Rankings / Metabolic Health

Naltrexone (low dose, LDN)

Metabolic Health · Opioid antagonist

Tier C+

Reviewed by Read Off Label · Last reviewed · How we grade

opioidprescription
5.3 / 10
Tier C+
Ev 3 Bn 2 Sf 9

Bottom line

Read Off Label grades Naltrexone (low dose, LDN) as C+ (5.3/10) based on weak evidence, low benefit magnitude, and a low-risk safety profile.

Evidence for weight loss with low-dose naltrexone alone is thin; naltrexone is also studied as part of the Contrave combination.

Studied, labeled, or reported-use context: 1. — Rx; not individualized guidance.

Frontier potential — editorial judgment, not evidence

This is a separate axis from the grade above. It asks a different question: if this worked in humans, how much would it matter? It is our judgment, it is not part of the composite score, and it cannot raise a grade. A high number here is a statement about the idea, not about whether it works or whether anyone should take it.

3/10
Mechanistic story only Phase 2

What the ceiling rests on

A plausible mechanism — transient opioid-receptor blockade producing compensatory endorphin upregulation, plus TLR4-mediated glial anti-inflammatory effects — and a very benign safety profile at low dose, with early small crossover trials suggesting benefit in fibromyalgia and Crohn's.

Why it may not get there

The first long-term properly powered test, a 12-month randomised placebo-controlled trial in fibromyalgia, found no clinically meaningful benefit on pain or any secondary outcome. That is the strongest evidence available for the indication LDN is most used for, and it is negative. The remaining signals are small, unblinded, or in conditions where placebo response is high.

What would change this A properly powered trial in an indication other than fibromyalgia.

Citation correction in progress

1 PubMed link was found to be unrelated to this entry and removed from public output. The remaining sources are shown below, but this row's claims and score still need a full source-by-source revalidation.

What the evidence says

Evidence for weight loss with low-dose naltrexone alone is thin; naltrexone is also studied as part of the Contrave combination. Fibromyalgia and autoimmune-symptom uses are separate off-label evidence contexts. Widely used in biohacker/alt-med circles. INNOVA study (Eur J Pain 2026, n=98 women with fibromyalgia, 12-month RCT, LDN 4.5 mg/day vs placebo) -- the first long-term controlled trial of LDN for fibromyalgia -- found no clinically meaningful benefit over placebo on pain intensity (adjusted between-group difference 0.49, p=0.236) or secondary functional/psychological outcomes; well tolerated, no safety signal. Contradicts the prior small crossover-trial evidence base and downgrades confidence in the fibromyalgia indication specifically.

Mechanism

At low doses (1.5-4.5 mg): transient mu-opioid blockade triggers rebound endorphin release; modulates immune/microglial function; TLR4 antagonism

Studied, labeled, or reported dose & route

1.5-4.5 mg PO at bedtime

This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.

Citations

A link means the source informed this entry; it does not mean every claim on the page comes from that source. If a citation looks wrong or you want a claim re-checked, send a correction.

Common questions

What does the evidence show about Naltrexone (low dose, LDN)'s effects?
Read Off Label rates the evidence for Naltrexone (low dose, LDN) as Weak and the benefit magnitude as low, producing an overall grade of C+ (5.3/10). Evidence for weight loss with low-dose naltrexone alone is thin; naltrexone is also studied as part of the Contrave combination.
What safety findings are reported for Naltrexone (low dose, LDN)?
Naltrexone (low dose, LDN) has a low risk profile in the database. Low Legal status: Rx (off-label; compounded).
What doses or routes are reported for Naltrexone (low dose, LDN)?
1.5-4.5 mg PO at bedtime This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
How does Naltrexone (low dose, LDN) work?
At low doses (1.5-4.5 mg): transient mu-opioid blockade triggers rebound endorphin release; modulates immune/microglial function; TLR4 antagonism

This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.