Polysubstance Abuse: Definition, Examples, and Treatment

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Polysubstance abuse refers to the abuse of more than one addictive substance. Although polysubstance abuse is a term typically applied to the abuse of illicit drugs, it can also refer to the recreational abuse of prescription medications.

CDC (Centers for Disease Control and Prevention) report that polysubstance use can occur intentionally when someone takes drugs in combination to increase or decrease their effects – a speedball containing heroin and cocaine, for instance – or unintentionally, such as taking heroin that has been cut with fentanyl.

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In 2019, 50% of all drug overdose deaths in the United States involved more than one drug, according to this study.

What does polysubstance abuse mean, then?

What Is Polysubstance Abuse?

Polysubstance abuse refers to the use of multiple substances of abuse, such as alcohol, opioids, benzodiazepines, stimulants, and marijuana. Abuse may occur at the same time or within a short period of time. It can also refer to the use of different substances at different times, but in a pattern that is harmful to your physical and mental health.

Polysubstance abuse can be either intentional or unintentional, and it often occurs when someone develops a tolerance to one substance and seeks out other substances to enhance or prolong the high delivered. Additionally, some people may use multiple substances to self-medicate mental health conditions or to cope with stress.

Polysubstance abuse can increase the risk of overdose and other health complications like liver damage, heart disease, and respiratory failure. It can also worsen mental health conditions and lead to addiction, making it more difficult for someone to stop using substances without professional help.

Polysubstance abuse treatment typically involves a combination of MAT (medication-assisted treatment), counseling, behavioral therapies, and support groups. A successful treatment plan will address all the substances you are abusing, as well as any underpinning mental health conditions.

How about a more precise polysubstance abuse definition?


Healthcare professionals and addiction specialists use APA’s reference publication, Diagnostic and Statistical Manual of Mental Disorders, to diagnose addictions and mental health conditions.

In DSM-IV, the fourth edition of this diagnostic tool published in 1994, polysubstance abuse disorder was included as a standalone diagnosis. DSM-5, the current edition, was published in 2013 and did not include polysubstance abuse as a classification.

Previously, polysubstance abuse was defined as a substance dependence disorder characterized by the use of three or more addictive substances or groups of substances.

Per DSM-5, substance use disorder is a clinical descriptor now applied to anyone addicted to alcohol or drugs, regardless of the number of substances used.

The old definition of polysubstance abuse did not require an individual to be dependent on any of the substances in isolation.

Regardless of the definition, most polysubstance abusers do not have a preferred substance. While someone with alcohol use disorder or opioid use disorder seeks out the specific effects of their preferred substance, many polydrug users are simply seeking a high.

Changes to this diagnosis were made in DSM-5 as the term was so little used and so widely misunderstood. According to recommendations for DSM-5 criteria, “With the new threshold for substance use disorders, the category became irrelevant.”

Dangers of Polysubstance Addiction

Polysubstance abuse can trigger a variety of consequences, both immediate and long-term. These effects will vary according to the combination of substances. The most common include:

  • Enhanced effects of each substance
  • Deterioration of dual diagnosis
  • More complicated treatment
  • Issues with physical health
An image of a woman feeling the enhanced feeling polysubstance abuse

Enhanced effects of each substance

All drugs carry the risk of adverse side effects. Using a combination of drugs will increases the severity of those side effects exponentially.

Additionally, layering more than one addictive substance can introduce new effects, such as the production of cocaethylene when alcohol and cocaine mix in the liver. 

Broadly, using a combination of substances can cause:

  • Vomiting
  • Nausea
  • Increased heart rate
  • Blood pressure fluctuations
  • Abnormal breathing
  • Body pains and aches
  • Problems with balance

Deterioration of dual diagnosis

Substance use disorder with a co-occurring mental health condition like depression or anxiety is known as dual diagnosis or co-occurring disorder. This can be exacerbated by the polysubstance abuse.

More complicated treatment

If you have been abusing more than one addictive substance and you’re ready to kickstart your recovery, look for a treatment center specializing in the treatment of polydrug abuse. You should look for a rehab center offering a personalized treatment plan accounting for all substances of abuse.

Issues with physical health

The interaction of addictive substances can trigger changes to the metabolism, as well as increasing the blood concentration of each individual substance. Toxicity can also increase. 

The risk factor for some chronic diseases like hepatitis C is increased in those who engage in a combination of heavy drinking and intravenous drug use. There is also an increased prevalence of myocardial infarction among those who abuse cocaine and smoke cigarettes.

Polysubstance Overdose

All forms of substance abuse carry the risk for overdose. Polysubstance abuse further increases this risk.

Using some substances can mask the effects of other substances – cocaine camouflaging the intoxicating effects of alcohol, for example – causing some people to take higher doses than usual. This can trigger overdose if the quantities are high enough. Overdose can lead to long-term health issues and can in some cases be life threatening. 

Data from NIDA (National Institute on Drug Abuse) shows that there were almost 92,000 fatal overdoses in the U.S. in 2020.

Examples of Polysubstance Abuse

While all cases of polysubstance use are unique, the primary motivator for most people abusing more than one drug is the way combining substances can intensify the physical and mental effects of those substances. 

If you mix alcohol with benzodiazepines, for instance, this leads to more rapid intoxication. Both alcohol and benzos work on GABA receptors in the brain. Taking the substances in combination increases their sedative effects and also heightens the risk of withdrawal.

 Multiple substances can be used unintentionally, either by mixing prescription medications with alcohol or other substances, or by taking a drug cut with other substances. Polysubstance abuse is mainly premeditated, though.

Common polysubstance abuse examples include:

  • Cocaine and alcohol
  • Opioids and benzos
  • Illicit drugs and prescription medications
  • Prescription drugs and alcohol

Cocaine and alcohol

Cocaine and alcohol are often used in combination. These substances each increase impulsive behavior in isolation. Both substances impair decision-making and cognitive function.

When you use cocaine and alcohol together, though, the substances mix in the liver, causing the formation of cocaethylene, a psychoactive metabolite with similar pharmacological properties to cocaine. This will intensify the effects of the substances. Cocaethylene can also cause your blood pressure and heart rate to increase more than if you were using either substance in isolation.

Beyond this, cocaethylene also increases toxicity in the heart, liver, and other organs.

Opioids and benzos

Opioids and benzodiazepines are classified as CNS depressants. Combining drugs in this class can bring about respiratory depression and a potentially fatal overdose.

SAMHSA (Substance Abuse and Mental Health Services Administration) reports that overdoses involving opioids and benzodiazepines are on the rise.

Mixing these drugs can be a dangerous and possibly deadly combination.

Illicit drugs and prescription medications

Many people believe that prescription drugs are safe to use in all circumstances. If abused, though, and if used in combination with other substances, they can be potentially unsafe.

If you are taking any prescription medications, you should refrain from using addictive substances. Consult your healthcare provider if you have any concerns about your medication.

Prescription drugs and alcohol

Mixing prescription drugs and alcohol can be dangerous and potentially life-threatening. These are some of the risks and dangers associated with combining prescription drugs and alcohol:

  • Increased risk of overdose: Alcohol can enhance the effects of prescription drugs, increasing the risk of overdose. This is because both drugs and alcohol can depress the CNS (central nervous system), potentially triggering respiratory failure and death.
  • Impaired judgment: Alcohol can impair your judgment and decision-making abilities. This can cause you to take more prescription drugs than you should, which can bring about dangerous side effects.
  • Risk of adverse drug interactions: Alcohol can interact with certain prescription drugs, making them less effective or more potent. It can also increase the risk of side effects like dizziness, nausea, and vomiting.
  • Increased risk of addiction: Mixing prescription drugs and alcohol can increase the risk of addiction to both substances. This is because alcohol can intensify the pleasure and reward effects of prescription drugs, making it more likely that you will continue to use them.
  • Worsening of existing medical conditions: Alcohol can exacerbate the symptoms of certain medical conditions like liver disease, high blood pressure, and heart disease. It can also interfere with the effectiveness of medications used to treat these conditions.

If you are taking prescription drugs, consult your prescribing physician about the risks of drinking alcohol while taking these medications. They can provide you with guidance on how to safely use prescription drugs and avoid potentially dangerous interactions with alcohol.

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Polysubstance Abuse Treatment at California Detox

If you have developed physical dependence or a diagnosable addiction to prescription medications, alcohol, or illicit drugs, we offer a variety of treatment programs at California Detox in Laguna Beach.

Take advantage of the smoothest pathway to inpatient or outpatient rehab with our supervised medical detox program. Access medications to streamline withdrawal and mitigate cravings. Detox addresses the issue of physical dependence, allowing you to transition into one of the following treatment programs:

  • Inpatient program (residential rehab)
  • PHP (partial hospitalization program)
  • IOP (intensive outpatient program)
  • OP (outpatient program)
  • Virtual IOP (remote rehab program)
  • Dual diagnosis treatment program (for co-occurring disorders)

All California Detox treatment programs provide individualized treatment that combines evidence-based interventions and holistic therapies for a whole-body approach to addiction recovery. These include:

  • MAT (medication-assisted treatment)
  • Group counseling
  • Individual counseling
  • Psychotherapy (CBT and DBT)
  • Family therapy
  • Holistic therapy

When you complete your California Detox treatment program, you can step down to a less intensive form of treatment or move back into day-to-day life. You will have an aftercare plan that includes relapse prevention techniques to maximize your chance of sustained recovery from addiction. Call admissions at 949.694.8305 for immediate assistance.


Polysubstance abuse is when one or more drugs are abused in combination. This form of substance use can be intentional (willfully combining different addictive substances) or unintentional (unwittingly taking adulterated drugs).
Polysubstance abuse has been eliminated as a diagnosis from DSM-5, the fifth edition of Diagnostic and Statistical Manual of Mental Disorders.


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