What kind of interaction is it?

Caution: an interaction that may reduce efficacy or raise side-effect risk and warrants monitoring.

Is this interaction backed by published research?

Yes. NutriStack lists 2 citation rows for the Cimetidine + Melatonin pair, each linking to PubMed by PMID where available. Full sourcing methodology at https://nutristackapp.com/methodology/interactions.

Interaction databaseSupplement × PrescriptionReviewed May 2026

Cimetidine and Melatonin, a caution.

Q: Can I take Cimetidine and Melatonin together?

Possibly, but with caution. Cimetidine and Melatonin have a documented caution-tier interaction. Cimetidine is a potent inhibitor of CYP1A2, the main enzyme that clears melatonin. Co-administration can substantially raise melatonin plasma levels and prolong its effects, increasing the chance of next-day sedation, vivid dreams, or morning grogginess. Older adults are most sensitive.

Q: How does this affect a NutriStack Stack Score?

-5 to your Stack Score per scored caution row.

Cimetidine is a potent inhibitor of CYP1A2, the main enzyme that clears melatonin. Co-administration can substantially raise melatonin plasma levels and prolong its effects, increasing the chance of next-day sedation, vivid dreams, or morning grogginess. Older adults are most sensitive.

2 primary source citations. Moderate evidence. Last verified May 30, 2026.

Open the interaction checker →Read the methodology

One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.

Sourcing standards·Evidence tiers

From the interaction database

What the row says.

Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.

At a glance

Substances: Cimetidine and Melatonin
Pair type: Caution
Evidence (highest tier): Moderate
Source citations: 2 sources
Stack Score effect: −5 to your Stack Score (per scored caution row).
Scope: Supplement × Prescription
Last verified: May 30, 2026

Caution · Moderate evidence

Caution

What is happening. Cimetidine is a potent inhibitor of CYP1A2, the main enzyme that clears melatonin. Co-administration can substantially raise melatonin plasma levels and prolong its effects, increasing the chance of next-day sedation, vivid dreams, or morning grogginess. Older adults are most sensitive.

Mechanism. Melatonin is metabolized primarily by hepatic CYP1A2 to 6-hydroxymelatonin. Cimetidine inhibits CYP1A2 (along with CYP2D6 and CYP3A) more potently than any other H2 blocker, reducing melatonin clearance and elevating plasma concentrations.

Recommendation. If you take cimetidine, start melatonin at the lowest dose (0.3-1 mg) and avoid the timed-release form unless directed. Take melatonin at least 30-60 minutes before bedtime and reassess after a few nights. If you become groggy or oversleep, lower the dose.

Sources (2)

Stack Score

How this pair moves the number.

Effect on the composite score

If both Cimetidine and Melatonin are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).

The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.

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