Drug & supplement interaction

Saffron + Methadone

Methadone brand name: Dolophine.

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

Saffron has a moderate interaction with Methadone. Theoretically, concomitant use of saffron and CNS depressants might have additive sedative effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Saffron and Methadone

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

Moderate

CNS DEPRESSANTS

Why this applies to Methadone

Methadone falls under CNS DEPRESSANTS — the group Saffron interacts with.

Theoretically, concomitant use of saffron and CNS depressants might have additive sedative effects.
Clinical research shows that taking saffron extract 60 mg orally daily for 26 weeks can cause drowsiness and sedation. Animal research suggests that adding saffron to hexobarbital further increases sleeping and slows motor activity.
Severity Moderate 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

Methadone is a strong opioid that calms the nervous system, and saffron in supplement form may add a mild sedative effect of its own. So the worry here is simply doubling up on that drowsy, slowed-down feeling. In a real-world sense, that could mean more sleepiness, foggy thinking, or feeling unsteady on your feet. With an opioid like methadone, deep sedation and slowed breathing are the serious concerns to watch for.

I want to be honest about the strength of this: it's theoretical, based on how the two work rather than studies pairing them directly. Saffron used as a kitchen spice is very unlikely to matter. Concentrated daily supplements are where I'd be more cautious. Please check with your pharmacist or doctor before adding a saffron supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Safarinejad MR, Shafiei N, Safarinejad S. A prospective double-blind randomized placebo-controlled study of the effect of saffron (Crocus sativus Linn.) on semen parameters and seminal plasma antioxidant capacity in infertile men with idiopathic oligoasth
  2. Zhang, Y., Shoyama, Y., Sugiura, M., and Saito, H. Effects of Crocus sativus L. on the ethanol-induced impairment of passive avoidance performances in mice. Biol.Pharm Bull. 1994;17(2):217-221. PubMed

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

Saffron Also Interacts With Other Medications

Saffron has 520 moderate known drug interactions in our database — the Methadone one above is one of them. If you take anything else, check it against the full list below.

Moderate 520 No known interaction 2,310 (incl. Methadone)
Taking anything else?

Check Another of Your Medications Against Saffron

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

From our Q&A

Questions About Saffron or Methadone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Saffron or Methadone, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Methadone

This page covers Saffron only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methadone page lists 223 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 10 major · 174 moderate · 39 minor.

From our pharmacist’s overview on the Methadone page

“If you take methadone, choose your supplements with genuine care. Of the 223 ingredients on this page, most either add to methadone's sedating effect or change how fast your body clears it, which can push its blood level up or down.”

Reviewed by 2 · Jul 18, 2026

Open the Methadone interaction page

One more smart check

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

We hold 418 real supplement products containing Saffron, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Saffron. Your product may carry other ingredients that interact with Methadone too, on top of Saffron — 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 Saffron and Methadone 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 Saffron
Top 25%

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

29 days ago today
Medication Methadone
Top half

#1,124 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 Saffron

What is Saffron?

Saffron
  • Depression and low mood
  • Anxiety
  • PMS symptoms
  • Memory and cognition
  • Eye health (age-related macular degeneration)

Saffron is a costly spice that has shown promise in early studies for mild-to-moderate depression and some mood and PMS symptoms, but most research uses small trials, so results are not definitive. It is generally well tolerated in food and small supplement amounts, but high doses can be harmful and it should be avoided in pregnancy. Talk to your pharmacist or doctor before using saffron supplements.

Read the full Saffron monograph & all interactions
Medication

About Methadone

What Is Methadone Used For?

Brand name: Dolophine

Methadone treats severe and persistent pain that requires daily, around-the-clock, long-term opioid treatment and cannot be managed adequately with other options. It is available in several forms for this use, including oral solution, oral tablets, oral concentrate, and injectable forms (intravenous, intramuscular, and subcutaneous). Injectable methadone is not approved for outpatient pain treatment — it is reserved for hospitalized patients unable to take oral medication.

Methadone is also used for the detoxification and maintenance treatment of opioid addiction (dependence on heroin or other morphine-like drugs). Oral forms — including tablets, dispersible tablets (such as Methadose Dispersible and DISKETS), and oral concentrates (such as Methadone Hydrochloride Intensol™, Methadose, and others) — are approved for this use. By law, methadone for opioid addiction treatment must be dispensed only by certified opioid treatment programs. Injectable methadone is not approved for outpatient addiction treatment.

See full Methadone drug information
Keep checking

Other Drugs & Saffron

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

0Major
520Moderate
0Minor
2,309No known interaction
520 Moderate 2,309 No interaction
Moderate

520 interactions

Showing 60 of 520 moderate interactions — see all 520 on the Saffron page.

No interaction 2,309 drugs checked — show the list

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

Showing the 60 most looked-up of 2,309 medications checked with no known interaction — see the full Saffron list.

See the full Saffron interactions page
See every supplement checked against Methadone, 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
Saffron monograph › Uses, safety, and every drug interaction in one place Methadone supplement interactions › Every supplement checked against Methadone, ranked by severity Methadone 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 Saffron and Methadone Together: Common Questions

Can you take Saffron with Methadone?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Saffron and Methadone interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About Methadone and Saffron?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.