In-Depth Review of Melatonin &

The Science of Micro-Dosing It

Nootropics Information
Original post on https://nootro.info/melatonin

Summary: Melatonin is known for helping insomnia, is a powerful

antioxidant and anti-inflammatory, protects against neurodegenerative
diseases, stroke and brain trauma. At a micro dose of 300mcg, Melatonin is
gaining wide popularity and most healthy nootropic users are found to
include it in their evening stack.

Introduction

What is Melatonin?

Melatonin is a multitasking hormone produced by the brain’s pinecone-

shaped pineal gland. It plays several roles in the body, including helping to
regulate blood pressure, boost immune function, and manage cortisol levels.
But melatonin is probably best known for its soporific powers. Chief among
its responsibilities is regulating the body’s circadian rhythm so it knows
when to rest and when to wake up. That’s why melatonin is often referred to
as the body’s sleep hormone.
Benefits & Effects

Melatonin Regulates Circadian Rhythm and Enhances Sleep Quality

Melatonin increases the quality of sleep. The Circadian Rhythm influences the body’s
sleeping habits. Think of it as a built-in clock that controls our bodies processes 24 hours a
day. Scientists have observed that Melatonin normalizes the Circadian rhythm which can
sometimes become distorted due to modern lifestyle. [R]

Melatonin Alleviates Anxiety and Depression Symptoms

Conditions like depression and anxiety usually worsen by a disturbed, intermittent or a

lack of a sleeping pattern.
Having these disturbances regulated can alleviate the symptoms of these conditions, not
mainly offering a cure but by far offering an improvement in the standard of life. [R]

Melatonin is a Potent Antioxidant

Antioxidant enzymes roles within our bodies are to help clean the cells in our bodies and
filter our bloodstream from harmful cells. Melatonin increases the rate at which our body
produces these enzymes that would be naturally.

These molecules in question can also bond to what is called Reactive Oxygen Species
(ROS) & Reactive Nitrogen Species (NOS) which can decrease the level of damage each
of these can cause respectively.

The benefits directly from this are that Melatonin prevents any harm coming to your organ
systems or tissues. These advantages combined make Melatonin a very useful protectorate
within your body internally. These antioxidants can also have benefits for the most critical
organ in our body, our brain. [R]

Melatonin Supports BDNF

Nerve cells are also protected by the increase of these enzymes produced by Melatonin,
having a positive onward affect towards the spinal cord including white matter and optic
nerves. Its regeneration is down to something called the ‘Brain-Derived Neurotrophic
Factor’ (BDNF); in simple terms, this is a protein responsible for the nerves regeneration
and well-being within our brains. [R]

Melatonin Strengthens the Blood-Brain Barrier

Melatonin strengthens the ever significant barrier between the brain and our blood. If the
strength of this barrier were to deteriorate and for example leak, this can lead to cognitive
dysfunction (also known as brain fog) and could potentially result in future to conditions
such as Alzheimer’s. [R]

Melatonin is Neuroprotectant
In addition to defending against conditions such as Alzheimer’s development, Melatonin
can also aid as a coping mechanism for users who have Parkinson’s.

Melatonin in tests was shown to prohibit cell death and brain damage, sometimes as a
cause of a leaky blood-brain barrier.

Referring back to the regulation of sleep, this can also help people who, however, there is
currently no proof it helps with any of the other side-effects of the condition. [R]

Melatonin Replaces Benzos for Sleep

Its widely known that benzos usually depress the natural levels of melatonin within our
bodies.

Our recommendation is if you are using one of these drugs for sleep, it would be wise to
start using melatonin instead. Moreover, start weaning yourself off the benzos. [R]

Mechanism of Action

Melatonin works together with your body’s circadian rhythm.

In simple terms, the circadian rhythm is your body’s internal clock. It lets you know when
it’s time to sleep, wake and eat.

Melatonin also helps regulate your body temperature, blood pressure and hormone levels
[R]

Melatonin levels start to rise in your body when it is dark outside, signaling to your body
that it is time to sleep [R]

It also binds to receptors in the body and can help you relax. For instance, melatonin binds
to receptors in the brain to help reduce nerve activity. In the eyes, it can help reduce
dopamine levels, a hormone that enables you to stay awake. [R] [R]
Melatonin is controlled by light and darkness. When we’re awake and the sun’s out, we
don’t produce any melatonin. But at night, the onset of darkness signals to our pineal
gland to release melatonin into the bloodstream.

Your melatonin levels begin to increase about two hours before you go to bed, typically
around 9 p.m., and peak about five hours later. As melatonin levels rise throughout our
body — it’s found in a variety of our organs, including our eyes, bones, ovaries/testes and
gut — our body knows it’s time to drift off to Slumber Town. [R]
Melatonin exerts many of its effects vicariously through melatonin receptors, similar to
how insulin affects the insulin receptor. The melatonin receptors are named MT1 and
MT2, and are G-protein coupled receptors (GPRCs) coupled to Gi proteins (a heterotrimer
of α, β, and γ that dissociates into α and βγ when the receptor is activated). These two
receptors are quite different from each other, as they structure pharmacological
characteristics and chromosomal location, yet both have high affinity for melatonin. A
third ‘receptor’ exists, known as MT3, but it is not a GPRC like MT1/2. Due to the
cytoplasmic protein quinone reductase II having the same melatonin binding properties as
‘MT3’, and deletion of quinone reductase II causing ‘MT3’ to disappear, MT3 may just be
quinone reductase II.
Examine.com

Dosage

You’ll see melatonin recommended in a range of doses, starting at around 0.5 milligrams
up to 10 milligrams for people with sleep disorders, with the most common dosage being
around 3 milligrams.

But even this is probably way more than you need.

You’re better off basing your melatonin intake on increments that mirror how much
melatonin our bodies produce at night. According to clinical studies, the optimal dose is
0.3 milligrams. [R]
Melatonin Overdose
Even though the overwhelming verdict is that melatonin is safe, you can have too much of
a good thing. Overdosing on melatonin has not been shown to be fatal, but it can produce
the aforementioned side effects, like dizziness and grogginess. In one known case, after
taking 24 milligrams of melatonin, a man became lethargic and disoriented, but returned
to normal and did not continue to have issues once he lowered his dosage.

In addition, large doses could potentially cause amenorrhea (skipped periods) in women,
due to it suppressing gonadotropin-releasing hormones, but if you can easily remedy this
side effect by simply stopping your melatonin supplements. [R]
Side Effects

Overall, the side effects of melatonin are pretty toothless. Unlike other sleep aids, like
benzodiazepines and z-drugs (think: Ambien and Lunesta), melatonin does not cause
dependence or withdrawal symptoms. [R]

The most commonly reported melatonin side effect is daytime drowsiness. Other
melatonin side effects include nausea, headache, and dizziness. [R]

If course, if you’re taking other medications, you should check with your physician before
popping a melatonin. It has been known to interact with some antidepressants, blood
pressure medications, sedatives, antibiotics, and antihistamines. [R]
Up to 240 mg and 500 mg oral and intravenous injections of melatonin taken acutely is
not associated with any toxicological effects. [R]
A handful of large scale, 6–12 month studies, suggest continued administration of
melatonin does not result in tolerance.
Examine.com

Conclusion
There’s great amount of evidence suggesting as well as proving the benefits of
supplementing with melatonin whether for sleep purposes or overall general health.

Best practices when supplementing with melatonin for long-term benefits is to take a
microdose of 300 mcg on daily basis before bedtime.

This microdose will serve a host of benefits most noteworthy of which is antioxidation
and supporting mitochondria and antioxidation.

Many Nootropic focused companies are now aware of this and its benefits and so finally
starting to see products in microdoses such as Nootropic Depot’s, which I have personally
been using for a long time. Prior to which, I tried a couple of different products at the
doses of 3 mg and it made me very heavy and groggy for a long time.
User Experience

First User Experience

A reddit user documented his experience after 2 years of using microdose of melatonin as
recommended alongside magnesium, and his realization of how beneficial it had been
working for him after he stopped.
I took Magnesium Citrate (200–400mg) and Melatonin (0.3mg) both every night for over
2 years and thought they didn’t make much difference in my sleep. It turned out to be very
wrong — I now remember how poor my sleep was 3 years ago, before starting to take
them. I wake up from the slightest noise and can’t go back to sleep for many hours
afterwards — even if I wake up after only 4 hours, I would need to wait 3 hours before I
fall asleep again, without Magnesium and Melatonin. This has been this way since I was a
child. I find Melatonin is better for actually falling asleep initially, while Magnesium is
better for maintaining quality sleep afterwards.

u/SuperAgonist on Nootropics subreddit

Second User Experience

I have learned the same lesson with melatonin in that less is more. I took 30 mg one
evening and had very unsettling and vivid dreams. Not restful at all. I find 5 mg timed
release works well. If you are interested in another natural sleep / relaxation aid, I have
had success with Red Bali Kratom.

u/beesler70
Further & External Readings

For more insight about melatonin and its benefits from a nootropic perspective, check out
our blog post Melatonin For Sleep: How Effective Is It? as well as the following articles:

• Melatonin in-depth review by David Tomen of Nootropics Expert

• Four Surprising Reasons Melatonin is More Than a Sleep Aid by Mansal Denton, the
editor of Nootropedia

• Melatonin for Sleep: Everything You Need to Know About the Snooze-Inducing
Hormone by Mary Squillace for The Bulletproof Blog

If you still have questions, please visit our Ultimate Frequently Asked Questions page.

Nootropics Information