Cortistatin
Cortistatin
Cortistatin is an endogenous neuropeptide structurally related to somatostatin, predominantly expressed in the brain and immune tissues. It exhibits broad immunomodulatory and anti-inflammatory properties, and has been investigated in research contexts for conditions such as inflammatory bowel disease, rheumatoid arthritis, and sepsis. Unlike somatostatin, cortistatin also binds ghrelin receptors and MrgX2, giving it unique neuroendocrine and sleep-promoting effects.
Mechanism of Action
Cortistatin binds to all five somatostatin receptors (SSTR1-5) with high affinity, suppressing pro-inflammatory cytokine production (TNF-α, IL-6, IL-12) while upregulating anti-inflammatory mediators such as IL-10. It additionally activates ghrelin receptors (GHS-R1a) and the Mas-related G protein-coupled receptor MrgX2, contributing to its roles in sleep regulation, cortical activity modulation, and mast cell degranulation inhibition. Through these pathways it dampens innate and adaptive immune responses and promotes slow-wave sleep.
Evidence by Health Goal(17 goals)
Dosing Protocols
Consistent daily timing; evening administration explored for sleep studies
Cycle: Protocols vary; research models typically use 7-28 day continuous administration
Administered subcutaneously or intravenously in research settings. Human clinical dosing is not established; all current data derive from preclinical animal models and early-phase trials. Dose ranges are extrapolated from published murine studies (1-100 mcg/kg IV/SC). No standardized human protocol exists.
Safety & Side Effects
Cortistatin has a favorable safety profile in preclinical animal studies with demonstrated therapeutic windows in inflammatory models, but robust human safety data are lacking and it remains an investigational compound with no approved clinical use. It should be treated as research-only material; self-administration outside supervised clinical or research contexts carries meaningful unknown risks given the absence of human pharmacokinetic and toxicology data.
Possible Side Effects
- !Transient hypotension following intravenous administration
- !Bradycardia at higher doses due to somatostatinergic cardiac effects
- !Excessive sedation or prolonged slow-wave sleep
- !Suppression of growth hormone and insulin secretion via SSTR2/5 activation
- !Injection site irritation or local erythema with subcutaneous use
- !Potential hypothermia in high-dose preclinical models
- !Gastrointestinal motility reduction at somatostatin-equivalent doses
Interactions
- -May potentiate hypotensive effects of antihypertensive medications due to vasodilatory actions
- -Additive immunosuppression possible when combined with corticosteroids or biologics (e.g., TNF-α inhibitors)
- -May reduce efficacy of growth hormone secretagogues or GH-releasing peptides by competing at GHS-R1a
- -Potential additive sedation with benzodiazepines, opioids, or other CNS depressants due to sleep-promoting activity
- -Co-administration with insulin or oral hypoglycemics requires caution due to possible suppression of counter-regulatory hormones
Cost & Where to Buy
Cortistatin is available only from specialized research peptide suppliers at very limited quantities; pricing is highly variable and dependent on purity, synthesis complexity, and quantity. No pharmaceutical-grade product exists commercially. Monthly cost estimates assume low-dose research use (1-5 mg total per month).
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