About Met-Enkephalin
Binds OGF receptors (zeta opioid receptors) on cell nuclei, regulating DNA synthesis and cell proliferation in a tonic inhibitory manner. Also binds delta opioid receptors. Intermittent blockade by low-dose naltrexone upregulates receptor expression and endogenous MENK tone.
Methionine enkephalin (Met-enkephalin; opioid growth factor, OGF) is an endogenous pentapeptide (Tyr-Gly-Gly-Phe-Met) that acts at classical mu- and delta-opioid receptors for pain modulation and, in its OGF role, functions as a tonic inhibitor of cell proliferation through interactions with the nuclear OGF receptor (OGFr, the zeta-opioid receptor), a pathway with distinct biological implications from classical analgesic opioid signaling. The OGF-OGFr axis operates as an endogenous homeostatic brake on cell cycle progression: OGF binds OGFr in the nucleus to upregulate cyclin-dependent kinase inhibitors p16 and p21, inhibiting S-phase entry; this mechanism has been characterized in models of wound repair, organ development, and immune cell regulation. Research from the Zagon laboratory has described the OGF-OGFr axis as a broad homeostatic regulator of cell proliferation and has established that the duration of opioid receptor blockade determines biotherapeutic response magnitude — the mechanistic basis for proposed low-dose naltrexone-mediated OGF upregulation in inflammatory and neoplastic conditions. Methionine enkephalin has no FDA-approved therapeutic applications as an exogenous agent; the OGF pathway has been characterized through preclinical and early-stage research, and exogenous OGF administration for any indication has not established a human clinical evidence base or received regulatory approval.
Met-Enkephalin Benefits & Research Areas
Regulatory & Evidence
Risk Profile
Moderate risk profile in research contexts. Review contraindications and administration guidelines before use.
Regulatory Status
- Availability Status
- Research Only
Regulatory status reflects publicly available information and may change. This is not legal or medical advice.
Research Sources
4 sources cited · 4 moderate
2 Cohorts · 2 Reviews
Endogenous opioid peptides in trichotillomania: An exploratory analysis of focused and automatic hair-pulling subtypes.
Psychoneuroendocrinology · 2026
# Summary This study demonstrated that adults with trichotillomania (hair-pulling disorder) have significantly lower peripheral levels of met-enkephalin and β-endorphin compared to healthy controls, with the focused hair-pulling subtype showing the lowest opioid peptide levels. Researchers observed that these reduced endogenous opioid levels may be associated with reward and stress-related mechanisms underlying the disorder, suggesting distinct neurobiological differences between hair-pulling subtypes.
Unraveling the role of iodide in photosensitized oxidation of Met-Enkephalin.
J Photochem Photobiol B · 2026
# Summary Research found that iodide ions competitively quench excited photosensitizer molecules during the photo-oxidation of Met-enkephalin, thereby reducing the peptide's oxidative damage. This study demonstrated that iodide's protective effect occurs through its ability to compete with the peptide for reaction with the excited photosensitizer, preventing the formation of oxidative products on the peptide's methionine and tyrosine residues.
Duration of opioid receptor blockade determines biotherapeutic response
Biochemical Pharmacology · 2015
This review summarizes 30 years of evidence that the duration of opioid receptor blockade by naltrexone determines the direction of the OGF-OGFr biotherapeutic response: intermittent low-dose blockade suppresses cell replication while continuous blockade enhances growth, with applications in diabetic wound healing, corneal repair, autoimmune disease, and cancer.
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The opioid growth factor-opioid growth factor receptor axis: homeostatic regulator of cell proliferation and its implications for health and disease
Biochemical Pharmacology · 2012
This review describes how [Met5]-enkephalin (opioid growth factor) tonically inhibits cell proliferation via the OGF receptor by modulating cyclin-dependent inhibitory kinase pathways, with implications for cancer, autoimmune diseases, and wound healing, and discusses how opioid receptor antagonist duration of exposure determines whether growth is inhibited or enhanced.
Met-Enkephalin Side Effects & Safety Considerations
Moderate risk profile. Review all reported considerations carefully before use.
Reported contraindications & considerations
Consult a qualified healthcare professional before making any health decisions. This information is educational only and does not constitute medical advice.
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Frequently Asked Questions — Met-Enkephalin
Methionine enkephalin (Met-enkephalin; opioid growth factor, OGF) is an endogenous pentapeptide (Tyr-Gly-Gly-Phe-Met) that acts at classical mu- and delta-opioid receptors for pain modulation and, in its OGF role, functions as a tonic inhibitor of cell proliferation through interactions with the nuclear OGF receptor (OGFr, the zeta-opioid receptor), a pathway with distinct biological implications from classical analgesic opioid signaling. The OGF-OGFr axis operates as an endogenous homeostatic brake on cell cycle progression: OGF binds OGFr in the nucleus to upregulate cyclin-dependent kinase inhibitors p16 and p21, inhibiting S-phase entry; this mechanism has been characterized in models of wound repair, organ development, and immune cell regulation.
immune modulation, cell proliferation regulation, anti-inflammatory, autoimmune support.
Research on Met-Enkephalin primarily documents effects related to immune modulation and cell proliferation regulation and anti-inflammatory and autoimmune support. These are areas covered in preclinical and clinical literature — individual response varies and effects depend on context of use.
Reported contraindications and considerations for Met-Enkephalin include active cancer history, pregnant or nursing. This is educational information only — consult a qualified healthcare professional before use.
5 providers in the directory currently offer Met-Enkephalin.
# Summary This study demonstrated that adults with trichotillomania (hair-pulling disorder) have significantly lower peripheral levels of met-enkephalin and β-endorphin compared to healthy controls, with the focused hair-pulling subtype showing the lowest opioid peptide levels. Researchers observed that these reduced endogenous opioid levels may be associated with reward and stress-related mechanisms underlying the disorder, suggesting distinct neurobiological differences between hair-pulling subtypes.