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Oncology & Specialized

Met-Enkephalin (OGF)

Natural opioid peptide that slows cell proliferation via the OGF receptor; studied as a cancer and immune modulator, closely linked to low-dose naltrexone.

InvestigationalEvidence level 2 of 5: Animal data, minimal humanAlso: Methionine-enkephalin, Opioid Growth Factor, OGF, Tyr-Gly-Gly-Phe-Met

Overview

Met-enkephalin is one of the body's own opioid peptides. Beyond pain signaling, researchers Ian Zagon and Patricia McLaughlin found that it acts as 'opioid growth factor' through a separate receptor, OGFr, located at the cell nucleus. There it slows the cell cycle by increasing cyclin-dependent kinase inhibitors, restraining the proliferation of cancer cells and overactive immune cells. Small trials in advanced pancreatic cancer suggested OGF infusions were well tolerated and might extend survival, but these were not randomized. The same pathway underlies low-dose naltrexone, which briefly blocks opioid receptors to boost the body's own enkephalin and OGFr levels — a far more practical and better-studied approach for most patients.

Classification
Endogenous opioid pentapeptide (Tyr-Gly-Gly-Phe-Met)
Route
Intravenous (clinical trials); subcutaneous or intranasal (investigational)
Half-life
Minutes (rapid enzymatic degradation)

Mechanism of action

Primary targetOpioid growth factor receptor (OGFr, perinuclear)
  1. OGFr bindingOGF binds its receptor at the outer nuclear membrane.
  2. Nuclear translocationOGF–OGFr complex moves into the nucleus.
  3. CDK inhibitor inductionUpregulates p16 and p21 cyclin-dependent kinase inhibitors.
  4. Cell-cycle slowingDelays G1-to-S transition, reducing DNA synthesis.
  5. Immune modulationTempers lymphocyte proliferation and inflammatory activity.
Downstream effects
  • Slowed tumor proliferation
  • Immune rebalancing
  • Wound and corneal healing effects

Researched for

  • Advanced pancreatic cancer (adjuvant)
  • Head and neck and other cancers (preclinical)
  • Autoimmune conditions (multiple sclerosis, Crohn's models)
  • Diabetic wound and corneal healing (topical, preclinical)

Research notes

  • Zagon & McLaughlin (multiple studies): OGF–OGFr axis inhibits proliferation of human cancer cells and xenografts.
  • Smith et al. (Phase 1, 2004; Phase 2, 2010): OGF IV in advanced pancreatic cancer was tolerated; survival signals in uncontrolled cohorts.
  • Low-dose naltrexone raises endogenous enkephalin/OGFr — the more practical, evidence-supported route.
  • Very short half-life complicates direct dosing; subcutaneous wellness protocols lack published data.

Reported side effects

  • Limited human data
  • Possible lightheadedness or GI upset
  • Theoretical interaction with opioid medications
  • Injection-site reactions

Contraindications & cautions

  • Concurrent opioid analgesic or full-dose naltrexone therapy (without physician coordination)
  • Pregnancy and breastfeeding
  • Use as substitute for standard cancer care

Lab monitoring

  • CBC with differential
  • CMP
  • CRP, ESR, hsCRP
  • Vitamin D (25-OH)
  • Immune panel / T-cell subsets if autoimmune indication

Dosing and pricing for Met-Enkephalin (OGF)

Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.

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