Drug & supplement interaction

Coffee + Esketamine

Esketamine brand name: Spravato.

Minor Interaction
Medically reviewed by · Updated September 2026
The bottom line Minor

Coffee has a minor interaction with Esketamine. Theoretically, TCAs might bind with coffee constituents when taken at the same time.

Read the full interaction report
SeverityMinor
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Coffee and Esketamine

Here is the interaction we found between these two, with the evidence behind it.

Minor

TRICYCLIC ANTIDEPRESSANTS (TCAs)

Why this applies to Esketamine

Esketamine falls under TRICYCLIC ANTIDEPRESSANTS (TCAs) — the group Coffee interacts with.

Theoretically, TCAs might bind with coffee constituents when taken at the same time.
In vitro research suggests that the tannins in coffee might cause precipitation of TCAs. However, this effect has not been reported in humans.
Severity Minor Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the honest picture: the interaction we have on file is between coffee and tricyclic antidepressants (TCAs), and it's a very weak one. The idea is that tannins in coffee might bind with the medicine if they mix together. But this was only seen in a lab dish (in vitro), never in actual people, and it's rated as minor.

With esketamine (Spravato), this concern barely applies anyway. Esketamine is a nasal spray that goes through the lining of your nose, not your stomach, so coffee in your gut isn't going to bind with it the way a swallowed pill might. There's no real-world evidence that your morning coffee would weaken esketamine's effect. Still, if you have questions about timing or your treatment, your care team at the clinic is the best place to ask.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lasswell WL Jr, Weber SS, Wilkins JM. In vitro interaction of neuroleptics and tricylic antidepressants with coffee, tea, and gallotannic acid. J Pharm Sci 1984;73:1056-8. PubMed
  2. Kulhanek F, Linde OK, Meisenberg G. Precipitation of antipsychotic drugs in interaction with coffee or tea. Lancet 1979;2:1130.

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Coffee Also Interacts With Other Medications

Coffee has 8 major, 467 moderate, 115 minor known drug interactions in our database — the Esketamine one above is one of them. If you take anything else, check it against the full list below.

Major 8 Moderate 467 Minor 115 No known interaction 2,240 (incl. Esketamine)
Taking anything else?

Check Another of Your Medications Against Coffee

Covers the 2,830 medications we’ve checked against Coffee. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Esketamine

This page covers Coffee only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Esketamine page lists 11 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Scopolia (major), Cowhage (moderate), Dhea (moderate), Griffonia Simplicifolia (moderate) and Indian Snakeroot (moderate).

By severity: 1 major · 6 moderate · 4 minor.

From our pharmacist’s overview on the Esketamine page

“Esketamine (Spravato) is the nasal spray for depression that hasn't responded to standard treatment, and its supplement list deserves genuine respect. Scopolia carries the only major rating and is the entry to understand before any other; pairing it with the medication can raise the risk of anticholinergic effects, meaning dry mouth, b…”

Reviewed by 2 · Jul 18, 2026

Open the Esketamine interaction page

One more smart check

Taking Coffee as Part of a Dietary Supplement Product? Check It for Interactions

We hold 716 real supplement products containing Coffee, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Coffee. Your product may carry other ingredients that interact with Esketamine too, on top of Coffee — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Coffee and Esketamine Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Coffee
Top 5%

#70 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Esketamine
Top 25%

#615 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Coffee

What is Coffee?

  • Alertness and reducing fatigue
  • Mental focus and concentration
  • Athletic performance
  • Headache relief
  • Weight management

Coffee is a widely consumed beverage made from roasted coffee beans, valued mainly for its caffeine, which boosts alertness and energy. For most healthy adults, moderate coffee intake is generally safe and may have some health benefits, but too much can cause jitteriness, poor sleep, and a faster heartbeat. People who are pregnant, breastfeeding, or sensitive to caffeine should limit their intake and check with a doctor or pharmacist.

Read the full Coffee monograph & all interactions
Medication

About Esketamine Nasal Spray

What Is Esketamine Nasal Spray Used For?

Brand name: Spravato

Spravato (esketamine) nasal spray is approved for two uses in adults. First, it treats treatment-resistant depression (TRD) — depression that has not responded to other antidepressants — either on its own or alongside an oral antidepressant. Second, it treats depressive symptoms in adults with major depressive disorder (MDD) who have acute suicidal ideation or behavior, always used together with an oral antidepressant.

Important limitations: Spravato has not been shown to prevent suicide or reduce suicidal thoughts or behavior directly. Even if you feel better after an early dose, hospitalization may still be needed if your doctor determines it's necessary. Spravato is not approved for use in children or as an anesthetic.

See full Esketamine Nasal Spray drug information
Keep checking

Other Drugs & Coffee

Browse every other medication we’ve checked against Coffee — both the ones with a known interaction and the ones without. Select any drug for the full detail.

8Major
467Moderate
115Minor
2,239No known interaction
8 Major 467 Moderate 115 Minor 2,239 No interaction
Major

8 interactions

Moderate

467 interactions

Showing 60 of 467 moderate interactions — see all 467 on the Coffee page.

Minor

115 interactions

Showing 60 of 115 minor interactions — see all 115 on the Coffee page.

No interaction 2,239 drugs checked — show the list

We also checked Coffee against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,239 medications checked with no known interaction — see the full Coffee list.

See the full Coffee interactions page
See every supplement checked against Esketamine, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Coffee monograph › Uses, safety, and every drug interaction in one place Esketamine supplement interactions › Every supplement checked against Esketamine, ranked by severity Esketamine Nasal Spray drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Coffee and Esketamine Together: Common Questions

Can you take Coffee with Esketamine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Coffee and Esketamine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Esketamine and Coffee?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.