Fentanyl and Polysubstance Use

Fentanyl, a synthetic opioid estimated to be 50 to 100 times more potent than morphine, has become a significant contributor to the opioid crisis in the United States. Its potency and relatively low production cost have led to its widespread use, both knowingly and unknowingly, in combination with other drugs of abuse. This practice has escalated the risk of fatal overdoses and complicated efforts to combat substance abuse nationwide.

Fentanyl’s Role in Polysubstance Use

Polysubstance use refers to the concurrent consumption of multiple drugs, either intentionally or inadvertently. Fentanyl is frequently combined with various substances, amplifying their effects and increasing the potential for overdose. Common combinations include:

• Stimulants (Cocaine and Methamphetamine): The simultaneous use of stimulants and opioids, often referred to as “speedballing,” produces intense euphoria. However, this combination is particularly hazardous, as stimulants increase heart rate and blood pressure, while opioids depress respiratory function, creating a dangerous physiological conflict. A study published in Addiction revealed that from 2010 to 2021, overdose deaths involving both fentanyl and stimulants surged 50-fold, accounting for 32% of U.S. overdoses in 2021, equating to nearly 35,000 deaths. Multnomah County reported a record 456 homeless deaths, predominantly due to fentanyl overdoses, which increased by 45% from the previous year. Of these, 282 were unintentional drug overdoses, with fentanyl contributing to 89% of cases. Methamphetamine was also involved in 81% of these deaths, underscoring the dangers of polysubstance use among vulnerable populations.
• Benzodiazepines: Combining fentanyl with benzodiazepines, such as Xanax or Valium, can enhance sedation and respiratory depression, significantly increasing the risk of fatal overdose. Research from the University of Washington School of Public Health found that patients prescribed both opioids and sedative-hypnotic drugs are six times more likely to die from an overdose compared to those taking opioids alone. The risk escalates with higher doses and the addition of multiple sedatives.
• Xylazine: Xylazine, a veterinary tranquilizer not approved for human use, has been increasingly detected in combination with fentanyl. This mixture is especially dangerous, as xylazine can exacerbate respiratory depression caused by opioids. The Centers for Disease Control and Prevention (CDC) reported that the presence of xylazine in drug overdoses has been rising across the United States. In 2023, a 27-year-old Connecticut woman was found unresponsive and later pronounced dead due to acute intoxication from a mixture of fentanyl, benzodiazepines, xylazine, and oxycodone. The individual who supplied the drugs was sentenced to over eight years in prison for his role in her death.
• Counterfeit Pills: Fentanyl is often found in counterfeit prescription pills, misleading users into believing they are consuming legitimate medications. This deception has led to numerous unintentional overdoses, particularly among individuals unaware of the pill’s true composition. The CDC highlighted that the percentage of overdose deaths involving counterfeit pills more than doubled from July–September 2019 (2.0%) to October–December 2021 (4.7%).

Statistical Overview of Fentanyl-Related Deaths

The proliferation of fentanyl in the drug supply has had a devastating impact on public health. In 2023, synthetic opioids, primarily fentanyl, were implicated in approximately 74,702 overdose deaths in the United States.

State-Specific Data

• Pennsylvania: The state reported 4,721 overdose deaths in 2023, with 82% linked to opioids and 76% involving fentanyl.

• Connecticut: Fentanyl was implicated in 83.1% of drug overdose deaths in 2023.

• Virginia: Out of 2,463 drug overdose deaths in 2023, nearly 79% involved fentanyl, fentanyl analogs, or tramadol.

• Oklahoma: Fentanyl was involved in 90% of opioid-related overdose deaths in 2023, a significant increase from the 10-20% range observed annually prior to 2020.

Emerging Trends

The theme above remains common throughout all 50 states with Fentanyl being a main proponent of polysubstance use for one reason or another. Whether individuals are unknowingly take their drug of choice with fentanyl laced in it or intentionally combining the two substances, the outcome remains the same. Extreme danger amongst all users. Statistics from 2024 are still being compiled, but expect to see similar trends.

Efforts to Mitigate Fentanyl’s Presence and Impact

Addressing the fentanyl crisis requires a multifaceted approach, encompassing legislative action, law enforcement initiatives, public health strategies, and international cooperation.

• Legislative Measures: In February 2025, the U.S. House of Representatives passed the Halt All Lethal Trafficking of (HALT) Fentanyl Act, classifying most fentanyl-related substances as Schedule I drugs. This designation places fentanyl alongside heroin and LSD, indicating a high potential for abuse and no accepted medical use. The act aims to impose stricter penalties on traffickers and close legal loopholes that previously allowed slight chemical modifications to evade regulation.
• Law Enforcement Operations: The Drug Enforcement Administration (DEA) has initiated operations targeting drug trafficking hubs. For example, Operation Overdrive focuses on dismantling drug networks in areas like Muskegon, Michigan, which serve as distribution centers for surrounding regions. These efforts aim to reduce the availability of fentanyl and associated violence in affected communities.
• Public Health Initiatives: Harm reduction strategies, such as the distribution of naloxone (an opioid overdose reversal agent), fentanyl test strips, and education on the dangers of polysubstance use, are being implemented to decrease overdose fatalities. States like Connecticut have reported declines in overdose deaths attributed to such community-based interventions, despite the increasing potency of street drugs.
• International Strategies: Efforts to curb the influx of fentanyl into the United States include diplomatic engagements and trade policies aimed at countries identified as sources of illicit fentanyl. For instance, discussions have involved imposing tariffs to encourage stricter drug control measures abroad.

The integration of fentanyl into various drugs of abuse, both knowingly and unknowingly, has significantly exacerbated the overdose crisis in the United States. The alarming rise in polysubstance use involving fentanyl underscores the need for comprehensive strategies that address the complexities of modern drug abuse patterns. Through continued legislative action, targeted law enforcement, robust public health initiatives, and international cooperation, there is hope to mitigate the devastating impact of fentanyl on individuals and communities nationwide.

References

• Centers for Disease Control and Prevention. (2024). Polysubstance Overdose. Retrieved from https://www.cdc.gov/overdose-prevention/about/polysubstance-overdose.html
• NPR. (2023). Fentanyl mixed with stimulants has created a polysubstance overdose crisis. Retrieved from https://www.npr

• Axios Denver. (2025, February 24). Overdoses rate Colorado 2023. Axios. https://www.axios.com/local/denver/2025/02/24/overdoses-rate-colorado-2023

• Oklahoma State Department of Health. (2025). Drug overdose data. Oklahoma State Government. https://oklahoma.gov/health/health-education/injury-prevention-service/drug-overdose/data.html

• Virginia Department of Health. (2025). Drug overdose data. https://www.vdh.virginia.gov/drug-overdose-data

• Connecticut Department of Public Health. (2025, January 17). Drug overdose deaths monthly report – Connecticut (December 2024). https://portal.ct.gov/-/media/dph/injury-and-violence-prevention/opioid-overdose-data/monthly-death-reports/2019-december-2024_drug-overdose-deaths-monthly-report_connecticut_updated-1-17-2025.pdf

• Commonwealth of Pennsylvania. (2025). Opioid resources for individuals & families. https://www.pa.gov/agencies/health/programs/opioids/individuals-families.html

• Centers for Disease Control and Prevention (CDC). (2025). Drug overdose deaths in the United States, 2023. https://www.cdc.gov/nchs/products/databriefs/db522.htm

• Bailey, M. (2024, May 12). Meriden man sentenced for role in fatal fentanyl overdose. CT Insider. https://www.ctinsider.com/capitalregion/article/meriden-fatal-overdose-lassus-sentenced-20160676.php

• National Institute on Drug Abuse (NIDA). (2025). Benzodiazepines and opioids. https://nida.nih.gov/research-topics/opioids/benzodiazepines-opioids

• Quest Diagnostics. (2017, September 28). One in four individuals combine opioids and benzodiazepines, a potentially lethal mix, according to Journal of Addiction Medicine study. https://newsroom.questdiagnostics.com/2017-09-28-One-in-Four-Individuals-Combine-Opioids-and-Benzodiazepines-a-Potentially-Lethal-Mix-According-to-Journal-of-Addiction-Medicine-Study

• Associated Press (AP). (2025). US overdose deaths fall for first time in five years. AP News. https://apnews.com/article/fe74f9747830a848aa28f82d93add582