PEA: A Potential Biomarker and Alternative Treatment for ADHD

Posted Ramona Richard, MS, NC Blog


Attention-deficit / hyperactivity disorder (ADHD) is a condition that affects 8-12% of children worldwide, and 4% of adults.[i] The disorder is diagnosed on an individual basis, depending on the patient’s history and symptoms. Common symptoms associated with ADHD include inattention, poor stress responses, excessive talking, impulsivity, disorganization, and fidgeting.[ii] The disorder is likely highly misdiagnosed and underdiagnosed due to the ambiguity of the diagnostic procedure. Symptoms typically manifest in childhood; though, in 80% of patients, symptoms persist into adulthood.[iii] Studies have found that people diagnosed with ADHD are nearly twice as likely to become addicted to nicotine.[iv] ADHD patients are also more likely to abuse recreational drugs, commit offenses, and have poor social relationships.[v] Currently, there are no laboratory diagnostic tests for ADHD. Many diseases are diagnosed based on a combination of the patient’s symptoms and biomarker levels. Mental disorders and learning disabilities are often diagnosed based on symptoms alone, with no laboratory diagnostic testing. The pharmaceuticals used in treatment of these disorders, however, function to alter biomarker levels.[vi] Therefore, researchers are attempting to find a biomarker for ADHD to reduce misdiagnosis of the disorder. Phenylethylamine (PEA), a neurotransmitter structurally similar to amphetamine, is a promising potential ADHD biomarker.

Amphetamines & ADHD

The most common treatment for ADHD symptomology is amphetamine drugs. These drugs can help ADHD patients to focus, reduce fatigue, and complete tasks that would otherwise prove very difficult.[viii] Amphetamines, like many drugs that affect dopamine, can be extremely addictive. These drugs—Ritalin, Adderall, and Vyvanse—have a high potential for recreational misuse.[ix] Studies have also suggested that children treated with amphetamines for ADHD may suffer from stunted growth.[x] Thus, the need for more controlled amphetamine use, safe and novel ADHD treatments, and less ambiguous diagnostic procedures is apparent.


PEA is almost identical to amphetamine, but is a natural compound produced by animals, algae, fungi, and bacteria.[xi] Studies have found that the urinary output of PEA is significantly lower in patients suffering from ADHD.[xii] PEA easily crosses the blood-brain barrier, and it has been shown that blood plasma concentrations of PEA parallel urinary PEA output.[xiii] Thus, PEA levels in the urine are thought to accurately represent PEA levels in the central nervous system. PEA is a “trace amine”, meaning it is a neurotransmitter found at much lower concentrations than the catecholamines, serotonin, and histamine.[xiv] While the exact cause, or root cause, of ADHD is unknown, dysregulation of the dopaminergic signaling system is thought to play a role in ADHD symptomology.[xv] PEA has high affinity for binding sites in the dopaminergic system and so is considered a dopamine agonist.[xvi] PEA also inhibits the reuptake of serotonin, dopamine, and norepinephrine (the same neurotransmitters that are the target of many antidepressants and stimulants).[xvii] It is thought that natural dopamine receptor agonists may be a safe and effective alternative to amphetamines.[xviii] Thus, PEA is a promising biomarker in both the diagnosis and treatment of ADHD. There is still much research to be done on PEA and ADHD, and there may be other biomarkers for mental and behavioral disorders we have yet to uncover.

For more information on amphetamine and neurotransmitters, see Sanesco’s blog post about methamphetamine (a drug nearly identical to pharmaceutical amphetamines):

And for more information about PEA, see Sanesco’s blog post on “the love molecule”:


[i] Gold, M. S., Blum, K., Oscar–Berman, M., & Braverman, E. R. (2014). Low dopamine function in attention deficit/hyperactivity disorder: should genotyping signify early diagnosis in children?. Postgraduate medicine126(1), 153-177.

[ii] Gold, Ibid.

[iii] Faraone, S. V., Sergeant, J., Gillberg, C., & Biederman, J. (2003). The worldwide prevalence of ADHD: is it an American condition?. World psychiatry, 2(2), 104.

[iv] Gold, op. cit.

[v] Faraone, op. cit.

[vi] Heal, D. J., Smith, S. L., Gosden, J., & Nutt, D. J. (2013). Amphetamine, past and present–a pharmacological and clinical perspective. Journal of Psychopharmacology, 27(6), 479-496.

[vii] Irsfeld, M., Spadafore, M., & Prüß, B. M. (2013). β-phenylethylamine, a small molecule with a large impact. WebmedCentral, 4(9).

[viii] Heal, op. cit.

[ix] Heal, Ibid.

[x] Powell, S. G., Frydenberg, M., & Thomsen, P. H. (2015). The effects of long-term medication on growth in children and adolescents with ADHD: an observational study of a large cohort of real-life patients. Child and adolescent psychiatry and mental health, 9(1), 50.

[xi] Irsfeld, op. cit.

[xii] Irsfeld, Ibid.

[xiii] Sabelli, H. C., & MOSNAIM, A. D. (1974). Phenylethylamine hypothesis of affective behavior. American Journal of Psychiatry, 131(6), 695-699.

[xiv] Irsfeld, op. cit.

[xv] Gold, op. cit.

[xvi] Ledonne, A., Federici, M., Giustizieri, M., Pessia, M., Imbrici, P., Millan, M. J., … & Mercuri, N. B. (2010). Trace amines depress D2‐autoreceptor‐mediated responses on midbrain dopaminergic cells. British journal of pharmacology, 160(6), 1509-1520.

[xvii] Irsfeld, op. cit.

[xviii] Gold, op. cit.

Clinical Contributor

Sophie Thompson

Sophie Thompson

Clinical Support Intern at Sanesco Health
Sophie recently obtained her degree in Biology from UNCA in Asheville. Born and raised in Asheville, her hobbies include painting, writing and spending quality time with her dog and her family.
Sophie Thompson

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    Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.