AUGUST 29, 2023
LAS VEGAS—When cocaine and alcohol collide, the consequences can be deadly, according to a literature review poster at PAINWeek 2022 (abstract 75).
“Cocaethylene is a metabolite that forms when an individual consumes cocaine and alcohol together,” said co-author Frank Breve, PharmD, MBA, CCP, the president and CEO of Mid Atlantic PharmaTech Consultants, in Ventnor, N.J. “For example, at a party, someone is snorting cocaine and then drinks some booze.”
The combination
LAS VEGAS—When cocaine and alcohol collide, the consequences can be deadly, according to a literature review poster at PAINWeek 2022 (abstract 75).
“Cocaethylene is a metabolite that forms when an individual consumes cocaine and alcohol together,” said co-author Frank Breve, PharmD, MBA, CCP, the president and CEO of Mid Atlantic PharmaTech Consultants, in Ventnor, N.J. “For example, at a party, someone is snorting cocaine and then drinks some booze.”
The combination can be problematic because of its more pronounced cardiopathic effects than cocaine by itself.
The review was inspired by a colleague of one of the other authors: an emergency department physician who was treating extremely severe cases of cocaine overdose. “The physician determined that that reason these cases were so severe is because the patient was mixing cocaine with alcohol,” Breve said.
The authors searched the PubMed, EMBASE, Web of Science and Cochrane Library databases to present a comprehensive overview of the definition of cocaethylene, how it occurs, and why clinicians need to consider it when treating patients who may have overdosed on cocaine.
The literature revealed that in the human body, cocaine is metabolized by carboxylesterase enzymes to produce two major metabolites: benzoylecgonine and ecgonine methyl ester. However, ethanol alters this metabolic pathway, so that instead of hydrolysis with water, a portion of the cocaine undergoes transesterification and produces cocaethylene.
Ethanol also diverts the metabolic pathway of cocaine so that less of the inactive metabolite benzoylecgonine is created, while more of the active metabolite cocaethylene is produced.
A randomized, double-blind study, published in the Journal of Pharmacology and Experimental Therapeutics (1995:274[1]:215-223), concluded that in eight humans administered either intranasal cocaine or intranasal cocaethylene, the subjects could not distinguish between the two agents, but both generated euphoria. Although psychoactive effects were similar for cocaethylene and cocaine, the former cleared the body more slowly, had a larger volume of distribution and had roughly twice as long an elimination half-life.
A second study, published in Drug and Alcohol Dependence (2003;72[2]:169-182), found that in 10 healthy volunteers, the combination of cocaine and ethanol was more intoxicating and pleasurable than either agent alone.
Cocaethylene is believed to be 10 times more cardiotoxic than cocaine. It is also a significantly more potent sodium channel blocker than cocaine.
“A lot of clinicians are unaware that this combination can result in the formation of a distinct metabolite that is more toxic than either of the parent compounds,” said Breve, an adjunct clinical professor at Temple University School of Pharmacy, in Philadelphia. “This is the only known situation in which a novel psychoactive substance is created entirely within the human body.”
The mixture is something to be aware of and should not be ignored, according to Breve. “Education of clinicians, patients and their families is needed to recognize the potential negative consequences of the combination,” he said.
However, identifying cocaethylene is a judgment call. “There is no diagnostic test,” Breve said. “Instead, you need to ask the patient or a family member if the patient was drinking alcohol while concurrently snorting cocaine or taking it by other means.”
A blood test to determine the alcohol level in the bloodstream might also be valuable.
“Clinicians should be very alarmed because cocaethylene is a real problem that could adversely affect the patient,” Breve said. “If the clinician does not know why the patient is having such bad cardiopathic effects, this might be challenging when treating the patient.”
The under-recognition of the prevalence of cocaethylene is due to a lack of physician awareness and failure to realize that a toxic metabolite is created when a person takes cocaine and drinks alcohol. “The metabolite can also have a neurodegenerative effect,” Breve said.
More research is needed to develop assessment tools that might lessen the likelihood of a more toxic reaction to cocaethylene, according to Breve, who recommends that physicians carefully evaluate cocaine intoxication cases to rule out if alcohol may have been a contributing factor.
“You always want to discourage the recreational use of cocaine, but if someone is so compelled to do so, they need to know that drinking alcohol along with using cocaine can have detrimental effects,” Breve said. “That could be a fatal combination.”
Gustava Angarita, MD, an assistant professor of psychiatry at Yale University, in New Haven, Conn., noted that there are still several questions to be answered about the exact effects of cocaethylene in humans. “But the fact that cocaethylene is an active metabolite and with a longer half-life than cocaine could indeed be partially responsible for the many negative consequences of the combined consumption of cocaine and alcohol.”
Among the negative consequences are psychosocial, such as worsening or prolonging paranoia and altered mental status that can have dire public health consequences, like higher risk for motor vehicle accidents; neurologic, such as seizures; and cardiovascular, like higher or prolonged high blood pressure, heart attack or heart arrhythmias, according to Angarita, who was not a study author.
Angarita agreed with review author Breve that educating clinicians and patients about cocaethylene and its potential harm is a good step to reduce the detrimental impact of the metabolite.
—Bob Kronemyer
Angarita and Breve reported no relevant financial disclosures.
