Answer: Cocaethylene is an addictive substance produced by the body when both cocaine and ethyl alcohol are processed by the liver.
Both ethanol (alcohol) and cocaine are addictive substances that are commonly used. Alcohol and cocaine misuse both contribute to tremendous drug related costs, which include harms to both the individual and to society.
Both alcohol and cocaine are broken down after ingestion by enzymes in the liver. In particular, alcohol is degraded by alcohol dehydrogenase into acetaldehyde. Cocaine, on the other hand, is mostly broken down spontaneously by hydrolysis and esterase activity into the inert substance benzoylecgonine - but a small fraction of the cocaine in the body is converted by cytochrome P450s in the liver into norcocaine.
When both drugs are in the system at the same time during use of alcohol and cocaine, a different substance is produced as a result of metabolic breakdown of the two drugs. This substance is called cocaethylene. It is estimated that half life of cocaethylene is between 2 and 3 hours, much longer than that of cocaine. Additionally, the presence of cocaethylene can be detected in urine tests much longer than cocaine alone.
When cocaine alone is in the system, it undergoes hydrolysis due to carboxylase enzymes. When ethanol is present however, a transesterification chemical reaction happens to the cocaine byproduct benzoylecgonine, which results in cocaethylene being formed. (Cocaethylene metabolism and interaction with cocaine and ethanol: role of carboxylesterases)
Pharmacology of cocaethylene
Cocaethylene itself is considered an addictive drug. It’s pharmacological properties include inhibition of the reuptake proteins of three neurotransmitters: norepinephrine, dopamine, and serotonin. In this way, cocaethylene continues the pharmacological manipulation of these neurotransmitter systems as cocaine did, with a longer acting time course.
Self administration of a substance is a useful experimental technique to assess the rewarding properties of a substance. In self administration, it is possible to train an animal to perform some operant task such as lever pressing or nose poking to receive a direct infusion of a drug. It has been demonstrated that monkeys will lever press for intravenous infusions of cocaethylene (Cocaethylene: A neuropharmacologically active metabolite associated with concurrent cocaine-ethanol ingestion). This indicates that cocaethylene is inherently a rewarding substance.
