Comparison
Low-Dose Naltrexone vs Semaglutide
Side-by-side of Low-Dose Naltrexone and Semaglutide. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
Low-Dose Naltrexone
Low dose naltrexone at 1.5 to 4.5 mg, one-tenth the 50 mg addiction dose. Compounded Rx. Small trials in fibromyalgia, Crohn's, Hashimoto's.
Semaglutide
Semaglutide for weight loss: GLP-1 agonist (Ozempic, Wegovy) drives 15-17% mean loss at 2.4 mg/week in STEP trials. Watch lean-mass loss.
Effects at a glance
Low-Dose Naltrexone
- •Off-label use at 1.5 to 4.5 mg, roughly one-tenth the FDA-approved 50 mg addiction-treatment dose
- •Proposed mechanisms include brief opioid receptor blockade triggering rebound endogenous opioid release, plus TLR4 antagonism
- •Compounded prescription only; insurance rarely covers; cash prices 20 to 80 USD per month
- •Younger 2013 reported ~30% pain reduction in fibromyalgia at 4.5 mg in a small crossover trial
- •Smith 2011 reported endoscopic improvement in active Crohn's disease (n=40 placebo-controlled)
- •Vivid dreams affect 20 to 40% in first 2 weeks; manageable by switching to morning dosing
Semaglutide
- •Long-acting GLP-1 receptor agonist with a ~7-day half-life that supports once-weekly subcutaneous dosing
- •STEP trials reported ~15 to 17% mean body-weight loss at 2.4 mg/week over 68 weeks in adults with obesity
- •Lowers HbA1c by ~1.0 to 1.8 percentage points in type 2 diabetes versus placebo
- •SELECT trial showed reduced major cardiovascular events in adults with prior CVD and overweight or obesity
- •Up to 25 to 40% of weight lost can be lean mass; pairing with resistance training and protein intake mitigates this
- •GI effects (nausea, vomiting, constipation) drive most discontinuations and ease with slow titration
Side-by-side
| Attribute | Low-Dose Naltrexone | Semaglutide |
|---|---|---|
| Category | pharmaceutical | pharmaceutical |
| Also known as | LDN, naltrexone (low dose) | Ozempic, Wegovy, Rybelsus |
| Half-life (hr) ↗ | 4 | 168 |
| Typical dose (mg) ↗ | 4.5 | 2.4 |
| Dosing frequency | once daily, typically at bedtime | weekly (SC); daily (oral Rybelsus) |
| Routes | oral | subcutaneous, oral |
| Onset (hr) | 1 | 24 |
| Peak (hr) | 1.5 | 72 |
| Molecular weight | 341.4 | 4113.58 |
| Molecular formula | C20H23NO4 | - |
| Mechanism | Brief mu-opioid receptor antagonism proposed to trigger compensatory upregulation of endogenous opioids; secondary TLR4 antagonism on microglia and immune cells contributes to anti-inflammatory effect. | Long-acting GLP-1 receptor agonist; potentiates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and acts on hypothalamic satiety centers. |
| Legal status | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) | Prescription only (FDA-approved, EMA-approved) |
| WADA status | allowed | allowed |
| DEA / Rx | Rx only (not a controlled substance) | Rx only (not a controlled substance); FDA-approved for type 2 diabetes (2017) and chronic weight management (2021) |
| Pregnancy | Insufficient data; not routinely recommended | Not recommended; discontinue 2 months before planned pregnancy |
| CAS | 16590-41-3 | 910463-68-2 |
| PubChem CID | 5360515 | 56843331 |
| Wikidata | Q426444 | Q27089394 |
Safety profile
Low-Dose Naltrexone
Common side effects
- vivid dreams
- sleep disruption
- headache
- mild GI upset
- fatigue (early)
Contraindications
- concurrent opioid use
- acute hepatitis or liver failure
- opioid dependence
- pregnancy (insufficient data)
Interactions
- opioid analgesics (oxycodone, morphine, codeine): blocks analgesic effect; precipitates withdrawal in dependent users(major)
- tramadol: blocks opioid component of analgesia(major)
- thyroid hormone replacement: may alter dose requirements after immune modulation; monitor TSH(minor)
Semaglutide
Common side effects
- nausea
- vomiting
- diarrhea
- constipation
- decreased appetite
- injection-site reactions
- fatigue
Contraindications
- personal or family history of medullary thyroid carcinoma
- multiple endocrine neoplasia type 2
- pregnancy
- history of pancreatitis (use caution)
Interactions
- insulin: additive hypoglycemia risk; insulin dose typically reduced(major)
- sulfonylureas (glipizide, glyburide): hypoglycemia risk, sulfonylurea dose often reduced(major)
- oral medications (general): delayed gastric emptying can alter absorption kinetics(moderate)
- warfarin: monitor INR due to altered absorption(moderate)
Which Should You Take?
Low-Dose Naltrexone and Semaglutide score evenly on the criteria we weight (goal breadth, legal accessibility, evidence depth). The conditionals below should drive the decision more than any aggregate score.
- → If your priority is immune support, pick Low-Dose Naltrexone.
- → If your priority is pain modulation, pick Low-Dose Naltrexone.
- → If your priority is metabolic health and glucose control, pick Semaglutide.
- → If your priority is fat loss, pick Semaglutide.
Edge case: Half-lives differ materially (Low-Dose Naltrexone ~4 hr vs Semaglutide ~168 hr). Semaglutide reaches steady state faster; Low-Dose Naltrexone is easier to dial in if tolerability is uncertain.
Default choice: either is defensible. Low-Dose Naltrexone edges out on goal breadth + legal accessibility; Semaglutide is the right call if your priority sits in the goals listed above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between Low-Dose Naltrexone and Semaglutide?
Low-Dose Naltrexone and Semaglutide differ in category (pharmaceutical vs pharmaceutical), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Low-Dose Naltrexone or Semaglutide?
Low-Dose Naltrexone half-life is 4 hours; Semaglutide half-life is 168 hours.
Can you stack Low-Dose Naltrexone with Semaglutide?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper