HPA Profile
The HPA Profile measures urinary concentrations of nine neurotransmitters — serotonin, dopamine, norepinephrine, epinephrine, GABA, glutamate, glycine, histamine, and phenylethylamine — normalised to creatinine and compared against proprietary functional ranges.
9
Biomarkers
Urine (random)
Sample
10–14 business days
Turnaround
No
Fasting
What is the HPA Profile test?
The HPA Profile is a functional neurotransmitter and neuroendocrine assessment offered by specialty laboratories to explore the biochemical underpinnings of mood, stress resilience, and cognitive function. It measures urinary concentrations of key neurotransmitters — serotonin, dopamine, norepinephrine, epinephrine, GABA, glutamate, glycine, histamine, and phenylethylamine — normalised to creatinine and compared against proprietary functional reference ranges. The test is rooted in the hypothesis that peripheral neurotransmitter metabolites provide insight into central nervous system tone and that imbalances contribute to symptoms such as depression, anxiety, insomnia, fatigue, and impaired focus. Practitioners in integrative and functional medicine order the HPA Profile to guide targeted interventions — amino acid precursors, botanical adaptogens, or lifestyle modifications — intended to rebalance neurotransmitter systems. The profile is not a diagnostic tool for psychiatric or neurological disease; it is a personalised functional assessment, and its clinical validity and reproducibility are not established by the standards applied to conventional laboratory markers. Results are interpreted in the context of a detailed clinical history, and interventions are empirical rather than evidence-based in the conventional sense.
What does the HPA Profile test measure?
Serotonin is a monoamine neurotransmitter synthesised from tryptophan, predominantly in enterochromaffin cells of the gut and in serotonergic neurones of the central nervous system. Peripherally, serotonin modulates gastrointestinal motility, platelet aggregation, and vascular tone; centrally, it regulates mood, sleep, appetite, and cognition. Urinary serotonin reflects predominantly peripheral turnover rather than central compartment activity, and interpretation of urinary levels as a proxy for brain function remains exploratory.
Functional assessment of serotonergic tone is used in complementary and integrative practice to explore mood disorders, anxiety, and sleep disturbance. Low urinary serotonin is hypothesised to correlate with depressive symptoms and impulse-control difficulties, though the relationship between peripheral metabolite excretion and central neurotransmitter activity is indirect and not validated for diagnostic purposes.
Dopamine is a catecholamine neurotransmitter and precursor to noradrenaline and adrenaline, synthesised from tyrosine. It plays a central role in reward, motivation, motor control, and executive function. Urinary dopamine includes renal production and spillover from sympathetic activity, so measured levels do not directly reflect synaptic dopamine in the nigrostriatal or mesolimbic pathways.
Functional practitioners interpret urinary dopamine in the context of motivation, focus, and reward-seeking behaviour. Low levels are associated with apathy, poor concentration, and anhedonia, while elevated levels may reflect stress or sympathetic activation. The relationship to central dopaminergic function is indirect and the clinical utility for psychiatric diagnosis is not established.
Norepinephrine is a catecholamine neurotransmitter and hormone synthesised from dopamine in sympathetic neurones and the adrenal medulla. It drives the fight-or-flight response, modulating arousal, vigilance, and cardiovascular tone. Urinary norepinephrine reflects sympathetic nervous system activity and adrenal output but does not directly measure central noradrenergic neurotransmission in regions such as the locus coeruleus.
Elevated urinary norepinephrine is interpreted as a marker of sympathetic activation or chronic stress, while low levels may suggest adrenal insufficiency, hypotension, or blunted stress response. In functional neurotransmitter profiling it is used to assess arousal, anxiety, and resilience, though the correlation with central nervous system noradrenergic tone is indirect.
Epinephrine is a catecholamine hormone synthesised in the adrenal medulla from norepinephrine. It is the primary effector of acute stress response, increasing heart rate, blood pressure, and metabolic rate. Urinary epinephrine primarily reflects adrenal medullary secretion rather than central nervous system activity.
Elevated urinary epinephrine suggests acute or chronic stress, sympathetic overactivation, or rarely a catecholamine-secreting tumour such as phaeochromocytoma. Low levels may indicate adrenal insufficiency or a blunted stress response. In functional neurotransmitter profiling it is used to assess stress resilience and autonomic balance.
Gamma-aminobutyric acid is the principal inhibitory neurotransmitter in the central nervous system, synthesised from glutamate by glutamic acid decarboxylase. It modulates neuronal excitability, anxiety, and sleep. Peripheral GABA is produced in the gut and other tissues; it does not cross the blood–brain barrier, so urinary GABA does not reflect central GABAergic neurotransmission.
Functional practitioners interpret urinary GABA as a marker of inhibitory tone and use it in the context of anxiety, insomnia, and stress. Low levels are hypothesised to correlate with anxiety and hyperarousal, though the validity of peripheral GABA as a biomarker of central nervous system GABAergic function is not established.
Glutamate is the principal excitatory neurotransmitter in the central nervous system, involved in learning, memory, and synaptic plasticity. Peripheral glutamate is abundant in diet and metabolism; it does not cross the blood–brain barrier, so urinary glutamate does not directly reflect central glutamatergic activity.
Functional assessment of urinary glutamate is used to explore excitatory-inhibitory balance, with elevated levels hypothesised to correlate with anxiety, agitation, and neurotoxicity. The relationship between peripheral glutamate excretion and central nervous system excitatory tone is indirect and not validated for clinical decision-making.
Glycine is an amino acid and inhibitory neurotransmitter in the central nervous system, particularly in the spinal cord and brainstem. It also modulates excitatory transmission at N-methyl-D-aspartate receptors. Urinary glycine reflects whole-body amino acid metabolism, including diet and renal handling, rather than central neurotransmitter activity.
In functional neurotransmitter profiling, glycine is interpreted as a marker of inhibitory tone and neuroprotection. Elevated urinary glycine may reflect increased turnover or dietary intake, while low levels are hypothesised to correlate with hyperexcitability, though the evidence base for these associations is limited.
Histamine is a biogenic amine synthesised from histidine, acting as a local mediator in allergic and inflammatory responses and as a neurotransmitter in the central nervous system. Peripherally, histamine is released from mast cells and basophils; centrally, it regulates wakefulness, appetite, and cognition. Urinary histamine primarily reflects peripheral release and metabolism.
Elevated urinary histamine is associated with allergic disorders, mast cell activation, and histamine intolerance. In functional neurotransmitter profiling it is also used to explore anxiety, insomnia, and cognitive symptoms, though the relationship between peripheral histamine and central nervous system histaminergic tone is indirect.
Phenylethylamine is a trace amine synthesised from phenylalanine, structurally similar to amphetamine. It modulates dopaminergic and noradrenergic neurotransmission and is rapidly metabolised by monoamine oxidase. Urinary phenylethylamine reflects peripheral metabolism, and its role as a neuromodulator is largely indirect.
Functional practitioners interpret urinary phenylethylamine as a marker of mood, motivation, and reward. Low levels are hypothesised to correlate with depression and attention deficits, though the evidence base is limited and the relationship to central nervous system monoaminergic activity is indirect.
Why is the HPA Profile test ordered?
- Integrative and functional medicine practitioners exploring refractory mood disorders — depression, anxiety, or bipolar spectrum — in patients who have not responded adequately to conventional pharmacotherapy
- Assessment of chronic stress, burnout, and adrenal dysregulation, interpreted alongside cortisol and DHEA profiling
- Investigation of insomnia and sleep disturbance when central inhibitory-excitatory balance is hypothesised to contribute
- Exploration of cognitive symptoms — poor focus, memory difficulties, or brain fog — in the context of suspected neurotransmitter imbalance
- Guidance of targeted amino acid, botanical, or nutraceutical interventions in patients with mood or cognitive symptoms
- Personalised assessment in patients with histamine intolerance, mast cell activation, or suspected neuroimmune dysregulation
- Functional profiling in paediatric developmental or behavioural disorders where neurotransmitter imbalance is hypothesised, though informed consent and appropriate clinical context are essential
Sample collection and turnaround
Sample type
Urine (random)
Fasting required
No
Collection method
At-home collection kit
Turnaround
10–14 business days
Collection notes
Sanesco supplies a collection kit with a sterile urine container and instructions. A random mid-morning or mid-afternoon urine sample is preferred to avoid the extremes of circadian variation. Patients should avoid foods high in biogenic amines — aged cheese, fermented foods, chocolate, bananas — for 24 hours before collection if possible. Note current medications and supplements, as these influence results. Collect the sample, refrigerate immediately, and ship on ice to the laboratory within 24 hours.
Specimen requirements
Minimum 10 mL random urine in the supplied sterile container. Refrigerate immediately after collection and ship cold. The laboratory measures neurotransmitter concentrations by liquid chromatography–tandem mass spectrometry and normalises to creatinine. Record collection time, recent diet, stress level, and current medications for interpretative context.
What can affect HPA Profile results?
Foods rich in tyramine, histamine, tryptophan, or phenylalanine — aged cheese, fermented foods, chocolate, bananas — can raise urinary levels of neurotransmitters and their precursors, confounding functional interpretation. A standardised diet before collection is ideal but rarely enforced.
Selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, stimulants, and other psychotropic drugs alter neurotransmitter synthesis, release, and degradation. Results should be interpreted in the context of current pharmacotherapy, and discontinuation solely for testing is not advised.
Acute stress increases sympathetic output and catecholamine release, elevating urinary norepinephrine and epinephrine. Collection during a period of relative calm is preferable.
Neurotransmitter levels are normalised to creatinine, so variations in muscle mass, hydration, or renal handling of creatinine can distort the ratio. Very low or very high creatinine may warrant repeat collection.
Neurotransmitter synthesis and release follow circadian rhythms; cortisol and catecholamines peak in the morning, while melatonin and serotonin metabolism shift across the day. Random urine collection does not account for this variation.
The gut microbiome produces GABA, serotonin precursors, and other neuroactive compounds. Dysbiosis or small intestinal bacterial overgrowth may alter urinary neurotransmitter profiles independently of central nervous system function.
What do HPA Profile results mean?
Elevated
Serotonin elevation may reflect high dietary tryptophan, carcinoid syndrome (rare), or high peripheral turnover. Catecholamine elevation (dopamine, norepinephrine, epinephrine) suggests sympathetic activation, chronic stress, or rarely a catecholamine-secreting tumour. Glutamate elevation is hypothesised to correlate with excitotoxicity and anxiety, though the evidence is limited. Histamine elevation points to mast cell activation, allergy, or histamine intolerance. Phenylethylamine elevation is uncommon and may reflect dietary intake or altered monoamine oxidase activity.
Normal
Neurotransmitter levels within the laboratory's functional reference range suggest balanced synthesis, metabolism, and excretion at the time of collection. A normal profile does not exclude central nervous system dysfunction, as peripheral metabolites are an indirect and incomplete reflection of synaptic neurotransmitter activity.
Reduced
Low serotonin is hypothesised to correlate with depression, poor impulse control, and sleep disturbance, though the relationship is indirect. Low dopamine is associated with apathy, poor motivation, and anhedonia. Low norepinephrine and epinephrine suggest blunted stress response or adrenal insufficiency. Low GABA and glycine are interpreted as markers of reduced inhibitory tone, associated with anxiety and hyperarousal. Low phenylethylamine is hypothesised to correlate with depression and attention deficits.
Note: The HPA Profile measures peripheral neurotransmitter metabolites, which do not cross the blood–brain barrier and are influenced by diet, gut microbiome, stress, and medication. Functional reference ranges are proprietary, not standardised, and not validated against psychiatric diagnostic criteria. Results are exploratory and should guide empirical interventions rather than diagnostic conclusions. The test is not a substitute for clinical assessment or evidence-based psychiatric care.
Frequently asked questions
The HPA Profile is a urinary neurotransmitter assessment measuring serotonin, dopamine, norepinephrine, epinephrine, GABA, glutamate, glycine, histamine, and phenylethylamine. It is used in functional medicine to explore neurotransmitter balance and guide interventions for mood, stress, and cognitive symptoms.
How to access the HPA Profile test
The HPA Profile reference page is free and open to all practitioners. Create a free practitioner account to see pricing, save tests to your list, and generate requisition forms. Verification takes 1–2 business days.
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Published: October 7, 2026
Last reviewed: October 7, 2026
- Nutt DJ. The role of dopamine and norepinephrine in depression and antidepressant treatment. J Clin Psychiatry. (2006)
- Nemeroff CB. The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacol Bull. (2003)
- Sabelli HC, Javaid JI. Phenylethylamine modulation of affect: therapeutic and diagnostic implications. J Neuropsychiatry Clin Neurosci. (1995)
- Haas HL, et al. Histamine in the nervous system. Physiol Rev. (2008)
This content is for licensed healthcare practitioners only and does not constitute medical advice. Clinical decisions should be based on the full clinical picture and not on any single test result.
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