Melatonin Stops Working: Causes & Solutions

Melatonin is an endogenous hormone produced by the pineal gland that helps regulate the circadian rhythm.

At night, melatonin levels increase (100-300 ng/mL) – and this serves as a physiological signal that it’s time for sleep, and thus we become drowsy/sedated – and inevitably fall asleep.

For a variety of reasons, many people decide to supplement with exogenous melatonin.  Reasons for melatonin supplementation include (but are not limited to):

  • Circadian rhythm disorders (such as “free running” rhythms among blind persons)
  • Primary insomnia (difficulty falling asleep)
  • Maintenance insomnia (some people find it useful)
  • Jet lag (this typically doesn’t require ongoing supplementation)

Doesn’t melatonin stop working because of tolerance?

Many people assume that you can build physiological “tolerance” to melatonin supplementation as a result of regular (nightly) long-term (e.g. months, years, etc.) use.

Commonly purported mechanisms for said physiological tolerance to melatonin include:

  • Desensitization of melatonin receptors (CNS & PNS)
  • Reorganization of melatonin receptors (CNS & PNS)
  • Decrease endogenous production of melatonin
  • Change in rate of hepatic melatonin metabolism (CYP1A2)
  • Change in rate of renal melatonin excretion
  • Altered distribution & deposition of melatonin in the body (e.g. accumulation in adipose tissue)

Despite the fact that many people (including melatonin experts like Dr. Richard Wurtman) believe melatonin tolerance occurs – there’s ZERO actual evidence that tolerance develops.

Read: Melatonin tolerance.

I do think that “partial tolerance” could develop – but there’s zero evidence that complete tolerance occurs wherein users need to continue “upping the dose” to get the same therapeutic effect.

In fact, many melatonin users actually benefit more from taking smaller doses over time.

For example: Someone will start with a large dose, find that it works well but causes problems after a few weeks – then switch to a really small dose (e.g. 0.3 mg) and find that it works “indefinitely.”

Why melatonin stops working over time (Causes & Solutions)

There are a variety of reasons as to why “melatonin” supplementation may stop working (i.e. providing therapeutic benefit) over time. Included below are my hypothesized reasons.

Keep in mind that reasons melatonin stops working are subject to significant interindividual variation.  The following are reasons I suspect melatonin “stops working” (in those who notice loss of effect).

Genetically-mediated CYP1A2 expression

Melatonin is metabolized almost exclusively by CYP1A2 enzymes in the liver.

Gene expression determines how efficient your CYP1A2 enzyme will be at metabolizing melatonin.  Metabolism of CYP1A2 can be: rapid/fast vs. poor/slow.

  • Fast CYP1A2 metabolizers: If you’re a rapid CYP1A2 metabolizer, you’ll metabolize melatonin efficiently – such that it won’t linger in your system.
  • Poor CYP1A2 metabolizers: If you are a poor CYP1A2 metabolizer, you won’t metabolize melatonin as efficiently as others.

Braam et al. (2010): “We hypothesize that loss of response to melatonin treatment can be caused by slow metabolism of exogenous melatonin.” (R)

What happens in poor CYP1A2 metabolizers that causes melatonin to stop working?

Though not scientifically confirmed, something like the following sequence of events is likely:

  1. Person uses melatonin at a normal or high dose: This would be a dosage above 300 mcg (0.3 mg). For example, someone might start taking 3 mg, 5 mg, or 10 mg.
  2. Melatonin works well for ~4 weeks: During this time, melatonin is accumulating in the body due to inefficient metabolism.
  3. Melatonin loses its effect: Loss of effect is likely due to melatonin accumulation to such high levels in poor metabolizers, that it dysregulates the circadian rhythm (e.g. levels are high when they should be low – altering innate physiological rhythms).
  4. Sleep eventually worsens (relative to before melatonin was even used): This is because the circadian rhythm is now fully dysregulated. Eventually the dysregulation will peak and if melatonin is continued at too high of a dose.

Solution: Stop melatonin “cold turkey” (4+ weeks) & restart at tiny dose (0.1-0.3 mg)

If you took melatonin for 4-8 weeks and noticed it’s no longer helping or that it’s worsening your sleep and/or functioning – the solution is to stop melatonin for at least 4 weeks.

Why 4 weeks? In normal metabolizers – melatonin stays in the body for about ~9.16 hours after use (based on a ~40 minute half life).

In slow metabolizers – the duration for which melatonin stays in circulation is likely much longer.

Giving your body ~4 weeks of ZERO melatonin supplementation guarantees that all exogenous melatonin stores will be eliminated (my guess is it’ll be fully gone in less than one week).

The main reason to wait around 4 weeks though isn’t to ensure melatonin is “out of your system”… it’s so that your body can recalibrate its circadian rhythm without exogenous melatonin.

Next, assuming you legitimately benefit from melatonin, reinstate supplementation at a much lower dose (0.1 mg to 0.3 mg).

Stay with the smallest possible dose to get an effect.  I’d say the maximum dose for poor CYP1A2 metabolizers should be around 0.5 mg – lower is better.

Can melatonin stop working in rapid metabolizers? Possibly, but usually not due to genetically-mediated CYP1A2 expression.

Addition/subtraction of other substances (OR altering their dosages)

Adding OR subtracting (i.e. removing) substances from your routine or “stack” could impact how well melatonin works.

The effect here should be relatively obvious – and most notable if the substances: modify or interact with, one or more of the following:

  • CYP1A2 enzymes (inducers vs. inhibitors)
  • Melatonin receptors
  • Endogenous melatonin production
  • Any aspect(s) of melatonin pharmacokinetics
  • Circadian rhythms (e.g. caffeine at night)

For example, if you started smoking cigarettes (which have tobacco), this can significantly induce CYP1A2 enzymes (or ramp up their activity such that melatonin is metabolized significantly faster than if you never smoked).

In the aforementioned case, melatonin would still work – but you might need an even higher dose for sleep maintenance because it’s being metabolized much quicker from the cigarette-mediated CYP1A2 induction.

(Note: Vaping doesn’t have the same effect because most vaping products don’t contain tobacco).

Conversely, if you recently stopped smoking cigarettes, your CYP1A2 enzyme function will decrease relative to when you smoked – and thus you’ll metabolize melatonin at a slower rate such that you may need to decrease your melatonin dosage such as to not dysregulate your circadian rhythm.

If you take any substances (dietary supplements, medications, recreational drugs, legal drugs, illicit drugs, etc.) – check whether they interact with the CYP1A2 enzyme.

Inducers of CYP1A2 will increase its activity and speed up melatonin clearance whereas inhibitors of CYP1A2 will decrease its activity and slow melatonin clearance.

Also remember that if you adjust (e.g. increase or decrease) the dosage of a substance you’re taking that interacts with CYP1A2 – the degree of CYP1A2 induction or inhibition will increase, respectively.

Although the most common way other substances you use will affect melatonin’s effect will be via CYP1A2 metabolism, they could also: (1) enhance OR (2) counteract – some of its actions in the CNS/PNS.

Solution: Be mindful of substance additions/subtractions AND dosing adjustments – these can impact the efficacy of melatonin.  To get melatonin “working” again, you may need to tweak its dosage (increase or decrease) OR simply modify your “stack” to what it was before the melatonin stopped working.

Switching suppliers OR poor quality control (from current supplier)

A really obvious potential reason that melatonin can stop working is because you switched suppliers/vendors (i.e. bought melatonin from a different company than your “usual”).

Why would this cause melatonin to stop working?

  • Even if the dosage listed is identical to your old melatonin supplier, the actual melatonin content within capsules/tablets might differ significantly (both from the listing and your old supplier)
  • Other psychoactive ingredients may be present (even if they aren’t listed). (Examples: B vitamins; 5-HTP/serotonin; theanine; etc.)

Is this really true, or am I just making up a hypothetical? Well, it seems to be true – at least in Canada.

Erland & Saxena (2017): Analyzed 31 OTC melatonin supplements in Canada with LC/MS and found: (R)

  • Melatonin content did NOT meet label within 10% of margin of the label claim in more than 71% of supplements (i.e. over 22 supplements of the 31 tested weren’t even close to containing the listed amount of melatonin).
  • 26% of melatonin supplements contained serotonin (i.e. 5-HT) (despite this not being listed as an ingredient).
  • Melatonin content ranged from -83% to +478% of the labeled content.
  • Lot-to-lot variability for a specific melatonin product from the same manufacturer varied by as much as 465% in some cases.

What can we take away from this study? Melatonin supplements (in Canada) typically do not contain the amount of melatonin listed (most aren’t even within 10% of listing dosage) – and some contain added ingredients like serotonin.

The variation is so significant, that if we bought melatonin listed at “5 mg” – its actual contents could be 0.85 mg (low end) or 23.9 mg (high end).

What about if you never switched to a different melatonin supplier and melatonin stopped working?  It could have to do with subpar or downright bad quality control.

  • Lot-to-lot (i.e. batch) variability for specific melatonin products (made by the same company) was as high as 465% (according to Erland & Saxena).
  • This means that if you bought a “5 mg” melatonin capsule – it might actually contain 23.25 mg of melatonin (way more than you intended to take).
  • (I’m just guessing here, but I’d go as far as to speculate that there might be intra-lot variability such that pills even within the same bottle could vary significantly in melatonin content).

Note: It is unclear as to whether Erland & Saxena chose products at random, chose popular melatonin supplements, and performed LC/MS effectively. It’s also unknown as to if results would’ve been similar with melatonin products in the United States.

Solution: Switch back to old supplier (if you changed) OR find a supplier with high quality control (e.g. Nootropics Depot).

Obviously if one specific melatonin product worked well for you – and you switched to a different one… and then melatonin “stopped working” – try switching back to the old product and see if it becomes effective again.

If you’ve been using melatonin from a company with poor quality control, consider finding melatonin from a company with USP cerification, ranked highly on Labdoor, or go with Nootropics Depot (a company that tests every single batch for precision… unfortunately for some, they only sell physiologic doses of 0.3 mg).

Switching melatonin formats (immediate-release vs. extended-release)

If you switched melatonin products recently (either from immediate-release to extended-release OR from one extended-release product to another) – and melatonin suddenly “stopped working” (i.e. providing benefit), the format switch may have been the reason for loss of effect.

Melatonin is manufactured in both (1) immediate-release (instant-release, fast-release, etc.) AND (2) extended-release (prolonged-release, timed-release, etc.) formats.

  • Immediate-release: Delivers full dose of melatonin “all-at-once.” Generally effective for sleep induction. Can be effective for sleep maintenance at higher doses.
  • Extended-release: Delivers full dose of melatonin over a specified period (e.g. 1 mg over 6 hours). Effective for sleep induction and sleep maintenance – even at low doses.

What happens if you switch melatonin formats?

Different formats exhibit discrepancies in: (1) melatonin release rate; (2) magnitude and duration of melatonin receptor saturation; (3) melatonin elimination rate.

Certain individuals may respond suboptimally or poorly to a change in melatonin format because the new format is altering physiology differently (e.g. over a different timespan, more/less significantly at specific time points, etc.) – than the old format.

Melatonin has a half-life of ~40 minutes.  Assuming you take immediate-release melatonin at a dosage of 10 mg, the full 10 mg will be “out of your system” in less than 4 hours on average (~3.7 hours) – assuming normative hepatic metabolism and function.

With immediate-release melatonin, plasma/neural melatonin concentrations exhibit an inverted-V type pattern – as evidenced by a rapid incline, large peak, and then a rapid decline.

Melatonin receptors end up significantly more saturated from immediate-release melatonin (albeit for a much shorter duration) relative to extended-release melatonin (assuming dosages are identical).

Immediate-release melatonin formats alter physiology most significantly within the first 40 minutes after administration – and thereafter physiologic impact rapidly diminishes.

With extended-release melatonin, plasma/neural melatonin concentrations exhibit a tabletop-like pattern – as evidenced by: a slight increase to peak, maintenance of peak levels for ~5-6 hours, and slight decrease to baseline.

Extended-release melatonin formats alter physiology over a specified time-release window (a popular time-release window is ~6 hours).

Melatonin receptors do NOT end up as saturated at any given time point from extended-release melatonin relative to immediate-release melatonin – assuming equipotent dosages.

Why? Because peak concentrations from extended-release formats do not reach the same threshold as immediate-release.

However, extended-release melatonin saturates melatonin receptors for a longer total duration than immediate-release melatonin.

Switching Formats (What to Know)

  • Immediate-release to extended-release: Switching from stronger magnitude of effect over shorter duration (inverted-V concentrations) to less significant magnitude of effect over prolonged duration (even-keel concentrations).
  • Extended-release to immediate-release: Switching from less significant magnitude of effect over prolonged duration (even-keel concentrations) to stronger magnitude of effect over shorter duration (inverted-V concentrations).

It’s important to underscore the fact that even switching from one extended-release product to another extended-release product might yield differences in efficacy of melatonin.

Why? Even if dosages are 100% identical, time-release melatonin products can differ in terms of:

  • Time-release window: Most products I’ve seen advertise a release of ~6 hours. However, others may release melatonin over different durations such as 5 hours, 7 hours, or 8 hours. Beware of the release window. A longer-release window = less significant melatonin receptor saturation at any given time than equally-dosed quicker release.
  • Release matrix/coating: The specific release matrix used by one company may be more effective in providing a steady or controlled release of melatonin relative to another – even if release rate/duration is advertised as being identical.
  • Release specifics: Certain time-release melatonin products (e.g. multi-layer matrix) may be engineered to deliver half the dose of melatonin upfront then the other half over a 6-hour period (e.g. 5 mg immediately + 5 mg over a 6-hour period). Others may be designed to deliver 10 mg gradually over a 6-hour period (e.g. 0.6 mg per hour).

Notes on switching melatonin formats

  • Certain people will notice a significant difference in melatonin efficacy after a format switch (immediate-release to extended-release [or vice-versa] OR extended-release to another extended-release with different release mechanisms).
  • Variables like: melatonin release rate, magnitude & duration of melatonin receptor saturation, melatonin elimination rate – could explain why some people respond better to one melatonin format over another.
  • Switching melatonin formats does NOT always cause melatonin to be more/less effective than a previously used format – some people respond well to melatonin regardless of its format.

Solution: Use the same melatonin brand, dosage, and release-pattern that worked in the past (i.e. historically). If that specific product is no longer available – search for a product similar in dosage and release-pattern.

Change in health & medical conditions

A less obvious reason that melatonin stops working could be due to change in general health and/or medical conditions.

Medical conditions that are most likely to interfere with melatonin’s efficacy, include those that:

  • Induce stimulatory effects (CNS & PNS)
  • Increase tone of sympathetic nervous system (SNS)
  • Disrupt or alter the circadian rhythm
  • Disrupt or alter melatonin pharmacokinetics (absorption, metabolism, distribution, elimination)
  • Disrupt or alter organ function
  • Significantly alter brain activity & neurotransmission
  • Counteract or antagonize melatonin’s actions (CNS & PNS)

Certain medical conditions may alter physiology so significantly, that the symptoms caused via these physiologic alterations “override” the effects of melatonin (even at high doses).

Read: High dose melatonin.

As a result, the melatonin user may suspect that melatonin has stopped working – when in reality it’s still delivering an effect, but the effect is overridden by a medical condition.

For example, someone who develops hyperthyroidism might wrongfully conclude that melatonin stopped working for primary insomnia – when in fact thyroid hormone abnormalities are to blame for its lack of noticeable effect.

Another example could be someone with bipolar mania who reports that melatonin is no longer working (or no longer working as effectively as in the past) – when in reality, physiologic changes associated with mania are to blame for its lack of noticeable effect.

Keep in mind that other medical conditions (even if not “stimulating”) could: modify melatonin’s pharmacokinetics (directly or indirectly) and/or alter the circadian rhythm (such that time of melatonin administration needs to be changed to regain efficacy) – to interfere with the effect of melatonin supplementation.

Other medical conditions might impair organ function such that melatonin is eliminated at a slower rate than usual wherein it accumulates and ends up dysregulating the circadian rhythm (resulting in the user concluding that it no longer works).

Included below are various medical conditions to check for and things to evaluate if melatonin stopped working…

  • Liver function: The liver metabolizes melatonin to a significant extent. Anyone with change in liver function (even if just age-related) may necessitate melatonin dosage adjustment. Why? Poorer liver function = slower melatonin elimination and potential melatonin accumulation. If melatonin isn’t efficiently eliminated and remains high at inappropriate times relative to circadian biology – it may disrupt the circadian rhythm and stop providing benefit.
  • Kidney function: The kidneys are responsible for excreting melatonin and its metabolites. If the kidneys are not functioning properly, melatonin and/or its metabolites may accumulate and dysregulate the circadian rhythm (as a result of remaining high at inappropriate times relative to circadian biology).
  • Neuropsychiatric conditions & mental states: ADHD, anxiety disorders, bipolar disorder, brain damage, chronic stress, concussions, epilepsy, neurodegenerative disorders, hyperarousal, OCD, PTSD, etc. – can organically modify neurobiology and the circadian rhythm in unique ways that might impact the effectiveness of melatonin.
  • Hormone abnormalities: Abnormalities in hormone concentrations might explain why melatonin is no longer working as well. If you develop a condition like hyperthyroidism or low testosterone – you might end up with significantly worse sleep than those with normal hormone concentrations.
  • Immune system: Autoimmune conditions or significant changes in immune function such as in response to an infection – may explain why melatonin’s perceived effect has diminished or ceased.
  • Sleep apnea: Certain people with undiagnosed sleep apnea and hypopnea may believe melatonin is no longer helping with “sleep maintenance” because they’re waking up more frequently and unable to fall back asleep. In this case, the sleep apnea (no breathing) and/or hypopnea (abnormally slow breathing) are changing sleep architecture and activating the sympathetic nervous system (in response to insufficient oxygen) resulting in poor sleep.
  • Autonomic nervous system (ANS): Imbalances within the autonomic nervous system may cause melatonin to stop working. Most common is when someone is subject to chronic or excessive stress (e.g. PTSD), they develop hyperarousal (which excessively activates the sympathetic branch of the ANS). The way to fix this is to increase parasympathetic activity (which should result in melatonin working well again).
  • Vitamin & mineral concentrations: Having either abnormally high or low concentrations of certain vitamins/minerals could cause physiologic changes that interfere with melatonin’s beneficial “sleep-inducing” effect. Get vitamin & mineral levels checked and ensure they’re within healthy ranges.
  • Infectious disease: Most infections will increase fatigue and might make you think that melatonin is working too well – or that its potency increased. Certain infections might alter melatonin kinetics, circadian rhythms, immune parameters, and/or physiology – in ways that interfere with sleep (and lead you to conclude melatonin no longer works).

Keep in mind that I did NOT list every single medical condition that might influence the efficacy of melatonin.  Other conditions (e.g. various types of cancer) might have a significant impact on how someone responds to melatonin.

If you’ve regularly used melatonin for years from the same quality provider, haven’t changed anything in your lifestyle/regimen, and it suddenly stops working – have a medical doctor rule out health conditions.

Assuming all health conditions are ruled out, I suspect the most common health-related reason that melatonin stops working – is stress (regardless of whether the stress is caused by an underlying psychiatric disorder or lifestyle/life events).

If you’ve ruled everything out and but are admittedly “stressed” – focus on ways to manage the stress (e.g. meditation AM/PM; cardio in AM; regular sex; eating enough calories – but not excess; etc.).

Solution: Adjust the dosage of melatonin (increase or decrease depending on the medical condition); adjust the timing of melatonin administration (earlier/later – relative to circadian shifts resulting from medical condition); OR stop melatonin altogether (if it’s worsening a specific condition).

Note: Treatments for various medical conditions may also interfere with the effect of melatonin – this was already mentioned (“addition/subtraction of other substances”), but figured it should be restated in this section.

Note: Regardless of health/medical status, melatonin itself is still usually “working” (i.e. inducing a physiologic effect). However, the subjectively noticeable effect is being overridden/diminished by a medical condition (such that melatonin no longer helps with a desired effect such as sleep induction).

Change in melatonin administration (specifics)

Any change in the time at which you administer melatonin might explain why it’s no longer working – or working as well as it used to work.

  • Time of administration: If you tweaked the time at which you regularly take melatonin, this might explain a change in its efficacy. Melatonin is generally most effective when administered at a time that’s compatible with your circadian rhythm. Generally, melatonin should be administered 1-2 hours before desired night sleep time (as this is synergistic with the normal rise in endogenous melatonin and the circadian rhythm).
  • Empty vs. full stomach: Melatonin is most effective when taken on an empty stomach – at least 1-2 hours after eating. If you started taking melatonin on a full stomach (such as after eating) – this could disrupt its effect. (Note: Taking melatonin on a full stomach can impair glucose tolerance – and impaired glucose tolerance could impact your sleep).

Example #1: If you were formerly taking melatonin at 9 PM, but switched to taking it at 12 AM, this might shift your circadian rhythm back by ~3 hours. It may also interfere with your homeostatic circadian rhythm (due to the late administration timing).

Example #2: If you formerly took melatonin on an empty stomach, but started taking it with food – this might decrease glucose tolerance and generate unwanted effects (some of which might interfere with its efficacy).

Solution: Revert to taking melatonin: (A) at the same time (e.g. 9 PM) AND (B) under the same conditions (with food or # of hours since eating) – as when it was most effective.

Change in lifestyle & routine

Any significant changes in your lifestyle or daily routine might impact your circadian rhythm and subsequently the efficacy of melatonin.

Diet (daily calories & macronutrients): Are you overeating, undereating, or eating approximately “maintenance” calories? Eating excessive amounts of calories – particularly late at night, might interfere with your sleep. Similarly, eating too few total calories – might cause you to wake up with hunger pangs (overriding the effect of melatonin). Macronutrient composition of your diet might have some subtle effects on how well you sleep and the efficacy of melatonin.

  • Total number of meals: How many total meals did you eat when melatonin worked well? Are you eating the same number of meals at similar times?
  • Specific eating times/windows: What specific times during the day did you eat or consume calories when melatonin worked well?
  • Specific meal variables: Were there any major changes to variables associated with specific meals? Calorie content, macronutrient composition, timing (relative to circadian rhythm), etc.

Sleeping conditions: Were there any major changes in your sleeping conditions? Temperature, mattress, blankets, sleepwear, noise level, darkness, etc.

Exercise type, intensity, duration, timing: If you exercise – has the type of exercise, intensity, duration, or timing (e.g. morning, afternoon, evening) changed? This may influence how well you sleep (and the perceived efficacy of melatonin).

Stress & anxiety level: Melatonin will not do much in persons with extreme stress or anxiety. They’ll probably notice it “kicking in” but it won’t help induce sleep because the stress/anxiety is overriding sleep induction/maintenance.

Sleep hygiene: Going from good to bad sleep hygiene will obviously interfere with melatonin’s perceived efficacy. Usually it’s not this, but if you’re doing something egregious like attempting to sleep in too hot of a room, eating a crazy amount of food right before bed, keeping bright lights on late at night, etc. – then there’s a problem.

Note: Many of these lifestyle factors don’t “interfere” with the actual physiologic effect of melatonin, but they do interfere with sleep induction/maintenance and thus the perceived efficacy of melatonin.

Solution: Switch back to your “old routine” (i.e. regular habits) when melatonin was most effective.

What if melatonin stopped working and none of the causes discussed in this article are to blame?

If you know for 100% fact (which is unlikely) that melatonin stopped working for reasons other than those listed in this article – then you’ll need to figure out solutions.

If melatonin stopped working, arguably the simplest solution is to stop taking it – as there’s no need to continue using a substance that isn’t providing any therapeutic benefit.

It’s possible that in some cases, melatonin’s effect is less significant as a result of “partial tolerance” in daily long-term users, however, there’s no evidence to support this hypothesis.

Melatonin doesn’t work “as well” as it did when I started taking it?

It’s difficult to know whether this is accurate.

The only way to really know is to stay off of it for at least 4 weeks (wash out), then placebo-control yourself.

Try to discern whether you’re on melatonin or the placebo. And document how well it’s working.

You could have a friend or partner dissolve either melatonin powder or something else in a flavored drink or yogurt – at random and document: (A) how you slept and (B) whether you think you received melatonin vs. placebo (and why you think that).

If you can taste a difference between melatonin and the placebo – your experiment is flawed; you shouldn’t be able to distinguish melatonin from the placebo during administration.

Do the experiment for 30 days or so and then evaluate your accuracy in selecting melatonin from the placebo control.

Did melatonin really “stop working” – or did something else change?

Melatonin should continue exerting a consistent effect on physiology – as there’s no evidence to support “tolerance” onset.

If it stopped working, it’s likely that something else in your life changed (most likely that variable was discussed within this article).

For example – you experienced higher-than-usual levels of psychological stress which may have reduced or counteracted the effect of melatonin on circadian rhythm regulation and sleep enhancement.

Or perhaps your routine changed significantly such that it’s drastically altered your circadian rhythm and thus rendered melatonin less effective than usual (leading you to believe it stopped working when it probably didn’t).

What have I noticed with melatonin?

Zero (noticeable) withdrawal effects

I’ve stopped melatonin from 10 mg per night “cold turkey” after months and had zero rebound effects.

(I suspect that persons who experience withdrawals are “expecting” them – and nocebo’ing themselves OR reverting back to pre-melatonin disordered states e.g. primary insomnia).

Higher doses work better

This is for me – but maybe not for everyone (pharmacokinetics vary significantly from person to person & melatonin supplements vary significantly in actual melatonin content).

For me, 5 mg, 10 mg, 15 mg, 20 mg – all work very well.

Lower doses such as 0.3 mg don’t produce a subjectively noticeable effect. (I’m a rapid CYP1A2 metabolizer FYI).

Read: Low dose melatonin.

Perhaps a partial tolerance (?)

I can’t be sure though because my neurochemistry isn’t “static” (perhaps I perceive partial tolerance due to higher stress & caffeine intake – both of which alter circadian systems).

Which melatonin supplements do I use?

Below are melatonin supplements I’ve used with good [subjective] effect.

Before using any supplement(s) – confirm safety with a medical doctor and/or pharmacist.

Note: Links below are affiliate links that help support this site. Price is the same either way.

Nootropics Depot: If you want a low-dose melatonin, Nootropics Depot is a quality supplement brand that allegedly tests every single melatonin batch to ensure that you’re getting exactly what is listed on the label.

Life Extension: Another solid low-dose melatonin option that I’ve personally used with success.

NOW Foods: Tested relatively well with Labdoor testing (B+).

Natrol: Another melatonin brand that tested well on Labdoor (B+). I like their extended-release version that contains B6 and calcium.

Nature Made: Tested an “A-” with Labdoor.

Pure Encapsulations: Product includes only melatonin with zero fillers or additives.

Note: The idea should NOT be to regularly switch brands. If you switch brands, you risk different melatonin content even if the dosage is the exact same. (“If it ain’t broke – don’t fix it.”)

Have you noticed melatonin stops working?

  • Why do you think melatonin stopped working (in your case)?
  • Were you using any other substances with melatonin?
  • Do you have any untreated medical conditions?
  • How long did you regularly use melatonin before it subjectively stopped working?
  • What dosage of melatonin were you taking?
  • Which specific brand of melatonin had you been using?
  • Which format of melatonin were you taking (immediate-release vs. extended/time-release)?

Final note: A loss of melatonin effect resulting from one or more of the aforementioned variables is NOT the same as developing physiological tolerance (i.e. tachyphylaxis) to melatonin.

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