Melatonin May Reduce Musculoskeletal Pain and Improve Sleep

A systematic review and meta-analysis published in PAIN indicates melatonin may modestly reduce pain intensity amongst adults with chronic musculoskeletal pain while also improving sleep quality. Across 23 randomized controlled trials involving 2028 participants, melatonin was generally well tolerated, although substantial differences among the included populations, treatment regimens, and study designs limit conclusions about its optimal use.¹

The findings suggest that melatonin could eventually serve as an inexpensive adjunct within multimodal pain management, particularly for patients whose chronic pain occurs alongside sleep disturbances. However, the researchers emphasized that the evidence does not support replacing established analgesic therapies with melatonin.¹

Exploring Melatonin for Pain Management

Melatonin is an endogenous hormone produced primarily by the pineal gland and is best known for helping regulate circadian rhythms and the sleep-wake cycle. Supplemental melatonin is widely available in the United States as a dietary supplement and is commonly used for concerns regarding sleep.²

Researchers have further explored its potential analgesic effects. Proposed mechanisms include modulation of melatonin receptors, inflammatory pathways, oxidative stress, and pain signaling within the central nervous system. Sleep may provide another important pathway because insufficient or disrupted sleep can amplify pain sensitivity, whereas persistent pain frequently interferes with sleep.

This connection makes melatonin particularly relevant to chronic musculoskeletal conditions, in which pain, impaired function, fatigue, and poor sleep may reinforce one another. Current CDC guidance recommends maximizing appropriate nonpharmacologic and nonopioid therapies for subacute and chronic pain and considering opioids only when their anticipated benefits for pain and function outweigh the risks.³

Meta-Analysis Includes More Than 2000 Participants

The systematic review evaluated 23 randomized controlled trials conducted in several countries, including the United States, Brazil, China, Egypt, and Russia. The trials included 2028 adults with chronic musculoskeletal conditions, such as low back pain, osteoarthritis, and fibromyalgia, as well as patients experiencing pain after procedures, including joint replacement and spinal surgery.¹

When data from chronic musculoskeletal conditions were pooled, melatonin was associated with a reduction in pain intensity compared with control interventions. The overall improvement was approximately 9 points on a 100-point pain scale, and analyses restricted to the most methodologically rigorous trials produced reductions closer to 10 points.¹

The magnitude of improvement was within the range previously reported for some commonly used analgesic treatments. However, this was an indirect comparison across separate bodies of evidence—not evidence from head-to-head trials demonstrating that melatonin is equivalent or superior to opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), or acetaminophen.

Melatonin also improved sleep quality, a finding that may be clinically meaningful for patients experiencing both pain and disrupted sleep. Nevertheless, the researchers observed variation in results across conditions and treatment settings.¹

Doses used for chronic musculoskeletal pain generally ranged from 3 to 10 mg, with 3 mg daily used most frequently. Postoperative studies evaluated doses ranging from 1 to 10 mg, most commonly 5 or 6 mg. Melatonin was generally administered at bedtime or within 1 hour before sleep.¹

Safety and Supplement Quality Require Consideration

Adverse effects reported across the trials were generally mild and included nausea, dizziness, and headache. Rates were similar to those observed with placebo, and no serious adverse events attributed to melatonin were reported.¹

Despite these reassuring findings, evidence concerning long-term supplemental melatonin use remains limited. The National Center for Complementary and Integrative Health states that short-term use appears safe for most individuals, but the long-term safety profile is uncertain. Potential adverse effects include headache, dizziness, nausea, and sleepiness.²

Patients taking anticoagulants or antiseizure medications should consult a health care professional before using melatonin. Additional caution may be appropriate for older adults because melatonin may remain active longer and contribute to daytime drowsiness. Evidence is also insufficient to establish safety during pregnancy or breastfeeding.²

Product quality is another important concern. Unlike prescription and over-the-counter medications, dietary supplements do not undergo FDA premarket review for efficacy and are regulated under a less stringent framework. Analyses of commercially available melatonin products have found discrepancies between labeled and measured quantities, emphasizing the importance of selecting products from reputable manufacturers that use independent quality testing.²,⁴

Implications for Practice

Patients should be advised that taking higher doses of melatonin does not translate to more effective results. Because the meta-analysis did not establish a dose-response relationship, escalating the dose may increase adverse effects without providing additional pain relief.

For patients with chronic musculoskeletal pain and co-occurring sleep disturbances, melatonin may warrant discussion as a carefully monitored adjunct to an individualized multimodal strategy. Larger, high-quality trials are still needed to identify which patients are most likely to benefit and to determine appropriate dosing, duration, comparative efficacy, functional outcomes, and long-term safety.

REFERENCES

1. Wu K, et al. Efficacy and effectiveness of melatonin for the management of musculoskeletal pain: a systematic review and meta-analysis of placebo and active controlled trials. . PAIN ():10.1097/j.pain.0000000000004045, June 30, 2026. | DOI: 10.1097/j.pain.0000000000004045 . Published online June 30, 2026. Accessed June 30th, 2026 https://journals.lww.com/pain/fulltext/9900/efficacy_and_effectiveness_of_melatonin_for_the.1225.aspx

2. Melatonin: what you need to know. National Center for Complementary and Integrative Health. Accessed June 30, 2026. https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know

3. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR Recomm Rep 2022;71(No. RR-3):1–95. DOI: http://dx.doi.org/10.15585/mmwr.rr7103a1

4. Using dietary supplements wisely. National Center for Complementary and Integrative Health. Accessed June 30, 2026. https://www.nccih.nih.gov/health/using-dietary-supplements-wisely