LDN (1.5–4.5 mg HS):

• Vivid dreams are nearly universal in the first 1-3 weeks. Some users find this neutral or pleasant; others find it disrupting. Usually quiets down by week 3-4. This is the single most reported acute effect.
• Insomnia or sleep disruption in week 1-2 is the second most common — usually mild, resolves with continued dosing or with shifting dose to early evening rather than HS.
• After the early dream/sleep settling period, the subjective experience is quiet — most users describe it as "I forgot I was taking it, but my [pain / fatigue / brain fog / autoimmune symptoms] is better."
• Mood smoothing is reported by a meaningful subset — reduced irritability, mild lift in baseline mood. This is consistent with the endorphin rebound mechanism. Not euphoric, not stimulating.
• Reduced inflammatory "feel" — users with chronic pain or autoimmune disease often describe reduced "low-grade flu feeling" / reduced background malaise.
• Onset of clinical benefit: generally 4-12 weeks. Fast responders see something by week 2; many require 8-12 weeks for stable effect. Some respond at 1.5 mg, others need full 4.5 mg.
• No euphoria, no abuse potential — naltrexone is an antagonist, not an agonist. There is no recreational use case at any dose.

Standard 50 mg:

• In someone not using opioids and without AUD: mostly nothing subjective. Mild GI upset, occasional headache, occasional dysphoria/anhedonia (reflecting blunted tonic endogenous opioid signal).
• In someone with AUD: alcohol "loses its kick" — drinking still happens initially but becomes less reinforcing.
• In someone using opioids: immediate severe precipitated withdrawal — see Side effects.

• Tolerance buildup at LDN: minimal-to-none reported. Long-term LDN users (5+ years) commonly maintain stable effect. The mechanism (transient blockade → endogenous opioid upregulation) does not appear to drive tolerance the way agonist therapies do. Some users report needing to adjust dose up or down over time but escalation is not the norm.
• Tolerance at standard 50 mg: receptor antagonism does not drive tolerance per se, but sustained 50 mg use is associated with upregulation of opioid receptor density — meaning if you stop, exogenous opioids may have an exaggerated effect (rebound supersensitivity). Clinically relevant if standard-dose naltrexone is stopped abruptly in someone who later resumes opioid use — overdose risk is elevated. Not relevant to Dylan.
• Recommended cycle (LDN): No formal cycling — most LDN protocols are continuous daily for as long as benefit persists. Reassess at 6 months and 1 year. If effect plateaus or symptoms resolve, taper-off trial is reasonable. Some users discontinue and find symptoms return; others maintain remission off-drug.
• Reset protocol: If LDN is stopped, the endogenous opioid system returns to baseline within ~1-2 weeks. Restarting at full dose is fine; no titration required for re-initiation in someone who previously tolerated it.

Synergistic with

• n-acetyl-cysteine (NAC): Different anti-inflammatory mechanism (glutathione precursor, glutamate modulation) — additive on neuroinflammation and oxidative stress without overlap. Clean stack.
• bpc-157 / tb-500: Both peptides target tissue repair and inflammation modulation through different pathways (BPC-157: angiogenesis, growth factor signaling; TB-500: actin sequestration, cell migration). LDN's TLR4-microglia arm is non-overlapping. For Dylan's elbow / cubital tunnel protocol, LDN could plausibly potentiate the local-systemic anti-inflammatory profile if added — but stage interventions to attribute effects.
• curcumin / phytosomal curcumin (in Dylan's V4): Both target inflammation but through different mechanisms (curcumin: NF-kB, COX, lipoxygenase; LDN: TLR4, endorphin rebound). Clean stack.
• omega-3 / DHA (in Dylan's V4): Different anti-inflammatory mechanism (resolvin/protectin/maresin signaling). No overlap concern.
• bromantane: Both have anti-inflammatory arms (bromantane: cytokine reduction in animal models; LDN: TLR4 microglia). No documented interaction; pharmacologically independent.
• cerebrolysin (in Dylan's V5): Neurotrophic peptide complex; no opioid-system overlap. Clean stack.

Avoid stacking with

• Any opioid analgesic (codeine, hydrocodone, oxycodone, morphine, tramadol, fentanyl, methadone, buprenorphine): Naltrexone blocks the opioid receptor at any dose — the analgesic will not work, or will work only at much higher doses. For Dylan: this is the critical MMA-emergency caveat. If any planned surgery or dental work, stop LDN 5-7 days prior. If unplanned injury → opioid analgesia, inform the medical team.
• Loperamide (Imodium): Loperamide is a peripheral mu-opioid agonist; naltrexone may reduce its anti-diarrheal efficacy. Mild interaction, generally not a problem at LDN doses but worth knowing.
• Tramadol: Tramadol is partial opioid + SNRI; naltrexone blocks the opioid component. Also tramadol lowers seizure threshold — combination is not recommended.
• Other antagonists (naloxone, methylnaltrexone): Redundant; no benefit.

Neutral / safe co-administration

Modafinil, bromantane, semax/adamax/NASA, selank, the entire V4 daily core (DHA, magnesium, citicoline, NAC, PS, curcumin, rhodiola, theanine, glycine/L-tryptophan, D3+K2, beta-alanine, vitamin C), creatine, caffeine, alpha-GPC, ALCAR, taurine, apigenin, astaxanthin, BPC-157, TB-500. SSRIs and most antidepressants. Statins. Most antihypertensives. NSAIDs (no opioid component, no interaction).

• Opioids — ALL: Complete or partial blockade. Most clinically important interaction. See Avoid stacking above. Includes prescription analgesics, cough suppressants with codeine, antidiarrheals (loperamide), tramadol, and any opioid-based anesthesia.
• Hepatotoxic drugs: Theoretical concern at standard 50 mg (additive liver burden). Not relevant at LDN.
• CYP enzymes: Not a major CYP substrate or inhibitor; metabolism is primarily UGT2B7 (glucuronidation). Few significant CYP-mediated interactions.
• Disulfiram: Both used in AUD; combination is sometimes used but increases liver burden — needs LFT monitoring at standard doses. Not relevant at LDN.
• Alcohol: No direct interaction (the whole point of standard-dose use is with alcohol). At LDN doses, no clinically relevant alcohol interaction; Dylan's zero-alcohol baseline makes this moot.
• Anesthesia: Critical — see Stacking. Discontinue LDN 5-7 days before elective surgery requiring opioid analgesia. For emergency surgery, anesthesiologist must be informed.

• OPRM1 A118G (mu-opioid receptor polymorphism): The most-studied naltrexone pharmacogenetic. G-allele carriers (~20-30% of European ancestry) have stronger response to naltrexone for AUD — this is the core finding from Oslin et al. 2003 and subsequent replications. However: most evidence is for the standard-dose AUD context, not LDN. Theoretical relevance to LDN (affects mu-receptor density and endogenous opioid response) but no direct LDN-specific pharmacogenetic data. Worth checking against Dylan's 23andMe results once available — if G-allele carrier, expect stronger response if/when LDN is trialed.
• OPRD1 / OPRK1 (delta and kappa receptor polymorphisms): Minor effects reported; not clinically actionable.
• CYP / UGT polymorphisms: UGT2B7 polymorphisms affect glucuronidation rate; clinical impact is small. CYP2D6 is minor pathway.
• DRD2, COMT: Some AUD-response correlations reported but inconsistent.

Sourcing reality 2026: Standard 50 mg is trivially available with any Rx. LDN requires (a) a doctor willing to prescribe off-label at sub-therapeutic dose AND (b) a compounding pharmacy that does the small-dose preparation. Total cost is manageable (~$30-60/mo) but the friction is real. For Dylan, neither path is currently warranted — both standard and LDN naltrexone are downstream-of-bloodwork decisions.

• Baseline (before starting): Standard: ALT, AST, GGT (LFTs); CBC; CMP. LDN-specific: hsCRP, IL-6 (if available — uncommon in standard panel), ESR, ferritin (inflammation-sensitive), TSH + anti-TPO + anti-TG (autoimmune thyroid screen if relevant). For Dylan: align with June 2026 baseline panel — if doing LDN trial, add hsCRP and IL-6 to the order.
• During use (week 4, week 8, week 12, then q6mo): Subjective symptom scales relevant to indication (Fibromyalgia Impact Questionnaire if FM, MFI-20 / Chalder Fatigue if fatigue, PROMIS pain if chronic pain, GAD-7 if anxiety component). HRV trend (Dylan's Colmi R06 is ideal). hsCRP and IL-6 at week 12 to confirm anti-inflammatory effect. LFTs at week 12 (unlikely to shift at LDN dose but conservative).
• Post-cycle (if discontinued): Re-baseline subjective scales 4 weeks after stopping to assess durability of effect / need to restart.