Polysubstance Use: The Effects and Dangers of Mixing Drugs

When a person uses more than 1 substance at the same time, it’s known as polysubstance use (also sometimes referred to as simultaneous substance use, concurrent substance use, co-occurring substance use, and polydrug use).^{1, 2}

In this article, you’ll learn about polysubstance use; polysubstance examples, effects, and dangers; polysubstance use and addiction; and how to find help and treatment for polysubstance use.

What Is Polysubstance Use?

Polysubstance use is the use of 2 or more drugs, medications, or other psychoactive substances together or within a short period of time.^{1, 2} A person may use multiple substances for several reasons, including to:¹

• Enhance or modify the effects of a substance (e.g., increase feelings of euphoria or to get high).
• Escape certain life circumstances, health issues, or trauma.
• Compensate for the effects of another substance.
• Prevent withdrawal symptoms from another substance.
• Substitute when a primary drug of choice is unavailable.

In addition, polysubstance use can be unintentional if a person uses a substance laced or mixed with another without their knowledge.²

Whether the substances have been combined intentionally or unintentionally, all polysubstance use can have significant consequences. Not only can concurrent substance use increase a person’s chances of experiencing financial, legal, and relationship issues, but it can lead to serious physical and mental health risks, including addiction, mental illness, overdose, and death.^{1, 2}

Use of multiple substances is common and occurs frequently. The majority of people who enter publicly funded substance use disorder (SUD) treatment use multiple substances.¹ Between 1998 and 2008, there was a 76% increase in inpatient hospitalization admittance involving alcohol polydrug use.³  Furthermore, having a SUD with one substance increases a person’s susceptibility to developing dependence on additional substances.³

One study found that of people who used methamphetamines in the last year, 68% also used marijuana, 44% also used opioids, and 32% also used cocaine.¹ People who reported using marijuana daily were also more likely to use cocaine, hallucinogens, inhalants, and tobacco.¹ Data suggest that the majority of people who have died from overdoses had multiple substances in their system.^{4, 5}

Concurrent substance use is a growing problem in the United States that affects multiple populations and subcultures.^{1, 6} Intentional polysubstance use is more prevalent among certain populations, including young adults aged 18-25, those who identify as lesbian, gay, or bisexual, and subcultures such as ‘ravers.’^{1, 6}

Almost 80% of synthetic opioid overdose deaths involved another substance, such as alcohol, antidepressants, benzodiazepines, cocaine, psychostimulants, or prescription opioids.⁷

Examples of Polysubstance Use

Several combinations of concurrent substance use can occur. Polysubstance use can include 2 or more substances from the same drug classification (e.g., a depressant mixed with another depressant) or different drug classifications (e.g., a depressant taken with a stimulant).²

Polysubstance use can be combining illicit drugs. However, concurrent substance use and its dangers also apply to alcohol, prescription medications, and tobacco.^{1, 2}

For example, a person may consume alcohol while taking a prescription central nervous system depressant (e.g., Xanax) prescribed by their doctor without realizing the potential dangers. This is why it’s important to read prescription drug labels, talk to your pharmacist about any concerns, and inform your doctor of what medications or substances you are taking, which can reduce your risk of potentially harmful side effects and dangerous drug combinations.^{2, 8}

Dangerous drug/alcohol combinations can include:

Dangers of Polysubstance Use

Concurrent substance use can increase your risk of both physical and mental health problems, including overdose and death.^{1, 2}

While the effects of polysubstance use are dependent on the combination of substances involved, concurrent substance use of any kind is dangerous as the effects can be unpredictable and potentially fatal.^{1, 2}

Some of the more specific dangers of mixing drugs include:^{1-3, 9-12}

• Combining alcohol and drugs: Combining alcohol with other drugs can cause several adverse effects depending on the substances alcohol is combined with. Alcohol and cocaine, for example, can increase a person’s risk of damage to the heart muscle and overdose. Alcohol in combination with opioids or benzodiazepines can increase respiratory depression and combining these drugs will increase your risk of a life-threatening or deadly overdose. Concurrent drug use with alcohol is associated with additional comorbidities, including higher rates of anxiety and mood disorders and more intense drug consumption and drug cravings. Furthermore, antidepressants and other therapeutic medications may not work as well when combined with alcohol.
• Combining marijuana and drugs: Marijuana is commonly combined with other substances, particularly alcohol and cocaine. In addition to a variety of adverse effects, concurrent drug use among marijuana users has been correlated with mood disorders, self-harm, financial instability, and reduced socioeconomic mobility. Studies also show that people who combine alcohol and marijuana are more than twice as likely to drive while under the influence than people who don’t combine the two.
• Combining depressants or combining opioids with depressants: Combining multiple types of depressants, including alcohol, opioids (e.g., heroin, hydrocodone, morphine, and oxycodone), and prescription central nervous system depressants (e.g., hypnotics, sedatives, and tranquilizers), can typically have an additive effect. This is also true when combining depressants with opioids. These combinations can increase a person’s risk of accident or injury due to sedation as well as overdose, which can lead to permanent brain damage and death.
• Combining stimulants: Combining stimulants, including cocaine, khat, MDMA, methamphetamine, and prescription stimulants such as ADHD medications (e.g., Adderall), can increase a person’s blood pressure and heart rate to dangerously high levels. They can also cause anxiety and panic, brain and liver damage, heart attack, and stroke. High doses of stimulants can also induce symptoms of mania and psychosis similar to those of bipolar or schizophrenic illnesses.
• Combining depressants and stimulants: Combining depressants and stimulants can mask the effects of each drug. This can increase a person’s risk of overdose, which may lead to permanent brain damage or death. Combining these drugs can also lead to cardiovascular problems including heart failure as well as bronchitis, respiratory infections, dehydration, kidney failure, and overheating.
• Combining hallucinogens: This classification includes classic hallucinogens like LSD and dissociative drugs like PCP, both of which can cause hallucinations. These drugs can have several short-term effects including amnesia, anxiety, panic, and seizures when taken in high doses. Combining hallucinogens with other hallucinogens or other drugs is dangerous as these substances can profoundly alter a person’s perception, which can make them do something they would never do otherwise. Combing certain hallucinogens and dissociative drugs with alcohol or benzodiazepines can lead to coma.

If you have any concerns about combining medications with other substances, be sure to talk to your doctor or pharmacist.

Unintentional Polysubstance Use

Unintentional polysubstance use can occur as a result of unintentional drug exposure. That is, a person purchasing illicit substances or prescription drugs, which are often counterfeit, off the streets are at increased risk of ingesting other substances without their knowledge, which can increase their risk for overdose and death. Counterfeit pills are often made to look like prescription opioids or stimulants.¹³

Meanwhile, cocaine, heroin, methamphetamine, and other illicit drugs are often sold in impure forms as dealers “mix” or “cut” the drug with other adulterants to increase their profit margins. This puts people at risk as adulterants can cause additional potential health threats. Counterfeit pills are also a potential health threat.^{14, 15}

According to the Centers for Disease Control and Prevention (CDC), opioid-involved overdose deaths can, and frequently do, occur in combination with other opioids.¹⁵ Examples of overdose deaths because of unintentional exposure combinations include illicitly manufactured fentanyl (IMF) and cocaine; IMF and heroin; IMF, cocaine, and heroin; IMF and prescription opioids; IMF and methamphetamine.¹⁵

Polysubstance Use and Addiction

Once a person begins using multiple substances, they may find it difficult to stop and subsequently develop 1 or more substance use disorders.¹ A substance use disorder is a chronic but treatable medical condition characterized by continued, compulsive substance use despite its adverse consequences.¹⁶

Although research is limited, studies suggest that when compared to people with a single substance use disorder, those who have a substance use disorder and use other substances or have concurrent substance use disorders may experience higher rates of:¹

• Arrests and incarceration.
• Suicide attempts.
• Financial and legal issues.
• Increased chance of overdose.
• More severe co-occurring medical and mental health disorders.

Treatment for Polysubstance Use

If you or someone you care about are struggling with polysubstance use, it may be time to seek professional help. The good news is that several types of treatment for polysubstance use are available.

Medical detox can be an important first step for many people in recovery. People who are dependent on multiple substances may benefit from detox in an inpatient setting, as the presence of multiple substances may alter the severity of withdrawal symptoms or otherwise affect the course of detox.^{17, 18}

During this time, patients receive 24-hour care and supervision from medical professionals. They may also receive medication to help manage withdrawal symptoms and facilitate the transition into ongoing addiction treatment. ^{17, 18}

Following detox, addiction treatment, such as inpatient and/or outpatient care, can help patients identify and modify damaging behavioral patterns.¹⁸ While there is no one-size-fits-all treatment for everyone, effective treatment programs will address a patient’s unique needs and individual recovery goals.¹⁵ For those struggling with polysubstance use, treatment that addresses both substance use disorders, as well as co-occurring mental health disorder treatment, can lead to better outcomes and higher quality of care.¹⁹ 

If you’re struggling with polysubstance use or addiction, or you know someone who is, please contact American Addiction Centers at to learn more about addiction treatment options.

You can also look at the facilities listed below to see if they provide the program you are looking for:

• California: Laguna Treatment Center
• Florida: Recovery First Treatment Center
• Florida: River Oaks Treatment Center
• Nevada: Desert Hope Treatment Center
• Mississippi: Oxford Treatment Center
• Texas: Greenhouse Treatment Center

Getting Help for Polysubstance Use

If you or someone you care about are struggling with polysubstance use or addiction, help is available. American Addiction Centers (AAC) is a leading provider of evidence-based addiction treatment. AAC admissions navigators are available 24 hours a day, 7 days a week when you call . They can help you find an addiction treatment center as well as verify your insurance coverage.

For those who have insurance, using health insurance to pay for rehab should cover at least some of the cost of addiction treatment. Coverage may vary depending on your needs and insurance plan. To find out if your policy covers rehab, click here, or fill out the form below. Your information is kept 100% confidential. You can also click here to find a rehab near me.