Schisandra chinensis
Schizandra
Wu Wei Zi
Omija
Five-Flavor Berry
Magnolia Berry

---
canonical_name: Schisandra
alternate_names: Schisandra chinensis, Schizandra, Wu Wei Zi, Omija, Five-Flavor Berry, Magnolia Berry
canonical_topic: Schisandra for Health & Longevity
short_topic_lc: schisandra
creation_date: 2026-0626-0348
creator_ai_fullname: Opus 4.8
---

# Schisandra for Health & Longevity

Evidence Review created on 06/26/2026 using [AI4L](https://github.com/forever-healthy/AI4L) / Opus 4.8

**Also known as:** Schisandra chinensis, Schizandra, Wu Wei Zi, Omija, Five-Flavor Berry, Magnolia Berry

## Motivation

Schisandra is the dried red berry of the woody vine *Schisandra chinensis*, native to northeastern China, Korea, and the Russian Far East. In Chinese it is called Wu Wei Zi, the "five-flavor berry," because a single fruit carries sour, sweet, salty, bitter, and pungent tastes at once. It belongs to a small group of plants known as adaptogens — substances claimed to help the body resist a wide range of physical and mental stressors. Its main active compounds are a family of plant chemicals called lignans, concentrated in the berry's seed.

The berry has a long parallel history. Chinese medicine used it for centuries as a tonic for the liver, kidneys, and "vital energy," while Soviet researchers from the 1940s onward studied it as a way to improve the stamina and concentration of soldiers, pilots, and factory workers. It later became an official remedy in the national pharmacopoeia of the former USSR. Modern interest centers on its liver-protective and antioxidant properties.

This review examines what the human and laboratory evidence shows about Schisandra, centered on its best-studied areas of liver health and stress resilience, and where the gaps between traditional claims and controlled data remain widest.

**[Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol) - [Conclusion](#conclusion)**

## Recommended Reading

This section lists high-level overviews and expert commentary that introduce Schisandra's traditional use, active compounds, and research base for a non-specialist reader.

* [Schisandra: Benefits, Side Effects, and Forms](https://www.healthline.com/health/schisandra) - Lindsay Boyers

  A plain-language consumer overview of Schisandra's proposed uses, traditional context, and safety, useful as an accessible entry point before reading the primary literature.

* [Schisandra (Schisandra chinensis): Benefits, Safety, Uses](https://www.herbalreality.com/herb/schisandra/) - Sebastian Pole

  A practitioner-oriented herbal monograph covering traditional indications, preparation, and clinical herbalism perspective on the berry's "five flavors" and adaptogenic positioning.

* [Schisandra fruits for the management of drug-induced liver injury in China: A review](https://pubmed.ncbi.nlm.nih.gov/31004881/) - Zhu et al., 2019

  A focused narrative review of how Schisandra-derived preparations are used clinically against drug-induced liver injury, summarizing the human and laboratory evidence and the antioxidant, anti-inflammatory, and cytochrome-P450 mechanisms behind the berry's hepatoprotective reputation.

* [Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine](https://pubmed.ncbi.nlm.nih.gov/18515024/) - Panossian & Wikman, 2008

  A detailed review of the large but little-known Soviet-era pharmacological and clinical literature, valuable for understanding the historical basis of Schisandra's stamina and stress claims.

* [Potential of Schisandra chinensis (Turcz.) Baill. in Human Health and Nutrition](https://pubmed.ncbi.nlm.nih.gov/30720717/) - Nowak et al., 2019

  A broad modern narrative review summarizing the berry's phytochemistry, antioxidant and hepatoprotective activity, and therapeutic prospects across organ systems.

*Note: No dedicated, substantial Schisandra-specific content was found from the priority experts (Rhonda Patrick, Peter Attia, Andrew Huberman, Chris Kresser, Life Extension Magazine); the berry appears only within broader, often access-restricted coverage. The items above are the most relevant qualifying overviews located.*

## Grokipedia

* [Schisandra chinensis](https://grokipedia.com/page/Schisandra_chinensis) - Grokipedia

  The Grokipedia entry compiles botanical description, traditional use, lignan chemistry, and a survey of preclinical and clinical research, offering a single consolidated reference page for the species.

## Examine

* [Schisandra](https://examine.com/supplements/schisandra/) - Examine

  Examine's independent, citation-based summary grades the human evidence for Schisandra across outcomes and is the most rigorous consumer-facing analysis of what the controlled data actually support.

## ConsumerLab

No dedicated ConsumerLab article or product-test report for Schisandra was found.

## Systematic Reviews

The following systematic reviews and meta-analyses represent the highest-tier synthesized evidence currently indexed on PubMed for Schisandra; both are syntheses of animal (preclinical) studies, as no meta-analysis of human Schisandra trials yet exists.

* [Efficacy of Schisandra chinensis in liver injury: a systematic review and preclinical meta-analysis](https://pubmed.ncbi.nlm.nih.gov/40832608/) - Huang et al., 2025

  Pooling 54 animal studies, this meta-analysis found Schisandra compounds markedly lowered liver-enzyme markers (ALT and AST — alanine and aspartate aminotransferase, enzymes that leak from damaged liver cells) and oxidative-stress and inflammation markers, while cautioning that high variability between studies and the absence of human data limit translation.

* [Effects of schisandra extract on muscle atrophy: a systematic review and meta-analysis of preclinical studies](https://pubmed.ncbi.nlm.nih.gov/41982662/) - Liu et al., 2026

  Across 11 animal studies, Schisandra significantly increased muscle weight and antioxidant-enzyme activity, but grip strength and body weight were unchanged, so the authors concluded that functional muscle benefits remain unconfirmed and human trials are needed.

## Mechanism of Action

Schisandra's effects are attributed mainly to its dibenzocyclooctadiene lignans — a family of fat-soluble plant compounds (the best-studied are schisandrin, schisandrin B, gomisin A, and schisandrin C) concentrated in the seed.

* **Antioxidant and Nrf2 activation:** The lignans activate the Nrf2 pathway (a master switch, short for "nuclear factor erythroid 2–related factor 2," that turns on the cell's own antioxidant and detoxification genes). This raises levels of protective enzymes such as superoxide dismutase (SOD) and glutathione, lowering oxidative damage to cells. This is the leading explanation for the berry's liver-protective and general antioxidant activity.

* **Liver enzyme and detoxification modulation:** Schisandra influences the cytochrome P450 enzyme system (CYP — a family of liver enzymes that break down drugs and toxins). It can induce some enzymes (notably CYP3A4) while protecting liver cells from toxin-induced injury, which underlies both its traditional hepatoprotective use and its potential to alter drug metabolism.

* **Anti-inflammatory signaling:** The lignans suppress NF-κB (nuclear factor kappa B, a central controller of inflammatory gene expression), reducing pro-inflammatory messengers such as TNF-α (tumor necrosis factor alpha) and IL-6 (interleukin-6). This contributes to the proposed benefits in liver and metabolic conditions.

* **Stress-axis ("adaptogen") modulation:** Proposed adaptogenic effects involve modulation of the hypothalamic-pituitary-adrenal axis (HPA axis — the body's central stress-hormone system), with reported changes in cortisol (the main stress hormone) and nitric oxide signaling, plus induction of stress-defense proteins (heat-shock proteins). This mechanism is the most debated.

Two competing mechanistic interpretations exist. Proponents argue the lignans produce genuine, dose-dependent cellular stress-resistance ("hormesis," a brief beneficial stress that strengthens cells). Skeptics contend that most mechanistic data come from cell-culture and animal models at doses or routes not achievable in humans, and that human bioavailability of the lignans is low and variable, so the in-vivo relevance of these pathways remains uncertain.

## Historical Context & Evolution

* **Original use:** Schisandra was first used as a food and medicine in China, Korea, and the Russian Far East. In traditional Chinese medicine it is classed as an "astringent" tonic prescribed for cough, night sweats, chronic diarrhea, and as a restorative for the liver, kidney, and "qi" (vital energy); the berry is also brewed into the Korean tea and drink "omija-cha."

* **Path to health optimization:** The modern interest traces less to Chinese medicine than to Soviet research. From the 1940s onward, Russian scientists investigated Schisandra as a stimulant-free way to increase the physical working capacity, endurance, and concentration of pilots, soldiers, and laborers, classifying it — alongside *Rhodiola rosea* and *Eleutherococcus* — as an "adaptogen." It was entered into the State Pharmacopoeia of the USSR.

* **What the historical research actually found:** The Soviet-era studies, summarized in detail by Panossian and Wikman, reported that Schisandra increased endurance, accuracy of movement, and mental performance in healthy subjects, and produced stress-protective effects across many animal challenge models. Much of this literature, however, was published in Russian, often without the blinding, placebo controls, or statistical reporting expected today.

* **Evolution of scientific opinion:** Western evaluation has been cautious rather than dismissive. The adaptogen concept itself was long viewed skeptically because it lacked a clear mechanism; more recent work identifying Nrf2 activation, heat-shock-protein induction, and HPA-axis effects has given it a plausible molecular basis, while rigorous modern human trials specific to Schisandra remain scarce. The current standing is best read as "biologically plausible and historically supported, but under-tested by modern standards" rather than settled in either direction.

## Expected Benefits

The benefits below are graded by the strength of the human evidence specifically for Schisandra. Because most controlled data come from animal or cell studies and the few human trials are small, evidence levels are generally modest, and findings are framed for a health-optimizing adult rather than as population guidance.

### High 🟩 🟩 🟩

No benefit currently qualifies for a High evidence grade. The human trial base for Schisandra is too small and heterogeneous to support a high-confidence claim for any single outcome.

### Medium 🟩 🟩

#### Hepatoprotection (Liver Enzyme Support)

Liver protection is Schisandra's most consistently supported benefit, attributed to Nrf2-driven antioxidant defense and reduced inflammatory signaling in liver cells. The evidence basis is strong preclinically — a 2025 systematic review and meta-analysis of 54 animal studies found large reductions in the liver-injury markers ALT and AST — and supported by older Russian and Chinese clinical use in hepatitis. The key limitation is that rigorous modern human trials are lacking, so the magnitude of benefit in people who are not acutely ill is uncertain.

**Magnitude:** In pooled animal data, ALT fell by a standardized mean difference of about −4.7 and AST by about −5.1 (both large effects); human-equivalent magnitudes are not established.

#### Menopausal Symptom Relief

A small randomized, double-blind, placebo-controlled trial found a Schisandra extract reduced overall menopausal symptom scores, with the clearest effects on hot flushes, sweating, and heart palpitations. The proposed mechanism combines mild central-nervous-system and possible weak estrogen-like activity of the lignans. The evidence basis is a single 36-completer trial over 12 weeks, which limits confidence and generalizability, though the result is internally consistent and the extract was well tolerated.

**Magnitude:** Total Kupperman Index symptom scores were significantly lower with Schisandra than placebo (p = 0.042) in one 36-participant trial.

### Low 🟩

#### Glycemic Control (Blood Sugar)

A 12-week randomized, double-blind, placebo-controlled trial of an Omija (Schisandra) extract-and-soybean mixture in adults with mildly elevated fasting glucose showed reductions in fasting and post-meal glucose, insulin response, and LDL cholesterol (low-density lipoprotein, the "bad" cholesterol fraction). The proposed mechanism involves improved insulin sensitivity and antioxidant effects. The evidence is graded Low because the product combined Schisandra with soybean, so the berry's independent contribution cannot be isolated, and the trial was small.

**Magnitude:** Significant decreases versus placebo in fasting and 30/60-minute post-meal glucose, insulin area-under-the-curve, fructosamine, and LDL cholesterol in 80 participants.

#### Physical Endurance & Anti-Fatigue (Stress Resilience)

The traditional and Soviet-era basis for Schisandra is improved stamina, mental performance, and resistance to fatigue, typically as part of adaptogen combinations such as the Schisandra–Rhodiola–Eleutherococcus blend "Adapt-232." The proposed mechanism is HPA-axis and heat-shock-protein modulation. Evidence is graded Low because most supportive human data are older, lower-quality, or test multi-herb blends rather than Schisandra alone, making the berry's specific contribution hard to quantify.

**Magnitude:** Not quantified in available studies.

### Speculative 🟨

#### Cognitive Function & Neuroprotection

Lignans such as schisandrin B show neuroprotective and memory-supporting effects in cell and animal models of cognitive impairment, acting through antioxidant and anti-inflammatory pathways in the brain. No controlled human trials test Schisandra alone for cognition; the basis is mechanistic and preclinical only.

#### Muscle Preservation (Anti-Sarcopenia)

A 2026 meta-analysis of animal studies found Schisandra increased muscle weight and antioxidant-enzyme activity, suggesting possible value against age-related muscle loss. However, grip strength was unchanged in animals and no human efficacy trial has confirmed a functional benefit, so this remains mechanistic and anecdotal.

## Benefit-Modifying Factors

* **Baseline liver and metabolic status:** The clearest signals appear in people with elevated liver enzymes or impaired glucose; an already-healthy adult with normal markers may see little measurable change, since antioxidant and enzyme-normalizing effects have less room to act.

* **Sex-based differences:** The menopausal-symptom benefit is, by definition, specific to peri- and postmenopausal women. Whether the berry's possible weak estrogen-like activity meaningfully differs by sex for other outcomes has not been studied.

* **Pre-existing conditions:** Those with existing inflammatory or oxidative-stress-driven conditions (e.g., metabolic dysfunction, early liver disease) are the populations in which preclinical benefits are largest; benefits in disease-free individuals are extrapolated, not demonstrated.

* **Genetic polymorphisms:** Variation in cytochrome P450 enzymes (especially CYP3A4 activity) may influence both how the lignans are metabolized and how strongly Schisandra alters the clearance of co-administered drugs, indirectly shaping any benefit derived from combination regimens.

* **Age-related considerations:** Older adults — including those at the upper end of a health-optimizing range — are the target group for the muscle-preservation and stamina claims, but these rest on animal data; age-specific human dosing has not been defined.

## Potential Risks & Side Effects

Schisandra has a long record of food and medicinal use and is generally well tolerated in the short term, but its modern human safety data are thin and its effect on drug-metabolizing enzymes is the most important practical concern. Risks are framed for a health-optimizing adult who may be combining it with other supplements or medications.

### High 🟥 🟥 🟥

No risk currently qualifies for a High evidence grade; no serious adverse effect has been reliably established in controlled human use.

### Medium 🟥 🟥

#### Drug–Herb Interactions via Liver Enzymes

Schisandra lignans modulate cytochrome P450 enzymes — particularly inducing or inhibiting CYP3A4 depending on compound and dose — which can raise or lower blood levels of many medications. This is a pharmacokinetic effect demonstrated in human and animal studies (notably with the immunosuppressant tacrolimus, whose levels rise substantially when taken with Schisandra). The consequence ranges from reduced drug efficacy to toxicity, making this the berry's most clinically meaningful risk.

**Magnitude:** Co-administration with tacrolimus has increased its blood concentration roughly 2-fold or more in clinical pharmacokinetic studies.

### Low 🟥

#### Gastrointestinal Upset

Mild stomach upset, heartburn, decreased appetite, or acid reflux are the most commonly reported direct side effects, consistent with the berry's sour, astringent nature. The basis is consumer reports and trial tolerability data; effects are mild, dose-related, and reversible on stopping.

**Magnitude:** Reported in a small minority of users; not consistently quantified across trials.

#### Allergic or Skin Reactions

Isolated reports describe skin rash or urticaria (hives) with Schisandra use. The mechanism is presumed individual hypersensitivity. Evidence is limited to case-level reports, so the absolute risk appears low but is not well characterized.

**Magnitude:** Not quantified in available studies.

### Speculative 🟨

#### Effects in Pregnancy

Traditional sources caution against Schisandra in pregnancy because animal data show it can stimulate uterine muscle activity, raising a theoretical risk of inducing contractions. No controlled human safety data exist; the concern is mechanistic and precautionary only.

#### Central Nervous System Overstimulation

Because Schisandra has mild stimulating and CNS-active properties, restlessness or sleep disturbance is biologically plausible at higher doses or late-day timing. This rests on its pharmacology and scattered anecdote rather than controlled data.

## Risk-Modifying Factors

* **Genetic polymorphisms:** Individuals who are CYP3A4 poor or extensive metabolizers may experience exaggerated or blunted interaction effects when Schisandra is combined with CYP3A4-substrate drugs, altering the magnitude of any interaction risk.

* **Baseline liver function:** Those with significant liver disease process the lignans and co-administered drugs differently; impaired liver function may amplify both benefits and interaction risks and warrants extra caution.

* **Sex-based differences:** The uterine-stimulant concern applies specifically to women who are or may become pregnant; no clear sex difference in other adverse effects has been established.

* **Pre-existing conditions:** People with gastroesophageal reflux or peptic ulcers may be more prone to the gastrointestinal and acid-related side effects, given the berry's acidic, astringent character. Those with epilepsy or on multiple medications face elevated interaction risk.

* **Age-related considerations:** Older adults are more likely to take CYP3A4-substrate medications (e.g., statins, calcium-channel blockers, certain blood thinners), so the drug-interaction risk is practically greater in this group even though no age-specific toxicity is documented.

## Key Interactions & Contraindications

* **Immunosuppressants (tacrolimus, sirolimus, cyclosporine):** Severity — caution to avoid. Schisandra markedly raises blood levels of these CYP3A4-substrate drugs, risking toxicity (kidney injury, tremor); any combination requires close drug-level monitoring under a physician.

* **CYP3A4-substrate prescription drugs (statins such as simvastatin, calcium-channel blockers, midazolam, some chemotherapy agents):** Severity — caution. Altered metabolism can raise or lower drug levels, changing efficacy or toxicity; separating timing does not reliably prevent enzyme-level interactions, so monitoring is preferred.

* **CYP3A4-inducing or -inhibiting agents (rifampicin, ketoconazole, ritonavir, grapefruit juice):** Severity — caution. Combining Schisandra with other agents that act on the same enzyme compounds the unpredictability of drug levels.

* **Over-the-counter medications (acetaminophen/paracetamol, NSAIDs — non-steroidal anti-inflammatory drugs such as ibuprofen):** Severity — monitor. Acetaminophen is cleared partly by liver enzymes Schisandra modulates; while Schisandra is hepatoprotective in models, the interaction direction in humans is not well defined, so caution with regular high-dose use is reasonable.

* **Supplements with additive liver or sedative effects (milk thistle, kava, valerian, other adaptogens such as Rhodiola and ashwagandha):** Severity — monitor. Adaptogen blends are common and traditional, but stacking multiple CNS-active or liver-active herbs increases the chance of overstimulation or unpredictable enzyme effects.

* **Blood-glucose-lowering drugs (metformin, sulfonylureas, insulin):** Severity — monitor. Given Schisandra's glucose-lowering signal, additive effects could lower blood sugar further; glucose monitoring is prudent.

* **Populations who should avoid Schisandra:** Pregnant women (uterine-stimulant concern); people with active peptic ulcer disease or severe acid reflux; those with epilepsy or uncontrolled seizure disorders (traditional caution and CNS activity); organ-transplant recipients on immunosuppressants unless supervised; and anyone with significant liver disease (e.g., decompensated cirrhosis, Child-Pugh Class C) without medical oversight.

## Risk Mitigation Strategies

* **Medication review before starting:** Have a pharmacist or physician screen for CYP3A4-substrate drugs — to prevent the drug-interaction risk, the most serious concern — before adding Schisandra, especially for anyone on immunosuppressants, statins, or seizure medications.

* **Low starting dose with gradual increase:** Begin at the low end of standardized extract dosing (e.g., the equivalent of ~500 mg dried berry or ~100 mg of a standardized extract daily) and increase over 1–2 weeks; this limits gastrointestinal upset and overstimulation while gauging individual tolerance.

* **Take with food, earlier in the day:** Dosing with meals reduces the acid-related stomach upset associated with the sour berry, and morning-to-midday timing mitigates the risk of sleep disturbance from its mild stimulating effect.

* **Avoid during pregnancy and around conception:** To prevent the theoretical uterine-stimulant risk, Schisandra is best discontinued by women who are pregnant or trying to conceive until human safety data exist.

* **Monitor drug levels and glucose when stacking:** For those who must combine Schisandra with narrow-therapeutic-index drugs (e.g., tacrolimus) or glucose-lowering agents, scheduled blood-level or glucose monitoring detects clinically important shifts before they cause harm.

* **Use single-ingredient, standardized products when isolating effects:** Choosing a product standardized to schisandrin/schisandrin B content, rather than an undefined multi-herb blend, reduces the risk of unexpected additive interactions and makes dose-response easier to judge.

## Therapeutic Protocol

No standardized, evidence-based clinical protocol for Schisandra exists; the approaches below reflect how it is most commonly used in herbal medicine, supplement practice, and the adaptogen literature.

* **Standard dosing (whole berry / extract):** Traditional and supplement use ranges widely — roughly 0.5–3 g of dried berry daily, or standardized extracts providing the equivalent, often standardized to schisandrin or total lignan content. Tincture and decoction (tea) forms are also used in herbalism.

* **Adaptogen-blend approach:** A distinct tradition, popularized by Soviet/Scandinavian researchers (Panossian, Swedish Herbal Institute), uses fixed combinations such as "Adapt-232" pairing Schisandra with *Rhodiola rosea* and *Eleutherococcus senticosus* for stress and fatigue rather than Schisandra alone.

* **Best time of day:** Because of its mild stimulating, CNS-active nature, morning or early-afternoon dosing is generally preferred to avoid interfering with sleep; this is a practical convention, not a trial-derived rule.

* **Half-life:** The principal lignans have relatively short plasma half-lives (on the order of a few hours), and bioavailability is low and variable, which is one reason divided or repeated daily dosing is common.

* **Single versus split dosing:** Given the short half-life, split dosing (e.g., twice daily with meals) is often used to maintain exposure and reduce per-dose gastrointestinal load, though no trial has compared single versus split regimens head-to-head.

* **Genetic considerations:** CYP3A4 metabolizer status may influence both lignan clearance and interaction potential; there is no validated pharmacogenetic dosing guidance, so this informs caution rather than a specific dose.

* **Sex-based considerations:** Dosing for menopausal symptom relief follows the single trial's extract (BMO-30) rather than whole-berry equivalents; no sex-specific dosing exists for other goals.

* **Age-related considerations:** Older adults on multiple medications should favor lower doses and closer interaction monitoring; no age-stratified dosing has been established.

* **Baseline biomarkers:** Where the goal is liver or metabolic support, baseline liver enzymes and fasting glucose help define a measurable starting point against which to judge response.

* **Pre-existing conditions:** Those with reflux, ulcers, or on interacting drugs should adjust dose, form, and timing accordingly, as described under Risk Mitigation.

## Discontinuation & Cycling

* **Lifelong versus short-term:** Schisandra is generally used as a short- to medium-term supportive agent (weeks to a few months) for specific goals such as stress, liver support, or menopausal symptoms, rather than as a lifelong daily supplement; long-term continuous-use data are lacking.

* **Withdrawal effects:** No characterized withdrawal syndrome is reported; because it is not known to cause dependence, abrupt discontinuation is not associated with documented rebound effects.

* **Tapering:** No formal tapering protocol is needed or established; the berry can generally be stopped without a step-down schedule.

* **Cycling:** As with other adaptogens, some practitioners recommend cycling (e.g., several weeks on followed by a break) on the theory that it preserves responsiveness and limits any unknown long-term effects, but this practice is traditional and precautionary rather than supported by controlled efficacy or safety data.

## Sourcing and Quality

* **Species and plant part:** Confirm the product is *Schisandra chinensis* (or the closely related *S. sphenanthera*, used in some Chinese preparations) and is derived from the berry/fruit, where the active lignans concentrate; leaf or undefined "schisandra" material may differ in composition.

* **Standardization:** Prefer extracts standardized to a defined lignan content (e.g., schisandrin or total dibenzocyclooctadiene lignans), which allows consistent dosing and is the form used in research, rather than non-standardized powders.

* **Third-party testing:** Look for independent verification (e.g., USP, NSF, or third-party certificates of analysis) for identity, lignan content, and contaminants such as heavy metals and pesticides, which are a recognized concern for imported botanicals.

* **Reputable formats:** Established herbal and supplement brands offering single-ingredient, standardized Schisandra, or well-characterized traditional preparations (dried berry, tincture, decoction) from suppliers that publish testing, are preferable to undefined proprietary blends.

* **Adulteration and blends:** Be cautious with multi-herb "adaptogen" or "energy" blends that list Schisandra without disclosing dose or standardization, since the berry's contribution and interaction risk cannot be assessed.

## Practical Considerations

* **Time to effect:** Liver-enzyme and metabolic changes in trials were assessed over 8–12 weeks, and the menopausal-symptom trial measured benefit at 12 weeks; subjective stress/energy effects, if present, are reported within days to weeks. A multi-week trial is therefore reasonable before judging response.

* **Common pitfalls:** Expecting whole-berry tea to match standardized-extract doses; using undefined blends and attributing effects to Schisandra; ignoring drug-interaction screening; and taking it late in the day, which can disturb sleep.

* **Regulatory status:** In the United States and most Western markets Schisandra is sold as a dietary supplement, not a regulated drug, so claims and quality are not pre-approved; in the former USSR it held official pharmacopoeial status. It is generally recognized as a food in its native regions.

* **Cost and accessibility:** Schisandra is inexpensive and widely available as berries, powders, tinctures, and capsules; cost and access are not meaningful barriers.

## Interaction with Foundational Habits

* **Sleep:** Direction — potentially blunting if mistimed. Schisandra's mild CNS-stimulating activity can interfere with sleep onset when taken late in the day; the practical step is to dose in the morning or early afternoon. Some traditional use claims it improves sleep quality over time, but this is not established in controlled data.

* **Nutrition:** Direction — indirect, potentiating with food. Taking the berry with meals reduces its acid-related stomach upset, and its fat-soluble lignans may be better absorbed alongside dietary fat. There is no evidence it depletes specific nutrients, and it is traditionally consumed as a food (omija tea).

* **Exercise:** Direction — potentially potentiating (anti-fatigue). The historical rationale for Schisandra is improved physical working capacity and endurance, which would complement training; however, the human performance data are old and largely from multi-herb blends, so any ergogenic effect should be treated as unproven. No evidence suggests it blunts training adaptations.

* **Stress management:** Direction — direct, potentiating (proposed). As an adaptogen, Schisandra's central claim is improved resilience to mental and physical stress via HPA-axis modulation, positioning it as a complement to behavioral stress-management practices; the supporting human evidence, however, is limited and often from combination products.

## Monitoring Protocol & Defining Success

Baseline and follow-up testing should be matched to the user's specific goal (liver support, glycemic control, or menopausal symptoms). Establish baseline values before starting so that change can be measured rather than assumed.

For ongoing monitoring, a reasonable cadence is to recheck relevant labs at baseline, again at 8–12 weeks, and then every 6–12 months if use continues; those combining Schisandra with interacting medications should monitor drug levels per their physician's schedule.

| Biomarker | Optimal Functional Range | Why Measure It? | Context/Notes |
|-----------|--------------------------|-----------------|---------------|
| ALT (alanine aminotransferase) | ~10–25 U/L | Tracks liver-cell health and hepatoprotective response | Conventional upper limit (~40–55 U/L) is higher than the optimal functional target; fasting not required |
| AST (aspartate aminotransferase) | ~10–25 U/L | Complements ALT for liver status | Also released from muscle; interpret alongside ALT and after avoiding intense exercise |
| Fasting plasma glucose | 70–90 mg/dL | Assesses the glycemic-control goal | Requires 8–12 h fast; pair with HbA1c |
| HbA1c (glycated hemoglobin, 3-month average blood sugar) | <5.4% | Confirms sustained glucose effect | No fasting needed; reflects ~3 months, so recheck no sooner than 8–12 weeks |
| LDL cholesterol | <100 mg/dL (lower if higher-risk) | One trial showed LDL reduction with Schisandra extract | Part of a fasting lipid panel; best paired with triglycerides and HDL |
| Kupperman Index / menopause symptom score | Lower score = fewer symptoms | Quantifies menopausal-symptom benefit | Self-report questionnaire; track at baseline and 12 weeks |

Qualitative markers complement the labs:

* Perceived energy and physical stamina through the day
* Stress resilience and mood under load
* Sleep quality and whether dosing timing disturbs it
* Frequency and severity of hot flushes, sweating, or palpitations (for menopausal use)
* Digestive comfort (absence of reflux or stomach upset)

## Emerging Research

Active research on Schisandra in humans is concentrated in multi-herb traditional formulas rather than the single berry, and in preclinical mechanism studies; entries below span directions that could strengthen or weaken the case.

* **Schisandra-containing formula for long-COVID fatigue:** [NCT06980636](https://clinicaltrials.gov/study/NCT06980636) — a Phase 4 trial of Shengmai Liquid (a classical formula containing Schisandra) in ~100 participants, with fatigue improvement (Modified Fatigue Impact Scale) as the primary endpoint; relevant to the berry's anti-fatigue claims but confounded by the multi-herb formulation.

* **Schisandra-containing formula for chemotherapy-related cardiotoxicity:** [NCT06214195](https://clinicaltrials.gov/study/NCT06214195) — a Phase 3 trial of Shengmai San in 276 breast-cancer patients testing prevention of heart toxicity, an example of Schisandra's cardiovascular/tonic tradition being tested in a modern controlled design.

* **Preclinical liver synthesis as a translation gap:** The 2025 hepatoprotection meta-analysis ([Huang et al.](https://pubmed.ncbi.nlm.nih.gov/40832608/)) explicitly calls for human trials to confirm the large animal-model liver benefits; whether those effects translate to people is the single biggest open question and could strengthen or weaken the liver claim.

* **Preclinical muscle synthesis with negative functional signal:** The 2026 muscle-atrophy meta-analysis ([Liu et al.](https://pubmed.ncbi.nlm.nih.gov/41982662/)) found structural muscle gains but no improvement in grip strength, a result that tempers enthusiasm for an anti-sarcopenia indication and flags the need for functional human endpoints.

* **Drug-interaction pharmacology:** Ongoing pharmacokinetic interest in Schisandra's CYP3A4 effects (e.g., its documented interaction with tacrolimus) is a research direction that could materially weaken the case for routine use by people on chronic medications if interactions prove larger or more common than currently appreciated.

## Conclusion

Schisandra is the five-flavor berry of an East Asian vine, valued for centuries in Chinese medicine and studied since the mid-twentieth century in the former Soviet Union as a stamina- and stress-supporting "adaptogen." Its plant compounds, called lignans, act mainly as antioxidants and switch on the body's own protective and detoxifying systems, which is the leading explanation for its liver-supportive reputation.

The evidence is uneven. Animal studies for liver protection and, to a lesser degree, muscle preservation are fairly consistent, and small human trials suggest benefits for menopausal symptoms and blood sugar. But the human research is sparse, often tests the berry inside multi-herb blends, and rarely meets modern quality standards, so confidence in any single benefit for an otherwise healthy person remains modest. The berry is inexpensive, widely available, and generally well tolerated in the short term; mild stomach upset is the most common complaint.

The most important practical caution is that Schisandra can change how the liver processes many medications, raising or lowering their levels — a real concern for anyone on prescription drugs. Overall, Schisandra stands as a low-cost, biologically plausible, and historically supported option, with strong traditional and laboratory backing and a modest, mixed picture from the small body of modern human studies.

**[Top](#top) - [Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol)**


TP-7
Thr-Lys-Pro-Arg-Pro-Gly-Pro
Tuftsin analog TP-7

---
canonical_name: Selank
alternate_names: TP-7, Thr-Lys-Pro-Arg-Pro-Gly-Pro, Tuftsin analog TP-7
canonical_topic: Selank for Health & Longevity
short_topic_lc: selank
creation_date: 2026-0702-0134
creator_ai_fullname: Opus 4.8
---

# Selank for Health & Longevity

Evidence Review created on 07/02/2026 using [AI4L](https://github.com/forever-healthy/AI4L) / Opus 4.8

**Also known as:** TP-7, Thr-Lys-Pro-Arg-Pro-Gly-Pro, Tuftsin analog TP-7

## Motivation

Selank is a synthetic peptide — a short chain of seven amino acids — modeled on tuftsin, a small immune-signaling fragment the body produces naturally. It was created in Russia to calm anxiety without the drowsiness, memory dulling, and dependence that accompany conventional sedatives. Unusually, the same compound appears to sharpen focus and steady mood rather than blunt them, which is why it draws attention from people looking for a "clean" sense of calm.

Selank has been approved and prescribed in Russia since 2009 for generalized anxiety, yet almost all of its research comes from Russian laboratories and small clinical studies, with little independent replication elsewhere. Outside its home country it circulates largely as an unregulated research peptide, typically used as a nasal spray. This mix of decades of use and thin international evidence is exactly what makes it interesting to examine closely.

This review examines what is known about Selank: how it may work, what benefits and risks the evidence supports, how it is typically used, and where the gaps and uncertainties in the science remain.

**[Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol) - [Conclusion](#conclusion)**

## Recommended Reading

This section collects accessible, high-level overviews of Selank aimed at a knowledgeable general audience, drawn from expert commentary and practitioner writing.

* [Selank Peptide Dosage, Benefits & Side Effects](https://jaycampbell.com/blog/selank-the-anti-anxiety-peptide/) - Jay Campbell

A practitioner-oriented overview framing Selank as an anxiolytic and nootropic alternative to conventional sedatives, with practical discussion of dosing, expected effects, and safety caveats for an optimization-minded reader.

* [My Deep Dive into Selank: The Nootropic Peptide for Anxiety, Focus, and Cognitive Performance](https://faisal798.substack.com/p/my-deep-dive-into-selank-the-nootropic) - FluxFitness

A long-form personal deep dive that walks through Selank's chemistry, mechanism, and real-world use, useful for understanding how the "calm focus" profile is experienced and interpreted by end users.

* [Selank: The Russian Anti-Anxiety Peptide That Doubles as a Nootropic](https://chameleonpeptides.com/2026/03/10/selank-comprehensive-research-review-of-the-anxiolytic-nootropic-peptide/) - Stuart Ratcliff & Kai

A structured research-oriented overview summarizing the GABAergic (relating to GABA, the brain's main calming signal) modulation, BDNF (brain-derived neurotrophic factor, a protein that supports the growth and survival of neurons), and enkephalin mechanisms and the animal-model evidence base, with an emphasis on what has and has not been demonstrated.

* [Selank Peptide: Benefits, Dosage & Why It's the Best Anti-Anxiety Nootropic](https://www.peptidedeck.com/blog/selank-peptide-guide) - PeptideDeck

A concise consumer-facing guide summarizing benefits, dosing ranges, and administration routes, helpful for a quick orientation to how Selank is typically used in practice.

* [Selank: Complete Guide to the Anti-Anxiety Peptide](https://thepeptideindex.com/post/selank-complete-guide-anti-anxiety-peptide) - The Peptide Index

A broad guide covering the science, protocol timelines, and stacking considerations, giving context on how Selank is positioned relative to benzodiazepines and other anxiety approaches.

## Grokipedia

* [Selank](https://grokipedia.com/page/Selank) - Grokipedia

A dedicated encyclopedia entry covering Selank's structure, development history, Russian regulatory approval, mechanism, and clinical and preclinical evidence, useful as a broad orientation to the compound.

## Examine

No dedicated Examine.com article for Selank was found. Examine.com focuses on dietary supplements and nutrients with a substantial evidence base and does not typically cover investigational research peptides such as Selank.

## ConsumerLab

No ConsumerLab article or product test for Selank was found. ConsumerLab independently tests commercially marketed consumer supplements and does not cover investigational research peptides such as Selank, which are not sold as regulated dietary supplements.

## Systematic Reviews

No systematic reviews or meta-analyses for Selank were found on PubMed as of 07/02/2026.

## Mechanism of Action

Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) is a synthetic heptapeptide (seven-amino-acid chain) built by adding a stabilizing Pro-Gly-Pro tail to tuftsin, a naturally occurring immune-signaling fragment. Its biological effects are attributed to several overlapping mechanisms, though most have been characterized in animal or cell models rather than in humans.

* **GABAergic modulation:** Selank appears to act as a positive allosteric modulator (a compound that gently tunes a receptor's response rather than switching it fully on) of the GABA-A receptor — the brain's main "braking" system that calms neural activity. Radioligand-binding work shows Selank alters GABA binding and can modify the effects of benzodiazepines (a class of sedatives such as diazepam) without simply mimicking them, which is proposed to explain its calming effect without heavy sedation.

* **Enkephalin stabilization:** Selank inhibits enkephalin-degrading enzymes (enzymes that break down the body's natural opioid-like "feel-good" peptides). By slowing this breakdown it raises and prolongs enkephalin activity, which is one proposed route to its anti-anxiety and mood effects. This was demonstrated in human blood plasma as well as animal tissue.

* **Monoamine and BDNF effects:** In animals Selank influences serotonin and dopamine turnover (brain chemicals governing mood, motivation, and focus) and raises brain-derived neurotrophic factor, BDNF (a protein that supports the growth and survival of neurons), particularly in the hippocampus and prefrontal cortex — regions tied to memory and executive function. These are proposed to underlie its cognitive ("nootropic") and antidepressant-like effects.

* **Immune and inflammatory signaling:** Retaining tuftsin-like activity, Selank modulates the balance of Th1/Th2 cytokines (signaling molecules that steer the immune response) and the expression of inflammation-related genes, which is the basis for its claimed immunomodulatory and adaptogenic properties.

Where mechanistic explanations compete, the picture is unsettled: some work frames the GABA-A interaction as central, while other lines emphasize enkephalin-system and monoamine effects as primary, and the relative contribution of each in humans is not established.

**Key pharmacological properties:** Selank is a peptide and is not metabolized by the cytochrome P450 (CYP) liver-enzyme system that handles most small-molecule drugs; instead it is broken down by peptidases into shorter fragments, several of which retain activity. Its intact plasma half-life is very short (on the order of minutes), but its behavioral effects last far longer — reportedly hours to days after a dose — attributed to active metabolites and downstream gene-expression changes. It is not orally bioavailable in a meaningful way (peptides are digested), so it is given intranasally or by injection; intranasal delivery is proposed to allow some direct nose-to-brain transport.

## Historical Context & Evolution

* **Original development:** Selank was developed in the early 1990s at the Institute of Molecular Genetics of the Russian Academy of Sciences, in collaboration with what is now the Zakusov Institute of Pharmacology, as a deliberately engineered stable analog of tuftsin. Tuftsin itself is an endogenous immune-modulating peptide with anxiolytic and nootropic properties in animals but is too short-lived to be a practical drug; adding the Pro-Gly-Pro tail was intended to slow enzymatic breakdown while preserving activity.

* **Path to health optimization use:** The original intended use was as an anxiolytic (anti-anxiety agent) that could rival benzodiazepines without their sedation, memory impairment, and dependence. Early Russian studies reported that it not only reduced anxiety but also improved learning and mood, which broadened interest toward cognitive enhancement, stress resilience, and immune support — the properties that later attracted the peptide-optimization community outside Russia.

* **Findings, not just reception:** Preclinical work reported dose-dependent inhibition of enkephalin-degrading enzymes, allosteric effects on GABA-A binding, increased hippocampal BDNF, and shifts in inflammation-related gene expression. Small Russian clinical studies in anxiety and asthenic (fatigue-and-weakness) disorders reported reduced anxiety scores and a favorable tolerability profile, including when Selank was combined with benzodiazepines to reduce their side effects.

* **Standing of the evidence:** Selank has not been "debunked," but neither has its early promise been independently confirmed. Its approval and nearly all of its human data originate from Russia, and the clinical trials are small, often not blinded to modern standards, and rarely replicated by independent Western groups. The evolution of opinion is therefore less a shift in consensus than a persistent gap: enthusiasm in the peptide-use community versus caution from the broader scientific community, which regards the human evidence as preliminary. What would change this is independent, adequately powered, placebo-controlled trials, which have not yet been published.

## Expected Benefits

### Medium 🟩 🟩

#### Anxiety Reduction

Selank's best-supported benefit is reduction of anxiety. Its proposed mechanism combines positive allosteric modulation of GABA-A receptors with stabilization of the body's natural enkephalins, producing a calming effect described as occurring without the sedation or cognitive dulling of benzodiazepines. The evidence includes several small Russian clinical studies in generalized anxiety and phobic-anxiety disorders — including a randomized comparison with the benzodiazepine phenazepam — reporting comparable anxiolytic effect with better tolerability, plus consistent animal data. The main limitation is that these trials are small, single-region, and not independently replicated, so the grade reflects genuine but low-certainty human signal for this specific target audience.

**Magnitude:** In small clinical studies, anxiety-scale reductions were reported as comparable to the benzodiazepine phenazepam, with the effect reportedly persisting up to roughly a week after the last dose; exact effect sizes are not robustly established.

#### Cognitive Enhancement (Nootropic Effect)

Selank is reported to improve attention, learning, and mental clarity, an unusual pairing with its calming effect. The proposed mechanism involves raised BDNF in the hippocampus and prefrontal cortex and modulation of serotonin and dopamine turnover. Evidence is stronger in animals (improved learning and memory, especially in animals with initially poor performance) than in humans, where nootropic effects appear mainly as mild secondary observations within the anxiety trials rather than as primary endpoints. The benefit is plausible and consistent across preclinical data but under-tested as a stand-alone human outcome.

**Magnitude:** Not quantified in available studies.

### Low 🟩

#### Mood Support and Antidepressant-Like Effect

Beyond anxiety, Selank is reported to lift low mood, attributed to enkephalin stabilization and effects on serotonin and dopamine systems. Animal models of depression show antidepressant-like behavioral effects, and human anxiety studies noted improvements in mood and quality of life. However, no dedicated human trials in depression exist, the human data are secondary, and the effect is not separable from the anxiety improvement, so certainty is low.

**Magnitude:** Not quantified in available studies.

#### Immune Modulation

As a tuftsin analog, Selank retains immune-signaling activity and is reported to rebalance Th1/Th2 cytokines and influence inflammation-related gene expression. A small human study in anxiety-asthenic patients reported cytokine changes suggestive of immunomodulation, and animal work shows shifts in inflammatory gene expression. This is proposed as an "adaptogenic" benefit potentially relevant to stress-related immune suppression, but human evidence is minimal and no clinical endpoints (e.g., infection rates) have been demonstrated.

**Magnitude:** Not quantified in available studies.

#### Stress Resilience and Physiological Protection

Selank is reported to buffer the physiological consequences of chronic stress. Animal studies under chronic restraint or foot-shock stress report protective effects on liver function, gut-lining structure, gut microbiota composition, and cytokine profiles. This broad "adaptogenic" protection is biologically coherent with its stress-modulating and anti-inflammatory actions but rests almost entirely on rodent models with no direct human confirmation.

**Magnitude:** Not quantified in available studies.

### Speculative 🟨

#### Metabolic and Hemostatic Effects

A small number of animal studies report that Selank can favorably influence blood sugar, lipid profile, and clotting parameters in models of metabolic syndrome, and that related glyproline peptides have mild anticoagulant activity. These findings are isolated, mechanistically preliminary, and derive solely from rodent experiments with no human data, so any relevance to metabolic health or longevity in people is purely hypothetical at this stage.

#### Longevity and Healthspan

No direct evidence links Selank to extended lifespan or healthspan in any species. The longevity rationale is entirely indirect and mechanistic: chronic anxiety, dysregulated stress physiology, low BDNF, and chronic inflammation are each associated with worse long-term health, and Selank plausibly touches all of these. This chain of reasoning is speculative, with no controlled aging or hard-outcome studies of any kind.

## Benefit-Modifying Factors

* **Baseline anxiety level:** The clearest benefit appears in people with elevated anxiety; effects in already-calm individuals are less evident. Animal work notably showed cognitive gains concentrated in subjects with initially poor performance, suggesting Selank may normalize a dysregulated baseline more than it enhances an optimal one.

* **Baseline enkephalin and stress-system state:** Because a proposed mechanism is stabilizing enkephalins and dampening an over-active stress response, individuals with a more dysregulated baseline (high chronic stress, low endogenous opioid tone) may notice more benefit, whereas those with balanced stress physiology may notice little.

* **Concurrent benzodiazepine use:** Human studies suggest Selank's value is amplified as an add-on to benzodiazepines, where it improved outcomes and reduced the sedative's side effects; benefit as a stand-alone agent, while reported, is less firmly established.

* **Pre-existing health conditions:** Benefit is characterized only in anxiety and stress-related and asthenic conditions. Its relevance to people without these conditions — the healthy-optimizer use case — is inferred, not demonstrated.

* **Sex-based differences:** No human data isolate sex-based differences in Selank response. Preclinical studies use predominantly male animals, so sex-specific efficacy in humans is unknown.

* **Age-related considerations:** One human study specifically suggested Selank's adaptogenic and immune effects might benefit older adults and those under environmental stress, but this was not tested in a dedicated older-adult trial, so age-specific efficacy — including at the older end of the target range — remains unconfirmed.

## Potential Risks & Side Effects

### Low 🟥

#### Generally Mild, Transient Adverse Effects

Across the available (predominantly Russian and small) clinical studies, Selank is consistently described as well tolerated, with a favorable side-effect profile relative to benzodiazepines and no reported dependence or withdrawal. The most commonly noted effects are mild and transient. The key caveat is that this reassuring profile rests on small, short-duration studies without rigorous long-term safety surveillance, so absence of reported harm is not the same as demonstrated long-term safety.

**Magnitude:** In small studies, adverse effects were infrequent and mild; no serious drug-related adverse events were reported, though sample sizes were too small to detect uncommon harms.

#### Nasal and Local Irritation (Intranasal Route)

Because Selank is most often given as a nasal spray, the most practically relevant side effects are local: nasal irritation, dryness, stinging, or a transient unpleasant taste. These reflect the delivery route rather than the peptide's systemic action and are generally minor and self-limiting, but they are the effects a typical user is most likely to encounter.

**Magnitude:** Not quantified in available studies.

### Speculative 🟨

#### Unknown Long-Term and Immune Effects

Selank's immune-modulating activity is presented as a benefit, but chronic modulation of cytokine balance and inflammatory signaling has no long-term human safety data. Sustained shifts in immune signaling could in principle be undesirable in some individuals (e.g., those with autoimmune conditions), but this is a theoretical concern extrapolated from mechanism, not an observed harm.

#### Product Quality and Contamination Risks

Outside Russia, Selank is sold almost exclusively as an unregulated "research chemical," not a pharmaceutical or dietary supplement. The dominant real-world risk is therefore not the peptide itself but the product: incorrect dosing, degradation, bacterial contamination (a particular concern for injectable or reconstituted material), and undisclosed impurities. This is a supply-chain risk rather than a demonstrated pharmacological effect, hence speculative as a property of Selank, but practically important.

#### Additive Central Nervous System Effects

Given GABAergic activity, combining Selank with other sedating or GABA-active substances could theoretically compound central nervous system effects. Human data specifically show interaction with benzodiazepines (used deliberately to reduce their side effects), but the safety of combinations with alcohol, other sedatives, or additional GABAergic compounds is not characterized.

## Risk-Modifying Factors

* **Genetic polymorphisms:** No pharmacogenetic data exist for Selank. Because it is peptidase-metabolized rather than CYP-metabolized, common drug-metabolism gene variants (e.g., CYP2D6 and CYP3A4, liver enzymes that break down many small-molecule drugs) are unlikely to be relevant, but this has not been formally studied.

* **Baseline immune status:** Individuals with autoimmune or inflammatory conditions may theoretically be more sensitive to Selank's cytokine-modulating effects; this is a mechanistic caution, not an established risk factor, and warrants conservative consideration in such populations.

* **Sex-based differences:** No human data characterize sex-based differences in Selank's side effects. Preclinical safety work is predominantly in male animals.

* **Pre-existing health conditions:** Risk has been characterized only in relatively healthy anxiety-disorder patients. People with significant psychiatric, immune, or other chronic conditions were not represented, so the side-effect profile in those groups is unknown.

* **Age-related considerations:** No dedicated safety data exist for older adults despite suggestions of benefit in that group; age-related differences in tolerability, including at the older end of the target range, are unstudied.

* **Product source and route:** The largest modifiable risk factor is product quality and administration route — unregulated sourcing and injectable use raise contamination and dosing risks far more than the peptide's intrinsic pharmacology.

## Key Interactions & Contraindications

* **Benzodiazepines (diazepam, phenazepam, alprazolam):** Documented interaction — additive/modifying. In human and animal studies Selank was combined with benzodiazepines and altered their effect, reducing benzodiazepine side effects while maintaining anxiolysis. Severity: caution/monitor. Consequence: potentiated or modified central nervous system effects. Mitigating action: use combinations only under clinical supervision with attention to sedation.

* **Other GABA-active or sedating drugs (barbiturates, "Z-drugs" such as zolpidem, gabapentinoids):** Theoretical additive central nervous system depression given Selank's GABAergic activity. Severity: caution. Consequence: possible excess sedation. Mitigating action: avoid unmonitored stacking; separate introduction to observe effects.

* **Alcohol and other over-the-counter sedatives (e.g., antihistamines such as diphenhydramine):** Over-the-counter sedating agents and alcohol could theoretically add to central nervous system effects; notably, animal studies show Selank interacts with alcohol-related behaviors and may protect against alcohol-induced memory impairment, but combined human safety is uncharacterized. Severity: caution. Consequence: unpredictable sedation or interaction. Mitigating action: avoid concurrent use pending data.

* **Antidepressants and other serotonergic/dopaminergic agents:** Because Selank affects serotonin and dopamine turnover, theoretical additive effects with antidepressants (e.g., SSRIs, or selective serotonin reuptake inhibitors — a common class of antidepressants such as sertraline) cannot be excluded. Severity: caution. Consequence: unknown; monitor for mood or activation changes. Mitigating action: clinical oversight if combined.

* **Supplement interactions (additive):** Supplements with calming/GABAergic or serotonergic activity — e.g., L-theanine, magnesium, valerian, kava, 5-HTP, or high-dose glycine — could be additive with Selank's anxiolytic effect. Consequence: enhanced sedation/calming; generally low severity but relevant when stacking.

* **Immunomodulatory agents:** Given tuftsin-like immune activity, combining Selank with other immunomodulators or immunosuppressants is theoretically capable of additive or opposing effects. Severity: caution. Consequence: unpredictable immune effects. Mitigating action: avoid in those on immune-modifying therapy without oversight.

* **Populations who should avoid Selank:** Pregnant or breastfeeding individuals (no safety data); people with autoimmune or significant immune-mediated conditions (theoretical immune modulation); individuals with serious psychiatric illness managed with multiple central nervous system agents; and anyone unable to verify product quality. Because Selank is not an approved drug outside Russia and lacks pediatric, pregnancy, and chronic-use safety data, its use in these groups has no supporting evidence.

## Risk Mitigation Strategies

* **Verify product identity and purity:** Because the dominant risk is unregulated sourcing, product obtained with a certificate of analysis confirming identity and purity plus third-party testing for contaminants directly mitigates the risks of mislabeled dose, degradation, and impurity exposure described in the Risks section.

* **Prefer intranasal over injectable use:** Use of the intranasal route over reconstituted injectable material mitigates the bacterial-contamination and injection-site risks that are the most consequential practical hazards; where injection is used, strict sterile technique and single-use vials are essential.

* **Start low and assess individually:** Starting at the low end of typical protocols (e.g., a single low daily intranasal dose) and observing response before any escalation mitigates the risk of additive central nervous system effects and unexpected individual sensitivity.

* **Avoid unmonitored central nervous system stacking:** Avoiding simultaneous combination of Selank with alcohol, sedatives, or multiple GABAergic supplements mitigates the risk of compounded sedation and the unpredictable interactions identified in Interactions.

* **Limit duration and reassess:** Given the absence of long-term human safety data, time-limited courses (e.g., 2–4 weeks) with reassessment rather than indefinite continuous use mitigate the speculative long-term immune and unknown chronic-exposure risks.

* **Screen for immune and psychiatric conditions:** Accounting beforehand for autoimmune conditions, pregnancy, and complex psychiatric medication regimens — the populations flagged to avoid — mitigates the risk of immune modulation or drug interactions in vulnerable individuals.

## Therapeutic Protocol

* **Standard approach (Russian clinical use):** As used in Russian clinical practice, Selank is administered as a 0.15% intranasal solution, with typical daily doses in the range of roughly 250–3,000 micrograms (commonly cited as about 2–4 drops per nostril, one to three times daily), given in courses of about 10–14 days. This regimen underlies the anxiety and asthenic-disorder studies and is the closest thing to a validated protocol.

* **Competing approaches (integrative/optimization use):** Outside clinical medicine, the peptide-optimization community typically uses intranasal Selank at similar or somewhat higher daily totals (often cited around 300–900 micrograms/day, sometimes up to ~3,000 micrograms), self-administered in cycles. Neither the clinical nor the optimization approach is framed here as definitive; the clinical regimen has study support, while community protocols are experience-based and not validated.

* **Practitioners and origin:** The intranasal clinical protocol traces to the developing institutions — the Institute of Molecular Genetics and the Zakusov Institute of Pharmacology (Russian Academy of Sciences), with clinical work led by groups including Medvedev and colleagues; optimization protocols are popularized largely by peptide-focused clinicians and writers rather than a single authority.

* **Best time of day:** Dosing is generally split across the day (e.g., morning and midday) rather than at night, since Selank is reported to be non-sedating and mildly stimulating in some users; timing earlier in the day is preferred to avoid any activation near sleep.

* **Half-life considerations:** The intact peptide's plasma half-life is very short (minutes), but behavioral effects reportedly persist for hours to days owing to active metabolites and downstream effects — one reason short courses can produce lasting effects and why anxiety benefit was reported to persist after stopping.

* **Single vs. split dosing:** Because of the short intact half-life but prolonged downstream effect, protocols typically use split daily dosing (two to three times daily) rather than a single dose, to maintain steady exposure across waking hours.

* **Genetic polymorphisms:** No pharmacogenetic guidance exists. As a peptidase-metabolized peptide, Selank dosing is not expected to hinge on common CYP variants (e.g., CYP2D6, CYP3A4) or on APOE (a gene affecting fat transport and brain aging risk), MTHFR (a gene for an enzyme in folate and homocysteine processing), or COMT (a gene for an enzyme that clears dopamine and related signals) status, but this has not been studied and no dose adjustment is defined.

* **Sex-based differences:** No sex-specific dosing has been established; trials did not report dose differences by sex, and preclinical work is predominantly male.

* **Age-related considerations:** No age-specific dosing is defined. Suggestions of benefit in older adults were not paired with dose-finding, so conservative low-dose starting is reasonable at the older end of the target range in the absence of data.

* **Baseline biomarkers:** No biomarker is validated to guide dosing. Where an immune or inflammatory rationale is invoked, baseline markers such as CRP (C-reactive protein, a general marker of inflammation) or a cytokine panel are sometimes checked, but these do not have established dose-response value for Selank.

* **Pre-existing conditions:** Dosing was studied in anxiety and asthenic-disorder patients; there is no protocol for people with major psychiatric, immune, or other chronic conditions, who fall outside the evidence base.

## Discontinuation & Cycling

* **Lifelong vs. short-term:** Selank is designed for short-term, course-based use (typically ~10–14 day courses) rather than continuous lifelong administration; the human evidence base covers only short courses, and there is no support for indefinite use.

* **Withdrawal effects:** No withdrawal syndrome has been reported. A central selling point in the clinical literature is that, unlike benzodiazepines, Selank produced no dependence or withdrawal in the studies conducted, and its anxiolytic effect reportedly persisted for about a week after stopping.

* **Tapering:** Because no dependence or withdrawal has been observed, no tapering protocol is described or considered necessary; courses are simply stopped at completion. This reflects the absence of observed withdrawal rather than long-term proof of safety.

* **Cycling:** Cycling (courses separated by off-periods) is the norm both in clinical use and in optimization protocols, consistent with its course-based design and the reported carry-over of effect after stopping. There is no evidence that continuous use maintains or improves efficacy over cycled use, and cycling is generally preferred given the lack of long-term data.

* **Practical discontinuation:** In practice, users complete a defined course and reassess after an off-period, resuming only if the earlier benefit was clear; this course-and-reassess pattern is the de facto discontinuation strategy.

## Sourcing and Quality

* **Regulatory reality:** Selank is an approved pharmaceutical only in Russia (and some neighboring countries); elsewhere it is sold as an unregulated "research chemical," meaning no pharmacopeial quality standards apply and product quality is the single most important sourcing concern.

* **What to look for:** Prioritize suppliers providing a recent certificate of analysis (COA) with identity confirmation (e.g., mass spectrometry) and quantified purity (ideally ≥98%), plus independent third-party testing for sterility and endotoxin where relevant — these directly address the mislabeling and contamination risks.

* **Formulation:** Intranasal solutions (the form used clinically) are generally preferable to self-reconstituted lyophilized (freeze-dried) powder for injection, which introduces sterility and dosing-accuracy challenges; if using powder, correct reconstitution and cold storage matter.

* **Reputable options:** There are no regulated Western brands. In Russia, Selank is marketed as a registered nasal-spray pharmaceutical; outside Russia, only research-chemical suppliers exist, and even those that third-party test cannot substitute for pharmaceutical-grade regulation. Compounding pharmacies in some jurisdictions may prepare peptides, but availability and legality vary.

* **Storage and handling:** Peptides are sensitive to heat and degradation; reputable practice is refrigerated storage, protection from light, and use within the supplier's stated stability window to prevent loss of potency or breakdown-product accumulation.

## Practical Considerations

* **Time to effect:** Some users report acute calming within hours of a dose, but the more consistent pattern in the literature is subtle onset over 1–3 days, with noticeable anxiety reduction and improved focus over roughly 1–2 weeks of a course; cognitive effects tend to build over the course rather than appear immediately.

* **Common pitfalls:** Frequent mistakes include using unverified research-chemical product, over-dosing in pursuit of a stimulant-like effect (Selank's effect is subtle, not dramatic), expecting benzodiazepine-like acute relief, injecting reconstituted powder without sterile technique, and continuous long-term use despite the absence of long-term safety data.

* **Regulatory status:** Selank is a prescription pharmaceutical in Russia but is not approved by the FDA or EMA; in most Western countries it is neither an approved drug nor a legal dietary supplement, and is sold only labeled "for research use, not for human consumption." Personal use therefore sits in a legal grey area and is entirely off-label/unapproved.

* **Cost and accessibility:** Selank is relatively inexpensive as research peptides go, but accessibility outside Russia is limited to unregulated online suppliers, and reliable, quality-assured product is the main access barrier rather than price.

## Interaction with Foundational Habits

* **Sleep:** Direction — indirect/potentiating on sleep quality. By reducing anxiety without sedation, Selank may indirectly improve sleep in anxious individuals; however, because some users find it mildly activating, dosing is best kept to earlier in the day to avoid interfering with sleep onset. No direct effect on sleep architecture has been demonstrated.

* **Nutrition:** Direction — largely none/indirect. No specific dietary requirement or nutrient depletion is established for Selank. As an intranasal peptide it is not meaningfully affected by food, and no diet is required to be paired with it; any interaction is indirect via general stress and metabolic health.

* **Exercise:** Direction — indirect. No evidence indicates Selank blunts or enhances training adaptations such as hypertrophy. Its potential relevance to exercise is indirect — through reduced anxiety and improved stress resilience and focus — rather than any demonstrated effect on performance or recovery, and there is no established timing relative to workouts.

* **Stress management:** Direction — direct/potentiating. This is the habit domain most aligned with Selank's proposed effects: it directly targets the stress and anxiety axis (via GABAergic and enkephalin mechanisms) and animal studies show protection against the physiological damage of chronic stress. It is best viewed as a potential complement to — not a replacement for — foundational stress-management practices such as sleep, exercise, and behavioral techniques.

## Monitoring Protocol & Defining Success

Because Selank is used for anxiety, mood, and stress-related goals, monitoring is primarily clinical and qualitative, supported by a small set of optional labs where an immune or metabolic rationale is invoked. Baseline assessment before starting establishes a reference point, and periodic reassessment gauges whether the intended benefit is materializing.

Baseline testing should include documenting current anxiety and mood status (ideally with a simple standardized self-rating) and, where an immune or metabolic rationale is being pursued, optional baseline inflammatory and metabolic markers. Given the absence of validated Selank-specific biomarkers, these labs are supportive context rather than required gating tests.

Ongoing monitoring is best structured around the course: reassess subjective anxiety, mood, focus, and sleep at roughly 1 week and at the end of a 2–4 week course, then again after an off-period before deciding whether to repeat; optional labs, if used, can be rechecked every 3–6 months only if there is a specific reason.

| Biomarker | Optimal Functional Range | Why Measure It? | Context/Notes |
| --- | --- | --- | --- |
| hs-CRP (high-sensitivity C-reactive protein) | < 1.0 mg/L | Tracks systemic inflammation, relevant if pursuing an anti-inflammatory/adaptogenic rationale | Fasting not required; avoid testing during acute illness or injury, which transiently raises it. Conventional "normal" extends to 3.0 mg/L, but functional target is < 1.0 |
| Fasting glucose | 70–85 mg/dL | Context for the speculative metabolic-syndrome findings | Requires 8–12 h fasting; best drawn in the morning. Conventional range extends to 99 mg/dL |
| Fasting insulin | 2–5 µIU/mL | Metabolic context if a metabolic rationale is being pursued | Requires fasting; pair with glucose to assess insulin sensitivity. Conventional labs often flag only > 25 µIU/mL |
| Lipid panel (total, LDL, HDL, triglycerides) | Triglycerides < 80 mg/dL; HDL > 50 mg/dL | Context for reported lipid effects in animal metabolic-syndrome models | 9–12 h fasting typically requested; best paired with glucose/insulin drawn the same morning |

Qualitative markers are the primary success measures for Selank:

* Reduction in day-to-day anxiety and a sense of calm without sedation
* Improved focus, mental clarity, and freedom from "brain fog"
* Stable or improved mood
* Sleep quality (improved indirectly via lower anxiety; not disrupted)
* Subjective stress resilience — feeling less reactive to stressors

## Emerging Research

* **Sparse registered-trial landscape:** No active clinical trials of Selank are registered on ClinicalTrials.gov as of this review; because Selank's development and approval are Russia-based, any ongoing structured research is likely registered in Russian systems and not indexed in Western registries, which is itself a notable gap.

* **Mechanistic neuroimaging:** A functional-connectivity line of work has examined how Selank and the related peptide Semax affect brain network connectivity, moving beyond behavioral endpoints toward objective imaging measures ([Panikratova et al., 2020](https://pubmed.ncbi.nlm.nih.gov/32342318/)). Direction — could strengthen the case by providing an objective biomarker of central effect.

* **GABAergic and gene-expression mechanisms:** Ongoing preclinical work continues to characterize Selank's allosteric modulation of GABA-A receptors and its effects on the expression of neurotransmission-related genes ([Volkova et al., 2016](https://pubmed.ncbi.nlm.nih.gov/26924987/)). Direction — refines (and could either support or complicate) the proposed mechanism.

* **Stress-protection and gut/microbiome effects:** A cluster of rodent studies on chronic stress has extended into gut microbiota and intestinal-structure protection ([Mukhina et al., 2019](https://pubmed.ncbi.nlm.nih.gov/31236882/)). Direction — could broaden the "adaptogenic" rationale but remains far from human validation and could equally fail to translate.

* **Addiction and withdrawal applications:** Newer animal work explores Selank in morphine-withdrawal and alcohol-related models ([Konstantinopolsky et al., 2022](https://pubmed.ncbi.nlm.nih.gov/36322304/)). Direction — an emerging therapeutic direction that could expand indications, though it is preliminary and in animals.

* **Future research that could change understanding:** The decisive open question is whether independent, adequately powered, placebo-controlled human trials — conducted outside the originating institutions — can replicate the reported anxiolytic and nootropic effects and establish long-term safety. Evidence that could weaken the case includes failure to replicate the small Russian trials or discovery of long-term immune or other harms; evidence that could strengthen it includes objective neuroimaging biomarkers and confirmed human efficacy. Until such studies exist, the human evidence base remains preliminary and single-region.

## Conclusion

Selank is a synthetic peptide developed in Russia and used there since 2009 to ease anxiety. Its appeal is an unusual combination: calming effects that, in the available studies, come without the drowsiness, memory dulling, or dependence linked to conventional sedatives, alongside modest gains in focus, mood, and stress resilience. Proposed actions include tuning the brain's main calming system and slowing the breakdown of the body's own feel-good peptides, together with effects on immune signaling.

The central limitation is the evidence itself. Nearly all human data come from small studies in Russia, tied to the groups that developed the compound, and have not been independently repeated. Its calming effect is the best supported; cognitive, mood, immune, and stress-protection benefits rest mostly on animal work, and any link to long-term health or longevity is purely theoretical. Reported safety is reassuring but comes from short, small studies rather than long-term monitoring, and outside Russia the compound is sold unregulated, making product quality a real-world concern in its own right.

Selank is best understood as a promising but under-proven compound: decades of use and a coherent mechanism on one side, thin and unreplicated human evidence on the other. What is genuinely known and what is merely plausible remain far apart, and that gap is the defining feature of the current picture.

**[Top](#top) - [Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol)**