Fentanyl is a synthetic opioid developed for managing severe pain, often after surgery or for cancer patients. It is approximately 50 to 100 times more powerful than morphine, making it effective in clinical settings but also dangerous when produced and distributed illicitly. The danger escalates when it is combined with other substances, as these interactions can lead to severe and often fatal outcomes.
Interactions with Central Nervous System Depressants
Central nervous system (CNS) depressants are substances that reduce brain activity, causing drowsiness and slowed breathing. When taken with fentanyl, these drugs produce a synergistic effect where the combined impact is greater than each drug taken alone. This interaction amplifies respiratory depression, the main cause of fatal opioid overdoses, as both substances suppress the drive to breathe.
Mixing fentanyl with other opioids like heroin or prescription painkillers like oxycodone increases the overdose risk. Since these substances act on the same opioid receptors, their combined use can quickly overwhelm the respiratory system. This can lead to a rapid shutdown of breathing.
A lethal combination involves fentanyl and benzodiazepines, a class of drugs that includes medications like Xanax and Valium. Benzodiazepines enhance the neurotransmitter GABA, which causes sedation. When combined with fentanyl, which also causes sedation and respiratory depression, the effects compound and increase the likelihood of a fatal overdose. Toxicology reports from overdose deaths frequently show the presence of both substances.
Alcohol is another CNS depressant that poses a threat when consumed with fentanyl. It suppresses respiratory function and impairs judgment, which can lead a person to miscalculate dosages or fail to recognize overdose signs. Nearly 15% of all deaths involving synthetic opioids like fentanyl also involved alcohol. Other depressants, such as barbiturates and certain sleep aids, produce similar risks by adding to the cumulative sedative effects.
Interactions with Stimulant Drugs
Combining fentanyl, a depressant, with stimulant drugs creates a “push-pull” dynamic within the body. This interaction places a strain on the cardiovascular system as it copes with conflicting signals to simultaneously speed up and slow down. The competing effects increase the risk of cardiac arrest and other severe complications.
A danger of this combination is that stimulants can mask the initial sedative effects of fentanyl. A person may feel more alert and believe they are not as intoxicated as they are, leading them to use more of the opioid than their body can handle. When the stimulant’s effects wear off, the full respiratory depression from the fentanyl can set in suddenly, leading to an unexpected overdose.
This mixture is sometimes consumed intentionally, as in the case of a “speedball.” However, many overdoses occur because illicitly manufactured stimulants, such as cocaine and methamphetamine, are unknowingly contaminated with fentanyl. Fentanyl is also found in counterfeit prescription stimulant pills, meaning individuals may consume a lethal dose without awareness.
Interactions with Prescription and Over-the-Counter Medications
Common prescription and over-the-counter (OTC) medications can also create dangerous interactions with fentanyl. Some interactions are metabolic, interfering with how the body processes fentanyl. Others involve overlapping side effects that become life-threatening when combined.
A metabolic interaction involves drugs that inhibit the enzyme CYP3A4. This enzyme is primarily responsible for breaking down and clearing fentanyl from the body. When a person takes a CYP3A4 inhibitor, the enzyme’s activity is blocked, causing fentanyl to accumulate to toxic levels. Common CYP3A4 inhibitors include certain antibiotics like clarithromycin, antifungal drugs such as ketoconazole, and grapefruit juice.
Combining fentanyl with serotonergic drugs can lead to serotonin syndrome, a condition caused by excess serotonin activity. Fentanyl can increase serotonin levels, and the risk is higher when taken with medications like certain antidepressants, such as MAOIs and SSRIs. Symptoms include agitation, rapid heart rate, high blood pressure, and muscle rigidity, and can become life-threatening.
Common OTC medications like the antihistamine diphenhydramine (Benadryl) can also be problematic. These drugs cause drowsiness and have sedative properties. When taken with fentanyl, these effects are additive, contributing to CNS depression and increasing the risk of sedation and respiratory compromise.
Recognizing a Fentanyl-Related Overdose
The most prominent signs of a fentanyl overdose are related to breathing. A person’s breathing may become slow and shallow, or it may stop altogether. This lack of oxygen can lead to choking or gurgling sounds. The skin may feel cold and clammy, and due to poor circulation, the lips and nails may turn blue or purple.
Another indicator is extremely small, “pinpoint” pupils that do not respond to light. The person will likely be unconscious or unresponsive, unable to be woken even when shaken or called by name. Their body may become limp.
If any of these signs are observed, call 911 immediately. If available, naloxone (Narcan) should be administered right away. Naloxone is a medication that can rapidly reverse an opioid overdose and is safe to use even if the person is not overdosing on an opioid. Stay with the person and provide information to emergency responders upon their arrival.