Pain · Research Phase
Endomorphin-2
No lawful US pathway
01 · Overview
Endomorphin-2 is an amidated tetrapeptide (Tyr-Pro-Phe-Phe-NH2) that, like endomorphin-1, is a highly selective mu-opioid receptor agonist (PMID 9087409). The two endomorphins differ by a single amino acid (PMID 9087409).
Endomorphin-2 is concentrated in the spinal cord dorsal horn and lower brainstem, where it appears to come from pain-sensing primary afferent neurons (PMID 10676442). This location has generated interest in analogues that retain analgesic efficacy while minimizing respiratory depression and other opioid side effects.
02 · Research summary & key findings
Animal studies show that the endomorphins have potent analgesic and gastrointestinal effects (PMID 10676442). As with endomorphin-1, therapeutic use is limited by rapid peptidase degradation and poor blood-brain barrier penetration (PMID 18718496, PMID 21287571). In rats, stable endomorphin analogues produced analgesia with less respiratory depression, motor impairment, tolerance, and abuse-related behavior than morphine (PMID 26748051). No endomorphin-2 analogue is known to have advanced to late-stage clinical trials.
03 · Regulatory status
Endomorphin-2 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-2 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-2 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]A potent and selective endogenous agonist for the mu-opiate receptor Nature, 1997. PMID 9087409
Primary literature
- PubMed: "Endomorphin-2"
Peer-reviewed literature indexed by the National Library of Medicine.
- ClinicalTrials.gov: "Endomorphin-2"
Registered interventional and observational studies, including status and phase.
- PubChem: "Endomorphin-2"
Chemical structure, molecular properties, and bioactivity data.
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