Cocaethylene: a novel - and psychoactive - cocaine metabolite.

Recent research reveals that cocaine, when consumed with alcohol, forms a unique cocaine metabolite that is psychoactive, euphoric, addictive, and toxic. It is important for addiction professionals, and those who sponsor their treatment programs, to understand this relatively recent knowledge

A UNIQUE METABOLITE

Researchers have discovered that when cocaine and alcohol are consumed together, the body forms a unique cocaine metabolite named cocaethylene. It is unique because it is formed only during the combined ingestion of cocaine and alcohol. (The name "cocaethylene" is derived from the words "cocaine" and "ethyl alcohol.") It is unique also because it is the first known example of the body forming a third drug following ingestion of two other drugs. It is not a natural alkaloid of the coca leaf, and is not found in street cocaine.

DETECTING AND IDENTIFYING COCAETHYLENE

Cocaethylene was identified in 1979 in urine samples that were positive for both cocaine and alcohol. Since then, cocaethylene has been identified in the urine, blood, and hair of cocaine-alcohol users, and the liver and brain tissue of cocaine-alcohol fatalities. It is not detected in individuals unless they have consumed both cocaine and alcohol.

Its identity was confirmed when researchers designed a double-blind, randomized sequence study that involved four drug combinations: cocaine with alcohol; cocaine with an alcohol placebo; a cocaine placebo with alcohol; and a cocaine placebo plus alcohol placebo.(1) Cocaethylene was formed following only the co-administration of cocaine and alcohol.

IS COCAETHYLENE EUPHORIC?

The euphorigenic properties of cocaine are related to the increased availability of the neurotransmitter dopamine in the synapse between neurons in certain areas of the brain, caused by the inhibition of dopamine reuptake in presynaptic neurons.(2) By blocking the dopamine carrier or transporter on dopaminergic presynaptic nerve terminals, the amount of dopamine in the synapse is increased, resulting in enhanced activation of postsynaptic receptors. This results in stimulation, euphoria, a sense of reward, and self-administration.

Cocaethylene has a pharmacologic profile similar to cocaine with regard to these dopamine transport sites. For example, cocaethylene has an equally high affinity for the dopamine transporter as cocaine,(3)(4) and cocaine and cocaethylene cause a similar increase of dopamine in the synapse between neurons. During cocaine-alcohol consumption, both cocaine and cocaethylene will cause increases in dopamine availability, resulting in greater dopamine than with either drug alone, causing greater euphoria.