reported pain rather than using objective pain assessments.

The participant will not know when they are taking placebo or the study medication.