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Botanical & herbal supplements

Synephrine

p-Synephrine from bitter orange (Citrus aurantium)

Synephrine on labels usually means p-synephrine, the stimulant-adjacent amine associated with bitter orange (Citrus aurantium); a standalone synephrine HCl powder is a different product form from a botanical extract. It is not a validated nootropic. A 2022 meta-analysis of 18 placebo-controlled human trials found significant blood-pressure increases after prolonged use and no evidence of meaningful weight-loss benefit. NCCIH likewise describes cardiovascular evidence as inconclusive and reports substantial label-accuracy and adulteration concerns in bitter-orange products. Avoid assuming a generic product is equivalent to bitter orange extract, and consider caffeine or multi-stimulant stacks higher-risk combinations.

Standardized ExtractSports NutritionLimited Human EvidenceMixed EvidenceDose Dependent EvidenceModerate Risk ProfileOverstimulation Risk
Updated August 2026/7 min read/11 citations
Reviewed by the NootropicsIndex editorial team.Method: prioritize cited human research and official safety or regulatory sources; compare retailer-listed prices without endorsing products.Affiliate disclosure
01

What is it?

What synephrine is

2

Synephrine in supplements usually refers to p-synephrine from bitter orange (Citrus aurantium). It is commonly sold in weight-loss, pre-workout, and sports-nutrition products, often alongside caffeine or other stimulants.

Not a primary nootropic3
The available human evidence does not make synephrine a reliable focus, memory, mood, or productivity supplement. Use this page as stimulant-safety and product-quality context rather than a cognitive-enhancement recommendation.

Human evidence is not nootropic evidence

3

A 2022 meta-analysis of 18 placebo-controlled human trials found no significant weight-loss benefit and reported higher blood pressure after prolonged use: systolic pressure increased by 6.37 mmHg and diastolic pressure by 4.33 mmHg. Small exercise studies are inconsistent and do not establish focus, memory, mood, or productivity benefits.

02

Names, aliases and forms

Common NamesSynephrine; Bitter orange extract
Active Constituentsp-Synephrine; para-synephrine
Latin NameCitrus aurantium
Chemical Name4-[1-hydroxy-2-(methylamino)ethyl]phenol
Molecular FormulaC9H13NO2
Pubchem Cid7172
InchikeyYRCWQPVGYLYSOX-UHFFFAOYSA-N
Regulatory NameWADA Monitoring Program stimulant
03

Mechanisms of action

Stimulant-adjacent adrenergic pharmacology

2

p-Synephrine is an amine structurally related to ephedrine but not pharmacologically identical to ephedrine. Its practical relevance is still stimulant-adjacent: formulas may affect heart rate, blood pressure, perceived energy, appetite, or exercise metabolism, especially when combined with caffeine.

04

Potential effects and evidence map

Synephrine has human research, but not a reliable nootropic evidence base. The 2022 systematic review and meta-analysis included 18 placebo-controlled clinical trials and found that prolonged use increased systolic blood pressure by 6.37 mmHg and diastolic blood pressure by 4.33 mmHg; weight loss was not significant. Small exercise studies are inconsistent and often cannot separate p-synephrine from caffeine or other ingredients. NCCIH notes that bitter-orange evidence for weight loss or performance is unclear, that cardiovascular findings are inconclusive, and that product analyses found substantial label-amount discrepancies and some synthetic-amine adulteration. Evidence for focus, memory, mood, or productivity is absent.

Effect domainMagnitudeGrade
Focus / attention3
UnknownConfidence: Medium

No direct human evidence establishes a synephrine benefit for focus or attention.

Note Human studies are primarily cardiovascular, weight-loss, metabolic, or exercise research.

0/5
D
Mental energy / wakefulness2
AcuteConfidence: Low

Any stimulant-like energy effect is indirect and not well validated as a healthy-user nootropic effect.

Note Caffeine-stacked formulas should not be interpreted as synephrine-only evidence.

1/5
D
Physical energy / endurance3
AcuteConfidence: Medium

Small exercise findings are inconsistent and often limited by combination formulas; they do not establish a general performance benefit.

Note Caffeine and other ingredients cannot count as p-synephrine-only evidence.

2/5
C
Cellular / long-term brain support3
UnknownConfidence: Medium

No long-term brain-health or neuroprotective benefit has been established for synephrine.

Note Do not infer brain support from weight-loss or sports-supplement marketing.

0/5
D
05

Typical dosages and timing

Product-form caution3No validated consumer dose

There is no validated consumer nootropic or weight-loss dose for synephrine. p-Synephrine HCl, bitter-orange extracts, and caffeine-stacked formulas are different products; compare the exact amount, form, and other stimulants rather than converting one study into a general dose.

06

Timing & effect horizon

Effect horizonUnknown
Unknown
Timing depends on stimulant sensitivity8

Exercise studies often use acute pre-exercise dosing, but that does not create a cognitive timing guide. People sensitive to stimulants, anxiety, insomnia, palpitations, or blood-pressure changes should avoid late-day use and avoid caffeine-heavy stacks.

07

Safety, side effects and risk profile

Blood pressure is the main safety screen3
The 2022 meta-analysis found increased systolic and diastolic blood pressure after prolonged use. NCCIH describes cardiovascular evidence as inconclusive and warns that multi-ingredient bitter-orange products complicate attribution. Review blood pressure, heart rhythm, stimulant sensitivity, and caffeine intake before comparing products.
Cardiovascular caution3
Confidence: High

A 2022 meta-analysis of 18 placebo-controlled trials found prolonged-use increases in systolic and diastolic blood pressure; risk rises with stimulant stacks or cardiovascular history.

Note The effect estimate is evidence of a caution, not a guarantee that every product has the same effect.

3/5
B
Overstimulation / insomnia2
Confidence: Medium

Synephrine is stimulant-adjacent and is often sold in pre-workout or weight-loss formulas, so insomnia, jitteriness, anxiety, and palpitations are practical concerns.

Note Late-day and caffeine-stacked use are higher-risk patterns.

3/5
C
Interaction risk5
Confidence: High

Use extra caution with caffeine, yohimbine, stimulant medications, MAOIs, decongestants, blood-pressure drugs, arrhythmia history, or other products affecting heart rate or blood pressure.

Note Combination-product evidence cannot be assigned cleanly to p-synephrine alone.

4/5
C
Pregnancy / lactation caution2
Confidence: High

Pregnancy, attempts to conceive, lactation, adolescence, uncontrolled hypertension, and arrhythmia-sensitive contexts should avoid unsupervised synephrine exposure.

Note No strong reproductive safety margin was identified for concentrated p-synephrine products.

4/5
D
Legal / regulatory risk10
Confidence: High

WADA lists synephrine in the 2026 Monitoring Program for in-competition stimulant monitoring, not on the Prohibited List; other sport bodies, employers, and jurisdictions may differ.

Note Product adulterants such as synthetic amines can create separate legal and anti-doping risk.

2/5
B
Evidence uncertainty2
Confidence: High

Human evidence is mixed and often confounded by multi-ingredient formulas, caffeine, extract standardization, and label accuracy.

Note NCCIH notes FDA analysis found only a minority of labeled synephrine amounts close to label claims in analyzed products.

3/5
C
Combination risk5Higher caution

A synephrine-only study does not make a pre-workout or fat-burner stack safe. Caffeine, yohimbine, decongestants, stimulant medications, or undisclosed synthetic amines can change heart-rate, blood-pressure, anxiety, and insomnia risk.

Medical review first2Blood pressure / rhythm / pregnancy

Avoid unsupervised concentrated synephrine if you have hypertension, arrhythmia, heart disease, panic/anxiety sensitivity, insomnia, stimulant medication use, MAOI use, pregnancy, lactation, or complex medication regimens.

08

Legal and regulatory status

United States - FDA dietary-supplement context, as of August 202611

In the United States, FDA generally does not approve dietary supplements or their labeling before marketing. A synephrine product sold as a supplement is not FDA-approved for cognitive, weight-loss, or cardiovascular claims; laws outside the United States vary.

International anti-doping monitoring context, 202610

WADA lists synephrine in its 2026 Monitoring Program for in-competition stimulant monitoring. Monitoring is not the same as inclusion on the WADA Prohibited List; athletes should still verify the exact product and the current rules of their sport body and jurisdiction.

09

Practical buying and quality notes

  • Verify whether a product is p-synephrine HCl or a bitter-orange extract, and compare the stated amount, caffeine, other stimulants, and recent third-party testing. NCCIH summarizes FDA testing in which only 5 of 23 labels stating synephrine amounts were close to their claims, and some products contained synthetic amines.2
  • Product-analysis literature found that only a minority of Citrus aurantium-labeled pre-workout supplements appeared to contain the plant extract. A low price is not useful if botanical identity, synephrine amount, caffeine dose, or banned-stimulant screening is unclear.9
10

FAQ

Is synephrine a reliable nootropic?

3

No. Synephrine is mainly studied for metabolic, exercise, and cardiovascular outcomes. Reliable human focus, memory, mood, or productivity benefits are not established.

How should a Synephrine label be compared?

3

Compare the exact form (p-synephrine HCl or bitter-orange extract), stated amount, caffeine and other stimulant content, batch testing, and the product’s anti-doping documentation when relevant. Do not infer a validated consumer dose from a heterogeneous clinical literature.

Does synephrine cause high blood pressure?

3

It can be a concern. NCCIH describes the cardiovascular evidence as inconclusive, and a 2022 meta-analysis reported blood-pressure and heart-rate signals. People with cardiovascular risk should be conservative.

Is synephrine banned by WADA?

10

Synephrine appears in WADA’s 2026 Monitoring Program for in-competition stimulant monitoring, not the WADA Prohibited List. Athletes should still verify their exact product and the current rules of their sport body and jurisdiction.

Why is caffeine mentioned so often?

5

Many bitter orange products are sold with caffeine or other stimulants. That changes the safety profile and makes it harder to attribute benefits or side effects to synephrine alone.

11

References

  1. PubChem. p-Synephrine, CID 7172. Accessed 2026-06-30.
  2. National Center for Complementary and Integrative Health. Bitter Orange: Usefulness and Safety. Accessed 2026-06-30.
  3. Koncz D, Tóth B, Bahar MA, Roza O, Csupor D. The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis. Nutrients. 2022;14(19):4019.
  4. Guti?rrez-Hell?n J, Del Coso J. Effects of p-Synephrine during Exercise: A Brief Narrative Review. Nutrients. 2021;13(1):233.
  5. Shara M, Stohs SJ, Smadi MM. Acute cardiovascular effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine in human subjects: A placebo-controlled, double-blind study. Phytotherapy Research. 2018;32(1):94-102.
  6. Stohs SJ, Shara M, Ray SD. Cardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial. Phytotherapy Research. 2016;30(5):842-847.
  7. Ratamess NA, Bush JA, Kang J, et al. The effects of supplementation with p-synephrine alone and in combination with caffeine on resistance exercise performance. Journal of the International Society of Sports Nutrition. 2015;12:35.
  8. Ratamess NA, Bush JA, Kang J, et al. The Effects of Supplementation with p-Synephrine Alone and in Combination with Caffeine on Metabolic, Lipolytic, and Cardiovascular Responses during Resistance Exercise. Journal of the American College of Nutrition. 2016;35(8):657-669.
  9. Pawar RS, Grundel E. HPLC-UV-QDa analysis of Citrus aurantium-labelled pre-workout supplements suggest only a minority contain the plant extract. Journal of Pharmaceutical and Biomedical Analysis. 2021;194:113746.
  10. World Anti-Doping Agency. The 2026 Monitoring Program. Version effective 1 January 2026.
  11. U.S. Food and Drug Administration. Questions and Answers on Dietary Supplements. Accessed 2026-08-21.
Note

This page is informational and summarizes available evidence. It is not medical advice, a recommendation, or a substitute for guidance from a qualified clinician.