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Polysubstance Use

Polysubstance Use

Polysubstance use, also known as multi-drug use, refers to using two or more drugs at a time, including prescribed medications, non-prescription drugs, and alcohol.

Intentional: Intentional polysubstance use occurs when a person takes a drug to increase or decrease the effects of a different drug or wants to experience the effects of their combination. For example, using alcohol or benzodiazepines to "come down" from stimulants.

Unintentional: Unintentional polysubstance use occurs when a person takes drugs that have been mixed or cut with other substances without their knowledge. For example, consuming cocaine that also contains fentanyl.

Whether intentional or not, mixing drugs is never safe because the effects from combining drugs may be stronger and more unpredictable than one drug alone, even deadly.

With a rise in counterfeit prescription medications across the United States over since 2019 contaminated with stimulants, fentanyl and xzylazine it is important to take harm-reduction measures to reduce the risk of a polysubstance overdose (see prevention section below).

Download the CDC Polysubstance Fact Sheet to learn more (PDF)

Polysubstance use is one of the greatest risk factors for fatal overdose in Oregon. The polysubstance use of fentanyl and methamphetamine remains the most significant driver of the polysubstance overdose crisis in Oregon. In 2022, there were 543 Oregonians that lost their lives to a fatal polysubstance overdose that included a stimulant and an opioid. Among all fatal polysubstance overdoses 27.6% involved a mixture of methamphetamine and fentanyl, 3.6% involved a mixture of methamphetamine and another substance (either an opioid or stimulant), and 3.3% involved a mixture of an opioid and cocaine.​ (Data source: CDC SUDORS Dashboard: Fatal Drug Overdose Data​)

According to the Oregon-Idaho HIDTA Performance Management Process 2024, fentanyl and methamphetamine remain the principal drugs that threaten the illicit drug supply with contamination in Oregon. Thus, all polysubstance use should be approached with harm-reduction measures to ensure that an unintentional overdose does not occur (reference the “Preventing Polysubstance Overdose" section below).​

Polysubstance Overdose​ Prevention

To prevent a polysubstance overdose, it is important to follow to suggested harm-reduction steps below:​
  • Unless a pharmacist or your healthcare provider directly hands you a prescription pill, assume it is counterfeit and contains fentanyl or another substance such as a stimulant.
  • Assume any pills from friends, social media, or the internet are counterfeit and contain fentanyl and other substances.
  • When using any substances, start low and go slow, checking the strength and the effects of the substance.
  • Never use alone.
  • Always carry naloxone with you.
  • When using substances, have naloxone where it can be seen in case of overdose so that someone can use the naloxone on you.
  • Test all the substances you are planning to use with fentanyl test strips​ (FTS). It is important to note that FTSs are not always accurate or reliable. Therefore, always assume that any substance that is not prescribed contains fentanyl. You may be able to get drug testing strips at local syringe services or harm reduction program sites. Ask syringe service and harm reduction service providers how to correctly use stimulants. Please contact your local public health authority to learn more about services nearest to you.
  • If you call police or 911 to get help for someone having a drug overdose, Oregon's Good Samaritan law protects you and the person who has overdosed from being arrested or prosecuted for drug-related charges or parole/probation violations based on information provided to emergency responders.
Recognizing Signs and Symptoms of Polysubstance Overdose 
Combining substances can amplify their individual effects, significantly increasing the risk of overdose and death. There are several different mixtures of drugs that cause an array of different signs and symptoms of polysubstance overdose.

Mixing Stimulants

​Examples of stimulants: ecstasy (MDMA), cocaine, methamphetamines, amphetamines (speed)

Stimulants, also known as “uppers," can increase your heart rate and blood pressure to dangerous levels and increase your risk of several serious health problems. Combining stimulants may even directly or indirectly increase your risk of:
  • Brain injury
  • Liver damage
  • Heart attack
  • Stroke

Signs of use/overdose that may occur when mixing stimulants:

  • Fast/troubled breathing
  • Increased body temperature
  • Nausea or vomiting
  • Chest pain
  • Seizures or tremors

Mixing depressants

Examples of depressants: opioids (heroin, morphine, oxycodone, hydrocodone, fentanyl), benzodiazepines

Depressants (also known as downers) can slow down your breathing and increase your risk of several adverse health outcomes. Combining depressants can also directly or indirectly increase your risk of:
  • Damage to the brain and other organs
  • Overdose
  • Death

Signs of use/overdose when mixing depressants:

  • Slow breathing
  • Weak pulse
  • Altered mental status or confusion
  • Passing out
  • Unconsciousness


Mixing stimulants and depressants

Mixing stimulants and depressants doesn't balance or cancel them out. In fact, the results of combining drugs are unpredictable, often modifying or even masking the effects of one or both drugs. This may trick you into thinking that the drugs are not affecting you, making it easier to overdose.

Drinking alcohol while using other drugs

Drinking alcohol while using other drugs isn't safe. Alcohol is a depressant with similar effects to other downers. Mixing alcohol with other drugs can increase your risk of overdose and cause serious damage to the brain, heart, and other organs.

Responding to a polysubstance overdose

It may be hard to tell whether someone is experiencing an overdose from a single substance or from multiple substances.  When a person survives an overdose, it's because someone was present, recognized that the person was overdosing, and responded to help them.​
If you are concerned you may witness an opioid overdose, you can get naloxone at a pharmacy in Oregon. If you are prescribed an opioid medication to treat pain, you can ask for a co-prescription of naloxone. ​

If you or someone you care about is struggling with substance use, please reach out for help. Speak with a healthcare provider or visit the links below for support and treatment resources. You are not alone.
If you have additional questions about polysubstance use, please contact the Injury & Violence Prevention Program at