Low-dose naltrexone is a prescription medication for alcohol and opioid dependence, taken at a small fraction of its usual dose in the hope of easing pain, fatigue and immune-driven inflammation. Small early trials suggest modest fibromyalgia pain relief; the largest independent trials found no difference from placebo. Safety is a genuine strength; the firm hazards are blocked opioid pain relief and severe withdrawal. It has no demonstrated effect on longevity. (Full Review)

Protocol

Standard dose

4.5 mg once nightly

Dose in the main fibromyalgia, Crohn's disease and multiple sclerosis trials; 6 mg once daily in the Danish FINAL trial

Titration

1.5 mg start, +1.5 mg weekly

Four-week titration in the FINAL protocol; integrative clinicians use 0.5–1 mg steps for sensitive patients

Time of day

Bedtime, single daily dose

Splitting would lengthen blockade; morning dosing is the usual switch when sleep is disturbed

Time to effect

8–12 weeks

When trials judged outcomes; clinicians typically allow two to three months before deciding

Benefits

Medium: Chronic Pain Relief

Low: Crohn's Disease Activity; Fatigue in Long COVID and Inflammatory Disease; Mental Well-Being and Quality of Life; Lower Use of Rheumatic Medications; Inflammatory Skin Disorders; Cancer Outcomes

Speculative: Lifespan and Healthspan Extension; Systemic Inflammation Reduction

Contraindications

Opioid analgesics (morphine, oxycodone, tramadol, codeine)

Opioid maintenance (methadone, buprenorphine)

Current opioid dependence, or opioid-free for less than 7–10 days after short-acting opioids or under two weeks after methadone or buprenorphine

Positive urine opioid screen or failed naloxone challenge test

Symptoms or signs of acute hepatitis

Decompensated liver cirrhosis

Pregnancy

Known hypersensitivity to naltrexone

Under 18 outside a supervised study

Kratom (mitragynine) (theoretical)

Key Interactions

Opioid-containing over-the-counter products (loperamide, codeine cough syrups)

Benzodiazepines (such as diazepam)

Thioridazine

Liver-toxic drugs (disulfiram; others such as high-dose acetaminophen or ketoconazole theoretical)

Acamprosate

Thyroid hormone (levothyroxine, liothyronine) (theoretical)

Immunosuppressants (tacrolimus, cyclosporine, mycophenolate) (theoretical)

Additive supplements (palmitoylethanolamide, curcumin, omega-3 fatty acids) (theoretical)

Other interventions (rapamycin, metformin, NAD+) (theoretical)

Cannabis (THC)

Alcohol

Risk & Side Effects

High: Vivid Dreams and Sleep Disturbance

Medium: Blocked Opioid Analgesia and Precipitated Withdrawal; Nausea, Headache and Other Mild Adverse Events

Low: Liver Injury; Depression and Suicidal Thoughts; Opioid Hypersensitivity During Use

Speculative: Harm in Pregnancy; Thyroid Hormone Over-Replacement; Cell Growth with Continuous Blockade

Monitoring

Marker	Target	Why
ALT	7–56 U/L	Liver injury stops use
AST	10–40 U/L	Liver injury stops use
eGFR	≥60 mL/min/1.73 m²	Kidney impairment changes use
Urine opioid screen	Not specified in the ER	A positive result stops use
TSH	0.4–4.0 mIU/L	Over-replacement changes thyroid dosing; only for people on thyroid hormone
Pregnancy test	Not specified in the ER	Pregnancy stops use
Pain score	≥30% fall from baseline	Responder threshold used in fibromyalgia trials

Cadence: Baseline before starting; thyroid tests and symptom scores 4–8 weeks after starting or after a dose change; response review at 12 weeks; liver and kidney tests every 6–12 months while use continues; symptoms of hepatitis prompt immediate testing

Qualitative Assessment

Target symptoms: pain, fatigue or disease activity versus baseline
Sleep: dream intensity, insomnia, sleep quality
Mood and energy: daily well-being
Side effects: nausea, headache, dizziness

Low-Dose Naltrexone for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment