Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Low-Dose Naltrexone | Semaglutide | |
|---|---|---|
| Category | Pharmaceuticals | Pharmaceuticals |
| Standard Dose | — | Research indicates 0.25 mg weekly SC for 4 weeks, escalating to 0.5 mg, then 1.0 mg, then 1.7 mg, then 2.4 mg weekly (FDA weight management protocol). Oral: 3 mg daily for 30 days, then 7 mg, then 14 mg daily. |
| Timing | — | SC injection any time of day, with or without food, on the same day each week. Oral: take on empty stomach with no more than 4 oz water, 30+ minutes before first food/drink/medications. |
| Cycle Duration | — | Long-term/continuous use. Weight regain occurs upon discontinuation (67% regain within 1 year in trials). |
| Evidence Level | Emerging | Strong (FDA-approved) |
Transient opioid receptor blockade that may increase endogenous endorphin signaling and modulate immune tone in off-label protocols.
Semaglutide is a GLP-1 receptor agonist with 94% structural homology to native GLP-1, modified with amino acid substitutions and a C-18 fatty acid chain that enables albumin binding, extending half-life to approximately 7 days. Centrally, it activates anorexigenic POMC/CART neurons and inhibits orexigenic NPY/AgRP neurons in the arcuate nucleus of the hypothalamus, reducing hunger and increasing satiety. Peripherally, it slows gastric emptying, enhances glucose-dependent insulin secretion from pancreatic beta-cells, and reduces glucagon secretion, providing comprehensive metabolic regulation.
Research indicates 0.25 mg weekly SC for 4 weeks, escalating to 0.5 mg, then 1.0 mg, then 1.7 mg, then 2.4 mg weekly (FDA weight management protocol). Oral: 3 mg daily for 30 days, then 7 mg, then 14 mg daily.
SC injection any time of day, with or without food, on the same day each week. Oral: take on empty stomach with no more than 4 oz water, 30+ minutes before first food/drink/medications.
Long-term/continuous use. Weight regain occurs upon discontinuation (67% regain within 1 year in trials).
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