Supplement·Interactions·Reviewed June 9, 2026
Melatonin interactions.
Melatonin has 79 documented interactions in the NutriStack database: 2 to avoid or watch closely, 56 that need timing or caution, and 21 that work synergistically. The full list, with what each pairing does, is below.
In short
Melatonin at a glance.
A quick, data-grounded summary. The full table is below.
Melatonin has 79 documented interactions in the NutriStack database: 2 to avoid or watch closely, 56 that need timing or caution, and 21 that work synergistically. The full list, with what each pairing does, is below.
Interactions
Everything that interacts with melatonin.
Every supplement and medication in the NutriStack database with a documented interaction with this substance, highest-severity first. Open any pair for the mechanism and sources.
| Substance | Interaction | What happens |
|---|---|---|
| Caffeine | Conflict | Caffeine can delay sleep onset and counteract melatonin timing goals. |
| Theophylline | Conflict | Theophylline can worsen insomnia and may counter sleep-promoting strategies such as melatonin. |
| 5-HTP | Caution | 5-HTP is a serotonin precursor, and serotonin is converted to melatonin. Taking both may lead to excessive serotonergic/melatonergic activity. details → |
| Alcohol | Caution | Combining alcohol with melatonin can increase sedation and drowsiness, while alcohol itself disrupts the body's natural melatonin rhythm and overall... details → |
| Alprazolam | Caution | Melatonin has mild sedative properties that can add to alprazolam's CNS depressant effects. While the interaction is generally less dangerous than... details → |
| Azelastine | Caution | Melatonin can add to azelastine-related somnolence and impairment. |
| Cannabis (THC-Dominant) | Caution | Both promote sedation, so taken together they can cause additive drowsiness, grogginess, and next-day impairment. |
| Cimetidine | Caution | Cimetidine is a potent inhibitor of CYP1A2, the main enzyme that clears melatonin. Co-administration can substantially raise melatonin plasma levels... details → |
| Citalopram | Caution | Severe sedation has been reported after melatonin was added to a regimen that included citalopram, with the authors judging a melatonin-citalopram... details → |
| Clonazepam | Caution | Both promote sleep through different mechanisms. Combined sedation may cause excessive drowsiness. However, melatonin may help facilitate... details → |
| Clonidine | Caution | Melatonin can add to clonidine-related sedation, dizziness, and blood pressure lowering. |
| Clozapine | Caution | Melatonin can add to clozapine-related sedation, dizziness, and impaired coordination. |
| Desloratadine | Caution | Melatonin may add to fatigue or somnolence in patients who are sensitive to desloratadine. |
| Dicyclomine | Caution | Melatonin may add to dicyclomine-related drowsiness, dizziness, and impaired alertness. |
| DIM | Caution | DIM is a documented CYP1A2 inducer (shown in cultured human liver slices via the AhR pathway), and melatonin is primarily metabolized by CYP1A2.... |
| Diphenhydramine | Caution | Melatonin can add to diphenhydramine's sleepiness and next-day grogginess when both are used as sleep aids. Melatonin has documented short-term... |
| Doxepin | Caution | Melatonin can add to doxepin-related sedation and next-day impairment. |
| DSIP (Delta Sleep-Inducing Peptide) | Caution | Both target sleep and may increase next-day grogginess or obscure adverse effects. |
| Epitalon | Caution | Both target circadian signaling and may increase vivid dreams or next-day sleepiness. |
| Fluvoxamine | Caution | Fluvoxamine is a potent CYP1A2 inhibitor, and melatonin is metabolized almost entirely by CYP1A2. Coadministration raises melatonin AUC about... details → |
| GABA | Caution | Combined use for sleep can produce additive drowsiness and next-morning grogginess, and both lower nighttime arousal. |
| Galantamine | Caution | Melatonin can add sedation, vivid dreams, or nighttime confusion in dementia patients taking galantamine. |
| Haloperidol | Caution | Melatonin can add to haloperidol-related sedation, dizziness, and psychomotor impairment. |
| Hydroxyzine | Caution | Melatonin can add to hydroxyzine's sedating effects, especially when hydroxyzine is used at night for itching, anxiety, or sleep. Hydroxyzine can... |
| Kava | Caution | Both can impair alertness; kava also carries liver safety concerns. |
| Ketamine | Caution | Melatonin taken as a sleep aid can add to ketamine's sedating effects, increasing drowsiness and impairing alertness and coordination. |
| Lacosamide | Caution | Melatonin can add to lacosamide-related dizziness and somnolence. |
| Levetiracetam Extended-Release | Caution | Melatonin can add to levetiracetam-related somnolence or dizziness. |
| Levocetirizine | Caution | Melatonin can add to levocetirizine-related somnolence and next-day impairment. |
| Lorazepam | Caution | Melatonin's sedative effects can compound lorazepam's CNS depression. While some research suggests melatonin may help facilitate benzodiazepine... details → |
| Lurasidone | Caution | Melatonin can add to lurasidone-related somnolence or dizziness. |
| Oxcarbazepine | Caution | Melatonin may add to oxcarbazepine-related dizziness and somnolence. |
| Paliperidone | Caution | Melatonin may add to paliperidone-related somnolence or dizziness. |
| Passionflower | Caution | Passionflower adds GABAergic sedation on top of melatonin's sleep-promoting effect, increasing overall drowsiness and next-morning grogginess in... |
| Phenobarbital | Caution | Melatonin can add to phenobarbital sedation and psychomotor impairment. |
| Pramipexole | Caution | Pramipexole can cause daytime sleepiness and sudden sleep episodes, and melatonin can add bedtime sedation and next-day grogginess. The combination... details → |
| Primidone | Caution | Melatonin can add to primidone and phenobarbital-metabolite sedation. |
| Prochlorperazine | Caution | Melatonin can add to prochlorperazine-related sedation, dizziness, and psychomotor impairment. |
| Promethazine | Caution | Melatonin can add to promethazine-related drowsiness, slowed reaction time, and next-day grogginess. Promethazine significantly impairs psychomotor... |
| Quetiapine | Caution | Both quetiapine and melatonin have sedative properties, and their combination produces additive CNS depression. Quetiapine is particularly sedating... details → |
| Reishi | Caution | Both have sedative properties. Reishi contains triterpenes that modulate GABAergic signaling. Combined with melatonin, may cause excessive drowsiness. |
| Rivastigmine | Caution | Melatonin can add sleepiness or dizziness to rivastigmine-related syncope or fall risk. |
| Ropinirole | Caution | Ropinirole can cause somnolence and sudden sleep episodes, and melatonin can add sleep-promoting effects. This may be useful for nighttime sleep but... details → |
| Selank | Caution | Melatonin can add sedation or vivid dreams when combined with CNS-active peptides. |
| Semax | Caution | Melatonin may counter activating effects but can confound sleep and cognition tracking. |
| Sermorelin | Caution | Both are often used at night and may cause sleepiness or obscure sleep-related adverse effects. |
| Solifenacin | Caution | Melatonin may add to solifenacin-associated somnolence or dizziness. |
| Tapentadol | Caution | Melatonin can add to tapentadol-related sedation, dizziness, falls, and respiratory depression risk. |
| Tart Cherry Extract | Caution | Tart cherry naturally contains small amounts of melatonin, so taking it alongside a melatonin supplement adds a small amount of exogenous melatonin... |
| Timolol Ophthalmic | Caution | Systemic absorption of timolol eye drops can blunt nocturnal melatonin production by blocking beta1 receptors on the pineal gland, similar to oral... |
| Tolterodine | Caution | Melatonin may add to tolterodine-associated somnolence or dizziness. |
| Valerian Root | Caution | Valerian root and melatonin both promote sleep through different mechanisms, so combining them can produce additive sedation and next-morning... details → |
| VIP (Vasoactive Intestinal Peptide) | Caution | Melatonin-related sleepiness may worsen dizziness from VIP-related hypotension. |
| Ziprasidone | Caution | Melatonin can add to ziprasidone-related somnolence, dizziness, and impaired coordination. |
| Zolpidem | Caution | Both zolpidem and melatonin promote sleep through different mechanisms. Combined use may cause excessive sedation but is sometimes used clinically... details → |
| Zonisamide | Caution | Melatonin can add to zonisamide-related somnolence, dizziness, or cognitive slowing. |
| Huperzine A | Timing Sensitive | Huperzine A may increase vivid dreams or sleep disruption, while melatonin changes sleep timing and dream intensity. |
| Theacrine | Timing Sensitive | Theacrine taken late can oppose melatonin-supported sleep onset. |
| Apigenin | Synergy | Apigenin is a natural flavonoid that binds GABA-A benzodiazepine receptors, promoting sleep through a different mechanism than melatonin. |
| Atenolol | Synergy | Beta-blockers suppress nocturnal melatonin production. Atenolol, being beta-1 selective, has a moderate effect on melatonin suppression.... details → |
| Bisoprolol | Synergy | Beta-1 selective blockers like bisoprolol moderately suppress melatonin. Supplementation can help with sleep disturbance. |
| Carvedilol | Synergy | Carvedilol, as a non-selective beta-blocker, suppresses nocturnal melatonin synthesis more than beta-1 selective agents. Melatonin supplementation... details → |
| Chamomile | Synergy | Both may promote sleepiness and can cause next-day grogginess. |
| Jujube | Synergy | Both may support sleep and can cause additive drowsiness. |
| L-Theanine | Synergy | L-theanine eases pre-sleep mental tension while melatonin signals sleep timing, so together they can shorten time to fall asleep and improve... details → |
| Lavender | Synergy | Both may promote evening calm or sleepiness. |
| Lemon Balm | Synergy | Both can promote sleepiness and may cause next-day grogginess when combined. |
| Magnesium Citrate | Synergy | Melatonin and magnesium are commonly used in sleep routines, but direct stack evidence and optimal dosing vary. |
| Magnesium Glycinate | Synergy | Melatonin and magnesium are commonly used in sleep routines, but direct stack evidence and optimal dosing vary. |
| Magnesium L-Threonate | Synergy | Melatonin and magnesium are commonly used in sleep routines, but direct stack evidence and optimal dosing vary. |
| Magnesium Malate | Synergy | Melatonin and magnesium are commonly used in sleep routines, but direct stack evidence and optimal dosing vary. |
| Magnesium Taurate | Synergy | Melatonin and magnesium are commonly used in sleep routines, but direct stack evidence and optimal dosing vary. |
| Magnolia Bark | Synergy | Both can promote sleepiness and may cause next-day grogginess. |
| Methylphenidate | Synergy | Melatonin may help counteract the insomnia commonly caused by stimulant medications like methylphenidate. Research supports the use of melatonin for... details → |
| Metoprolol | Synergy | Metoprolol suppresses endogenous melatonin production by approximately 50% through blockade of beta-1 adrenergic receptors on the pineal gland. This... details → |
| Olanzapine | Synergy | Melatonin has been studied as an adjunct to reduce some metabolic side effects of olanzapine, including weight and cardiometabolic changes.... details → |
| Omeprazole | Synergy | Melatonin has gastroprotective and lower esophageal sphincter-tonifying effects and shows additive symptom relief when combined with omeprazole for... |
| Pantoprazole | Synergy | Melatonin has gastroprotective effects and increases lower esophageal sphincter tone, and small randomized trials show additive GERD symptom relief... |
| Propranolol | Synergy | Propranolol suppresses nocturnal melatonin synthesis by blocking pineal beta-1 receptors. Melatonin supplementation can restore sleep quality in... details → |
Go deeper
The full melatonin profile.
Benefits, dosing by goal, forms, and the cited evidence for this supplement.
FAQ
Common melatonin questions.
Quick answers drawn from the table above.
What interacts with Melatonin?
In the NutriStack database, Melatonin has 79 documented interactions with other supplements and medications. The most notable include Caffeine, Theophylline, 5-HTP, Alcohol, and Alprazolam.
What should you not take with Melatonin?
Melatonin is flagged against 2 substances in the database, including Caffeine and Theophylline. Review these with a clinician before combining, especially alongside prescription medications.
What works well with Melatonin?
Melatonin pairs synergistically with Apigenin, Atenolol, Bisoprolol, Carvedilol, and Chamomile in the NutriStack database. Synergy still depends on dose and timing; open any pair for the detail.
Can you take Melatonin with Caffeine?
NutriStack classifies the Melatonin and Caffeine pairing as conflict: Caffeine can delay sleep onset and counteract melatonin timing goals. Avoid caffeine within 8-10 hours of planned sleep if insomnia-prone.
Check your whole stack
See how melatonin fits your routine.
NutriStack screens your full stack for interactions and timing conflicts, and updates the moment you change it.