Low-Dose Naltrexone for Health & Longevity - Quick Reference Sheet

Low-Dose Naltrexone for Health & Longevity

Created on 08/30/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5 – Audit

A small daily dose of an inexpensive prescription medicine; briefly blocking the body's own opioid signals appears to quiet inflammatory signalling. The clearest human signal is in active Crohn's disease; for widespread muscle pain the picture is split, and lifespan claims rest entirely on worm and mouse work. Safety is reassuring; the serious hazard is blocked opioid pain relief. (Full Review)

Protocol

Standard protocol
4.5 mg once daily
Immediate-release, compounded. Titration from 1.5 mg over 2–4 weeks is near-universal in practice, though the trials mostly started at the full dose.
Best time of day
Bedtime or morning
Bedtime dosing coincides with the overnight endorphin peak; morning dosing avoids dream and sleep disruption. No trial has compared the two directly.
Single versus split dosing
Single daily dose
Standard, since the transient blockade is central to the proposed mechanism. Splitting is reserved for people who cannot tolerate a single dose.
Time to effect
Autoimmune conditions
Up to 6 months
Clinical practice allows up to six months in autoimmune conditions before judging.
Standard trial period
8–12 weeks
The trials measured outcomes at 8 to 12 weeks; clinical practice allows a 12-week trial before judging.
Earliest change
Within days
Some report change within days; dream intensity in the first four weeks is the earliest sign the drug is pharmacologically active.

Benefits

Contraindications
  • Opioid analgesics, or any opioid or kratom use in the previous 7–10 days
  • Acute hepatitis, or decompensated cirrhosis at Child-Pugh Class C
  • Pregnancy and breastfeeding
  • Planned surgery within 72 hours where opioid analgesia is anticipated
  • Chronic kidney disease with eGFR below 30 mL/min/1.73 m², until reviewed by a prescriber
  • Currently taking disulfiram for alcohol use disorder
Key Interactions
  • Over-the-counter opioid-containing preparations (loperamide, codeine-containing cough and pain products)
  • Ketamine and esketamine
  • Thyroid hormone replacement (levothyroxine, desiccated thyroid)
  • Bupropion
  • Sedating supplements (melatonin, magnesium)
  • Alcohol
  • Additive anti-inflammatory supplements (palmitoylethanolamide, curcumin, long-chain omega-3 fatty acids): no restriction

Risk & Side Effects

  • High: Sleep disruption and vivid dreams; nausea and gastrointestinal upset; loss of opioid analgesia and precipitated withdrawal
  • Medium: Non-response and early discontinuation
  • Low: Liver enzyme elevation; attenuation of ketamine's antidepressant effect; destabilisation of thyroid hormone replacement
  • Speculative: Blunting of exercise- and reward-related endorphin signalling

Monitoring

Marker Target Why
ALT 10–26 U/L (women), 10–30 U/L (men) Detects the dose-related liver enzyme rise documented at higher naltrexone doses
AST 10–26 U/L Paired with ALT to separate liver from muscle sources of enzyme release
hs-CRP Below 0.5 mg/L Tracks the systemic inflammation the drug is intended to lower
ESR Below 10 mm/hour (men), below 15 mm/hour (women) A higher baseline value tracked with larger benefit in the fibromyalgia pilot
TSH 1.0–2.0 mIU/L Detects over-replacement once autoimmune thyroid inflammation settles
Free T4 1.0–1.5 ng/dL Confirms that a change in TSH reflects true thyroid status rather than assay drift
Urine opioid screen Negative Confirms opioid-free status before the first dose, preventing precipitated withdrawal
Fasting insulin Below 5 µIU/mL Baseline for the metabolic effects proposed from animal work
Symptom score (0–10 numeric rating scale) No established target; track change from the individual's own baseline, treating a 2-point fall as meaningful The only measure that determines whether treatment continues

Cadence: Baseline work-up before the first dose. Liver enzymes and the inflammatory marker at 12 weeks, then annually; thyroid function every 6 to 12 weeks for anyone on replacement; symptom scores at 4 and 12 weeks, when the decision to continue or stop is made.

Qualitative Assessment

  • Dream intensity and dream recall during the first four weeks — the earliest sign the drug is pharmacologically active
  • Sleep-onset latency and the number of night wakings
  • Morning stiffness, and how long it takes to loosen after waking
  • Mental clarity — word-finding, reading endurance, capacity for sustained work
  • Energy through the afternoon, and how long recovery takes after physical exertion
  • Overall impression of change, recorded monthly on a simple better, same or worse scale