Peptides for Anxiety: 6 Options Ranked by Evidence (2026)

Evidence level: STRONG (human clinical trials in GAD patients)

Selank is a synthetic heptapeptide based on tuftsin, developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It has been approved in Russia since 2009 for generalized anxiety disorder (GAD) and neurasthenia.

The clinical evidence:

The strongest study enrolled 62 patients with GAD. Selank was compared head-to-head with medazepam (a benzodiazepine). Anxiolytic effects were comparable, but Selank also demonstrated antiasthenic and psychostimulant properties (Zozulya et al., 2008; PMID 18454096).

Patients felt less fatigued and more mentally alert. No sedation was observed.

A second comparison study tested Selank against phenazepam, another benzodiazepine. Results: comparable anxiety reduction, zero sedation, no muscle relaxation side effects, no tolerance development, and no withdrawal symptoms (PMID 25176261).

A molecular study found Selank alters expression of 36 genes related to the nervous and immune systems, including genes governing GABAergic neurotransmission (PMC4757669). Another study showed Selank enhances the anxiolytic effect of diazepam in chronic mild stress models without increasing side effects (PMC5322660).

Mechanism: Positive allosteric modulation of the GABA system (not direct GABA-A binding). Stabilizes enkephalin degradation, extending the activity of the body's natural pain and anxiety-reducing peptides. Modulates serotonin turnover in the frontal cortex and hippocampus.

Protocol: - Dosage: 250-500 mcg intranasal, 1-2 times daily - Cycle: 14-30 days on, 2 weeks off - Onset: 15-30 minutes after administration - Duration of effect: 6-12 hours per dose

Key advantage: Anxiolytic potency matching benzodiazepines without sedation, tolerance, or dependency. No other peptide on this list has that clinical profile.

Evidence level: MODERATE (approved for human use in Russia; anxiety-specific data from animal models)

Semax is a synthetic analogue of ACTH(4-10), approved in Russia since the 1990s for cognitive and neurological conditions. Its primary reputation is as a nootropic, but mood stabilization and stress resilience are consistent secondary benefits.

The evidence:

Semax rapidly elevates BDNF and TrkB receptor expression in the hippocampus, the brain region most involved in emotional memory and anxiety regulation (PMID 20566356). BDNF promotes neuroplasticity, the formation of new neural connections that underpin recovery from chronic anxiety.

A human trial in healthy adults showed improved cognitive function alongside enhanced emotional stability (PMID 18611170). Anti-inflammatory and antioxidant neuroprotective effects have been documented across multiple studies (PMID 22946722).

Important caveat: A 1996 study noted a potential "anxiogenic component" in Semax, meaning it may increase anxiety at certain doses in people with high baseline anxiety. This is not widely discussed but is relevant. Semax is better suited for anxiety accompanied by brain fog and fatigue than for acute panic or severe GAD.

Protocol: - Dosage: 300-600 mcg intranasal daily - Cycle: 10-20 days on, 2 weeks off - Onset: 15-30 minutes - Best timing: Morning (it can be mildly stimulating)

Classic stack: Semax (morning for cognitive clarity) + Selank (midday for anxiety control). This combination was developed at the same Russian research institute and is the most established peptide stack for mental performance with mood support.

Evidence level: MODERATE (animal studies; no human anxiety-specific trials)

BPC-157 is a 15-amino acid synthetic peptide derived from a protein in human gastric juice. Most people know it for tendon and joint repair, but its anxiolytic properties in animal models are striking. Its mechanism is unique among the peptides on this list.

The evidence:

Anxiolytic effects were demonstrated in two validated behavioral models: the shock probe/burying test and the light/dark test. BPC-157 significantly reduced anxiety-like behaviors in both paradigms. Antidepressant effects were confirmed in Porsolt's forced swim test and chronic unpredictable stress models, with efficacy comparable to imipramine and other standard antidepressants.

BPC-157 modulates both dopaminergic and serotonergic systems simultaneously. Within 40 minutes of administration, it increases serotonin synthesis in the substantia nigra and olfactory nucleus while decreasing it in the hypothalamus and hippocampus (PMID 34380875). This is selective modulation. SSRIs push serotonin in one direction everywhere; BPC-157 adjusts it regionally.

The gut-brain angle: Many people with chronic anxiety have comorbid gut issues: IBS, inflammatory bowel conditions, food sensitivities. BPC-157 heals the gut lining while simultaneously modulating brain neurotransmitters. For individuals whose anxiety has a gut component, this dual action is unmatched by any other peptide.

Protocol: - Dosage: 250-500 mcg/day, subcutaneous injection or oral - Duration: 4-8 weeks - Onset: 1-2 weeks for anxiety effects (faster for gut symptoms) - Oral route works for gut-brain effects; injection for systemic distribution

Use our BPC-157 dosage calculator for precise dosing. For more on this peptide, see our BPC-157 profile and BPC-157 side effects guide. If you drink alcohol, review our BPC-157 and alcohol interaction guide.

Evidence level: MODERATE (human sleep studies; anxiety data from animal models and early human reports)

DSIP (Delta Sleep-Inducing Peptide) was first isolated in 1977. It targets the anxiety-insomnia cycle. Anxiety disrupts sleep. Poor sleep worsens anxiety. Breaking this cycle is often the fastest path to symptom improvement.

The evidence:

DSIP promotes natural delta-wave (stage 3) sleep without the forced sedation of sleeping pills. A 1983 human study found subjects reported "better relaxation" and "improved tolerance against psychic stress" (PMID 3791851).

DSIP dampens ACTH and cortisol surges, the hormones that keep anxious people awake at 3 AM replaying worst-case scenarios. By normalizing the HPA axis, DSIP addresses the neuroendocrine root of stress-driven insomnia.

In animal studies, DSIP injection increased substance P concentration in the hypothalamus and "sharply decreased classical manifestations of stress" (PMID 7628639). DSIP also enhances GABA signaling, providing a direct anxiolytic mechanism beyond its sleep effects.

A comprehensive review characterized DSIP as a stress-protective molecule with sleep-modulatory, analgesic, and neuroendocrine properties (PMID 9352530).

Protocol: - Dosage: 100-300 mcg subcutaneous or intranasal - Timing: 30 minutes before bed - Duration: 2-4 week cycles - Onset: Same night for sleep effects; cumulative anxiolytic benefit over 1-2 weeks

Best for: Anxiety-driven insomnia, nocturnal rumination, HPA axis dysregulation, stress-related sleep disruption. Not ideal for daytime-only anxiety without a sleep component.

Evidence level: MIXED (extensive preclinical data; inconclusive human trials)

Oxytocin is a naturally occurring neuropeptide, the "bonding hormone" released during social connection, physical touch, and breastfeeding. Its anti-anxiety effects in animal models are consistent and well-documented. The human data is more complicated.

The evidence:

Animal studies consistently show reduced anxiety-like behaviors with central oxytocin administration. The mechanism is clear: oxytocin activates GABAergic interneurons in the amygdala (the brain's fear center) and interacts with serotonergic systems to dampen threat perception.

The human picture is less encouraging. A systematic review of 15 randomized controlled trials found "no significant effects on core symptomatology" for anxiety and depressive disorders (PMC6361048). For social anxiety specifically, intranasal oxytocin improved observer-rated social behavior, but patients themselves did not perceive improvement.

One trial found intranasal oxytocin enhanced the effects of exposure therapy for social anxiety disorder (PMID 19246160), suggesting it may work best as a therapy adjunct rather than a standalone treatment.

Honest assessment: The mechanism is sound. The preclinical support is extensive. The clinical translation has been disappointing. Oxytocin shows the widest gap between animal results and human outcomes of any peptide on this list.

Protocol: - Dosage: 20-40 IU intranasal - Timing: 30-45 minutes before social situations or therapy sessions - Best for: Social anxiety, relationship-related anxiety, therapy augmentation - Not recommended as a standalone anxiety treatment based on current evidence

Evidence level: EARLY (preclinical only; no human trials)

PE-22-28 is a synthetic heptapeptide derived from spadin, a naturally occurring neuropeptide. It is included here as a "one to watch" rather than a current recommendation, because its mechanism is genuinely novel.

The evidence:

PE-22-28 inhibits TREK-1 potassium channels with high specificity (IC50: 0.12 nM versus 40-60 nM for its parent molecule spadin). TREK-1 knockout mice show resistance to depression across validated behavioral models. PE-22-28 produces rapid antidepressant-like effects in mice, within days rather than the weeks SSRIs require. Action duration reaches 23 hours, compared to 7 hours for spadin (PMC5601071).

The speed of action is notable. If these results translate to humans, PE-22-28 could function more like ketamine (rapid onset) than like SSRIs (4-6 week delay). PE-22-28 may also promote neurogenesis through enhanced BDNF pathway activation via TREK-1 inhibition.

Current status: No human safety or efficacy data. No approved use in any country. This peptide is years away from clinical application. The mechanism, a specific potassium channel target for mood regulation, represents a genuinely different approach to anxiety and depression.

The simplest starting point for anxiety. Appropriate for generalized anxiety, work stress, and anxious rumination.

• Selank 250-500 mcg intranasal, 1-2 times daily
• Morning dose + early afternoon dose (avoid evening dosing if it affects sleep)
• 14-30 day cycles, 2 weeks off between cycles
• Effects begin within 15-30 minutes of each dose

This is the most evidence-backed protocol on this list. Start at 250 mcg twice daily and increase only if needed.

The classic Russian nootropic stack. Developed at the same research institute that created both peptides. Appropriate for anxiety with brain fog, stress-related cognitive decline, or depression comorbidity.

• Semax 300-600 mcg intranasal, morning
• Selank 250-500 mcg intranasal, 30 minutes after Semax
• 10-20 day cycles, 2 weeks off
• Semax provides cognitive enhancement and BDNF elevation. Selank provides anxiolytic calm. The combination addresses both the mental fog and the anxiety.

Use our peptide stack calculator to plan dosing and cycling.

For people whose anxiety coexists with gut issues: IBS, bloating, food sensitivities, or inflammatory bowel conditions.

• BPC-157 250-500 mcg oral or subcutaneous, daily
• Selank 250-500 mcg intranasal, daily
• 4-8 week duration
• BPC-157 heals the gut lining and rebalances brain neurotransmitters. Selank provides immediate anxiolytic relief while BPC-157 builds its cumulative effect over 1-2 weeks.

See our guide on taking BPC-157 orally for administration details.

For people whose anxiety peaks at night: racing thoughts at bedtime, 3 AM waking, stress-disrupted sleep that worsens daytime anxiety.

• Selank 250-500 mcg intranasal, evening (addresses anxious rumination)
• DSIP 100-200 mcg subcutaneous, 30 minutes before bed (ensures restorative delta-wave sleep)
• 2-4 week cycles
• Breaking the sleep-anxiety cycle often produces faster improvement in daytime anxiety than targeting anxiety directly.

This combination is particularly useful during high-stress periods (exams, work deadlines, life transitions) when sleep disruption threatens to escalate into a full anxiety episode.

Selank: Excellent safety record across Russian clinical use. Side effects rare and mild: nasal irritation, occasional light headache. No tolerance, no dependency, no withdrawal in any published study. Approved in Russia; not FDA-approved in the US.

Semax: Good safety profile across decades of Russian clinical use. Occasional headache and, rarely, temporary hair shedding reported anecdotally. Possible anxiogenic effect at high doses in individuals with high baseline anxiety. Approved in Russia.

BPC-157: No recorded lethal dose (LD50) in animal studies. Side effects: mild nausea (oral route), injection site irritation. Avoid with active cancer; BPC-157 is pro-angiogenic and promotes cell proliferation.

No human clinical trials establishing long-term safety. FDA Category 2 substance. Cannot be legally compounded by US pharmacies.

DSIP: Limited long-term safety data. Avoid combining with sedative medications, alcohol, or CNS depressants. Not approved for medical use in any country.

Oxytocin: Prescription nasal spray in some countries. Side effects: nasal irritation, headache. Effects are context-dependent and may increase anxiety in some situations.

PE-22-28: No human safety data whatsoever. Research compound only.

Selank + SSRIs: Selank modulates serotonin turnover. Theoretical risk of serotonin syndrome when combined with SSRIs, SNRIs, or MAOIs. No cases reported, but caution is warranted. Discuss with your prescribing physician before combining.

DSIP + CNS depressants: DSIP enhances GABA signaling and promotes sleep. Combining with benzodiazepines, sleep medications, or alcohol could produce excessive sedation.

BPC-157 + blood thinners: BPC-157 affects the nitric oxide system and promotes angiogenesis. Theoretical interaction with anticoagulants. Consult physician if on blood-thinning medication.

General rule: If you take any psychiatric medication, discuss peptide use with your prescriber before starting. The interaction data is limited, which means risk cannot be ruled out.

None of the peptides in this article are FDA-approved for anxiety treatment in the United States. Selank and Semax are approved medications in Russia. In the US and most Western countries, these peptides are classified as research compounds.

BPC-157 was placed in FDA Category 2 in 2023, meaning it cannot be legally compounded by US pharmacies. It is not a controlled substance.

This regulatory status says nothing about safety. It means these peptides have not undergone the full FDA approval process, which costs $1-2 billion and takes 10-15 years. It also means quality control varies wildly between suppliers. Source only from vendors who provide third-party certificates of analysis.