Bitter Orange - Amphetamine Interaction
Herbal: Bitter Orange
Also Known As: Citrus aurantium, Aurantii Fructus, Aurantium, Bigarade, Chisil, Kijitsu, Marmalade Orange, Meta-Synephrine, Naranja Amarga, Neroli Oil, Norsynephrine, Octopamine, Orange Amère, Seville Orange, Shangzhou Zhiqiao, Sour Orange, Synephrine, Zhi Ke, Zhi Qiao, Zhi Shi
Drug: Amphetamine
Brand names:
Dyanavel XR, Adensys XR-ODT, Mydayis, Adzenys ER
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jun 29, 2025
Interaction Details
Amphetamine is classified as belonging to the following category: 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.
Interaction Rating
Likelihood of Occurrence
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
References
- 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.
Interaction Details
Amphetamine is classified as belonging to the following category: 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.
Interaction Rating
Likelihood of Occurrence
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
References
- 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.
- Keogh AM, Baron DW. Sympathomimetic abuse and coronary artery spasm. Br Med J 1985;291:940.
Interaction Details
Amphetamine is classified as belonging to the following category: Monoamine Oxidase Inhibitors (Maois)
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.
Interaction Rating
Likelihood of Occurrence
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.
References
- 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. .
- 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.
- Suzuki O, Matsumoto T, Oya M, Katsumata Y. Oxidation of synephrine by type A and type B monoamine oxidase. Experientia 1979;35:1283-4.
Bitter Orange Overview
Bitter orange, also known as Seville orange or sour orange, is a type of citrus fruit that is native to Southeast Asia. It is closely related to the sweet orange, but has a much more bitter and sour flavor.
Bitter orange is a rich source of vitamin C and other nutrients, including calcium, potassium, and folate. It is also a good source of antioxidants.
Bitter orange has been used in traditional medicine for a number of purported health benefits, including improved digestion, improved immune function, and reduced inflammation.
Bitter orange also contains synephrine, a compound similar in structure to ephedrine. Synephrine is thought to have stimulant effects and is often used to increase energy, improve athletic performance, and as a weight loss supplement. When used as a dietary supplement, the dosage is typically standardized by its synephrine content.
Amphetamine Overview
-
Amphetamine (Adzenys ER, Adzenys XR, Dyanavel XR, Evekeo, Evekeo ODT, others) is used as part of a treatment program to control symptoms of attention deficit hyperactivity disorder (ADHD; more difficulty focusing, controlling actions, and remaining still or quiet than other people who are the same age) in adults and children. Amphetamine (Evekeo, others) is also used to treat narcolepsy (a sleep disorder that causes excessive daytime sleepiness and sudden attacks of sleep). Amphetamine (Evekeo, others) is also used for a limited period of time (a few weeks) along with a reduced calorie diet and an exercise plan for weight loss in obese people unable to lose weight. Amphetamine is in a class of medications called central nervous system stimulants. It works by changing the amounts of certain natural substances in the brain.
Bitter Orange - More Interactions
Bitter Orange interacts with 931 drugs
Interaction Rating Key
These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.
| Major | The combined use of these agents is strongly discouraged as serious side effects or other negative outcomes could occur. |
| Moderate | Use cautiously under the care of a healthcare professional or avoid this combination. A significant interaction or negative outcome could occur. |
| Minor | Be aware that there is a chance of an interaction. Watch for warning signs of a potential interaction. |
| Unknown | No interactions have been reported or no interaction data is currently available. |
Return to the main supplement interaction checker page
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
Drug descriptions are provided by MedlinePlus.
Ask A Pharmacist About Your Herbal Questions!
Dr. Brian Staiger, PharmD
In addition to being a clinical pharmacist specializing in pharmacotherapy, Dr. Brian Staiger is a registered herbalist through the American Herbalist Guild. He has combined his passion for pharmacy practice with the study of medical ethnobotany to improve patient care. Feel free to reach out about any of your herbal or medication questions!
Ask A Pharmacist