Combining Selank and PE-22-28 into a nasal spray creates a comprehensive mental wellness protocol that targets both anxiety and mood regulation. This combination is often referred to as a “neuro-regenerative” stack due to its ability to influence brain plasticity and neurotransmitter balance.
Selank: The “Anxiolytic Nootropic”
Cheat Sheet
- Classification: Synthetic heptapeptide (analogue of the human tetrapeptide Tuftsin).
- Key Benefits: Reduces anxiety (anxiolytic), improves learning/memory, enhances focus without sedation, and modulates immune function.
- Pathways:
- Non-Genomic: Modulates GABAergic neurotransmission (increases GABA receptor affinity) and inhibits enkephalin-degrading enzymes.
- Genomic: Alters the expression of genes related to neurotransmission (GABA receptors) and inflammation (cytokines) within hours.
- Half-Life: Very short (approx. 2–10 minutes in plasma), but its biological effects last for several hours.
- Peak Saturation: Rapid; peaks in brain tissue within 30–60 minutes post-nasal administration.
- Dosing Range: 300 mcg to 750 mcg per day (typically 1–2 sprays per nostril).
- Duration of Use: 10–14 days for a “reset,” or used as needed for acute stress.
- Side Effects: Rare; may include mild nasal irritation or a temporary change in taste.
- Avoid: Large amounts of alcohol (may dull the effect) or heavy sedative medications unless supervised.
PE-22-28: The “Rapid Antidepressant”
Cheat Sheet
- Classification: Synthetic derivative of the peptide Spadin (a TREK-1 channel antagonist).
- Key Benefits: Fast-acting antidepressant effects (48–72 hours), increases neurogenesis, and enhances synaptogenesis (new neuron connections).
- Pathways:
- TREK-1 Inhibition: Specifically blocks TREK-1 potassium channels, mimicking the downstream effects of SSRIs without the delay.
- Neurotrophic Support: Increases BDNF levels in the hippocampus.
- Half-Life: Highly stable; has a biological activity duration of >24 hours.
- Peak Saturation: Reaches effective concentrations in the brain quickly; systemic saturation typically occurs within 2–4 days of daily use.
- Dosing Range: 400 mcg to 1 mg per day.
- Duration of Use: Typically 4 weeks followed by a 2-week break.
- Side Effects: Minimal; occasional reports of mild headache or lightheadedness upon initial use.
- Avoid: Avoid combining with other experimental TREK-1 inhibitors or high-dose MAOIs without medical guidance.
Synergy, Strategy & Detectability
- Synergy: * Anxiety + Mood: Selank handles the immediate “fight or flight” response, while PE-22-28 repairs the “baseline” mood.
- Nootropic Stack: Often combined with Semax for increased cognitive clarity and drive.
- Strategy: Administer in the morning. PE-22-28 can be slightly “up-regulating,” so morning doses help align with natural circadian rhythms.
- Detection: These are naturally derived peptide sequences and are generally not detectable on standard drug screens (WADA-restricted lists focus on growth hormones and performance enhancers, though regulations change; always check specific league rules).
- Genomic vs. Non-Genomic: Both peptides offer a “hybrid” approach. They provide immediate signaling changes (non-genomic) while triggering long-term changes in gene expression and brain structure (genomic).
General Notes:
The Selank + PE-22-28 combination represents a frontier in “Precision Psychiatry.” Unlike traditional oral medications that must pass through the digestive system and liver—often losing potency and causing systemic side effects—nasal administration allows these peptides to cross the blood-brain barrier directly via the olfactory and trigeminal nerves.
Selank acts as a stabilizer. It doesn’t “force” a feeling of relaxation like a sedative; rather, it restores the natural balance of the brain’s internal opioids and GABA. This makes it ideal for users who need to remain sharp and productive while managing high-stress environments.
PE-22-28 addresses the “slump” often associated with chronic stress. By targeting the TREK-1 channel, it effectively “unlocks” the brain’s ability to produce BDNF, which is the fuel for neuroplasticity. This stack is less about “numbing” the mind and more about giving the brain the biochemical tools it needs to repair itself and maintain resilience.