Drug Interactions, Kratom Guides

Kratom & Melatonin: How Do They Interact?

Does Kratom Interact With Melatonin?

Kratom and melatonin interact in two ways: agonistically and antagonistically. The former means they produce the same effects, and the latter has opposite effects. The interaction between these two compounds is mild to moderate in severity.

Kratom acts as a partial agonist at μ-opioid receptors, causing various effects like anxiolysis, euphoria, and improved mood [1]. On the other hand, melatonin helps regulate the body’s sleep-wake cycle [2]. The best-known purpose of melatonin is sleep. Thus, it may be considered a sedative.

There is a difference in the metabolism of these drugs. Kratom is mainly metabolized by CYP3A4. But, the metabolism of melatonin is through CYP1A2.

Kratom and melatonin interact with each other in the following ways:

Kratom Enhances the Effect of Melatonin (Agonistic Interaction)

When two drugs enhance the effect of each other, they are said to exhibit pharmacologic agonism.

Kratom acts as a calming agent and sleep-inducer when used in a high dose (6 – 12 g). Therefore, if a high amount of kratom is combined with melatonin, the final effect is enhanced sedation. The enhancement may not always be beneficial and could be too much.

Hypersomnolence will ensue as a combined effect of these drugs, leading to excessive sleepiness.

The induced hypersomnolence also may cause sleep apnea due to deep sedation. Sleep apnea is defined as the cessation of breathing while asleep.

Kratom Decreases the Effects of Melatonin & Vice-Versa (Antagonistic Interaction)

When two drugs together cause decreased effects on each other, they show pharmacologic antagonism.

Low doses of kratom (less than 5 g) promote concentration and wakefulness. If it’s combined with a sleep-inducing drug such as melatonin, there will be decreased effects due to opposite effects, thus showing antagonistic properties.

Kratom & Melatonin Interactions

Melatonin belongs to the acetamide class of hypnotics. Hypnotics are the drugs that induce sleep. The following drugs stimulate receptors similar to melatonin and interact with kratom:

  • Ramelteon
  • Tasimelteon
  • Agomelatine

Is It Safe To Take Kratom With Melatonin?

As mentioned in the paragraphs above, kratom with melatonin can either cause agonistic or antagonistic interaction, depending on the dose of kratom. Either interaction may not be optimal, but increased sedation can be dangerous if you’re not expecting it.

It’s best to talk to your doctor before combining them.

Kratom leaf and flower.

What Is Melatonin?

Endogenous melatonin is a hormone produced by the pineal gland. Melatonin comes from tryptophan. Tryptophan is converted to serotonin in ‘raphe nuclei’ present in the midbrain.

Some amount of serotonin makes its way to the pineal gland and is converted to melatonin in a light-dependent process. The conversion of serotonin to melatonin occurs in the suprachiasmatic nucleus, the coordinator of the body’s circadian rhythm. Melatonin production increases in the dark, inducing sleep and regulating the sleep-wake cycle [3].

Synthetic melatonin is not FDA-approved and is a dietary supplement rather than a drug [4]. It has a similar action to that of endogenous melatonin.

Melatonin Specifications & Details

Drug NameMelatonin
Trade NameCircadian, Sleynto
ClassificationAcetamide class of hypnotics
CYP metabolismCYP1A2
Interaction With KratomAgonistic or antagonistic
Risk Of InteractionMild

What Is Melatonin Used For?

Melatonin is used for the following purposes:

  • Primary insomnia
  • Age-related insomnia
  • Jet lag disorder
  • Shift work sleep disorder
  • Post-traumatic brain injury
  • Neurodegenerative disorders
  • Chronic fatigue syndrome
  • Winter depression
  • Tardive dyskinesia (side effect of antipsychotics)
  • Encephalopathy
  • Benzodiazepine withdrawal
  • Migraine headache
  • Acetaminophen overdose
  • Short bowel syndrome
  • Heat-stroke

Several types of research are ongoing for the following disorders:

  • Cancer
  • Cardiovascular disorders
  • Gastrointestinal conditions
  • Mental disorders
  • Pain Syndromes
  • Reproductive dysfunctions

What Is the Appropriate Dose of Melatonin?

The appropriate dose of synthetic melatonin is 5 to 10 mg per day, taken 2 hours before bedtime.

What Are the Side Effects of Melatonin?

An average dose is safe. Even more significant amounts don’t cause severe problems. Some common side effects include:

  • Drowsiness
  • Narcolepsy or daytime sleepiness
  • Headache
  • Nausea
  • Vomiting

What  Is Kratom?

Kratom is a south Asian evergreen tree. It is also known as Mitragyna speciosa. There are several alkaloids present in kratom leaves, the most important being mitragynine. Mitragynine and its metabolite 7-hydroxymitragynine are responsible for the major effects, including euphoria, anxiolysis, and sedation.

In low doses, kratom has an overall stimulatory action. But, in high doses, its actions are more aligned toward sedation. Both mitragynine and 7-hydroxymitragynine are agonists at μ-opioid receptors [5]. The analgesic effect of kratom is brought about by action on supraspinal μ and δ-opioid receptors. Its action on central opioid receptors

 brings about the psychoactive effects of kratom.

Cases of toxicity and death due to kratom have been reported in poly-drug exposure cases. Thus, before taking kratom with any other drug, you must talk to a specialist or a doctor.

What Is Kratom Used For?

Kratom is popular for its opiate-like effects and is chewed or brewed into a tea for its euphoriant and mood-enhancing effects. Historically, kratom has been used by the farmers of Southeast Asia to boost productivity and as a substitute for opium. Based on its mechanism of action, kratom may also help with the following:

What Is the Proper Dose of Kratom?

Before you start using kratom, you should buy a scale. You may purchase a small digital scale that tells you accurately the amount you should take. You can also opt for tinctures or capsules since both contain a pre-measured amount of kratom.

You want to start on the low end regardless of what you’re using kratom for. Use small doses (2-6 g) for energy and mood and larger doses (6-12 g) for pain, anxiety, and sleep. Work your way up only as needed. A dosage calculator can help you determine what you need.

Take a break every week to avoid building a tolerance. 

What Are the Side Effects of Kratom?

Side effects are not so common with regular doses of kratom. The more you take, the more likely you will experience the following side effects.

What Are the Different Strains of Kratom?

For simplicity, kratom has been classified into various strains based on the color of the mid-vein of the leaf. They are:

White Vein Kratom

White vein kratom is derived from young plants. These strains promote a healthier and happier disposition and improve focus and energy.

Red Vein Kratom

Red strains contain the highest amount of 7-hydroxymitragynine and provide effective pain relief and sedation. The effects of this strain are very close to that of typical opiates.

Green Vein Kratom

Green vein kratom strikes a perfect balance between acting as a stimulant and an analgesic. It has both white and red kratom properties and can even help you get comfortable in social meetings.

Yellow Vein Kratom

Yellow strains are often derived from green vein kratom, usually fermented. These strains create soothing effects similar to green kratom but are mellow and long-lasting.

Key Takeaways: Kratom & Melatonin

Kratom and melatonin interact, with kratom either enhancing melatonin’s sedating effects or canceling them out. Thus, it is best not to combine these drugs.

You should take these drugs at different times and pay careful attention to your kratom dosage.

As always, it’s best to follow the advice of your primary care physician before combining these two drugs.


  1. Singh, D., Narayanan, S., & Vicknasingam, B. (2016). Traditional and non-traditional uses of Mitragynine (Kratom): A survey of the literature. Brain Research Bulletin, 126, 41–46.
  2. Brown, G. M. (1994). Light, melatonin, and the sleep-wake cycle. Journal of Psychiatry and Neuroscience, 19(5), 345.
  3. Savage, R. A., Zafar, N., Yohannan, S., & Miller, J.-M. M. (2021). Melatonin. StatPearls.
  4. Abstract – Europe PMC. (n.d.). Retrieved May 3, 2022, from https://europepmc.org/article/nbk/nbk534823
  5. Kruegel, A. C., & Grundmann, O. (2018). The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse. Neuropharmacology, 134, 108–120.
  6. Langman, L. J., Betchel, L. K., Meier, B. M., & Holstege, C. (n.d.). Clinical Toxicology – ClinicalKey. Tietz textbook of clinical chemistry and molecular diagnostics, 41(26), 832-887

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