Octopamine in Humans: Role, Effects, and Safety

Octopamine is a biogenic amine chemically related to the human neurotransmitter norepinephrine. In invertebrates like insects and mollusks, octopamine is a well-established neurotransmitter and neuromodulator involved in various physiological processes. This role in simpler organisms has prompted investigation into its presence and effects within human biology, including its natural occurrence and safety profile.

Natural Occurrence and Role of Octopamine in the Human Body

In mammals, including humans, octopamine is a trace amine, meaning it is naturally present in very small quantities. It is produced in the brain and nerve tissues from the trace amine tyramine and is subsequently broken down by monoamine oxidase (MAO) enzymes. Its levels can be measured in the blood of healthy individuals.

The precise natural function of octopamine in human neurophysiology is not fully understood. Its low levels contrast with its abundance and functional importance in invertebrates, where it regulates complex behaviors. In humans, variations in blood levels have been observed in connection with certain neurological and liver diseases, though the specifics of its involvement remain unclear.

Unlike insects, vertebrates have no dedicated receptors for octopamine. Instead, it interacts weakly with the adrenergic receptors that normally bind norepinephrine and epinephrine. This limited interaction and its low natural concentration mean its physiological impact in humans is subtle compared to major neurotransmitters.

Octopamine in Supplements and Performance Products

Octopamine is an ingredient in some dietary supplements marketed for weight loss, athletic performance, and cognitive benefits. Its inclusion stems from its structural similarity to other stimulant compounds. Manufacturers often promote it with claims of:

• Boosting energy
• Increasing focus
• Suppressing appetite
• Accelerating fat metabolism

A common source of octopamine in these supplements is bitter orange (Citrus aurantium) extract, which also contains the similar compound synephrine. In some products, octopamine may be a natural part of the extract, while in others it might be added synthetically.

Marketing for these supplements often suggests octopamine can unlock metabolic or energetic pathways similar to its role in invertebrates. However, despite claims of fat-burning or performance enhancement, the scientific evidence supporting its effectiveness in humans is lacking.

How Octopamine Interacts with Human Physiology

When taken as a supplement, octopamine interacts with the sympathetic nervous system. Its chemical structure allows it to bind to adrenergic receptors, which also respond to adrenaline (epinephrine) and noradrenaline (norepinephrine). However, its binding affinity for these receptors is significantly weaker than that of norepinephrine.

This interaction can produce stimulant-like effects. As an α-adrenergic agonist, it causes vasoconstriction, which is the narrowing of blood vessels. While some research suggests a modest binding to beta-3 adrenergic receptors involved in fat breakdown, there is no conclusive evidence this leads to significant weight loss in humans.

Human studies on the effects of oral octopamine are limited. For instance, early research indicated that taking octopamine did not improve exercise duration or reduce feelings of tiredness in active men. The overall physiological impact appears to be less potent when compared to norepinephrine.

Safety Profile and Regulatory Oversight

The use of octopamine supplements raises safety concerns related to its stimulant properties. Potential side effects include cardiovascular issues like increased blood pressure, heart palpitations, and an irregular heart rhythm. Because it is structurally similar to the stimulant synephrine, it may contribute to heart problems, especially at high doses or when combined with other stimulants like caffeine.

Due to its potential as a stimulant, octopamine is banned in competitive sports by the World Anti-Doping Agency (WADA). It is listed under the S6 Stimulants category on its Prohibited List, meaning athletes are forbidden from using it during competition. This ban reflects concerns that it could offer an unfair performance advantage or pose a health risk.

Regulatory bodies like the U.S. Food and Drug Administration (FDA) have also scrutinized its use in dietary supplements. Limited information exists on drug interactions, but a theoretical risk is present with medications that affect blood pressure. A risk also exists with monoamine oxidase inhibitors (MAOIs), which could prevent octopamine’s breakdown and elevate its levels in the body.