Peptides For Anxiety, Depression, and Mental Health

Researcher interested in studying the effects of peptides for anxiety, depression, and mental health have come to the right place. 

Here, we will dissect the topic of research peptides and mood disorders and present the latest clinical data available. Researchers will also discover the latest evidence on their mechanisms of action inside the brain, including:

• Interactions with neurotransmitters
• Modifying cell signaling processes
• Upregulating specific receptors

Moreover, we will share details about our most trusted vendors of research peptides for educational and experimental purposes.

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Top 3 Peptides For Anxiety and Depression

Here are the three most notable peptides for anxiety and depression that should be considered by researching delving into this field:

Selank for Anxiety

Selank is a synthetic heptapeptide clinically used in Russia and Ukraine as a nootropic and anxiolytic agent that is designed to pass through the blood-brain barrier. Selank’s primary mechanisms involve interaction with neurotransmitter signaling—opioid, GABA, and serotonergic receptor signaling. Clinical studies show that Selank may be equivalent to medazepam in mitigating generalized anxiety disorder symptoms while exhibiting antiasthenic and psychostimulant effects [1, 2, 3].

PE-22-28 for Depression

PE-22-28 is a heptapeptide that inhibits the activity of TREK-1 channels found in the brain, which, when overactive, can induce depressive states. The peptide is a shortened analog of the naturally-occurring antidepressant peptide spadin. PE-22-28 demonstrates greater specificity and affinity for TREK-1 than spadin and requires lower quantities to yield the desired effect. Studies on murine models of depression also support PE-22-28's potent antidepressant properties [4, 5].

Ghrelin and Ghrelin-Mimetics for Mood Disorders

Ghrelin (the hunger hormone) may exhibit antidepressant-like effects, though the exact mechanism remains unclear. A clinical trial showed that ghrelin administration reduced depressive symptoms in male subjects and improved mood in healthy individuals. Further, laboratory animal studies suggest that ghrelin and other ghrelin-receptor mimetics, such as GHRP-6, can alleviate stress and decrease symptoms of depression in rats [6, 7, 8].

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What is Peptide Therapy?

Peptide therapy involves the clinical use of therapeutic peptides. Peptides are oligomers and polymers of amino acid building blocks, which are joined together in series by peptide bonds. Consequently, peptides are proteins, but they are small proteins.

Generally, a compound consisting of just one polypeptide chain no more than 40 or 50 residues long is called a peptide. This is an arbitrary cutoff amount, but larger proteins with hundreds of amino acids are not called peptides, but simply proteins. Like larger proteins, peptides form complex three-dimensional structures that account for their functions, which include targeting specific receptors and consequently regulating biological functions [9].

Peptides carry out a myriad of essential functions within the human body. They play a key role in facilitating various processes, including, but not limited to:

• Cellular communication
• Enabling cellular motility
• Aiding neurotransmission
• Executing endocrine signaling
• Managing metabolic processes
• Stimulating growth
• Promoting recovery

Therapeutic peptides can be developed by modifying endogenously-produced peptides or by synthesizing new oligopeptide sequences from scratch. Either way, the results are substances with improved pharmacokinetics, increased specificity, or reduced side effects [10].

The pharmaceutical industry has observed an upswing in developing and approving therapeutic drugs based on peptides. As of now, more than 60 such drugs have been approved for human use. Additionally, a large number of peptides currently under investigation display considerable promise for treating a wide array of health conditions [9, 10].

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How Do Peptides Work For Anxiety and Depression?

Research peptides work for anxiety and depression by interacting with various neurotransmitters and ion channels that regulate the function of brain cells. For example, peptides may improve mood and reduce anxiety by:

• Upregulating serotonin levels: Selank and Pinealon are two peptides that work primarily by increasing serotonin levels, a neurotransmitter that plays a crucial role in mood regulation [11, 12]. In fact, serotonin is considered a natural mood stabilizer as it regulates the activity of several other neurotransmitters and promotes an overall calming effect [13].
• Upregulating GABA signaling: Selank has also been reported to increase the activity of the GABA receptors in the brain [2]. GABA is the primary inhibitory neurotransmitter in the brain, and upregulating it can help alleviate anxiety by reducing neuronal excitability and promoting a calming effect [14].
• Upregulating enkephalin levels: Selank has been reported to reduce the degradation of enkephalins in the brain [15, 16]. Enkephalins are endogenous opioids that play a significant role in regulating pain and emotional responses. By upregulating enkephalin levels, the body's natural stress response can be modulated, reducing anxiety symptoms and promoting feelings of well-being and relaxation [17].
• Inhibiting TREK-1: PE-22-28 is a research peptide that exerts antidepressant activity by blocking TREK-1 (TWIK-related potassium channel-1) channels in the brain [5]. TREK-1 channels are believed to contribute to depressive states by decreasing neuronal excitability [4].

Thus, research peptides offer a multifaceted approach to managing anxiety and depression, targeting different aspects of these complex conditions.

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Do Peptides *Actually* Work For Mental Health?

Several peptides have been shown to work for anxiety and depression in clinical trials, confirming their beneficial effects on mental health.

For example, a 5-day clinical study of Selank, administered as 0.15% intranasal drops, demonstrated several benefits in treating psychogenic anxiety disorders in a group of 21 patients aged 18-45 years [18]. Here is a breakdown of this study’s notable findings.

• Quick onset and duration: The anxiolytic effects of a single 900µg dose of Selank started within 30-40 minutes and lasted for 6-12 hours. An initial tranquilizing effect was observed in 67% of patients, and it was noted to reduce anxiety, emotional and muscular tension, restlessness, and fatigue, improve activity, and increase workability.
• Increased effectiveness after repeated use: In 71% of patients, psychopathological symptoms reduced significantly in the initial days of therapy, while in 29% of patients, the improvement was gradual.
• Combination of anxiolytic and nootropic effects: Anxiety, irritability, and affective liability decreased rapidly within 1-3 days of therapy. At the same time, there was a significant decrease in fatigue, apathy, psychomotor retardation, and somnolence.
• Sleep Normalization: Selank administration was associated with sleep normalization.
• Significant overall effectiveness: A 5-day course of Selank therapy was effective, with a significantly marked improvement observed in 81% of patients and mild improvement in 19% of patients.

Owing to these beneficial effects, intranasal Selank has received regulatory approval in Russia for the treatment of generalized anxiety disorder and cognitive impairments [1].

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Best Peptides For Anxiety, Depression, and Mental Health

Below, researchers can find detailed information about the research peptides with the highest potential for their anxiolytic and antidepressant benefits.

Selank

Selank is a synthetic heptapeptide predominantly employed as a nootropic and anxiolytic agent in Russia and Ukraine. It was developed in the 1990s by scientists at the Institute of Molecular Genetics of the Russian Academy of Sciences [1].

Its N-terminus is represented by a lab-made version of the human tetrapeptide tuftsin (Thr–Lys–Pro–Arg), which operates as an immunomodulatory peptide forming a part of immunoglobulin G found in various mammals' bloodstreams, and incorporates a Pro-Gly-Pro sequence at the C-terminus [19].

Selank can be further enhanced via methods such as acetylation and amidation, producing a derivative termed N-acetyl Selank Amidate, which may exhibit enhanced stability [20].

The peptide has been engineered to pass through the blood-brain barrier and reach the central nervous system via either injection or intranasal delivery [21].

Its primary mechanisms of action in the brain involve interactions with neurotransmitter signaling, including:

• Opioid signaling
• GABA signaling
• Serotonergic signaling

The peptide facilitates an increase in GABA and serotonergic signaling, which are recognized for their relaxant, antidepressant, and anxiolytic properties [2, 3, 11].

As mentioned, Selank works through opioid signaling, which is a system associated with pain, stress, and mood regulation. More specifically, Selank prevents the degradation of enkephalins, which are the natural ligands of these opioid receptors [15, 16].

A clinical study involving 62 patients suffering from generalized anxiety disorder and neurasthenia was designed to evaluate the anxiolytic efficacy of intranasal Selank compared to medazepam.

The findings from this study revealed a potential equivalence between Selank and medazepam in their capability to mitigate the symptoms of generalized anxiety disorder. Additionally, Selank exhibited supplementary benefits such as antiasthenic and psychostimulant effects, enhancing the patients’ quality of life [3].

Studies propose that intranasally delivered Selank may also augment the expression of BDNF (brain-derived neurotrophic factor) within the hippocampal region of rat brains. Thus the peptide may also have neuroprotective effects [22].

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PE-22-28

PE-22-28 is a synthetic heptapeptide that is purported to work via its inhibitory effect on TREK-1 potassium channels, which are found in the brain and other tissues, where they regulate and suppress the electrical activity of cells [4].

Overactivity of TREK-1 channels has been hypothesized to lead to a decrease in neuronal excitability, which is associated with depressive states. Therefore, inhibiting the activity of TREK-1 channels could potentially alleviate depressive symptoms by increasing neuronal excitability [4].

PE-22-28 is a shortened analog of spadin, an endogenously-produced peptide that has been shown to have antidepressant activity by blocking TREK-1. PE-22-28 specifically blocks the TREK-1 channel, with higher specificity and affinity for the channel than spadin. It also has lower IC50, meaning that less of the compound is needed to achieve the desired effect [5].

TREK-1 blockage can increase the excitability of neurons, potentially counteracting the decreased neuronal excitability associated with depression. Further, rat studies involving research protocols used to investigate depression, including the Forced Swim Test and the Novelty Suppressed Feeding Test, have demonstrated the strong antidepressant properties of PE 22-28 [5].

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Ghrelin

Ghrelin is a gut-derived peptide that is also known as the hunger hormone. It increases under conditions of negative energy balance, such as fasting, and decreases with re-feeding and obesity.

In addition to its metabolic and appetite-regulating effects, ghrelin may also possess antidepressant-like effects, although the exact mechanism of this potential benefit remains unknown [23].

Currently, there is only one published clinical trial on the effects of ghrelin on subjects with depression. This research demonstrated an amelioration of depressive manifestations in male subjects (with no observable effect in female participants) following administration of 50μg ghrelin [6].

The possible antidepressive effect of ghrelin was similarly observed in mentally healthy individuals. After an injection of up to 100μg ghrelin, a mood enhancement was noted in 3 out of the 9 individuals participating in one study [7].

Laboratory animal studies also suggest that both ghrelin and ghrelin mimetics (aka growth hormone secretagogues), such as GHRP-6 (growth hormone-releasing peptide-6), may alleviate stress and reduce depression symptoms in rats [8].

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Pinealon

Pinealon, also known as EDR (Glu-Asp-Arg), is a short synthetic peptide bioregulator found in a compound called Cortexin—a lyophilized extract of the animal cortex, comprising neuropeptides, amino acids, and trace elements [24].

Pinealon is believed to have neuroprotective effects and the potential to improve brain function by regulating the metabolism and functions of neurons, thereby enhancing memory, attention, and cognitive abilities [24].

It has also been reported to potentially reduce depressive mood by influencing serotonin levels in the brain. One study found that Pinealon promotes the accumulation of serotonin in the cerebral cortex of aged rats, a region of the brain associated with mood regulation [12].

Another in vitro study demonstrated that Pinealon stimulates serotonin synthesis in aging brain cortex cells by regulating the gene encoding 5-tryptophan hydroxylase, the enzyme responsible for serotonin production [25].

By both increasing the accumulation and stimulating the synthesis of serotonin, a neurotransmitter known to contribute to feelings of well-being and happiness, Pinealon may potentially alleviate symptoms of depressive mood.

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Oxytocin

Oxytocin is a hormone produced in the hypothalamus and secreted by the pituitary gland, which plays a crucial role in the childbirth process and also helps with male reproduction. It is often administered via injection to women in labor, as it helps with uterine contractions.

In addition, oxytocin can be administered intranasally and has been studied for its potential in various mood disorders. One meta-analysis of several clinical trials reports that intranasally administered oxytocin significantly reduced behaviors of attachment anxiety, insecurity, and avoidance [26].

This suggests that intranasal oxytocin could be a viable approach for reducing anxiety-related behaviors of attachment insecurity and attachment-related dysfunctions [26]. Unfortunately, the effects of oxytocin on other forms of anxiety or depression remain inconclusive [27].

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Peptides For Mental Health | Side Effects and Safety

Peptides for anxiety and depression like Selank have demonstrated safety in clinical research settings. In fact, clinical studies on Selank have reported no adverse effects, even with repeated use, underscoring its potential as safe in research settings [1].

This safety profile extends to other peptides with potential anxiolytic properties, such as oxytocin and ghrelin, which have also undergone clinical scrutiny. In fact, ghrelin also has not been associated with any side effects after a single use [6]. Repeated usage may lead to an increase in hunger.

Despite the potential of oxytocin in reducing attachment anxiety, it may have an overall anxiogenic effect in some subjects and a sedating effect in others. Studies report that the peptide causes the following side effects [27]:

• Jitteriness/restlessness (17%)
• Nervousness (11%)
• Dry mouth (7%)
• Sedation/drowsiness (7%)

However, it is crucial to note that not all peptides have been subjected to such rigorous clinical evaluation. For instance, peptides like PE-22-28 and Pinealon, despite their potential therapeutic benefits, lack clinical study data. Consequently, their safety profiles and potential side effects remain largely unknown.

This gap highlights the need for researchers to prioritize safety assessments during clinical trials for these peptides. While laboratory animal studies have shown favorable safety outcomes, it is imperative to understand that this may not translate to human trials in treating anxiety and depression [5, 12].

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Peptides and Depression | FAQ

Below we have provided evidence-based answers to some of the most commonly asked questions by researchers interested in peptides for anxiety, depression, and mental health.

What is the best peptide for anxiety?

Selank is arguably the best peptide for anxiety, as it has been shown to upregulate several neurotransmitters with anxiolytic potential. Its mechanisms include enkephalins, serotonin, and GABA receptor signaling. The peptide is clinically shown to reduce anxiety levels, and it's approved in Russia for the treatment of generalized anxiety disorder.

Are peptides good for anxiety?

Several peptides, including Selank, Pinealon, and oxytocin, stand out among the most common compounds used for anxiety research. Preclinical and clinical studies suggest that these peptides work via various mechanisms, including upregulating various neurotransmitters or directly interacting with their receptors, to ultimately reduce anxiety symptoms.

What is the best natural substance for anxiety?

The strongest anti-anxiety herb may be Ashwagandha (Withania somnifera), as shown by a meta-analysis encompassing 12 randomized controlled trials with a total sample size of 1,002 subjects. The research reported that the herb reduced both anxiety and stress [28].

What peptides increase serotonin levels?

The peptides Selank and Pinealon have both been shown to increase serotonin levels. Increasing serotonin is a common target of many prescription anxiolytic and antidepressant medications. Moreover, Selank has also shown anxiolytic properties in clinical trials.

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Peptides and Anxiety | Verdict

The most actively researched peptides for anxiety, depression, and mental health are Selank, PE-22-28, Pinealon, ghrelin, and oxytocin.

They provide anxiolytic and antidepressant effects via a variety of mechanisms, including by increasing serotonin levels, upregulating GABA receptors, and interacting with neurotrophic factors.

Nevertheless, researchers should note that many of our listed peptides for mood and mental health are yet to be extensively studied in clinical settings. Therefore, extra caution is required when handling these substances in experiments.

For researchers looking for high-quality peptides for anxiety and depression, we highly recommend this world-class research peptides source.

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