Melatonin Lotion for Sleep Disorders

Overseen By Steven Moore, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Redlands

Must not be taking: Antidepressants, Anti-anxiety, Sleep meds

Disqualifiers: Pregnancy, Lotion allergies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 3 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if melatonin lotion can improve sleep and mental health in young adults. Melatonin, a natural hormone that regulates sleep, might also alleviate depression and anxiety. Participants will use both a melatonin lotion and a non-melatonin lotion to compare effects. Ideal candidates are those with sleep issues and mild anxiety or depression, who can maintain a consistent bedtime during the trial.

As an unphased trial, this study provides a unique opportunity to explore new methods for enhancing sleep and mental health.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any antidepressant, anti-anxiety, or sleep medications, including melatonin, to participate in this trial.

Is there any evidence suggesting that melatonin lotion is likely to be safe for humans?

Research shows that melatonin is generally safe for short-term use, which reassures those considering participation in a trial testing melatonin lotion for sleep problems. Melatonin, a hormone that helps regulate sleep, typically does not lead to dependency, unlike some other sleep medications.

Studies have examined melatonin in various forms, including lotions, and suggest that it is well-tolerated when applied to the skin. No evidence indicates serious side effects from short-term use of melatonin lotion. However, while melatonin is often marketed as a safe sleep aid, less information exists about its long-term safety, particularly concerning heart health.

Overall, current research suggests that melatonin lotion is likely safe for short-term use for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike typical sleep disorder treatments that often involve oral medications or behavioral therapies, melatonin lotion offers a unique delivery method through topical application. This approach could potentially provide a more direct and faster absorption of melatonin, directly targeting sleep issues without the need for systemic distribution. Researchers are excited about this treatment because it could minimize side effects associated with oral intake and provide a more natural, non-invasive option for enhancing sleep quality.

What evidence suggests that melatonin lotion might be an effective treatment for sleep disorders?

Research has shown that melatonin can improve sleep and overall well-being. Some studies have found that melatonin enhances sleep and quality of life, although results vary. This trial will compare melatonin lotion with a placebo lotion to evaluate its effectiveness. Early findings suggest that melatonin lotion might be effective, as it significantly increases melatonin levels in the body. This increase could positively affect sleep and mental health. However, more research is needed to confirm its effectiveness specifically for sleep disorders. ^{3 6 7 8 9}

Who Is on the Research Team?

Lisa E Olson, Ph.D.

Principal Investigator

University of Redlands

Are You a Good Fit for This Trial?

This trial is for young adults with sleep issues and mild symptoms of depression or anxiety. Participants must have specific scores on the PROMIS measures for sleep disturbance, anxiety, or depression to join.

Inclusion Criteria

My sleep disturbance score is 48 or higher.

T score ≥ 55 on the anxiety or depression short form PROMIS measures (mild symptoms or more)

Exclusion Criteria

Pregnancy

I am currently taking medication for depression, anxiety, or sleep issues.

Allergies/sensitivities to scented lotion

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive melatonin lotion or placebo lotion in a randomized crossover design for one week each, with a one-week washout period in between

3 weeks

3 visits (in-person) for equipment and sample return

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Melatonin Lotion

Trial Overview The study tests if melatonin lotion improves sleep quality and mental health in young adults. It involves comparing a placebo lotion (no active ingredient) with a melatonin-infused lotion over separate weeks, using surveys, actigraphs, heart rate monitors, and saliva samples.

How Is the Trial Designed?

Group I: Placebo lotion first Experimental Treatment 2 Interventions

Participants will be randomized to one week of treatment with placebo lotion, followed by a week washout, then one week of treatment with melatonin lotion

Group II: Melatonin lotion first Experimental Treatment 2 Interventions

Participants will be randomized to one week of treatment with melatonin lotion, followed by a week washout, then one week of treatment with placebo lotion

Who Is Running the Clinical Trial?

University of Redlands

Lead Sponsor

Trials

4

Recruited

160+

Published Research Related to This Trial

A systematic review of 37 randomized controlled trials found that melatonin is generally safe and well tolerated, with only mild to moderate adverse events reported, such as daytime sleepiness and headache.

Despite the overall safety profile, the lack of long-term studies limits our understanding of potential risks, especially in vulnerable populations like children and those with epilepsy or asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Associated with Melatonin for the Treatment of Primary or Secondary Sleep Disorders: A Systematic Review. Besag, FMC., Vasey, MJ., Lao, KSJ., et al.[2020]

Melatonin treatment in children and adolescents with chronic insomnia does not appear to cause serious adverse events, but there is an increased risk of non-serious adverse events, with a relative risk of 1.56 based on 17 studies involving 1350 patients.

Long-term use of melatonin may have little to no effect on pubertal development in most cases, but there is a potential for delays in development after more than 7 years of treatment, highlighting the need for further research to clarify these long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The short-term and long-term adverse effects of melatonin treatment in children and adolescents: a systematic review and GRADE assessment. Händel, MN., Andersen, HK., Ussing, A., et al.[2023]

Transdermal delivery of melatonin (MEL) can effectively increase plasma MEL levels and improve sleep maintenance in healthy individuals, particularly during the latter part of an 8-hour sleep opportunity.

This method may offer advantages over traditional oral melatonin, especially for shift workers or those experiencing jet lag, by promoting better sleep during challenging circadian phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of transdermal melatonin delivery to improve sleep maintenance during daytime. Aeschbach, D., Lockyer, BJ., Dijk, DJ., et al.[2021]

In a 3-month study involving 22 women with moderate to severe skin aging, topical application of melatonin-based creams significantly reduced crow's feet wrinkles by 15% and improved skin tonicity by 30%.

The melatonin creams also led to a 59.5% reduction in skin dryness and a 26.5% improvement in surface microrelief, demonstrating their efficacy as an anti-aging treatment with good tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiaging efficacy of melatonin-based day and night creams: a randomized, split-face, assessor-blinded proof-of-concept trial. Milani, M., Sparavigna, A.[2022]

Melatonin (MLT) showed the highest permeation through skin and buccal tissues when formulated with Montanov® 68 (M68) and sodium carboxymethylcellulose (NaCMC), suggesting these vehicles could enhance its systemic effects.

For local action in the skin and buccal mucosa, M68, poloxamer 407 (P407), and Pluronic® lecithin organogel (PLO) are recommended, while oral adhesive paste Orabase® (OB) was found to be the least effective vehicle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin Delivery: Transdermal and Transbuccal Evaluation in Different Vehicles. Flo, A., Calpena, AC., Halbaut, L., et al.[2018]

Melatonin may improve sleep by correcting circadian phase abnormalities and has a modest direct sleep-inducing effect, particularly when taken during the day by younger individuals.

The effectiveness of melatonin is influenced by the dose, the type of subjects (like insomniacs or the elderly), and the timing of administration, suggesting that its mechanism of action involves specific receptors in the brain that help regulate the body's internal clock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep-promoting effects of melatonin: at what dose, in whom, under what conditions, and by what mechanisms? Sack, RL., Hughes, RJ., Edgar, DM., et al.[2022]

Ramelteon and agomelatine are melatonergic agonists that effectively improve sleep quality and duration in patients with insomnia and major depressive disorder, respectively, by targeting MT1 and MT2 receptors in the brain.

A slow-release formulation of melatonin, Circadin, has been shown to be effective for treating sleep disorders in the elderly, highlighting the importance of formulation in enhancing therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of melatonin agonists. Cardinali, DP., Pandi-Perumal, SR., Srinivasan, V., et al.[2019]

Melatonin significantly reduces the time it takes to fall asleep (by about 7 minutes) and increases total sleep time (by about 8 minutes) in patients with primary sleep disorders, based on a meta-analysis of 19 studies involving 1683 participants.

While the effects of melatonin on sleep quality are modest, it is considered a safer alternative to other insomnia medications due to its benign side-effect profile, making it a viable option for treating sleep issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis: melatonin for the treatment of primary sleep disorders. Ferracioli-Oda, E., Qawasmi, A., Bloch, MH.[2021]

A systematic review of 17 randomized controlled trials involving 651 participants found no evidence that exogenous melatonin effectively treats secondary sleep disorders or sleep disorders related to sleep restriction, such as jet lag and shift work disorder.

The review also indicated that melatonin is safe for short-term use (up to three months), showing no adverse effects in the studied populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. Buscemi, N., Vandermeer, B., Hooton, N., et al.[2018]

Melatonin shows potential as a treatment for sleep disorders related to melatonin deficiency, supported by basic research and initial clinical experiences.

However, more clinical studies are needed to confirm its effectiveness for other indications, as many findings from animal studies do not translate well to humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Melatonin: is there a rationale for the clinical use of this hormone in sleep therapy?]. Fauteck, JD.[2015]

Melatonin effectively phase shifts circadian rhythms, making it a useful treatment for sleep disorders related to circadian misalignment, such as jet lag and shift work.

In specific conditions like delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake disorder, melatonin has been shown to advance sleep onset and improve overall sleep quality compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of melatonin in the treatment of phase shift and sleep disorders. Skene, DJ., Lockley, SW., Arendt, J.[2019]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK605080/

Melatonin for the Treatment of Insomnia: A 2022 Update - NCBI Some studies reported improvement in sleep and quality of life outcomes with melatonin, and some studies reported no difference between patients who ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06768749/the-impact-of-melatonin-lotion-on-sleep-and-mental-health?state=CA&city=Redlands

The Impact of Melatonin Lotion on Sleep and Mental Health The purpose of this study is to examine the effect that melatonin lotion has on sleep quality, the nervous system, and mental health.

3. medrxiv.org medrxiv.org/content/10.1101/2023.10.16.23297058v1.full.pdf

Impact of an over-the-counter “sleep lotion” on salivary ... Our data show extremely high salivary melatonin levels in response to sleep lotion application, and it complements appeals for increased ...

4. withpower.com withpower.com/trial/phase-sleep-wake-disorders-1-2025-3f554

Melatonin Lotion for Sleep Disorders The purpose of this study is to examine the effect that melatonin lotion has on sleep quality, the nervous system, and mental health. Melatonin is a hormone ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11121188/

Clinical Studies Using Topical Melatonin - PMC This review focuses on the clinical studies in which melatonin was applied on the skin as a photoprotective, anti-aging, or hair growth-promoting agent.

6. mayoclinic.org mayoclinic.org/healthy-lifestyle/adult-health/expert-answers/melatonin-side-effects/faq-20057874

Melatonin side effects: What are the risks? Melatonin is generally safe for short-term use. Unlike with many sleep medications, with melatonin you are unlikely to become dependent on it.

7. sleepfoundation.org sleepfoundation.org/melatonin

Melatonin: Usage, Side Effects, and Safety Melatonin for Sleep Disorders. Melatonin supplements are likely to benefit people with sleep disorders that affect their circadian rhythms.

8. newsroom.heart.org newsroom.heart.org/news/long-term-use-of-melatonin-supplements-to-support-sleep-may-have-negative-health-effects

Long-term use of melatonin supplements to support sleep ... Melatonin supplements are promoted and marketed as a safe sleep aid; however, data demonstrating their long-term cardiovascular safety are ...

9. webmd.com webmd.com/vitamins/ai/ingredientmono-940/melatonin

Melatonin - Uses, Side Effects, and More Melatonin should only be used in children with a medical need, starting with the lowest dose of 0.5 mg. There isn't enough evidence to know if melatonin is safe ...