Comparison
Low-Dose Naltrexone vs Tirzepatide
Side-by-side of Low-Dose Naltrexone and Tirzepatide. 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.
Tirzepatide
Tirzepatide for weight loss: dual GIP/GLP-1 agonist sold as Mounjaro and Zepbound. SURMOUNT-1 showed 22.5% mean body-weight loss at 15 mg over 72 weeks.
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
Tirzepatide
- •Dual GIP plus GLP-1 receptor agonist with a ~5-day half-life supporting once-weekly subcutaneous dosing
- •SURMOUNT-1 reported ~22.5% mean body-weight loss at 15 mg over 72 weeks versus 2.4% on placebo
- •Lowers HbA1c by ~1.9 to 2.6 percentage points in type 2 diabetes across SURPASS trials
- •Outperformed semaglutide 1.0 mg head-to-head on weight loss and HbA1c in SURPASS-2
- •GI effects (nausea, diarrhea, vomiting) drive most discontinuations and ease with slow titration
- •Lean-mass loss observed in body-composition substudies; resistance training and protein intake mitigate this
Side-by-side
| Attribute | Low-Dose Naltrexone | Tirzepatide |
|---|---|---|
| Category | pharmaceutical | pharmaceutical |
| Also known as | LDN, naltrexone (low dose) | Mounjaro, Zepbound, LY3298176 |
| Half-life (hr) ↗ | 4 | 120 |
| Typical dose (mg) ↗ | 4.5 | 10 |
| Dosing frequency | once daily, typically at bedtime | weekly |
| Routes | oral | subcutaneous |
| Onset (hr) | 1 | 24 |
| Peak (hr) | 1.5 | 72 |
| Molecular weight | 341.4 | 4813.45 |
| Molecular formula | C20H23NO4 | C225H348N48O68 |
| 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. | Synthetic 39-amino-acid peptide that activates both GIP and GLP-1 receptors. Potentiates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and acts on hypothalamic and brainstem satiety circuits. |
| Legal status | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) | Prescription only; FDA-approved 2022 (T2DM, Mounjaro) and 2023 (chronic weight management, Zepbound) |
| WADA status | allowed | allowed |
| DEA / Rx | Rx only (not a controlled substance) | Rx only (not a controlled substance) |
| Pregnancy | Insufficient data; not routinely recommended | Not recommended; discontinue 2 months before planned pregnancy |
| CAS | 16590-41-3 | 2023788-19-2 |
| PubChem CID | 5360515 | 156588324 |
| Wikidata | Q426444 | Q105099794 |
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)
Tirzepatide
Common side effects
- nausea
- diarrhea
- vomiting
- constipation
- decreased appetite
- injection-site reactions
- fatigue
- abdominal pain
Contraindications
- personal or family history of medullary thyroid carcinoma
- multiple endocrine neoplasia type 2
- pregnancy
- history of pancreatitis (use caution)
- severe gastroparesis
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)
- oral contraceptives: reduced exposure after first dose; backup contraception recommended for 4 weeks after initiation and each dose escalation(moderate)
- warfarin: monitor INR due to altered absorption(moderate)
Which Should You Take?
Low-Dose Naltrexone and Tirzepatide 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 Tirzepatide.
- → If your priority is fat loss, pick Tirzepatide.
Edge case: If you cannot self-administer injections, Low-Dose Naltrexone is the only oral option in this pair.
Default choice: either is defensible. Low-Dose Naltrexone edges out on goal breadth + legal accessibility; Tirzepatide 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 Tirzepatide?
Low-Dose Naltrexone and Tirzepatide 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 Tirzepatide?
Low-Dose Naltrexone half-life is 4 hours; Tirzepatide half-life is 120 hours.
Can you stack Low-Dose Naltrexone with Tirzepatide?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper