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Learn how polysubstance use involving alcohol, opioids, and benzodiazepines can raise overdose risk, slow breathing, and signal a need for treatment today.
New Hope Health
Editorial Team
Polysubstance use occurs when a person takes drugs or alcohol involving more than one substance, whether through intentional polysubstance use or unintentional polysubstance use. As the opioid crisis continues to affect public health, substance abuse involving multiple drugs, illicit substances, and drinking alcohol has become an important concern linked to drug overdose deaths. This guide explains polysubstance abuse, its connection to drug addiction and mental health conditions, and the treatment approaches available for people who need support.
Polysubstance use means using two or more substances at the same time or within a short period. This can involve alcohol, opioids, benzodiazepines, stimulants, prescription medications, or illicit drugs, and the combination may be intentional or unintentional, because mixing drugs or combining drugs can produce unpredictable effects, especially when certain substances are used together. Because different substances can interact and change how each drug affects the central nervous system, polysubstance use can increase the risk of impaired judgment, respiratory depression, loss of consciousness, overdose, and other serious health problems, and these interactions can push breathing, heart rate, or blood pressure to dangerous levels.
Signs can vary based on the substances used, the dose, and the person’s health. Warning signs may become more severe when alcohol, opioids, benzodiazepines, or other central nervous system depressants are combined. Watch for the following symptoms as common warning signs of polysubstance use and overdose.
Severe breathing problems, unconsciousness, or suspected overdose require immediate emergency medical attention.
Polysubstance use can develop for several reasons. A person may combine drugs to increase certain effects, reduce unwanted effects from another substance, manage withdrawal symptoms, cope with stress or mental health symptoms, respond to peer pressure, or because multiple substances are readily available. Polysubstance use can also happen unintentionally. Illicit drugs may contain unexpected substances such as fentanyl, which can expose a person to a dangerous drug combination without their knowledge.
Common drug combinations can create serious and unpredictable effects:
Alcohol, opioids, and benzodiazepines can each depress central nervous system activity, and they are especially risky when mixing drugs because their effects can amplify each other. Using them together can intensify sedation and respiratory depression, causing breathing to become dangerously slow or stop altogether. A person may also experience poor coordination, impaired judgment, memory problems, unconsciousness, coma, or overdose, and combining drugs from different classes creates an increased risk of overdose and death. The danger can increase because the combined effects of these substances may be stronger and less predictable than using one substance alone, and one substance may hide the effects of another until the body is under severe stress.
Polysubstance use can affect brain functions involved in breathing, alertness, judgment, memory, coordination, and reward. Combining depressants such as alcohol, opioids, and benzodiazepines can produce intense sedation and suppress the brain signals that control breathing.
Repeated substance use can also affect the heart, liver, lungs, and other organs while contributing to tolerance and physical dependence. Over time, changes in the brain’s reward system can make it harder to control substance use despite harmful consequences.
In 2019, nearly half of drug overdose deaths involved multiple drugs, often opioids such as illicit fentanyl combined with alcohol, benzodiazepines, cocaine, or methamphetamine. Research suggests polysubstance use has a higher prevalence in overdose cases and can decrease verbal learning ability, while unintentional fentanyl exposure remains a concern in Tennessee. The Substance Abuse and Mental Health Services Administration, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute, and American Psychiatric Association address using more than one drug, mixing stimulants, and conditions in the Diagnostic and Statistical Manual, while few studies, including results in Mol Psychiatry, show future research is needed on one or both drugs over longer periods. Results suggest that using a different drug with other substances can increase health risks, according to research supported by the U.S. Department of Health and Human Services.
Assessment reviews all substances used, including alcohol, opioids such as fentanyl or heroin, benzodiazepines, stimulants, cannabis, and prescription drugs. Providers may evaluate frequency, dose, withdrawal, overdose history, mental health symptoms, and toxicology results. In the general population, approximately 0.5% of US adults have polysubstance use disorder. Among adults with opioid use disorder, 93.3% used two or more substances, which is why full screening should cover all substances used rather than relying on rates seen only in treatment settings.
Physical dependence can develop when the body adapts to repeated alcohol, opioid, benzodiazepine, or other drug use. Stopping several substances at once can cause overlapping withdrawal symptoms and may make the withdrawal process harder to predict.
Alcohol and benzodiazepine withdrawal can cause severe complications, including seizures, while opioid withdrawal can cause intense flu-like symptoms, anxiety, insomnia, and cravings. Medical supervision may be needed when several substances are involved.
Polysubstance use can occur alongside depression, anxiety disorders, PTSD, bipolar disorder, ADHD, personality disorders, and patterns such as alcohol abuse that should be identified when evaluating mood symptoms and substance-related impairment. For example, a person may use alcohol or benzodiazepines to reduce anxiety, stimulants to increase energy or focus, or opioids to cope with emotional or physical pain.
Substance use can also worsen psychiatric symptoms, while untreated mental health disorders can increase the risk of continued drug or alcohol use. Dual diagnosis treatment addresses both conditions within the same treatment plan.
Several factors can increase the risk of developing harmful polysubstance use.
Different levels of care can support recovery based on the severity of substance use, withdrawal risk, mental health symptoms, and daily support needs.
Behavioral therapies can help patients identify triggers, change substance use patterns, improve coping skills, and manage cravings. Cognitive behavioral therapy, motivational approaches, group therapy, and individual counseling may all be part of treatment. Medication-assisted treatment may be used for opioid use disorder with medications such as buprenorphine, methadone, or naltrexone when clinically appropriate. Relapse prevention also focuses on trigger management, recovery planning, medication adherence, peer support, and ongoing mental health care.
Family members can support recovery by learning about addiction, recognizing relapse warning signs, and encouraging consistent treatment participation. Family therapy or education can also help improve communication, rebuild trust, and establish healthier boundaries.
Families may also learn how to recognize overdose signs and respond during an emergency. Support for family members can reduce stress and help them maintain their own health during the recovery process.
Polysubstance use is not always intentional. Illicit pills, powders, or other drugs may contain fentanyl or additional substances that a person did not expect to consume. Unintentional exposure can make the strength and effects of a drug much harder to predict. People who inject drugs also face a higher risk of infectious diseases, along with overdose, when multiple substances are involved.
This can increase the risk of severe sedation, respiratory depression, and overdose even when a person believes they are using only one substance.
A suspected overdose requires immediate emergency medical attention, especially when a person is unconscious, cannot be awakened, or has slow, shallow, or stopped breathing. Naloxone can temporarily reverse opioid effects when fentanyl, heroin, or prescription opioids are involved.
Naloxone does not reverse alcohol, benzodiazepines, stimulants, or other non-opioid substances. Emergency care is still necessary because several drugs may be contributing to the overdose.
Help may be needed when a person cannot control substance use, regularly mixes drugs, experiences withdrawal, or continues using despite harmful consequences. Overdose, loss of consciousness, or severe mental health symptoms require urgent attention.
Manages withdrawal and related health risks.
Provides structured daily addiction care.
IOP provides frequent treatment while patients live at home.
Offers ongoing counseling and recovery support.
May help treat opioid use disorder.
Dual Diagnosis Treatment addresses addiction and mental health disorders together.
Addresses triggers, coping skills, and substance use patterns.
Supports relapse prevention and continued recovery.
Insurance may cover detox, residential treatment, IOP, outpatient care, therapy, and medication services based on the individual plan. Patients should verify benefits, network requirements, copays, deductibles, and prior authorization before treatment.
Polysubstance use can increase the risk of overdose, polysubstance dependence, impaired cognitive functioning, and serious damage to physical and mental health. Effective treatment can address alcohol use disorder, drug abuse, co-occurring mental disorders, and related conditions through appropriate addiction and mental health services. If multiple substances are affecting daily life, professional assessment can help identify the right level of care and support long-term recovery.
At New Hope Healthcare, as an in-network provider we work with most insurance plans, such as:
If you or a loved one are struggling with mental health challenges or substance abuse, seeking treatment and emotional support is crucial. Consulting a doctor can provide the necessary support and guidance for your teen.
Reach out to New Hope Healthcare today. Our team of compassionate professionals is here to support your journey towards lasting well-being. Effective medication management is a crucial part of the treatment process to ensure safety and success.
Give us a call at 866-799-0806.
Polysubstance use means using two or more substances together or within a short period, either intentionally or unintentionally.
Combining substances can cause unpredictable effects and increase the risk of respiratory depression, overdose, and death.
Yes. Treatment may include withdrawal management, behavioral therapy, medication-assisted treatment, dual diagnosis care, and ongoing relapse prevention.
Common combinations can include alcohol, opioids, benzodiazepines, stimulants, and other prescription or illicit drugs.
Both substances can suppress the central nervous system and slow breathing, which can significantly increase overdose risk.
Naloxone can reverse the effects of opioids, but it does not reverse alcohol, benzodiazepines, or other non-opioid substances.
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