Medically Reviewed

Dangers of Mixing Fentanyl With Other Substances

4 min read · 6 sections

Fentanyl is a powerful synthetic opioid drug.1 It is legally used and prescribed for severe pain associated with surgery and cancer, and it is occasionally used for people with chronic pain for whom other opioids are no longer effective. It can also be misused like other opioid medications, resulting in dependence and addiction. Cheap and relatively easy to produce in a well-equipped lab, fentanyl is increasingly being found mixed into other drugs sold on the street, including heroin, cocaine, methamphetamine, MDMA (ecstasy, molly), and counterfeit pills (Adderall, Xanax, OxyContin), delivering a more potent (and potentially life-threatening) high while increasing profits for illicit drug dealers.

Fentanyl is approximately 100 times more powerful than morphine (a naturally-derived opioid) and 50 times stronger than heroin, and this potency makes it extremely dangerous, whether it is taken knowingly—and especially when taken unintentionally.1

The number of overdose deaths from synthetic opioids (primarily fentanyl) rose from 57,834 in 2020 to 71,238 in 2021.2

Why is Fentanyl so Dangerous?

Fentanyl is dangerous because of its potency.1 It is illegally sold on its own as nasal sprays, eye drops, dissolvable paper, small candies, and pills that resemble prescription opioids, and is increasingly being found as a contaminant in other street drugs.1,3 Synthetic opioids like fentanyl and its analogs (substances that are similar to fentanyl but with a slightly different chemical structure)—kill nearly 150 people every day in the United States.3

It takes very little fentanyl to produce a high and it’s relatively inexpensive to make with easily obtained ingredients. This has made fentanyl a common additive in illicit drugs, such as heroin, cocaine, and methamphetamine to boost the high.1,4 The individuals who use these drugs may unknowingly take fentanyl or a stronger-than-intended opioid and experience an overdose.1,4

If you or a loved one buy substances on the street, it’s important to keep yourself safe from these fentanyl-laced substances. Rapid fentanyl test strips (FTS) detect the presence of fentanyl in illicit substances and can help you make an informed decision before using it.5

The Dangers of Mixing Fentanyl with Other Opioid Drugs

Mixing fentanyl with other opioids, including morphine, heroin, oxycodone, hydrocodone, codeine, hydromorphone, and tramadol, enhances its effects because all of these opioids work on the same parts of the brain.6 Combining opioids can magnify the euphoric effects but also the dangerous ones as well, including slowed or stopped breathing, decreased heart rate, and increased risk of overdose.6

The Dangers of Mixing Fentanyl with Sedatives and Other CNS Depressants

Opioids, including fentanyl, have cumulative and synergistic effects when combined with drugs that depress the central nervous system (CNS). CNS depressant substances calm an otherwise over-excited nervous system.7 CNS depressants, such as benzodiazepines and alcohol, suppress the respiratory drive and have synergistic effects with opioids. In fact, in 2016, the U.S. Food and Drug Administration added a boxed warning to all prescription opioid pain and prescription opioid cough medications and benzodiazepines stating that concomitant use of CNS depressant substances can cause extreme sedation, respiratory depression, coma, and death.7,8

Fentanyl and Benzodiazepines

Benzodiazepines, also known as benzos, are a type of drug that works by increasing the body’s inhibited neural tone by allowing the body’s primary inhibitory neurotransmitter GABA to more tightly bind to its receptors in your brain.9 GABA increases the body inhibitor tone, which results in calming an otherwise over-excited nervous system.9 Fentanyl works through a different pathway to provide pain relief and relaxation, but combining both increases the risk of overdose because together each causes sedation and depresses the body’s respiratory drive, which can slow and even stop breathing.9 During January–June 2020, 92.7% of benzodiazepine-involved deaths also involved opioids, and 66.7% involved illicitly manufactured fentanyl.10

Fentanyl and Alcohol

Alcohol is another CNS depressant. Combining alcohol and opioids has caused a number of overdose deaths. In 2017, nearly 15% of all the deaths that involved synthetic opioids (including fentanyl) also involved alcohol.11

The Dangers of Mixing Fentanyl with Hallucinogens and Dissociative Drugs

Research suggests that classic hallucinogens (e.g., LSD, mushrooms.) and dissociative drugs (e.g., PCP, ketamine) work by temporarily disrupting the usual communications between a person’s brain and spinal cord.17 Hallucinogens and dissociative substances interfere with the actions of different chemicals in the brain, which may affect mood, emotions, learning or memory, or basic bodily needs like food or sleep.12 Short-term effects of classic hallucinogens and dissociative drugs vary, but they generally cause hallucinations, where individuals see, feel, or hear things that are not happening in real life, or other profound distortions in a person’s perceptions of reality.12,13 Dissociative drugs can cause one to feel like they are out of control or disconnected from their body and environment.12,13

Most hallucinogens and dissociative drugs on their own don’t produce life-threatening events—even at high doses (although PCP may be an exception). Many of these substances, particularly dissociative drugs like PCP and ketamine, have sedative-like properties which can be dangerous when combined with opioids or CNS depressants.

As with the other illicit drugs discussed in this article, there’s an increased risk of fentanyl contamination, which can lead to unintentional, life-threatening overdose.12

Fentanyl and Ketamine

Ketamine is a fast-working drug used to help with medical anesthesia that can also cause dissociative symptoms.14 It is legally prescribed for anesthesia and has been found to be helpful as an antidepressant and pain reliever, with anti-inflammatory side effects.14

In clinical settings, ketamine has been found to increase the analgesic effects of fentanyl without potentiating respiratory depression, making the combination a potentially safer form of analgesia than fentanyl alone,

Mixing ketamine and opioids like fentanyl can cause potentially life-threatening respiratory depression as well as other adverse symptoms, such as oversedation.17,19

Like other illicit drugs, illicitly manufactured fentanyl is being found as a contaminant or additive in ketamine. The Centers for Disease Control and Prevention (CDC) and various state public health departments are working to ensure those who take club drugs like ketamine are aware of the dangers. Additionally, these agencies are initiating harm reduction steps, such as the use of testing drugs for fentanyl using test strips.20,21

Fentanyl and MDMA (Ecstasy/Molly)

MDMA is a synthetic drug that is chemically similar to both hallucinogens and stimulants.22 Many so-called ecstasy tablets contain other substances (e.g., MDMA, amphetamines, ketamine, and opioids like fentanyl, among others).23

On its own, MDMA is associated with heart disease, impulsivity, and depression. When mixed with other substances, including fentanyl, it can lead to respiratory arrest or coma.21

The Dangers of Mixing Fentanyl with Stimulants

The growing use of synthetic opioids, such as illicitly manufactured fentanyl, in combination with stimulants such as cocaine, methamphetamine and prescription stimulants, has resulted in a significant increase in overdose deaths.24 Stimulants may be combined with fentanyl intentionally (e.g., taken together or one after the other as a “speedball”) or products are laced with fentanyl and lead to unintentional use, which increases the risk of overdose.24

Fentanyl and Cocaine

Opioids may be mixed with cocaine to elicit a more intense high. “Speedballing” involves the simultaneous administration of both cocaine and opioids/heroin. It can be a particularly lethal combination, as the initial stimulating effects of cocaine can mask symptoms of an impending opioid overdose.25 It may or may not be known to someone taking a speedball if the combination includes fentanyl or not.

As previously mentioned, fentanyl is relatively inexpensive compared to other substances, and is increasingly being found in cocaine and other street drugs. The practice has become so common that the Drug Enforcement Administration (DEA) issued nationwide warnings about fentanyl-laced substances, including cocaine.26

Cocaine is an illicit stimulant resulting in feelings of increased energy. Opioids like fentanyl, on the other hand, are depressants and result in sedation. When taken together, a short-acting stimulant like cocaine may mask symptoms of an impending opioid overdose. Since 2014, the number of overdose deaths involving cocaine and synthetic opioids (primarily fentanyl) increased steadily, nearing 15,000 people in 2020.27

Fentanyl and Methamphetamine

Reports of methamphetamine mixed with fentanyl seized by the DEA and other law enforcement agencies rose 1,342% since 2015, in the United States. While it’s still a relatively uncommon combination (this combo represents a very small number of total seizures), the mixture is sometimes taken intentionally, similar to a “speedball” which is traditionally a combination of cocaine and heroin.28  The combination may also be consumed unintentionally, and fentanyl has been found not only in methamphetamine but also counterfeit Adderall pills and other counterfeit stimulant medications.29

Overdose deaths from synthetic opioids like fentanyl and methamphetamine and prescription stimulants steadily increased since 2014 to a total of 23,837 deaths in 2020.27

Getting Help for Polysubstance or Fentanyl Use

Polysubstance use (using multiple drugs at once) may be intentional or unintentional, but with fentanyl in the mix, it is riskier than ever.30 While addiction to multiple substances can complicate recovery, treatment is available.

If you or a loved one struggles with polysubstance misuse, get started on the road to recovery by reaching out to an admissions counselor. It may be the decision that saves your life.

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