Why Mixing Codeine With Other Drugs Can Be Fatal

Medically Reviewed

Codeine is a psychoactive opiate that can be found in opium poppy plants naturally. The chemical is one of the most abundant alkaloids in the plant after morphine. Unlike heroin or synthetic opioids, codeine doesn’t have to go through any extra processing to achieve its active chemical structure. It’s isolated from the other substances in the plant, including three other opioids, and included in a wide variety of medications. 

The drug is used to treat mild pain symptoms, diarrhea, and it is an ingredient in many cough medicines. Worldwide, it’s the most commonly used opiate — more than 200,000 kilograms were used in 2013.

Codeine has been used in modern medicine since the mid-19th century after its discovery in 1832. The drug makes up about two percent of liquid latex that’s produced by the poppy plant. However, this natural tincture has been used for centuries before the drug was isolated. 

Morphine had already been isolated in 1804, but it was much more powerful than was needed for specific kinds of medications. Codeine is significantly weaker as far as opioids go, allowing it to be used in milder medications. Today, codeine is one of the most commonly used drugs in the world. Plus, scientists are now able to synthesize it from the more abundant morphine, making it easier to produce the drug. 

Codeine is useful in treating mild-to-moderate pain that other more potent opioids wouldn’t be necessary for. The drug comes with some mild side effects including, itching, nausea, and dry mouth. In some cases, it can cause vomiting, hypotension, euphoria, and dysphoria. 

Though it’s weaker than other options, the drug can be abused, leading to tolerance, withdrawal, and dependence. In high doses, the drug can cause respiratory depression, which can be dangerous but rarely fatal. However, it can be deadly and would require immediate medical attention. 

But how would other drugs or psychoactive substances affect codeine in your system? Which substances should be avoided? Learn more about how codeine works in the body and how other drugs might affect it. 

How Codeine Works

Codeine works in a way that’s similar to other opioids but with some key differences. It’s a selective opioid agonist that binds to a specific opioid receptor called MOR. Codeine has a weak affinity for the receptor on its own, which means it doesn’t easily bind to and activate the receptor. Instead, codeine turns into morphine as it breaks down in your metabolism. 

Morphine has a much stronger affinity for MOR than codeine, activating the receptor’s painkilling functions. In general, opioids work to block the pain signals from reaching the brain. In higher doses, the drug can cause sedation in a way that’s similar to a central nervous system depressant. MOR can regulate nervous system excitability when it’s activated by interacting with GABA; the naturally occurring neurochemical that causes sedation.

Codeine is active at between 30 to 50 mg (milligrams), but a common dose is around 100 to 200 mg. By comparison, morphine reaches analgesic effects at 30 mg. To achieve the same effectiveness, you’d have to take 200 mg of codeine. It’s not usually the first choice for pain symptoms beyond moderate levels. 

Codeine is also very common in cough medicines, despite research that suggests it may be ineffective for that purpose. In controlled studies, codeine was found to be no more effective than placebos. Its wide use was based on animal studies and studies that applied it to chronic or induced coughs. However, it seems to have no significant effect on coughs that are caused by respiratory infections. 

How Codeine Interacts With Other Drugs

Like most medications, it’s important to be aware of the drugs you take alongside codeine. However, the drug is commonly prescribed with other substances and, in some cases, medications are sold that contain both codeine and other medications. 

Codeine is often combined with other medications to increase its painkilling effects. It’s most commonly combined with NSAID pain relievers such as ibuprofen. However, this combination can increase certain side effects, such as dizziness or drowsiness. In some cases, users can get headaches.

In cough medicines, codeine is typically combined with an antihistamine like promethazine to increase its efficacy as cold medicine. This combination is relatively safe when prescribed by a doctor. However, antihistamines dry up mucus in your lungs, which can make it more difficult to breathe. When this is combined with respiratory depression that can be caused by codeine, it can cause very labored breathing in a high dose. Be sure to use the drug as directed, drink plenty of water, and speak to your doctor if your breathing becomes difficult.

While there are a few medications that are safe to combine with codeine, there are others that can be dangerous and even deadly. The following combinations should be avoided:

Other Opioids

Taking other opioids alongside codeine can increase the potential for adverse side effects. If you are given prescriptions for two separate opioids, double-check with your doctor to make sure this is safe and correct, especially if the prescriptions came from two different doctors. If you take an effective dose of both drugs, it can cause your opioid receptors to be overactive, causing dangerous side effects like respiratory depression. 


Alcohol is one of the most common substances that people accidentally mix with medications and drugs that could be dangerous. Many people start taking prescriptions and unthinkingly drink in social settings later on. In other cases, codeine is used recreationally in party settings where alcohol is also common. This drug combination can make it more likely to lead to a fatal overdose because of a phenomenon known as potentiation, which is when two or more substances cause each other to become more effective. 

Alcohol is GABAergic, which means that it interacts with GABA in the central nervous system. GABA reduces excitability in the nervous system in a similar way that opioids like codeine do. When they’re combined, they can cause the nervous system to slow down to the point of stopping or slowing breathing.


Benzodiazepines, like alcohol, are GABAergic, and they’re often used to treat insomnia or anxiety. If you have a standing benzo prescription and are prescribed medication with codeine, it’s important to double-check that this combination is safe. In many cases, this combination can lead to the same respiratory depression that alcohol can. In fact, the National Institute on Drug Abuse reports that more than 30 percent of fatal overdoses that involved opioids also involved benzodiazepines. 


Promethazine, mixed with codeine, is commonly known on the street as lean, is a dangerous concoction that Houston rappers brought into existence. It is called lean because of the intoxication that takes place in the user. They tend to “lean,” which is where the name originates.

The cough syrup is often mixed with Sprite, and it is known as purple drank due to its dark purple color. The mixture of codeine not only makes it dangerous but makes it a very addictive option that people may use. It’s easy to overdose on this drug because there is no set standard. Promethazine itself can make its user extremely drowsy, and when it is combined with another depressant drug, it can spell disaster.

In some cases, it can lead to radically high amounts of codeine being consumed. It is common to mix up to 25 times the recommended dose in one sitting, which can easily lead to brain damage or overdose. The common misconception is that codeine is a weaker opiate, but when people use lean, they consume such massive amounts, it can be just as dangerous as using a needle.

Purple cough syrup being poured into a spoon

There has been an entire culture dedicated to this mix, and it has killed many during its popular stint. Famous rappers, such as Lil’ Wayne and Drake have made songs devoted to the drink. It has caused an uptick in those who are impressionable to use the drug. Unfortunately, there have been dire consequences as a result. Death is a real possibility with this combination and should be one that you skip altogether.

Tap to GET HELP NOW: (888) 263-0631