Drug & supplement interaction

Bitter Orange + Amphetamine

Amphetamine brand names: Dyanavel XR, Adensys XR-ODT, Mydayis, Adzenys ER.

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

Amphetamine falls into 3 drug categories that Bitter Orange can interact with; the most serious is rated major. Theoretically, taking MAOIs with synephrine-containing bitter orange preparations might increase the hypertensive effects of synephrine, potentially leading to hypertensive crisis.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Bitter Orange and Amphetamine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Bitter Orange interacts with whole categories of medication. Amphetamine falls into 3 of those categories, so it can interact with Bitter Orange in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

MONOAMINE OXIDASE INHIBITORS (MAOIs)

1 of 3

Why this applies to Amphetamine

Amphetamine falls under MONOAMINE OXIDASE INHIBITORS (MAOIs) — the group Bitter Orange interacts with.

Theoretically, taking MAOIs with synephrine-containing bitter orange preparations might increase the hypertensive effects of synephrine, potentially leading to hypertensive crisis.
Bitter orange contains tyramine, octopamine, and synephrine, which are MAO substrates.
Severity Major Likelihood Probable Evidence D

Interaction 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..

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

Here's the gist: both bitter orange and amphetamine are stimulants, and they push on the body in the same direction. Amphetamine already nudges up your heart rate and blood pressure and tells your body to release more of its own adrenaline-type chemicals. Bitter orange's main ingredient, synephrine, does something similar. Stack the two and you could see that effect amplified, meaning a racing heart, jitteriness, headache, chest tightness, trouble sleeping, or an uncomfortable spike in blood pressure.

To be fair, the interaction on file is graded as theoretical, drawn mostly from lab work, so we don't have strong human data. Still, since both are stimulants and the worst-case is a dangerous blood pressure surge, I'd play it safe. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Pellati F, Benvenuti S, Melegari M, Firenzuoli F. Determination of adrenergic agonists from extracts and herbal products of Citrus aurantium L. var. amara by LC. J Pharm Biomed Anal 2002;29:1113-9. . PubMed
  2. Visentin V, Morin N, Fontana E, et al. Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases. J Pharmacol Exp Ther 2001;299:96-104.
  3. Suzuki O, Matsumoto T, Oya M, Katsumata Y. Oxidation of synephrine by type A and type B monoamine oxidase. Experientia 1979;35:1283-4. PubMed
Moderate

STIMULANT DRUGS

2 of 3

Amphetamine also falls under STIMULANT DRUGS.

Theoretically, bitter orange might increase the risk of hypertension and adverse cardiovascular effects when taken with stimulant drugs.
Bitter orange appears to have stimulant effects.
Severity Moderate Likelihood Possible Evidence B

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 thing to keep in mind: amphetamine is already a strong stimulant. It speeds up your heart and can nudge your blood pressure up on its own. Bitter orange supplements contain synephrine, which is also a stimulant and acts a bit like adrenaline. So when you stack the two together, you're essentially layering one stimulant on top of another.

What that can look like in real life is a faster or pounding heartbeat, higher blood pressure, jitteriness, anxiety, or trouble sleeping. The concern here is mostly about your heart and blood vessels. To be fair, this is largely a theoretical, add-up-the-effects worry rather than something proven in big studies, but I'd still play it safe. Please check with your pharmacist or doctor before combining them, especially if you have any heart or blood pressure issues.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Penzak SR, Jann MW, Cold JA, et al. Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. J Clin Pharmacol 2001;41:1059-63. PubMed
  2. Keogh AM, Baron DW. Sympathomimetic abuse and coronary artery spasm. Br Med J 1985;291:940.
Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

3 of 3

Amphetamine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, bitter orange might increase levels of drug metabolized by CYP2D6.
In vitro research shows that octopamine, a constituent of bitter orange, weakly inhibits CYP2D6 enzymes. 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 thing to keep in mind with bitter orange and your amphetamine: lab studies suggest one compound in bitter orange (octopamine) can weakly block CYP2D6, an enzyme that helps clear amphetamine from your body. In theory, that could let amphetamine levels creep up a little, which might mean more of its usual effects, like a faster heart rate, higher blood pressure, jitteriness, trouble sleeping, or a reduced appetite.

But I want to be honest about the strength of this. It's only been seen in test-tube research, never confirmed in real people, so it's rated minor. My bigger concern is simpler: both are stimulants, so stacking them can strain your heart and blood pressure. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. 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

Bitter Orange Also Interacts With Other Medications

Bitter Orange has 9 major, 876 moderate, 71 minor known drug interactions in our database — the Amphetamine one above is among them. If you take anything else, check it against the full list below.

Major 9 Moderate 876 Minor 71 No known interaction 1,874 (incl. Amphetamine)
Taking anything else?

Check Another of Your Medications Against Bitter Orange

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

From our Q&A

Questions About Bitter Orange or Amphetamine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Bitter Orange or Amphetamine, 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 Amphetamine

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amphetamine page lists 130 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Brewer's Yeast (major), Cowhage (major) and Ephedra (major).

By severity: 16 major · 97 moderate · 17 minor.

From our pharmacist’s overview on the Amphetamine page

“Amphetamine (Dyanavel XR, Adzenys ER, Mydayis) is a prescription stimulant, usually taken for ADHD, and its interaction list is one to approach with genuine care. Of the 130 supplements and herbal ingredients on file, 16 carry a major rating, and many of those work the same way, either inhibiting monoamine oxidase, as yohimbe does, or…”

Reviewed by 2 · Jul 18, 2026

Open the Amphetamine interaction page

One more smart check

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

We hold 1,000 real supplement products containing Bitter Orange, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bitter Orange. Your product may carry other ingredients that interact with Amphetamine too, on top of Bitter Orange — 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 Bitter Orange and Amphetamine 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 Bitter Orange
Top 25%

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

29 days ago today
Medication Amphetamine
Top 5%

#46 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 Bitter Orange

What is Bitter Orange?

Bitter Orange
  • Weight loss
  • Athletic performance and energy
  • Digestive upset
  • Appetite control
  • Aromatherapy for stress (neroli oil)

Bitter orange is a citrus fruit whose extracts contain synephrine, a mild stimulant often added to weight-loss and energy supplements. Evidence that it works for weight loss or performance is limited, and because it can raise heart rate and blood pressure, people with heart problems, high blood pressure, or who are pregnant should avoid it. Talk to your pharmacist or doctor before using it, especially if you take other stimulants.

Read the full Bitter Orange monograph & all interactions
Medication

About Amphetamine

What Is Amphetamine Used For?

Brand names: Dyanavel XR, Adensys XR-ODT, Mydayis, Adzenys ER

Amphetamine treats Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older. Adzenys XR-ODT, Dyanavel XR, and the amphetamine extended-release orally disintegrating tablet formulations are specifically approved for ADHD in this age group.

Amphetamine Sulfate tablets and Evekeo (amphetamine sulfate tablets) are also approved for narcolepsy (a sleep disorder causing uncontrollable daytime sleepiness) and as a short-term aid in a calorie-restricted weight-loss program for exogenous obesity (weight gain from external factors like overeating) in patients who have not responded to other approaches.

See full Amphetamine drug information
Keep checking

Other Drugs & Bitter Orange

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

9Major
876Moderate
71Minor
1,873No known interaction
9 Major 876 Moderate 71 Minor 1,873 No interaction
Major

9 interactions

Moderate

876 interactions

Showing 60 of 876 moderate interactions — see all 876 on the Bitter Orange page.

Minor

71 interactions

Showing 60 of 71 minor interactions — see all 71 on the Bitter Orange page.

No interaction 1,873 drugs checked — show the list

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

Showing the 60 most looked-up of 1,873 medications checked with no known interaction — see the full Bitter Orange list.

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

Can you take Bitter Orange with Amphetamine?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Bitter Orange and Amphetamine?
Amphetamine belongs to more than one drug category, and Bitter Orange interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Bitter Orange and Amphetamine interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

Still Have a Question About Amphetamine and Bitter Orange?

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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.