In 2023, 69% of Ohio's 4,452 fatal overdoses involved multiple drugs, particularly the combination of fentanyl and other substances. Some people combine different drugs on purpose, but many have no idea that what they are taking is actually a dangerous mixture.
If you are using more than one drug, or you have lost someone to what turned out to be a deadly combination, we will explain what polydrug addiction really looks like and how Armada Recovery can help.
Polydrug addiction is when you have become addicted to more than one substance.
This might mean you deliberately use multiple drugs together, such as:
Mixing cocaine with ecstasy on a night out
Taking benzodiazepines to come down from stimulants
But it can also mean you are unknowingly taking drug combinations because of contamination in the drug supply.
| Drug Combination | Number of Deaths (2023) | Percentage of Total Overdoses | Key Takeaway |
|---|---|---|---|
| Fentanyl + Cocaine | 1,379 | 31% | Cocaine users are at extreme risk due to widespread fentanyl contamination. |
| Fentanyl + Methamphetamine | 971 | 22% | Mixing stimulants with opioids dramatically increases overdose unpredictability. |
| Fentanyl + Benzodiazepines | 275 | 6% | Combining depressants greatly raises the risk of fatal respiratory failure. |
| Cocaine Deaths Involving Fentanyl | — | 79% | Most cocaine-related overdoses now involve fentanyl, often unknowingly. |
| Methamphetamine Deaths Involving Fentanyl | — | 77% | Fentanyl has deeply penetrated the stimulant drug supply. |
In Ohio, fentanyl has spread widely through the drug market. In 2023:
79% of cocaine-related overdose deaths also involved fentanyl
77% of methamphetamine-related deaths involved fentanyl
73% of benzodiazepine-related deaths involved fentanyl
Many people had no idea fentanyl was present in the drugs they were taking. This makes polydrug addiction especially dangerous, increasing the risk of unpredictable effects and unintended addiction to substances you never meant to use.
Polydrug addiction can be harder to recognize than single-substance addiction because different drugs can mask or alter each other’s effects.
Common warning signs include:
Using one drug to counteract or enhance the effects of another
Needing multiple substances just to feel “normal” or get through the day
Withdrawal symptoms that don’t match what you thought you were taking
Unpredictable reactions or side effects that change from one use to the next
Mixing prescription medications with alcohol or street drugs
Using stimulants during the day and depressants at night
Physical symptoms suggesting multiple drugs, such as drowsiness and a racing heart
Erratic behavior that doesn’t fit a single drug pattern
Overdose scares or sudden “bad reactions”
Polydrug addiction can begin in several ways, but it usually follows a progression from occasional use into dependence and eventually addiction.
Polydrug abuse may start intentionally or accidentally.
Examples include:
Drinking alcohol with cocaine to “take the edge off”
Using benzodiazepines to sleep after stimulant use
Unintentional polydrug use can happen when:
Drugs are contaminated
One substance stops working and another is added
Polydrug dependence often follows quickly.
Each drug changes the brain differently:
Opioids reduce natural painkiller production
Stimulants disrupt dopamine regulation
When multiple substances are involved, the brain adapts to all of them. Stopping one drug while continuing another can trigger unexpected and confusing withdrawal symptoms.
At this stage, stopping becomes extremely difficult—even when the harm is obvious.
You may:
Try to quit one substance and increase use of another
Relapse on all substances when attempting sobriety
Feel trapped in a cycle you can’t control
In 2023:
Fentanyl + cocaine caused 1,379 deaths (31% of all overdoses)
Fentanyl + methamphetamine caused 971 deaths (22%)
Fentanyl + benzodiazepines caused 275 deaths
Additional data:
79% of cocaine-related deaths involved fentanyl
77% of methamphetamine-related deaths involved fentanyl
Polydrug addiction is driven by the same brain changes as single-substance addiction, but the causes are often more complex.
Common contributors include:
Using one drug to manage side effects of another
Chasing a specific high that requires multiple substances
Drug supply contamination
Using whatever drug is available
Self-medicating multiple symptoms (energy, anxiety, sleep)
Escalating tolerance to one drug
Social environments where mixing drugs is normalized
Underlying mental health conditions
Mixing substances multiplies the risks of each individual drug.
Serious dangers include:
Fatal overdose (especially opioids + depressants)
Unpredictable drug interactions
Seizures or cardiac events
Respiratory failure
Liver and kidney damage
Extreme cardiovascular strain
Dangerous withdrawal requiring medical supervision
Increased risk of psychosis
Memory loss and cognitive impairment
Severe mental health decline
Higher accident risk
Greater difficulty achieving long-term recovery
Armada Recovery specializes in treating people struggling with multiple substances.
Treatment begins with inpatient detox, where medical staff:
Monitor overlapping withdrawal symptoms
Intervene quickly if complications arise
Safely manage complex drug interactions
After detox, clients transition into outpatient rehab in Akron or Dayton.
Outpatient treatment allows you to:
Attend scheduled therapy
Live at home
Maintain work and family responsibilities
Treatment focuses on all substances together, addressing the underlying reasons for polydrug use.
After rehab, continued support may include:
Partial hospitalization (if needed)
Ongoing outpatient therapy
Armada Recovery’s alumni network
Our alumni community provides connection, accountability, and long-term support.
If you are caught in a cycle of using multiple drugs—or worried about someone who is—Armada Recovery can help.
Polydrug addiction is complicated, but it is 100% treatable with the right support. Contact us today, and our team will help you take the next step.
Can you die from polydrug addiction?
Yes. A polydrug overdose occurs when multiple substances interact in the body, increasing the risk of respiratory failure, heart complications, and death.
What are the most dangerous drug combinations?
Opioids mixed with benzodiazepines or alcohol, and stimulants mixed with opioids, are among the deadliest combinations.
How can I help a loved one with polydrug addiction?
Encourage professional treatment, avoid enabling behaviors, and seek guidance from addiction specialists who understand polydrug use.
Is there a cure for polydrug addiction?
There is no instant cure, but polydrug addiction is highly treatable with medical detox, therapy, and ongoing support.
Ohio 2023 Unintentional Drug Overdose Annual Report
https://content.govdelivery.com/attachments/OHIOGOVERNOR/2024/10/30/file_attachments/3052169/2023%2BUnintentional%2BDrug%2BOverdose%2BAnnual%2BReport_FINAL.pdf
SAMHSA Ohio Substance Use Data
https://www.samhsa.gov/data/sites/default/files/reports/rpt39467/2021NSDUHsaeSpecificStatesTabs122022_0/NSDUHsaeOhio2021.pdf