A new non-melatonin sleep aid was found in a peer reviewed study to significantly improve sleep quality and reduce stress. The results found that the particular balance of ingredients in MDsleep + hemp produced a better night’s rest than a formula with higher THC and less botanical ingredients. A balanced brain arrives at sleep while a stressed and unbalanced brain will race at night. A balanced sleep supplement helps your brain return to its resting state. The problem is that long-term use of melatonin can create imbalances in your brain, making it harder to sleep over time. MDsleep + hemp offers the delicate balance between amino acids, botanicals, and full spectrum hemp to return your brain to a resting state.
MDsleep + hemp Study Summary
A large, double-blind, placebo-controlled clinical trial led by Radical Science and major research institutions found that MDSleep, a natural, non-melatonin sleep supplement called MDsleep + hemp by MDbio – The Doctors Brand™, significantly improved sleep quality, reduced anxiety and stress, and enhanced overall well-being compared to placebo.
The study, one of the largest ever for a sleep supplement, included 620 participants and tested two formulations: one with lower THC and higher amounts of GABA, hops oil, and valerian oil, and another with higher THC and lower amounts of these botanicals.
The formulation with lower THC and higher botanicals showed statistically significant improvements in sleep quality, anxiety, stress, and well-being—with no serious side effects—while the higher THC version did not show significant benefits. This research highlights the effectiveness of combining cannabinoids with botanical ingredients for sleep and well-being, providing a clinically proven, non-melatonin alternative for those seeking better sleep and mental health support. The full peer-reviewed study was published in the journal Nutrients.
Can a Multi-Ingredient Sleep Aid Really Help You Sleep Better? Here’s What a New Study Found
Getting a good night’s sleep can feel impossible for many of us. Whether it’s stress, anxiety, or just tossing and turning, millions struggle to get enough rest. But what if a new kind of sleep supplement—a blend of low-dose THC, CBD, botanicals, and amino acids—could help? A recent clinical study set out to find the answer.
What Was This Sleep Study About?
Researchers wanted to know if a combination of plant-based ingredients and cannabinoids (like THC and CBD) could improve sleep better than a placebo (a fake pill). Over 600 adults who wanted to sleep better took part in this 4-week study. They were randomly given one of three options:
- Formula A – MDsleep + hemp: Low dose THC (0.35 mg) + higher levels of hops oil, valerian oil, GABA, L-theanine, CBD, and CBN
- Formula B – Higher THC: Higher dose THC (0.85 mg) + lower levels of hops oil, valerian oil, GABA, but same CBD, CBN, and L-theanine
- Placebo: No active ingredients
Everyone took their assigned softgel before bed for four weeks. The researchers tracked their sleep disturbance, anxiety, stress, pain, and overall well-being through weekly online surveys.
Key MDsleep Study Findings?
- Formula A – MDsleep + hemp (low THC, more botanicals) worked better than placebo for improving sleep, reducing anxiety and stress, and boosting well-being.
- Formula B – Higher THC with Low Botanicals did not show significant improvement over placebo for any outcome. This shows that the balance between THC with key amino acids and botanicals is essential to arriving at sleep. THC gummies and products alone may not produce the sleep inducing effects.
- Side effects were mild between all groups.
Why Did MDsleep’s Formula Work?
The key seems to be the combination of a low dose of THC with higher amounts of botanicals like hops oil, valerian oil, and GABA. These ingredients may work together (a “synergy” or “entourage effect”) to help people fall asleep, stay asleep, and feel better overall—without needing a high dose of THC, which can cause unwanted side effects.
The combination of sleep aids is what makes the formula ingenious. This formulation of lower THC and higher select botanicals was clinically shown to:
- Improve sleep disturbance (sleep quality)
- Aspects that include:
- Enhance sleep onset
- Support restful and healthy sleep
- Improve feeling well rested upon waking
- Reduce feelings of anxiety and stress
- Promote well-being
MDsleep + hemp Study Results
| Group | Sleep Improvement vs Placebo | Anxiety/Stress Reduction | Well-being Boost | Side Effects |
|
Sleep A MDsleep |
Yes (Significant) | Yes (Significant) | Yes | Mild/Moderate |
| Sleep B | No (Not Significant) | No | No | Mild/Moderate |
| Placebo | No | No | No | Mild/Moderate |
What About Safety?
No serious side effects were reported. Most people tolerated the supplements well, with only mild or moderate issues, similar to the placebo group.
Side Effects by Study Formulas
| Side Effect | Sleep A (Low THC + Botanicals) | Sleep B (Higher THC) | Placebo |
| Drowsiness | 5.90% | 8.30% | 3.60% |
| Dry Mouth | 2.10% | 3.60% | 1.80% |
| Headache | 2.10% | 1.80% | 1.20% |
| Dizziness | 1.20% | 2.10% | 0.90% |
| Nausea | 1.50% | 1.20% | 0.60% |
| Fatigue | 1.80% | 2.10% | 1.20% |
| Anxiety | 0.90% | 1.50% | 0.60% |
| Any Side Effect | 12.40% | 15.70% | 9.90% |
Key Points on Safety:
- Most side effects were mild, none were severe.
- The most common side effect was drowsiness.
- Side effects were slightly more common in both active supplement groups compared to placebo, especially in the higher THC group (Sleep B).
- No serious side effects were reported.
These percentages are based on the proportion of participants in each group who reported each side effect at any time during the 4-week study.
If you’re seeking a better night’s sleep, this study suggests that a multi-ingredient supplement with low-dose THC and higher levels of sleep-supporting botanicals could help—not just with sleep, but with anxiety, stress, and overall well-being. However, always talk to your healthcare provider before starting any new supplement, especially if you take other medications or have health conditions.
Discover MDbio’s full line of +hemp products.
Reference: Kolobaric, A., et al. “Comparative Effects of Two Multi-Ingredient Supplements on Sleep Relative to Placebo: A Randomized, Double-Blind, Placebo-Controlled Trial.” Nutrients, 2023.
What Is a Non Melatonin Sleep Aid?
Non melatonin sleep aids provide options for people who cannot or prefer not to use melatonin. These products use different ingredients and target various aspects of sleep, such as relaxation, anxiety, and nervous system support.
A non melatonin sleep aid is any supplement or medication intended to support sleep that does not contain melatonin as an active ingredient. These products may be herbal, mineral, or synthetic and are often chosen by individuals sensitive to melatonin or who experience side effects like vivid dreams.
Common examples include valerian root, magnesium, and L-theanine. Herbal blends are also widely available. Some over-the-counter medications for sleep contain antihistamines or herbal extracts instead of melatonin.
These sleep aids can be purchased as tablets, capsules, powders, or teas. Many are available without a prescription and are marketed for short-term or occasional use. People seeking alternatives to melatonin often turn to these products for milder or different effects.
Comparison With Melatonin-Based Products
Melatonin-based products deliver a synthetic or natural version of the sleep hormone melatonin to promote sleep onset. In contrast, non melatonin sleep aids do not affect melatonin levels directly. Instead, they may target calming neurotransmitters or help relax muscles and nervous tension.
While melatonin supplements typically work by influencing the body’s circadian rhythm, non melatonin options may have broader or different mechanisms. For example, GABA and L-theanine encourage relaxation by impacting brain chemicals related to stress and calmness.
The table below highlights key differences:
| Feature | Melatonin-Based | Non Melatonin Sleep Aids |
| Main Action | Regulates sleep-wake cycle | Calms body/brain, reduces anxiety |
| Typical Ingredients | Melatonin | Magnesium, valerian, L-theanine, GABA |
| Common Side Effects | Vivid dreams, grogginess | Mild stomach upset, rarely drowsiness |
Common Uses and Benefits
Non melatonin sleep aids are used by adults seeking help with falling or staying asleep, especially those who cannot take melatonin. These include people on certain medications or those with sensitivities to hormonal supplements.
Individuals often report benefits like reduced sleep latency, milder side effect profiles, and improved relaxation before bed. Supplements such as valerian root, magnesium, and herbal mixtures offer calming effects without altering hormonal balance.
Some products in this category appeal to people who want non-habit forming options. They are usually marketed as safe for short-term or occasional use, especially for temporary insomnia related to stress or lifestyle changes. Natural blends and minerals are popular among those who prefer holistic remedies or have specific health considerations.
Types of Non Melatonin Sleep Aids
Individuals seeking alternatives to melatonin for sleep support often turn to herbal or nutritional supplements, as well as over-the-counter medications. Each type works through different mechanisms and carries its own advantages and considerations.
Non Melatonin Herbal Supplements
Herbal sleep aids are popular for their natural origins and long history of use. Valerian root is among the most studied; it may help some people fall asleep faster, though results vary.
Passionflower and chamomile are also common. They are often taken as teas or capsules and are considered calming, especially in mild sleep difficulties. Lemon balm is another herb that is sometimes blended with others to promote relaxation.
While these supplements are available without a prescription, their effects can be subtle and gradual. They are not regulated as strictly as medications, and quality can differ by brand. Side effects are generally mild but can include stomach upset or headache. It’s important to choose products from reputable manufacturers.
Non Melatonin Nutritional Supplements
Certain vitamins and minerals play a role in sleep quality. Magnesium supports relaxation and healthy sleep cycles, with some evidence suggesting it may help people who have low levels fall asleep more easily.
Glycine, an amino acid, is another supplement often used for sleep support. Small studies suggest it might help people feel more refreshed in the morning by supporting restful sleep. L-Theanine, found naturally in tea leaves, promotes calmness and may reduce the time it takes to fall asleep.
Other ingredients sometimes included in nutritional sleep aids are GABA (gamma-aminobutyric acid) and reishi mushroom. These can be used alone or as part of blended formulations. Nutritional supplements are generally considered safe, but it is important to use appropriate dosages and consult with a healthcare provider if unsure.
Non Melatonin Over-the-Counter Medications
Several non-prescription medications for sleep do not contain melatonin. The most common are sedating antihistamines such as diphenhydramine (Benadryl) and doxylamine (Unisom).
These medications help induce drowsiness and are primarily intended for short-term use. Side effects may include next-day drowsiness, dry mouth, or confusion, especially in older adults. They are not recommended for regular or long-term use because tolerance can develop quickly.
Over-the-counter sleep medications are easy to find and inexpensive, but they should be used cautiously. Individuals with chronic sleep problems should speak with a healthcare professional before using these products.
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Non Melatonin Herbal Alternatives for Sleep Chart
There are several herbal supplements people use as non-melatonin sleep aids. Each option has different active components and may suit different needs or preferences.
Common Herbal Sleep Aids
| Herb | Typical Form | Possible Benefits | Notes |
| Valerian Root | Tea, capsule, extract | May shorten time to fall asleep | Earthy flavor, mild odor |
| Chamomile | Tea, capsule | May promote relaxation | Common in nighttime teas |
| Lavender | Tea, oil, supplement | May improve sleep quality | Used aromatically or orally |
| Passionflower | Tea, extract, capsule | May calm the mind | Subtle floral taste |
| California Poppy | Tea, tincture, capsule | May reduce sleep latency | Mildly sedating effect |
Some users choose valerian root for its potential to help them fall asleep slightly faster. Others prefer chamomile for its gentle calming effects and long-standing use in teas.
Lavender is often inhaled as an essential oil but can also be found in tea or supplement form. Passionflower and California poppy are less common but are included in some sleep blends for their soothing properties.
It is important to note that the scientific evidence for these herbs varies, and effects may differ between individuals. Consulting a healthcare professional before starting any new herbal regimen is advised.
Safety and Side Effects
Non-melatonin sleep aids can cause side effects that vary based on the specific substance used. Certain products may also pose risks for specific groups or interact with other medications.
Possible Adverse Reactions
Common non-melatonin sleep aids such as diphenhydramine and doxylamine succinate often cause drowsiness, dry mouth, constipation, and dizziness. Many people experience next-day grogginess or a “hangover effect,” making daytime activities challenging.
Some herbal aids like valerian can trigger mild reactions, including headaches or stomach upset. In rare cases, paradoxical effects like increased wakefulness may occur.
Chronic use, especially of antihistamine-based aids, has been linked to confusion and memory issues in older adults. Side effects are more likely or severe at higher doses or with repeated use.
Consumers should monitor for new or worsening symptoms and seek medical advice if adverse effects persist.
Drug Interactions
Non-melatonin sleep aids can interact with a range of medications. Antihistamine-based aids may enhance the sedative effect when combined with alcohol, opioids, or other central nervous system depressants.
Mixing these with antidepressants, antipsychotics, or muscle relaxants can increase the risk of confusion, excessive sedation, or respiratory depression.
Valerian may interact with medications that affect liver enzymes, including some antifungal drugs and anticonvulsants.
Users taking prescription medicine should check with a doctor or pharmacist before starting non-melatonin sleep aids.
Below is a table summarizing common interactions:
| Sleep Aid Type | Risky Combinations |
| Antihistamines | Alcohol, benzodiazepines, opioids, antidepressants |
| Valerian | Anticonvulsants, antifungals, barbiturates |
Suitability for Different Age Groups
Older adults face an increased risk of confusion, unsteadiness, and falls when using antihistamine-based aids. These products are generally not recommended for those aged 65 or older.
Children should not use over-the-counter non-melatonin sleep aids unless directed by a healthcare provider, as side effects are less predictable in younger individuals.
Pregnant and breastfeeding women should avoid most non-melatonin sleep products due to limited safety data.
Individuals with chronic illnesses, such as glaucoma, enlarged prostate, or heart disease, should use caution, as certain ingredients can worsen these conditions.
Medical advice should be sought before use in any vulnerable population.
Frequently Asked Questions
Several non-melatonin sleep aids are available that include natural remedies, over-the-counter medications, and behavioral strategies. Safety, effectiveness, and age-appropriateness vary depending on individual needs and possible medical conditions.
What are effective natural alternatives to melatonin for improving sleep?
Herbal options such as valerian root, chamomile, and passionflower have research supporting their use for mild sleep disturbances. Magnesium and glycine, which are minerals and amino acids already present in human diets, may also promote relaxation and sleep quality. These options are often considered for those who prefer to avoid hormones like melatonin.
What is the most potent over-the-counter sleep aid available?
Diphenhydramine and doxylamine succinate are strong antihistamines commonly found in non-prescription sleep aids. These drugs can cause drowsiness and are widely used for short-term relief of insomnia. However, side effects such as dry mouth, grogginess, and next-day sedation are common, so they are not generally recommended for long-term use.
How can I choose a safe sleep aid for my child that doesn’t contain melatonin?
Parents should consult with a pediatrician before giving any sleep aid to a child. Options may include non-melatonin herbal teas such as chamomile, or focusing on bedtime routines and behavioral changes. Over-the-counter medications are generally not recommended for children unless directed by a healthcare professional.
Are there any sleep aids that are particularly suitable for adults suffering from anxiety?
Herbal supplements like valerian root and passionflower are commonly chosen by adults with mild anxiety-related sleep problems. Prescription medications for anxiety and sleep should only be used under medical supervision. Cognitive behavioral therapy for insomnia (CBT-I) is also highly recommended for adults with anxiety and sleep issues.
Which gummy sleep aids are recommended for those who prefer not to use melatonin?
Gummies containing ingredients such as L-theanine, valerian, or magnesium are available as alternatives. It is essential to check ingredient lists for other sedatives or additives. These gummies can offer a convenient form, but users should monitor effects and consult a healthcare provider if unsure.
What non-pharmacological methods are proven to help with sleep besides supplements and medication?
Consistent sleep schedules, reduced screen time before bed, and creating a dark, quiet sleeping environment are all effective methods. Cognitive behavioral therapy for insomnia (CBT-I) has strong evidence for improving sleep without drugs. Relaxation techniques such as deep breathing and progressive muscle relaxation have also demonstrated benefits.
Kia Michel, MD
Physician
Kia Michel, MD is an urologist and staff surgeon at Cedars-Sanai Medical Center in Los Angeles. As a founding member of Comprehensive Urology in Beverly Hills, he believes in treating all aspects of a patient’s wellbeing in order to achieve optimal health. After 25 years in private practice, Dr. Michel believes that a good night’s sleep is essential to maintaining your health, which inspired him to co-create the MDsleep community and the Sleep Doctors Blog.
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List of References
- AASM Sleep Prioritization Survey: This survey by the American Academy of Sleep Medicine examines the use of melatonin among the public. It reveals trends and insights into how melatonin influences sleep patterns. For more information, visit AASM Sleep Prioritization Survey, Melatonin Use.
- Melatonin Overview: The A.D.A.M. Medical Encyclopedia provides a detailed entry on melatonin, discussing its role as a natural hormone and its applications in treating sleep disorders. More details can be found at Melatonin – MedlinePlus.