Met-Enkephalin

Methionine-Enkephalin (Opioid Growth Factor, OGF)

Evidence & Status

  • Preliminary / Experimental
  • Preliminary

At a Glance

One of the body's endogenous opioid peptides (as Opioid Growth Factor, OGF), studied mainly through preclinical and mechanistic cancer-biology research. Direct human evidence is limited to a single early-phase safety trial in pancreatic cancer.

Plain English

Researchers study Met-Enkephalin because, as the Opioid Growth Factor (OGF), it appears to help regulate cell growth through a receptor distinct from the classical opioid receptors, primarily in preclinical (lab and animal) cancer research. The main direct human study identified administered it to pancreatic cancer patients to test safety and find a tolerable dose — not to test whether it treats cancer. This remains an early-stage, exploratory research area.

Overview

Methionine-enkephalin (Met-enkephalin) is an endogenous pentapeptide opioid (YGGFM) produced throughout the body, including the immune system, adrenal glands, and CNS. As an Opioid Growth Factor (OGF), it acts on the OGF receptor (OGFr, the zeta opioid receptor) to inhibit cell proliferation — a mechanism distinct from classical mu/kappa/delta opioid receptors. In a phase I trial in patients with advanced pancreatic cancer, IV and subcutaneous OGF/Met-enkephalin administration was evaluated for safety and maximum tolerated dose; hypotension was dose-limiting (Smith et al., 2004). This is an early-phase safety/feasibility study, not evidence of anticancer efficacy. The OGF-OGFr axis has a substantial preclinical and mechanistic literature, reviewed in the oncology literature (Zagon & McLaughlin, 2014), describing anti-proliferative signaling in animal and cell models (e.g., McLaughlin et al., 2015, gastric cancer xenograft model). Low-dose naltrexone (LDN) is a different drug, sometimes discussed in relation to endogenous opioid signaling; its dosing and clinical evidence are not evidence for Met-Enkephalin administration and are not represented in this entry.

Research Summary

Direct human evidence for Met-enkephalin (OGF) administration is limited to a single identified phase I trial in advanced pancreatic cancer patients, which established a maximum tolerated dose and found hypotension to be dose-limiting — a safety/feasibility result, not an efficacy finding. The broader OGF-OGFr literature is largely preclinical and mechanistic, describing anti-proliferative effects of the OGF-OGFr axis in animal and cell-culture cancer models. This entry is included as an educational reference for the OGF-OGFr axis rather than as a practical or clinically supported research peptide; its 1–2 minute plasma half-life makes sustained exposure pharmacologically difficult without a depot formulation.

Research Areas

  • Cancer immune modulation
  • Autoimmune disease
  • Cell proliferation control
  • Wound healing

Safety & Risks

Serious Risks

  • Direct opioid receptor activation risk at supraphysiologic doses; immune system modulation — avoid in transplant patients or active infections; rapidly degraded making consistent dosing difficult

Reported Side Effects

  • Opioid-like mild sedation at high doses (mu receptor cross-reactivity)
  • Nausea (uncommon)
  • Injection site reactions
United States
Research only; not FDA-approved; investigational use in cancer and autoimmune trials; synthesized as a compounded preparation in some integrative practices
United Kingdom
Research only; no MHRA approval
Australia
Research only
Canada
Research only; some compounding pharmacies prepare for off-label immune modulation

Citations & Sources