Home Ingredients Octopamine (p-Octopamine)

Octopamine (p-Octopamine)

Evidence Level
Preliminary
5 Clinical Trials
4 Documented Benefits
1/5 Evidence Score

Octopamine (p-octopamine, also sold as norsynephrine) is a trace amine made in small amounts in the body and present at low levels in some citrus fruits. It is the nor form of synephrine, one methyl group shorter, and has been listed as an ingredient in stimulant fat burners and pre-workout products. The World Anti-Doping Agency lists octopamine as a specified stimulant prohibited in competition, while synephrine is only monitored. The US FDA treats it as a new dietary ingredient with no safety notification on file and has called a supplement declaring it adulterated. Australia's food regulator concluded it has not been adequately tested for safety in animals or people. In the only human trial, a single 150 mg dose did not change endurance cycling performance. In lab and animal studies it constricted isolated arteries and, given intravenously to rats, raised blood pressure.

Studied Dose One 150 mg oral dose in the only human trial, with no effect on endurance cycling. Fat-burner labels have listed about 30 to 60 mg a day. No safe or effective dose is established; Health Canada requires label risk information for synephrine plus octopamine above 3 mg a day.
Active Compound p-Octopamine (norsynephrine; 4-(2-amino-1-hydroxyethyl)phenol), a trace amine. Synthetic material may contain other isomers, including m-octopamine (norfenefrine), which is likely the most active form at alpha-adrenergic receptors.

Benefits

Endurance cycling performance after a single 150 mg dose

In a double-blind crossover trial, 10 recreationally active men took 150 mg of octopamine or a placebo 60 minutes before 30 minutes of steady cycling and a 30 minute performance task. Work completed was nearly identical (about 351 vs 353 kJ), and fuel use, heart rate, perceived effort and hormone levels did not differ. Blood octopamine levels stayed low.

Supported by Trial 1

Fat breakdown in human versus animal fat cells

Lab work only. In isolated fat cells, octopamine fully switched on fat breakdown (lipolysis) in rat, hamster and dog cells through beta-3 receptors, but it was ineffective in human and guinea-pig fat cells, which respond weakly to beta-3 activation. No published human trial of octopamine has measured body weight or body fat.

Supported by Trial 5, Trial 1

Absorption and rapid breakdown in the liver

Lab work only. In an isolated perfused liver model, octopamine was taken up and broken down quickly, and the authors concluded that after swallowing, levels in the general circulation would be lower than in the blood reaching the liver, so its metabolic effects would occur mainly there. In the one human trial, blood levels after a 150 mg oral dose were also low.

Supported by Trial 1, Trial 5

Blood vessel tone and blood pressure in lab and animal studies

Lab and animal work only. Octopamine contracted isolated pig coronary and mesenteric arteries, partly through alpha-1 adrenergic receptors. Given intravenously in rising doses to conscious rats, it and several related pre-workout amines raised arterial pressure, with peak rises of 65 to 103 mmHg across the amines, and it lowered body temperature. Effects of oral doses in people are not known.

Supported by Trial 4, Trial 5

Mechanism of action

1

Weak at most adrenergic receptors, more active at beta-3

Octopamine binds poorly to alpha-1, alpha-2, beta-1 and beta-2 adrenergic receptors and more readily to beta-3 receptors. In cells carrying human receptors, its affinity at beta-3 was about half that of noradrenaline but about 200 times lower at beta-1 and beta-2. A manufacturer-funded review states that binding to rodent receptors is at least 10 times stronger than to human receptors, so animal results may overstate effects in people.

2

Direct and indirect actions on blood vessels

In isolated pig arteries, octopamine contracted mesenteric vessels partly by releasing the nerve's own noradrenaline and partly by acting directly on alpha-1 receptors; in coronary arteries part of the response persisted after alpha-1 blockade and appeared to involve trace amine-associated receptors. These are tissue findings, not measurements in people.

3

Several isomers with very different potency

Octopamine exists as ortho, meta and para forms, each with two mirror-image versions. The para form occurs naturally in plants such as citrus. The meta form, norfenefrine, is likely the most active at alpha-adrenergic receptors and is itself on the anti-doping stimulant list. Synthetic octopamine may contain any of these forms, and labels rarely say which.

Clinical trials

1
Octopamine 150 mg and Endurance Cycling: Double-Blind Crossover
PubMed

Double-blind, placebo-controlled crossover trial of a single oral dose of octopamine taken 60 minutes before exercise after an overnight fast. (Beaumont et al. 2017, J Sci Med Sport)

10 healthy, recreationally active men (mean age 24 years).

Work completed in the 30 minute performance task was similar with placebo and octopamine (352.8 vs 350.9 kJ; p = 0.380). Fat and carbohydrate use, free fatty acids, prolactin, cortisol, heart rate and perceived exertion did not differ. The authors noted that serum octopamine concentrations were low, which may explain the lack of effect. A single dose in 10 men; safety was not a primary outcome.

2
Analytical Study, Not a Trial: Octopamine in Doping-Control Urine Samples
PubMed

Analytical study from an anti-doping laboratory measuring urinary octopamine after use of supplements or medicines containing octopamine or synephrine. (Thevis et al. 2012, Biomed Chromatogr)

Urine samples collected after people took nutritional supplements containing octopamine and/or synephrine, and after therapeutic use of octopamine or synephrine medicines. Participant numbers are not given in the abstract.

After therapeutic octopamine use, urinary octopamine rose from below the detection limit to 142 micrograms per mL. Samples collected after synephrine or the dietary supplements showed no sign of raised octopamine excretion. The paper notes that octopamine is prohibited in sport, while synephrine is not banned but is monitored.

3
Case Report, Not a Trial: Heart Attack in a Bodybuilder Using a Multi-Stimulant Supplement
PubMed

Single case report published as a letter. (Smedema et al. 2008, S Afr Med J)

One previously healthy 39-year-old competitive bodybuilder who had taken a supplement containing synephrine, octopamine, tyramine, caffeine and St John's wort for several years.

During a competition he had a heart attack; angiography showed a clot in a major coronary artery with spasm further along it, and no plaque was demonstrated. In the prior 3 months he took about 40 mg synephrine and 400 mg caffeine a day plus unstated amounts of tyramine and octopamine, and he had restricted fluids before competing. He recovered after a stent. One case with several stimulants cannot show that octopamine caused the event.

4
Animal Study, Not a Trial: Intravenous Pre-Workout Amines in Rats
PubMed

Telemetry study in conscious rats given rising intravenous doses of phenethylamine and seven analogues found in pre-workout products, including p-octopamine. (Pinckaers et al. 2026, Eur J Pharmacol)

Wistar-Kyoto rats with implanted pressure telemetry; no human participants.

All compounds except phenethylamine and BMPEA significantly changed arterial pressure, with peak rises of 65 to 103 mmHg across the compounds; p-octopamine also quickly lowered body temperature. The authors judged that combining such substances with exercise may add to cardiovascular strain. Intravenous dosing in rats does not show what oral supplement doses do in people.

5
Lab Study, Not a Trial: Octopamine on Isolated Pig Arteries
PubMed

Isolated tissue study comparing octopamine, synephrine and tyramine on pig coronary and mesenteric arteries. (Koh et al. 2019, Sci Rep)

Isolated porcine coronary and mesenteric artery rings; no human participants.

All three amines contracted both artery types with similar potency. In mesenteric arteries the response depended partly on released noradrenaline and was abolished by the alpha-1 blocker prazosin; in coronary arteries a residual contraction remained that appeared to involve trace amine-associated receptors. Shows how these amines can tighten blood vessels, not what happens after oral use.

Side effects and drug interactions

Common Potential side effects

Not adequately safety-tested: Australia's food regulator (FSANZ) concluded that published evidence does not show octopamine has been adequately tested for safety in animals or humans, that it may raise blood pressure, and that people with blood-pressure disorders are at greatest risk.
Cardiovascular stimulant effects in lab and animal studies: octopamine constricts isolated arteries, and intravenous doses raised blood pressure sharply in rats.
A 39-year-old bodybuilder had a heart attack with coronary spasm and a clot after years of using a supplement containing octopamine, synephrine (about 40 mg a day), tyramine, caffeine (about 400 mg a day) and St John's wort; the case cannot single out octopamine.
Labels may not match contents: stimulant amounts, including octopamine, changed between purchases of the same sports supplements over 9 months, and FDA testing of bitter orange products found some with more amines than a typical extract supplies and one with the synthetic stimulant isopropyloctopamine.
Prohibited in competition by the World Anti-Doping Agency as a specified stimulant (2026 list). Athletes subject to testing should avoid it; labels may list it as norsynephrine.
The US FDA regards octopamine as a new dietary ingredient with no safety notification on file and has stated in a 2022 warning letter that a supplement declaring it is adulterated.
Because it has not been adequately safety-tested in humans, there is no basis for use during pregnancy or breastfeeding or by children and adolescents.

Important Drug interactions

Caffeine, synephrine, higenamine and other stimulants: often combined with octopamine in sports products; FSANZ notes each can affect blood pressure and the effects of the combination are not well understood.
Decongestants (phenylephrine, pseudoephedrine), ephedra or ephedrine, and other medicines that raise blood pressure: Health Canada's archived 2010 notice for synephrine and octopamine products said not to combine them.
Blood-pressure medicines, thyroid hormones, MAO inhibitors and tricyclic antidepressants: the same notice named these as examples of prescription medicines that call for a health care practitioner's advice before use.
Prescription drugs broken down by liver enzymes: FSANZ notes a suggested inhibitory effect of octopamine on a drug-metabolizing cytochrome P450 enzyme, with unclear relevance at the amounts found in sports products.

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Frequently asked questions about Octopamine (p-Octopamine)

Is octopamine the same as synephrine?

No. They are closely related amines found together in some citrus plants, and octopamine is sometimes called norsynephrine because it lacks one methyl group. They are regulated differently: the World Anti-Doping Agency prohibits octopamine in competition but only monitors synephrine, and supplements labeled with octopamine may contain synthetic forms that differ in potency.

Can athletes use octopamine?

Athletes subject to anti-doping rules should not. Octopamine is on the World Anti-Doping Agency's 2026 Prohibited List as a specified stimulant, banned in competition. Check labels for synonyms such as norsynephrine, and be aware that stimulant contents of sports supplements can differ from the label.

Is octopamine legal in US dietary supplements?

The FDA's position is that it is not lawful without a safety notification. In a 2022 warning letter the agency said octopamine is a new dietary ingredient, that no notification has been filed, and that a supplement declaring it is adulterated.

Does octopamine help with fat loss or workouts?

That has not been shown. The only human trial found that a single 150 mg dose did not change endurance cycling performance or fat use during exercise. Its fat-breakdown effect in animal fat cells did not appear in human fat cells, and no human trial has measured weight or body fat.

Is octopamine safe, and does it have side effects?

Its safety has not been adequately tested. Australia's food regulator judged it a potential risk to health because it may raise blood pressure, and it constricts arteries in lab studies. People with heart or blood-pressure conditions, those taking stimulants or blood-pressure medicines, and pregnant or breastfeeding women should avoid it.

What is Octopamine?

Octopamine (p-octopamine, also sold as norsynephrine) is a trace amine made in small amounts in the body and present at low levels in some citrus fruits. It is the nor form of synephrine, one methyl group shorter, and has been listed as an ingredient in stimulant fat burners and pre-workout products.

What is Octopamine used for?

NutraSmarts does not list Octopamine under a health category. What the research covers: In a double-blind crossover trial, 10 recreationally active men took 150 mg of octopamine or a placebo 60 minutes before 30 minutes of steady cycling and a 30 minute performance task.

What doses of Octopamine have been studied?

Octopamine is a drug or research chemical, not a dietary supplement: it is a prescription medicine in some countries, is not approved for sale as a supplement in the US, or has a regulatory warning against it. Doses used in studies: One 150 mg oral dose in the only human trial, with no effect on endurance cycling. Fat-burner labels have listed about 30 to 60 mg a day. This is not dosing advice.

Does Octopamine interact with any medications?

Possible interactions include: Caffeine, synephrine, higenamine and other stimulants: often combined with octopamine in sports products; FSANZ notes each can affect blood pressure and the effects of the combination are not well understood. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Octopamine?

NutraSmarts rates the evidence for Octopamine as Preliminary (1 out of 5). It is backed by 5 study summaries and 16 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies. For a drug or research chemical, this rating does not mean it is suitable for self-use.

References(16 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Beaumont RE, Cordery P, James LJ, Watson P. Supplementation with a low-dose of octopamine does not influence endurance cycling performance in recreationally active men. J Sci Med Sport. 2017;20(10):952-956. doi: 10.1016/j.jsams.2017.03.007.PubMedUsed to support: Double-blind crossover trial in 10 recreationally active men: a single 150 mg oral dose of octopamine taken 60 minutes before exercise did not change work completed in a 30 minute cycling performance task (352.8 vs 350.9 kJ, p = 0.380), substrate oxidation, free fatty acids, prolactin, cortisol, heart rate or perceived exertion. Serum octopamine concentrations were low. The only human trial of oral octopamine found.
  2. Stohs SJ. Physiological functions and pharmacological and toxicological effects of p-octopamine. Drug Chem Toxicol. 2015;38(1):106-12. doi: 10.3109/01480545.2014.900069.PubMedUsed to support: Narrative review: p-octopamine is made in mammalian brain and nerve tissue and is measurable in the blood of healthy people; it binds poorly to alpha-1, alpha-2, beta-1 and beta-2 adrenergic receptors and modestly to beta-3 receptors. At the time of writing no human studies had examined athletic performance or weight management, no human studies had reported cardiovascular effects after oral use, and the author called for animal and human safety and efficacy studies.
  3. Stohs SJ, Shara M, Ray SD. p-Synephrine, ephedrine, p-octopamine and m-synephrine: Comparative mechanistic, physiological and pharmacological properties. Phytother Res. 2020;34(8):1838-1846. doi: 10.1002/ptr.6649.PubMedUsed to support: Narrative review arguing that p-octopamine and p-synephrine bind poorly to alpha and beta-1/beta-2 adrenergic receptors and should not be equated with ephedrine or m-synephrine. The full text notes that p-octopamine (nor-synephrine) occurs in some citrus fruits, that receptor binding in rodents is at least 10 times stronger than in humans, and that no studies on p-octopamine half-life were found. The lead author discloses consulting for Innophos LLC, and the review was conducted under a grant from Innophos LLC.
  4. Carpéné C, Galitzky J, Fontana E, Atgié C, Lafontan M, Berlan M. Selective activation of beta3-adrenoceptors by octopamine: comparative studies in mammalian fat cells. Naunyn Schmiedebergs Arch Pharmacol. 1999;359(4):310-21. doi: 10.1007/pl00005357.PubMedUsed to support: In isolated fat cells from five species, octopamine fully stimulated lipolysis in rat, hamster and dog cells but was inefficient in guinea-pig and human fat cells, like synthetic beta-3 agonists. In cells expressing human receptors, its affinity at beta-3 was about twofold lower than noradrenaline but about 200-fold lower at beta-1 and beta-2. In vitro only.
  5. da Silva-Pereira JF, Bubna GA, Gonçalves Gde A, Bracht F, Peralta RM, Bracht A. Fast hepatic biotransformation of p-synephrine and p-octopamine and implications for their oral intake. Food Funct. 2016;7(3):1483-91. doi: 10.1039/c6fo00014b.PubMedUsed to support: Isolated perfused liver study: p-octopamine was extracted and transformed rapidly, with uptake showing no clear saturation. The authors concluded that after oral intake, portal vein concentrations of p-synephrine and p-octopamine exceed systemic ones, so their metabolic effects will occur mainly in the liver. Lab model only.
  6. Koh AHW, Chess-Williams R, Lohning AE. Differential mechanisms of action of the trace amines octopamine, synephrine and tyramine on the porcine coronary and mesenteric artery. Sci Rep. 2019;9(1):10925. doi: 10.1038/s41598-019-46627-5.PubMedUsed to support: Isolated pig artery study: octopamine, synephrine and tyramine all contracted coronary and mesenteric arteries with similar potency. Mesenteric responses were reduced by depleting noradrenaline and abolished by prazosin (indirect sympathomimetic plus direct alpha-1 action); coronary responses kept a residual component blocked by a high concentration of a trace amine receptor antagonist. Tissue study only.
  7. Pinckaers NET, Blankesteijn WM, Peeters R, Dijkstra P, Tinnemans R, Opperhuizen A, van Schooten FJ, Vrolijk M. Phenethylamines in pre-workout supplements alter arterial pressure, heart rate, and body temperature in rats. Eur J Pharmacol. 2026;1026:178966. doi: 10.1016/j.ejphar.2026.178966.PubMedUsed to support: Telemetry study in conscious rats given cumulative intravenous doses of phenethylamine and seven analogues including p-octopamine: all except phenethylamine and BMPEA significantly altered arterial pressure, with peak rises of 65 to 103 mmHg; p-octopamine also lowered body temperature. Funded in part by the Dutch agriculture and food ministry. Intravenous animal data, not oral human data.
  8. Thevis M, Koch A, Sigmund G, Thomas A, Schänzer W. Analysis of octopamine in human doping control samples. Biomed Chromatogr. 2012;26(5):610-5. doi: 10.1002/bmc.1705.PubMedUsed to support: Anti-doping laboratory study stating that octopamine is prohibited in sport and that synephrine is not banned but monitored. After therapeutic octopamine use, urinary octopamine rose from below the detection limit to 142 micrograms per mL, while urine after synephrine or octopamine and/or synephrine supplements showed no evidence of raised octopamine excretion.
  9. Pawar RS, Sagi S, Leontyev D. Analysis of bitter orange dietary supplements for natural and synthetic phenethylamines by LC-MS/MS. Drug Test Anal. 2020;12(9):1241-1251. doi: 10.1002/dta.2871.PubMedUsed to support: FDA laboratory analysis of 59 US products labeled as containing bitter orange or its amines: several contained more amines than a typical bitter orange extract would supply, only 5 of 23 with a synephrine claim were within 80 to 120% of the label, and one contained the synthetic stimulant isopropyloctopamine (up to 76 mg per daily serving). It notes that octopamine was then on the FDA's Dietary Supplement Ingredient Advisory List.
  10. Attipoe S, Cohen PA, Eichner A, Deuster PA. Variability of Stimulant Levels in Nine Sports Supplements Over a 9-Month Period. Int J Sport Nutr Exerc Metab. 2016;26(5):413-420. doi: 10.1123/ijsnem.2015-0177.PubMedUsed to support: Three samples each of nine popular US sports supplements bought over 9 months: stimulants including synephrine, octopamine, ephedrine and others occurred in variable amounts in eight of the nine products, and caffeine varied from -7% to +266% of the first measurement. The sample was too small for statistical analysis.
  11. Smedema JP, Müller GJ. Coronary spasm and thrombosis in a bodybuilder using a nutritional supplement containing synephrine, octopamine, tyramine and caffeine. S Afr Med J. 2008;98(5):372-3..PubMedUsed to support: Case report (letter, full text read via the Stellenbosch University repository): a previously healthy 39-year-old bodybuilder had a myocardial infarction with a proximal coronary thrombus and distal spasm after years of a supplement containing synephrine (about 40 mg a day), caffeine (about 400 mg a day), unstated amounts of octopamine and tyramine, and St John's wort, with fluid restriction before competition. The authors judged the supplement a likely trigger; a single multi-ingredient case.
  12. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. World Anti-Doping Agency. 2026;Section S6.B Specified Stimulants; in effect from 1 January 2026. Copy hosted by the Czech National Sports Agency (Narodni sportovni agentura), accessed 2026..SourceUsed to support: Not PubMed-indexed; official anti-doping list. Octopamine is named under S6.B Specified Stimulants, prohibited in competition, as is norfenefrine. Synephrine is listed instead in the 2026 Monitoring Program and is not considered a prohibited substance.
  13. US Food and Drug Administration. Warning Letter: Max Muscle, MARCS-CMS 622401. US Food and Drug Administration. 2022;Warning letter dated May 4, 2022. Accessed 2026..SourceUsed to support: Not PubMed-indexed; FDA enforcement letter. FDA states that octopamine, declared on a product label, is a dietary ingredient as a constituent of bitter orange and other botanicals, that there is no information showing it was lawfully marketed as a dietary ingredient before October 15, 1994, that no new dietary ingredient notification has been received, and that the product is therefore adulterated.
  14. Health Canada. Natural Health Products Ingredients Database: Octopamine. Health Canada. 2026;Ingredient record id 1552, date modified 2019-03-01. Accessed 2026..SourceUsed to support: Not PubMed-indexed; regulatory database. Octopamine is classed as a natural health product isolate with a medicinal role, with sources including bitter orange peel and lemon leaf. Limits apply to synephrine plus octopamine combined: no risk information needed at 3 mg a day or less; risk information required above 3 mg and below 50 mg without caffeine, or below 40 mg with up to 320 mg of caffeine; product-specific review with more caffeine.
  15. Health Canada. Notice: Guidelines for the Use of Synephrine in Natural Health Products (archived). Health Canada. 2010;Notice dated January 2010; archived and no longer updated. Accessed 2026..SourceUsed to support: Not PubMed-indexed; archived regulatory notice, superseded by later limits. It set 30 mg a day as the then maximum for total synephrine and octopamine, did not permit caffeine in such products without human clinical evidence, and required warnings: consult a practitioner with heart disease, high blood pressure, pregnancy or breastfeeding or prescription medicines (examples included blood-pressure drugs, thyroid hormones, MAO inhibitors and tricyclic antidepressants), and do not combine with decongestants, ephedrine or other drugs that raise blood pressure.
  16. Food Standards Australia New Zealand. Imported food risk statement: Supplementary sports foods and octopamine. Food Standards Australia New Zealand. 2020;Risk statement compiled July 2020. Accessed 2026..SourceUsed to support: Not PubMed-indexed; government risk assessment. Concludes octopamine in sports supplements presents a potential medium or high public health risk: it is an alpha-adrenergic agonist that may raise blood pressure, has no history of safe food use at the levels added, and has not been adequately tested for safety in animals or humans. It describes ortho, meta and para isomers (meta form norfenefrine likely the most active), fat-burner label intakes of about 30 to 60 mg a day, older human studies too limited for conclusions (one report of a blood-pressure rise after a single 100 mg oral dose of m-octopamine in 2 people), its past use as a medicine for low blood pressure at reported oral doses of 40 to 600 mg a day, and Health Canada's classing of p-octopamine up to 50 mg a day as low risk.