Author: John Carter

Cocaethylene: When Cocaine and Alcohol Are Taken Together PMC

When cocaine and ethanol are used together, a psychoactive metabolite is produced with similar pharmacological and psychoactive properties as cocaine [2]. This metabolite, cocaethylene, is considered more toxic to the cardiovascular and hepatic systems than cocaine, the parent drug, and it has a longer plasma elimination half-life (about 2 hours) than cocaine (about 1 hour) [3]. There are other metabolites produced as well but they go beyond the scope of this review. The serum concentration of cocaethylene is not readily predictable because it is based on the timing of the use of ethanol with cocaine and the quantities used [3]. While many cocaine users take ethanol together with cocaine, few understand that it produces a new potent metabolite in the body that has a longer half-life and potentially more dangerous cardiotoxic effects.

We publish material that is researched, cited, edited and reviewed by licensed medical professionals. The information we provide is not intended to be a substitute for professional medical advice, diagnosis or treatment. It should not be used in place of the advice of your physician or other qualified healthcare providers. People with a cocaine addiction and an alcohol addiction may crave the experience of using the drugs at the same time.

In another example, a person with great thirst who is given water will experience a rush of dopamine to the NA. Cocaine can cause dopamine build-up and dopamine activity in the NA that exceeds the levels of dopamine that might occur naturally [24]. For example, a thirsty person given water will remember the event, the source of the water, and the experience of drinking. Repeated cocaine use causes associations to form in the brain that try to link cocaine-induced delivery of dopamine to the external circumstances.

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In real-world clinical practice, it can be very difficult to predict cocaethylene concentrations in the blood, even when the exact amounts and timing of alcohol and cocaine use are known. The longer half-life of cocaethylene means that its measurable presence in the blood indicates that the person had used cocaine, even if cocaine is no longer detectable [3]. Dopamine is a reinforcing substance that plays a key role in the effects of many drugs of abuse, including cocaine and alcohol [21]. Independent of the route of administration, the initial effect of cocaine on the body is a rapid build-up of dopamine [22]. Dopamine originates in the dopaminergic cells of the brain and circulates throughout the body [22].

1. When people mix cocaine and alcohol, cocaethylene can stay around for days to even weeks in the body.
2. Cocaethylene, like its parent drug cocaine, blocks the reuptake of dopamine and increases post-synaptic neuronal activity and reinforces the stimulating effects of dopamine [3,11].
3. Cocaine and alcohol don’t actually negate the effects of one another.
4. Increased energy, alertness and focus are signs of cocaine use.
5. The substances disrupt the way the brain works, making the symptoms worse over time.
6. Because cocaethylene is a more potent sodium channel blocker than cocaine, it seems plausible that it would have more severe adverse effects on the cardiovascular system [25].

That means people feel the effects of cocaine for much longer when they mix it with alcohol than when they use cocaine alone. To remove cocaine, the body metabolizes the drug into chemicals called metabolites. The main cocaine metabolite is inactive, so it doesn’t interact with the body.

How Alcohol Disrupts Cocaine Metabolism

Thus, a person doesn’t feel the effects of cocaine once the drug is metabolized. Some people mix the drugs to ease the crash or hangover from cocaine or alcohol. A cocaine crash is a form of cocaine withdrawal that causes anxiety, irritability and agitation.

It also causes toxic levels of cocaine metabolites to build in the liver. That increases the risk of stroke and heart-related reactions for days to weeks. Because cocaethylene is a more potent sodium channel blocker than cocaine, it seems plausible that it would have more severe adverse effects on the cardiovascular system [25]. Sodium channel blockers can reduce the speed of action potential transmission in the heart, reducing conduction velocity [25]. In a study in which six healthy volunteers insufflated 2 mg/kg cocaine and then without delay consumed 1 g/kg ethanol, it was found that after consuming both drugs, all subjects had heart rates significantly elevated over baseline [32]. Central to the psychoactive effects of cocaine is the nucleus accumbens (NA) region of the brain, a major part of the ventral striatum that helps to mediate emotions, motivation, reward, and pleasure.

Cocaethylene also remains in the blood circulation three to five times longer than cocaine. Combining cocaine with alcohol and other substances also increases the risk of addiction. Cocaethylene is a toxic metabolite that forms when alcohol interacts with cocaine.

Signs of cocaine and alcohol dependence

Studies show alcohol and cocaine use during pregnancy have negative effects on both mother and fetus. These effects can have a lasting health impact on both mother and child. Cocaethylene can raise the risk of stroke even more because it can stay around in the body for days to weeks. There are quite a few known interactions between cocaine and other substances, including over-the-counter (OTC) and prescription medications and other drugs. People can receive help and treatment for alcohol and drug use disorder by contacting a drug and alcohol helpline or support network. Recovery will depend on the frequency and severity of cocaine and alcohol use and the overall health of the person.

Increased risk of heart-related problems

Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. The two main carboxylesterase enzymes in humans are carboxylesterase 1 (hCE1) and 2 (hCE2) mostly localized in the liver.

The hCE1 enzyme metabolizes certain endogenous esters, some pharmacological agents, and insecticides, while hCE2 metabolizes anticancer agents, such as capecitabine [15]. The hCE1 and hCE2 enzymes are high-capacity, low-affinity enzymes with the ability to hydrolyze structurally dissimilar esters to transform lipophilic esters into more water-soluble alcohol and acyl substituents [16]. Although it was long believed that cocaine was metabolized into benzoylecgonine via hCE1 and into ecgonine methyl ester via hCE2, this has come under question [17].

In a study of 66 adults in a methadone maintenance program who reported cocaine use, about 60% of subjects said they often took alcohol to help ease the discomfort or unpleasant transitions involved in the use of cocaine or crack [42]. Among polysubstance users, the use of alcohol, opioids, and cocaine is particularly prevalent. The serum concentrations of cocaethylene depend on both the amount and timing of the two agents (cocaine and ethanol) consumed. People who use cocaine without any ethanol would have no measurable amount of cocaethylene in their system, but the ingestion of even small amounts of ethanol may result in production of cocaethylene [3]. Likewise, people who consume ethanol but take no cocaine or very little cocaine would not produce cocaethylene [40]. The greatest cocaethylene production would theoretically occur in a person who has a relatively high blood-alcohol level at the point in which they used cocaine [40].

Despite this, an unknown consequence to many regular or even recreational users is that combining alcohol with cocaine is cardiotoxic. The short-lasting effects cause a user to repeat taking cocaine for the rewarding stimulus, which can result in a person eventually becoming addicted. The consequences of long-term use include an increased risk of stroke, heart attack and depression. Combined alcohol and cocaine use is also linked to an increase in suicide, according to a study at Brown University. Researchers looked at over 800 patients who reported to the emergency department for suicidal thoughts or suicidal behaviors. The study found that only the combination of alcohol and cocaine was linked to an increased suicide risk.