What Peptide Increases Serotonin? A Pharmacological Review

October 5, 2025 •

4 min read

Approximately 90% of the body's serotonin is produced in the gut, highlighting its systemic importance [1.7.4]. For those exploring pharmacology to influence mood, the question arises: what peptide increases serotonin and how effective are they?

Quick Summary

Certain research peptides, such as Selank and Semax, are noted for their ability to modulate serotonin pathways, reducing anxiety and enhancing cognitive function without the dependency of some traditional drugs [1.2.2, 1.2.4].

Key Points

Serotonin's Role: Serotonin is a key neurotransmitter regulating mood, sleep, appetite, and memory, with low levels linked to depression and anxiety [1.7.2, 1.10.1].
Indirect Action: Most peptides do not directly create serotonin but instead modulate its activity and metabolism in the brain [1.3.4, 1.4.1].
Selank: This anxiolytic peptide helps stabilize serotonin and modulates the GABA system, reducing anxiety without sedation [1.2.2, 1.3.3].
Semax: This nootropic peptide increases the turnover of serotonin, enhancing its functional activity, and also boosts dopamine and BDNF [1.4.1, 1.4.5].
BDNF Connection: Both Selank and Semax rapidly increase Brain-Derived Neurotrophic Factor (BDNF), which promotes neuron growth and brain plasticity [1.3.4, 1.4.3].
Precursor vs. Modulator: Unlike the supplement 5-HTP, which is a direct precursor to serotonin, peptides act as regulators of existing neurotransmitter systems [1.10.3, 1.3.4].
Safety Profile: Investigational peptides like Selank are reported to be well-tolerated with mild and rare side effects, but are not FDA-approved [1.11.2, 1.11.4].

The Intricate Role of Serotonin

Serotonin, or 5-hydroxytryptamine (5-HT), is a crucial neurotransmitter and hormone that regulates a vast array of physiological processes [1.7.1, 1.7.2]. While famously linked to mood, happiness, and well-being, its functions extend to sleep cycles, appetite, digestion, memory, and learning [1.7.1, 1.7.3]. The majority of the body's serotonin is found not in the brain, but in the gastrointestinal tract, where it influences gut motility [1.7.4]. Given its integral role, low levels of serotonin are associated with conditions like depression, anxiety, insomnia, and chronic pain [1.8.1, 1.10.1]. Consequently, many pharmacological interventions, from SSRIs to emerging peptide therapies, aim to modulate the serotonin system.

Peptides and Their Indirect Influence on Serotonin

Unlike direct precursors like 5-HTP, which the body converts into serotonin, most peptides influence serotonin levels and activity through more complex, modulatory mechanisms [1.10.3]. They don't simply supply the raw materials but instead interact with various receptors and signaling pathways in the brain. Research has identified several peptides that show promise in affecting the serotonergic system, often leading to anxiolytic (anti-anxiety) and nootropic (cognitive-enhancing) effects.

Two of the most studied peptides in this category are Selank and Semax, both originally developed in Russia [1.2.2].

Selank: The Anxiolytic Peptide

Selank is a synthetic peptide derived from the naturally occurring immunomodulatory peptide tuftsin [1.3.4]. It is primarily known for its anti-anxiety properties, which it achieves without the sedative effects common to many traditional anxiolytics like benzodiazepines [1.2.2, 1.3.5].

Mechanism of Action:

Serotonin Metabolism: Studies have shown that Selank can induce the metabolism of serotonin, which may help stabilize its levels and enhance its function [1.3.4]. By enhancing serotonin, it may elevate mood and combat symptoms of anxiety and depression [1.3.1].
GABAergic System: Selank also modulates the GABAergic system, the body's main inhibitory neurotransmitter system, which contributes to its calming effects [1.3.3].
BDNF Expression: It has been found to rapidly increase the expression of brain-derived neurotrophic factor (BDNF), a protein crucial for neuron growth, survival, and plasticity [1.3.4].

Semax: The Nootropic Peptide

Semax is a peptide renowned for its cognitive-enhancing and neuroprotective properties [1.2.4]. It is an analog of a fragment of the adrenocorticotropic hormone (ACTH) [1.4.5]. While its primary effects are on cognition, it also influences neurotransmitter systems, including serotonin.

Mechanism of Action:

Serotonin System Modulation: Research indicates that Semax has a modulatory effect on the brain's serotonergic systems, appearing to increase the turnover rate of serotonin [1.4.1]. This suggests an increase in the functional activity of this neurotransmitter system [1.4.2].
BDNF and Neurogenesis: Like Selank, Semax significantly increases BDNF levels, stimulating the formation of new neurons and enhancing the brain's ability to adapt and recover from injury [1.2.4, 1.4.3].
Dopamine Activation: It also rapidly activates the dopamine systems in the brain, which are crucial for motivation, focus, and reward [1.4.5].

Other Peptides and Their Mechanisms

While Selank and Semax are the most directly linked to serotonin modulation, other peptides are being explored for their effects on the brain. For instance, Dihexa is a potent peptide known for being more powerful than BDNF at promoting the formation of new synapses, though its direct link to serotonin is less studied than its neurogenic effects [1.5.3, 1.5.5]. Other compounds like Tesofensine have been found to increase serotonin, norepinephrine, and dopamine, aiding in mood, energy, and weight management [1.2.1].


Peptide/Compound	Primary Function	Mechanism Related to Serotonin	Other Key Actions
Selank	Anxiolytic (Anti-Anxiety)	Induces metabolism and may increase serotonin, modulating its activity [1.3.1, 1.3.4].	Modulates GABA system; increases BDNF [1.3.3, 1.3.4].
Semax	Nootropic (Cognitive Enhancer)	Increases serotonin turnover rate and functional activity [1.4.1, 1.4.2].	Significantly increases BDNF; activates dopamine systems [1.2.4, 1.4.5].
Tesofensine	Weight Management/Nootropic	Increases serotonin, norepinephrine, and dopamine [1.2.1].	Appetite suppression; mood and energy enhancement [1.2.1].
5-HTP	Supplement Precursor	Directly converts into serotonin in the body [1.10.2, 1.10.3].	Readily crosses the blood-brain barrier [1.10.3].

Safety and Considerations

Peptides like Selank and Semax are generally reported to be well-tolerated with a favorable safety profile compared to traditional medications [1.9.1, 1.11.2]. Side effects are typically mild and rare, but can include headaches, nasal irritation (from spray versions), dizziness, or nausea [1.11.1, 1.11.3, 1.11.4]. However, these are often classified as research chemicals and are not FDA-approved for clinical use in many countries, including the United States [1.5.1]. It is crucial to consult with a qualified healthcare provider before considering any peptide therapy, as they can interact with other medications and have contraindications [1.11.3].

Conclusion

While no single peptide 'boosts' serotonin in the simple way a precursor like 5-HTP does, several research peptides powerfully modulate the serotonergic system. Selank and Semax stand out for their documented effects on serotonin metabolism and turnover, contributing to their recognized anti-anxiety and cognitive-enhancing benefits [1.2.4, 1.3.1]. Their ability to influence the complex interplay of neurotransmitters and neurotrophic factors like BDNF makes them a significant area of interest in neuropharmacology. As research continues, these compounds may offer more nuanced approaches to supporting mental well-being and cognitive function.

For more information from an authoritative source, you can review publications on the National Institutes of Health (NIH) website, such as this study on neuropeptides: https://pmc.ncbi.nlm.nih.gov/articles/PMC9952193/ [1.9.3].

Frequently Asked Questions

An SSRI (Selective Serotonin Reuptake Inhibitor) works by blocking the reabsorption of serotonin in the brain, increasing its available levels. Selank, on the other hand, is believed to modulate the metabolism and turnover of serotonin and also influences other systems like GABA, offering a different, more multifaceted mechanism of action [1.3.3, 1.3.4].

While studies suggest peptides like Selank have antidepressant-like effects and can influence mood, they are largely considered research chemicals and are not FDA-approved for treating depression [1.3.4, 1.5.1]. You should always consult a healthcare professional for medical advice and treatment options.

Selank is more specifically identified as an 'anti-anxiety' peptide and is primarily studied for its anxiolytic effects without sedation [1.2.4]. While Semax can influence mood, its main focus is on cognitive enhancement [1.2.4].

Reported side effects for Selank are rare and generally mild. They can include minor headaches, nasal irritation if using a spray, and occasional dizziness or fatigue [1.11.1, 1.11.2, 1.11.3].

Increasing serotonin turnover suggests that Semax accelerates the process by which serotonin is used and replenished in the brain [1.4.1, 1.4.2]. This implies a higher rate of functional activity within the serotonergic system, rather than just a static increase in its level.

Peptides like Selank are reported to be well-tolerated in studies, but a lack of long-term safety data and FDA approval means caution is necessary [1.11.4]. Always consult with a doctor, as they can have contraindications and potential side effects [1.11.3].

Most research peptides, like Selank and Semax, act as modulators rather than direct precursors. The amino acid 5-HTP is a supplement that directly converts to serotonin in the body and is not a peptide itself [1.10.3].