Pain · Research Phase
Endomorphin-1
No lawful US pathway
01 · Overview
Endomorphin-1 is an amidated tetrapeptide (Tyr-Pro-Trp-Phe-NH2) isolated from brain in 1997 that binds the mu-opioid receptor with high affinity and about 4,000- and 15,000-fold selectivity over delta and kappa receptors (PMID 9087409). It is one of two endomorphins, and at discovery they had the highest mu affinity and selectivity of any known endogenous substance (PMID 9087409).
Endomorphin-1 is more widely distributed in the brain than endomorphin-2, in regions of high mu-receptor density (PMID 10676442). Its selective mu activity has prompted interest in analgesics with different side-effect profiles from conventional opioids.
02 · Research summary & key findings
In mice, endomorphin-1 produced potent and prolonged analgesia (PMID 9087409). Its use as an analgesic has been hindered by rapid enzymatic degradation and poor blood-brain barrier penetration (PMID 18718496, PMID 21287571). In rats, metabolically stable endomorphin analogues gave analgesia comparable to morphine with less respiratory depression, tolerance, and reward behavior (PMID 26748051). CYT-1010, a cyclized endomorphin-1 analogue, showed analgesia without respiratory depression in an initial phase 1 study (PMID 31165885), but the native peptide has not entered clinical trials.
03 · Regulatory status
Endomorphin-1 is in the research phase with limited clinical data in humans. Current evidence is primarily derived from preclinical (animal or in vitro) studies.
No lawful pathway today
Endomorphin-1 is not FDA-approved and does not currently have a lawful prescription or compounding pathway in the United States, so we do not sell it and will not book a consultation for it. That can change: in 2026 FDA began reviewing several peptides for compounding. If you are working on the goal it is studied for, a licensed clinician can tell you what is lawfully available, which may be something else.
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Endomorphin-1 is a research compound, is not FDA-approved, and has no lawful US compounding pathway, so we do not offer it and no clinician we work with will prescribe it. Products sold online as “research chemicals” are not made or tested to the standards required of medicines. If you are working on injury recovery and tissue repair, a licensed clinician can tell you at a free consultation whether an FDA-approved or lawfully compounded treatment fits you, or whether nothing does.
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04 · Administration routes
- Endogenous peptide
References
- [1]Endomorphins: novel endogenous mu-opiate receptor agonists in regions of high mu-opiate receptor density Ann N Y Acad Sci, 1999. PMID 10676442
- [2]Enzymatic degradation of endomorphins Peptides, 2008. PMID 18718496
- [3]Endomorphins: potential roles and therapeutic indications in the development of opioid peptide analgesic drugs Med Res Rev, 2012. PMID 21287571
- [4]Endomorphin analog analgesics with reduced abuse liability, respiratory depression, motor impairment, tolerance, and glial activation relative to morphine Neuropharmacology, 2016. PMID 26748051
- [5]Dilemma of Addiction and Respiratory Depression in the Treatment of Pain: A Prototypical Endomorphin as a New Approach Pain Med, 2020. PMID 31165885
- [6]A potent and selective endogenous agonist for the mu-opiate receptor Nature, 1997. PMID 9087409
Primary literature
- PubMed: "Endomorphin-1"
Peer-reviewed literature indexed by the National Library of Medicine.
- ClinicalTrials.gov: "Endomorphin-1"
Registered interventional and observational studies, including status and phase.
- PubChem: "Endomorphin-1"
Chemical structure, molecular properties, and bioactivity data.
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