Cocaine MOC
Hub
Mechanisms
- DAT blockade — primary: DAT/NET/SERT reuptake inhibition; secondary: voltage-gated Na⁺ channel blockade (arrhythmia risk)
- Cocaethylene — formed with ethanol; 18–25× ↑ sudden death risk; half-life 2–3× longer than cocaine; ~92% of users co-use alcohol
- Cocaine crash — D2 autoreceptor redistribution (not simple DA depletion); PKC-mediated DAT dysregulation; HPA axis disruption; TLR4/NF-κB/NLRP3 neuroinflammation persisting 10+ days; D2R PET: no recovery at 9 months (primate)
Pharmacogenomics
- BChE D70G: 10× reduced cocaine affinity → prolonged toxicity risk
- BChE rs1803274 AA: OR=4.36 for crack preference (n=1436)
- No FDA-approved treatment: 30+ agents failed over decades; 2019 meta-analysis: no drug class effective
Biometrics
- Cardiovascular signatures — acute HR ↑ 11–20+ bpm; synergistic ↑ 20–40 bpm with ethanol; 4 arrhythmia mechanisms; use-dependent Na⁺ blockade positive feedback loop
- Cocaine sleep architecture — acute REM suppression; abstinence REM rebound (SOREMPs); chronic users lose N3 slow wave sleep
Risks
- Cocaine risk profile — cardiotoxicity, hypertension, arrhythmia, cardiomyopathy; benzylated via β-blocker contraindication
- Cocaethylene — unique cocaine + ethanol hazard; majority of users co-use alcohol
- Cocaine crash — anhedonia timeline: hours (single) → weeks (binge) → months (chronic)
Recovery
- Cocaine crash — anhedonia driven by D2R redistribution; HPA axis suppression paradox; neuroinflammation persists 10+ days; D2R recovery with sustained abstinence
Detection
- Cocaine detection model — primary wearable signal: acute HR spike + HRV suppression; same-night REM reduction; next-day corroborating signals (cognitive, HRV)
Interactions
- Cocaine peptide interactions — BPC-157 most relevant (DA stabiliser from amphetamine data); Retatrutide: additive appetite suppression + BMJ 2026 reduced CUD risk signal (n=524,817); GHK-Cu likely safe; TB-500 cardiac repair unlikely relevant (wrong cardiomyopathy mechanism)