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Lethal Drug Combinations

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What are the Deadliest Drug Combos?

Most-dangerous-drug-comibinations-infographicCombining drugs (“polysubstance abuse”) is both common and potentially dangerous. There are various reasons why individuals use substances in combination. For some, the activity is done haphazardly, without pretense or forethought. For others, the combination is deliberate — the selection of drugs, their amounts, and even the timing of their consumption is planned in advance so the right effect is achieved when they are combined.

Regardless, when it comes to the danger of simultaneous drug use, not all combinations are created equal — a select number of them are especially lethal. They include the following:

Alcohol and Opioids

Opioids are a class of drug that includes both heroin, an opiate derived from the opium poppy, and synthetic opioids, many of which derive from opiate precursor substances such as morphine and thebaine. Common synthetic opioids are prescription pain medications like hydrocodone, oxycodone and tramadol.

Alcohol and pills on table

Opioids, including heroin and painkillers like OxyContin and Dilaudid, relieve pain and create a sense of euphoria and well-being in the user. These rewarding, pleasurable effects reinforce their addictive potential. Additional effects include:

  • Drowsiness.
  • Confusion.
  • Nausea.
  • Slowed breathing.

Alcohol is the most commonly used substance in the world.  Effects include:

  • Impaired motor coordination.
  • Impaired judgment
  • Reduced reaction time.

While alcohol and opiates look, taste, and feel vastly different, both substances are central nervous system depressants which, even when used alone, can impair brain activity and slow functioning throughout several organ systems, among other things. Unfortunately, it is common for people to abuse alcohol and opioids together to enhance the effects of each substance. Because these two substances work synergistically, there is an increased chance of toxicity and overdose.

Signs of overdose from concurrent use of alcohol and opioids include:

  • Profoundly depressed breathing rate or respiratory arrest.
  • Severely compromised motor coordination.
  • Loss of consciousness.
  • Coma.
  • Death.

Alcohol and Benzodiazepines

The benzodiazepine class of drugs comprise numerous anxiolytic (anxiety-reducing) medications, with some of the earliest examples being first discovered and soon thereafter manufactured for therapeutic use in the mid-20th century. They have since established a consistent presence in hospitals and doctors’ offices as some of the most frequently prescribed sedative medications for conditions such as anxiety, panic disorder, insomnia, seizures, and muscle spasms.  While effective at addressing these conditions, benzodiazepines, commonly referred to as “benzos,” are also highly addictive.

Through their interaction at various receptor sites throughout the brain, benzodiazepines elicit an increase in the activity of an inhibitory neurotransmitter called GABA. This biochemical process is associated with an accompanying increase in activity of the brain’s “reward” neurotransmitter, dopamine.

Like alcohol, benzodiazepines are central nervous depressants, and their use can blunt motor skills, slow reaction times, and impair various thought processes. Specific effects also include:

  • Inability to remember events that took place while intoxicated.
  • Slurred speech.
  • Paranoia.
  • Depression.

Combined with alcohol, the effects of benzodiazepines are enhanced (as are the effects of alcohol). The chances of overdose, as a result, increase dramatically.

In general, combining strong central nervous system depressants is very dangerous.  Other deadly combinations include alcohol and barbiturates (such as phenobarbital) or barbiturates and opioids.

Heroin and Cocaine (“Speedball”)

An especially dangerous combination of substances is that of cocaine and heroin. Commonly referred to by its descriptive street moniker, the “speedball, ” this injected combination of cocaine and heroin has been responsible for many fatal overdoses.

In examining the neurobiological effects of concurrent cocaine and heroin use, researchers have discovered that both substances have an impact on dopaminergic brain processes, making the combined effect more addictive than if using each drug separately (Leri, Bruneau, & Stewart, 2003).

The rewarding euphoric state associated with cocaine use results, in part, by the stimulant drug blocking the reabsorption of extra dopamine from the synaptic space — allowing it to remain active there longer. Levels of another neurotransmitter, norepinephrine, also increase after cocaine use, causing increased alertness and arousal. This effect actually works against the effects of heroin, which depresses the central nervous system.

Other potential effects of cocaine use include:


    • Agitation.



    • Paranoia.



    • Restlessness.



    • Panic.


The idea that each drug cancels the other out is both deceptive and dangerous. Indeed, a user may feel less drowsy if they have used cocaine with heroin, but this deception is a mere smokescreen.

The reason for many of the deaths as a result of this combination of drugs is that people feel less vulnerable to heroin overdose because of their cocaine intake.  In fact, users are no less vulnerable and may be more so due to the inability to sense the full effects of heroin and quit before the dose becomes fatal. If enough heroin is ingested, respiratory depression—often times the cause of death for heroin overdoses—can occur once the effects of cocaine wear off, which they do at a faster rate than heroin.

Signs of overdose from speedballs include:

  • Bluish skin or fingernails.
  • Extreme stomach pain.
  • Coma or loss of consciousness.
  • Respiratory depression (slowed breathing).

Cocaine and Alcohol

The concurrent use of cocaine and alcohol is one of the most common polysubstance combinations.

Glass of alcohol and cocaine on table

Cocaine and alcohol are commonly used together to counteract the unwanted effects of the other substance. By creating a surge of norepinephrine, cocaine increases alertness and motor activity in alcohol-intoxicated individuals, whose central nervous systems are slowed down. Conversely, alcohol calms down both physiological and psychological hyperactivity associated with cocaine use—some might claim that it “takes the edge off,” or somewhat eases the jitters associated with stimulant use.

Although alcohol is a depressant, it is commonly known to increase levels of aggression.  Cocaine, whose side effects include paranoia and agitation, can compound the aggression from alcohol and lead to violent behavior.

In addition to this risk, alcohol and cocaine combine to create a unique and dangerous toxic compound called cocaethylene, a chemical that forms in the liver when these drugs are mixed. Cocaethylene is cardiotoxic, meaning that it puts significant stress on the cardiovascular system, which includes the heart and lungs.

Because alcohol and cocaine counteract each other’s effects, it may be difficult to detect toxic and dangerous levels of the each separate drug, which increases the risk of overdose. However, the combined use, as previously stated, puts added stress on the heart, increasing the chance of cardiovascular complications, including heart attack and cardiac arrest.

Other symptoms of overdose include:

  • Extreme stomach pain or nausea.
  • Irregular heartbeat.
  • Seizures.
  • Coma.
  • Heart attack.

Getting Help for Substance Abuse

Combining substances may enhance feelings of pleasure and well-being, but that one “benefit” is dwarfed by the numerous consequences of polydrug use. Firstly, combining drugs can increase the risk of addiction and the speed at which addiction develops. Secondly, particular combinations of substances can lead to fatal overdose.

Whether you have a problem with a single substance or multiple substances, you should reach out for help immediately. Addiction to one drug can easily lead to experimenting with other drugs at the same time, especially at parties or other social gatherings where multiple substances are usually present.

If you feel that you have an addiction — a condition marked by a continuing need to take a substance regardless of the serious consequences its use entails — consider getting help. It can be extremely difficult to quit using on your own, especially if you are using multiple substances, but there is no shame in asking for help.

The first step to recovery, whether that’s treatment or just managing your addiction, should be one of the easiest, but is often times the hardest:  talking to someone.  Whether it is a friend, family member or doctor, reaching out to someone can be the engine that drives your treatment, sobriety, and long-term health. If you need assistance, call us for free at to speak with someone confidentially today. You can also contact free narcotics and drug abuse hotline numbers.

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Joe completed his Master of Arts in Psychology in 2013 at Boston University, focusing on clinical areas such as abnormal psychology, statistics, personality, neuroscience, and clinical psychology,

Originally from Texas, Joe moved to Boston in 2013 to complete his degree, at which time he was a teaching fellow and instructor at Boston University. There, he gave lectures on Psychology and Criminal Justice, Social Psychology, Abnormal Psychology, and other topics.

His Master's thesis delved into the associations and mediational relationships among treated individuals with bulimia and co-occurring borderline personality disorder symptomatology.

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