Phenethylamine (pea) Interactions Overview

Additional Details

Is Phenethylamine Safe? Are There Any Warnings?

Phenethylamine, a natural alkaloid, is present in various sources, such as plants, bacteria, fungi, and certain foods like chocolate and eggs. When taken orally, concerns about its safety arise. Limited clinical research, albeit of low quality, tentatively suggests that under medical supervision, doses up to 60 mg daily for 50 weeks may be used with apparent safety. However, caution is advised, particularly regarding dietary supplements that contain phenethylamine.

Notably, phenethylamine exhibits stimulant effects akin to amphetamines. A case report has associated a product containing phenethylamine with tachycardia, anxiety, and agitation, raising concerns about its potential adverse effects.

Pregnant and lactating individuals: Due to insufficient reliable information, it is advisable to avoid the use of phenethylamine during pregnancy and lactation.

How Is Phenethylamine Thought To Work? What Is the Mechanism of Action?

Phenethylamine's mechanism of action is multifaceted, originating from its formation through the decarboxylation of the amino acid L-phenylalanine. Within the central nervous system, it plays dual roles as a neuromodulator and neurotransmitter.

The chemical structure of phenethylamine closely resembles sympathomimetic amines, particularly amphetamine. This resemblance underlies its stimulant effects. Phenethylamine stimulates the release of serotonin and catecholamines while inhibiting their uptake. Additionally, it activates the trace amine-associated receptor 1 (TAAR1).

Unlike amphetamines, large doses of phenethylamine, or its concurrent use with a monoamine oxidase inhibitor (MAOI), are required to induce amphetamine-like effects. The concentration needed for such effects is approximately 100-fold higher than the basal levels of endogenous phenethylamine.

Moreover, phenethylamine exhibits antidepressant properties by modulating serotonin, dopamine, and norepinephrine levels. Studies suggest a potential link between increased phenethylamine levels and the mood-enhancing effects of physical activity.

Animal research provides insights into the activation of dopamine receptors and psychoactive behaviors associated with phenethylamine consumption, indicating its intricate role in the central nervous system.

Pharmacokinetics

The pharmacokinetics of phenethylamine involve its rapid metabolism primarily by monoamine oxidase (MAO) B or N-methyltransferase. This process results in the formation of inactive metabolites, including phenylacetic acid and N-methylphenylethylamine. Notably, the rate of metabolism by MAO-B is both rapid and extensive.

Animal research has elucidated that phenethylamine follows first-order kinetics and has a brief half-life of 1.1 minutes in the brain. Excretion occurs primarily through urine, with exogenous phenethylamine being eliminated as phenethylamine and metabolites such as 2-(2-hydroxyphenyl)acetamide sulfate and phenylacetylglutamine.

Interaction Overview (See Bottom of Page For Full List)

MAOIs: The interaction with MAOIs is considered moderate, with a cautionary stance recommended due to the potential for increased adverse effects when phenethylamine is taken concomitantly with MAOIs.

Serotonergic Drugs: Another moderate interaction exists with serotonergic drugs, indicating a possible heightened risk of serotonergic adverse effects when combined with phenethylamine.

Herbs and Supplements with Serotonergic Properties: Theoretically, phenethylamine may exert serotonergic effects when combined with herbs and supplements possessing similar properties.

Common Side Effects To Watch For

Despite the interest in phenethylamine, there is a dearth of comprehensive information regarding its potential adverse effects. Reported cases, albeit limited, highlight instances of tachycardia, anxiety, and agitation. These effects were observed, particularly in individuals using weight loss products containing phenethylamine alongside various other ingredients.

Are Supplements Standardized?

Unfortunately, there is insufficient reliable information available regarding the standardization of phenethylamine in dietary supplements. This lack of standardization poses challenges in ensuring consistent and predictable dosages.

What Is Phenethylamine Typically Used For?

Despite various claims and interests in the potential uses of oral phenethylamine, the current body of evidence is insufficient to make definitive statements about its effectiveness in specific areas.

Athletic Performance: Limited information is available, and there is an insufficient basis to evaluate the clinical effects of phenethylamine for enhancing athletic performance.

Depression: The effectiveness of oral phenethylamine in treating depression remains unclear. Preliminary evidence suggests potential benefits, but more research is needed.

Obesity: Similar to other potential uses, insufficient reliable information is available about the clinical effects of phenethylamine for obesity.

References:

1. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3.

2. Baker G, Bornstein R, Rouget A, et al. Phenylethylaminergic mechanisms in attention-deficit disorder. Biol Psychiatry. 1991;29(1):15-22.

3. Kusaga A. [Decreased beta-phenylethylamine in urine of children with attention deficit hyperactivity disorder and autistic disorder]. No To Hattatsu. 2002;34(3):243-8.

4. Kusaga A, Yamashita Y, Koeda T, et al. Increased urine phenylethylamine after methylphenidate treatment in children with ADHD. Ann Neurol. 2002;52(3):372-4.

5. Sabelli H, Fink P, Fawcett J, et al. Sustained antidepressant effect of PEA replacement. J Neuropsychiatry Clin Neurosci. 1996;8(2):168-71.

6. Xie Z, Miller G. Beta-phenylehtylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain. J Pharmacol Exp Ther. 2008;325(2):617-28.

7. Szabo A, Billett E, Turner J. Phenylethylamine, a possible link to the antidepressant effects of exercise? Br J Sports Med. 2001;35(5):342-3.

8. Lukasik-Glebocka M, Sommerfeld K, Tezyk A, et al. [Acute poisoning with weight-loss dietary supplement falsely suggesting the use of amphetamine]. Przegl Lek. 2013;70(10):880-3.

9. Nakamura M, Ishii A, Nakahara D. Characterization of beta-phenyltheylamine-induced monoamine release in rat nucleus accumbens: a microdialysis study. Eur J Pharmacol. 1998;349(2-3):163-9.

10. Kim B, Byun B, Mah J. Biogenic amine formation and bacterial contribution in Natto products. Food Chem. 2012;135(3):2005-11.

Drugs that interact with Phenethylamine (pea)