Cocaethylene
What it is
Cocaethylene (ethyl benzoylecgonine) is formed when cocaine and ethanol are co-ingested. It is NOT a hydrolysis product — it is a transesterification product: ethanol displaces the methyl group of cocaine via hepatic CES1 (hCE1).
Key numbers
| Half-life | ~2 h (vs cocaine ~1 h) |
| Sudden death risk | 18–25× greater than cocaine alone |
| Conversion rate | ~24% (IV), ~34% (oral), ~18% (smoked) when alcohol co-administered |
| % of cocaine users who co-use alcohol | ~92% |
Mechanism
- Produced by CES1-mediated transesterification in the liver
- Both cocaine and ethanol reduce the clearance of each other → prolonged exposure to both compounds
- Inhibits dopamine reuptake similarly to cocaine
- More cytotoxic than cocaine alone
- Produces more euphoria → increased abuse liability
- The ethanol + cocaine combination is uniquely cardiotoxic
Why worse than cocaine alone
- Longer half-life → prolonged cardiac exposure
- Mutual metabolic inhibition → cocaine clears more slowly
- Both compounds are independently cardiotoxic
- Euphoria enhancement increases binge likelihood
Clinical note
~92% of cocaine users co-consume alcohol — this means the “pure cocaine” risk profile is the minority case. Cocaine risk profile and Cocaine detection model both need to account for cocaethylene.
Related
Cocaine, DAT blockade, Cardiovascular signatures, Cocaine risk profile, Cocaine peptide interactions