Low-Dose Naltrexone (LDN)
LDN · Naltrexone Low-Dose
Low-dose naltrexone (LDN) refers to the use of naltrexone at doses of 0.5-4.5mg, which is roughly 1/10th of the standard 50mg dose used for opioid and alcohol addiction. At these low doses, naltrexone exhibits fundamentally different pharmacological properties - rather than sustained opioid receptor blockade, it produces a brief, transient blockade that triggers a compensatory upregulation of endogenous opioid production (endorphins, met-enkephalin) and opioid receptor sensitivity.
Take at bedtime (9-10 PM). Start at 0.5-1mg and increase by 0.5-1mg every 1-2 weeks until reaching target of 3-4.5mg. Some practitioners recommend morning dosing if vivid dreams are problematic.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
How it works
At low doses (0.5-4.5mg), naltrexone produces a brief (4-6 hour) blockade of opioid receptors, after which the body compensates by upregulating production of endorphins (beta-endorphin) and met-enkephalin. This 'rebound' effect results in higher baseline endogenous opioid levels over 18-20 hours of each 24-hour cycle. Endorphins have immunomodulatory effects, promoting NK cell activity and balancing T-helper cell responses.
LDN antagonizes Toll-like receptor 4 (TLR4) on microglia and macrophages, which is a pattern recognition receptor in the innate immune system. TLR4 blockade reduces microglial activation and the production of pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1beta, NF-kB signaling). This mechanism is independent of opioid receptor effects and may be the primary driver of benefits in autoimmune and neuroinflammatory conditions.
The net effect is a shift from a pro-inflammatory to a regulatory immune state - reduced autoimmune attack, decreased neuroinflammation, and improved immune surveillance. This dual mechanism (endorphin upregulation + TLR4 antagonism) explains LDN's broad applicability across seemingly unrelated conditions.
What to expect
Weeks 1-4: Titration phase. Vivid dreams common. Subtle mood and energy changes possible.
Evidence
Claims we could not support
No abstract we checked supports these for this molecule at this route. That is not the same as saying they are false — it marks where the evidence is missing.
Dose/route: 0.5-1mg; Oral; 1x daily at bedtime. No checked live PubMed abstract verified this exact displayed dose, route, and frequency for the same molecule/formulation and relevant population.
Mechanism: At low doses (0.5-4.5mg), naltrexone produces a brief (4-6 hour) blockade of opioid receptors, after which the body compensates by upregulating production of endorphins (beta-endorphin) and met-enkephalin. This 'rebound' effect results in higher baseline endogenous opioid levels over 18-20 hours of each 24-hour cycle. Endorphins have immunomodulatory effects, promoting NK cell activity and balancing T-helper cell responses.. No checked live PubMed abstract provided an exact-molecule/formulation sentence supporting this source-JSON mechanism claim.
Primary safety claim: Vivid or unusual dreams (most common, ~37%, typically transient). No checked live PubMed abstract directly verified this source-JSON safety claim at the displayed formulation, route, and regimen.
Interactions & stacking
Two different questions: what is documented about running these together, and what is documented about drawing them into the same syringe. A good pharmacological partner can still have to be pinned separately.
Documented together
Keep separate
Check any specific pair in the Stack & Interaction Checker, which answers both questions separately. Absence of a documented conflict is not evidence of safety.
Pharmacokinetics
(naltrexone), ~12 hours (6-beta-naltrexol active metabolite)
Oral
Complete clearance including metabolites
Oral (significant first-pass metabolism, variable between individuals)
Opioid receptor blockade: ~4-6 hours at LDN doses (brief, followed by 18-20 hours of endorphin rebound). TLR4 effects may persist longer.
Hepatic (extensive first-pass metabolism to 6-beta-naltrexol via dihydrodiol dehydrogenase). Renal excretion of metabolites.
Storage. Store compounded capsules or liquid at room temperature (20-25C) or refrigerate for longer stability. Compounded liquid formulations may have shorter shelf life (90 days typical). Keep away from light and moisture.
Regulatory status
Naltrexone is FDA-approved at 50mg for opioid and alcohol use disorders (ReVia, Vivitrol). Low-dose naltrexone (0.5-4.5mg) is entirely off-label. Available only from compounding pharmacies in the US - not commercially manufactured at LDN doses. No DEA scheduling (not a controlled substance). Prescription required.
Put it to work
Calculate, log & track
Open Low-Dose Naltrexone (LDN) straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.
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The guide & community
The complete Low-Dose Naltrexone (LDN) walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.
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