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Benzos, Opioids and Z-Drugs: Deadly Combos

With all the news media accounts and reports from governmental health organizations about the opioid epidemic, including the 70,237 drug overdose deaths in 2017, a newly emerging threat is gaining attention: use and misuse of benzodiazepines, opioid drugs and Z-drugs. Specifically, combining these three drugs can create a deadly combination that snuffs out lives.

Benzodiazepine Overdose Deaths on the Rise

Benzodiazepines, a class of sedative narcotic drugs including Xanax and Valium used to treat anxiety, insomnia and other disorders and classified as Schedule IV under the Controlled Substances Act by the Drug Enforcement Agency (DEA), are increasingly misused, diverted and abused. These are powerful drugs that are highly addictive and can be fatal, especially when combined with opioids, alcohol (and Z-drugs, per recent findings). Prescriptions filled for benzos jumped 67 percent, from 8.1 million in 1996 to 13.5 million in 2013, according to a 2016 study reported in the American Journal of Public Health. Benzodiazepines are also considered responsible for a dramatic increase in overdose deaths in recent years, rising from 1,135 in 1999 to 8,791 in 2015 and 10,684 in 2016. The Centers for Disease Control and Prevention (CDC)  highlighted the fact that benzodiazepine overdose deaths among women spiked 830 percent from 1999 (0.54 deaths per 100,000) to 2017 (5.02 deaths per 100,000).

Some 5.3 million people (of 30.6 million who said they used benzodiazepines) reported misuse, or not using them properly, according to a 2018 study published in the online version of Psychiatric Services. Misuse means taking the drug in a way other than prescribed by a doctor.

Why are benzos so dangerous?

Due to their sedative effect, benzodiazepines – especially when combined with other drugs and substances that slow breathing (such as opioids and alcohol) can result in a user falling asleep and never waking up. The fact that benzos are often prescribed along with opioid drugs is a major factor contributing to the 75 percent of benzodiazepine-involved overdose deaths.

The main effects of benzodiazepines is muscle relaxation, general anesthesia, sleepiness and drowsiness — the reason they’re prescribed to treat certain conditions. While benzos may be effective to treat insomnia and anxiety, when used in combination with painkilling narcotics (opioids), or other substances (Z-drugs, alcohol) that suppress breathing, the combination can prove fatal.

What are Z-Drugs?

The so-called Z-drugs are sedative hypnotics, classified as Schedule IV controlled substances under the Controlled Substances Act. They are usually prescribed for the short-term treatment of insomnia. They’re called Z-drugs because they begin with the letter “Z,” and include zolpidem (brand name, Ambien, Ambien CR), zaleplon (brand name, Sonata), and zoplicone (eszoplicone, sold in the U.S. under the brand name, Lunesta).

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Z-drugs are not benzodiazepines, but are a separate class of medicine, non-benzodiazepine sedative-hypnotic agent, although they do work in a similar manner. Both Z-drugs and benzodiazepines have a similar effect on brain cells. Both also have similar problems stemming from long-term use.

How do Z-drugs cause problems?

Just as with prescription benzodiazepines, when prescribed Z-drugs are used for the short-term treatment of a medical condition (such as anxiety, sleeping problems and other disorders), the user can generally stop taking the medication without problems. Short-term use is typically 2-4 weeks, depending on the treating physician’s prescription dose, duration and recommendations.

What happens when someone takes Z-drugs (and benzodiazepines) for longer than prescribed? The first noticeable symptom is tolerance, meaning the user has to take more of the medication to achieve the same effect it initially produced. This may mean taking more Z-drug to alleviate anxiety or to combat sleep problems. After a short period of time, the increased doses (or higher frequency of use) no longer works. Thus, the user enters the second stage: dependence. He or she has to take the medication in order to stave off withdrawal symptoms. These are physical and psychological symptoms, some of which may seem like the original symptoms of anxiety for which the drug(s) were prescribed. Finally, continuing to take Z-drugs leads to addiction, which often requires professional detox and counseling to successfully overcome.

Originally, Z-drugs were not thought to be as addictive or habit-forming as benzodiazepines, although that consensus has changed with reports of dependence and addiction. Z-drugs can cause problems with psychomotor impairment, especially in older users, and users are cautioned to avoid driving when taking the medication. Adverse reactions, tolerance, dependence and addiction can result. In addition, additive effects occur from combining Z-drugs with other central nervous system (CNS) depressants (benzodiazepines, opioids, and alcohol), which may lead to overdose and death.  

Opioid Drugs Add to the Risk of Overdose Deaths

Millions of Americans take prescription opioid drugs to combat pain, whether from a recent surgery or chronic pain due to cancer or other disease. Millions also become dependent upon and then addicted to the painkillers, taking them far longer than the short-term use for which they were originally prescribed. Yet, they’re mostly taking them for the same purposes they originally did – to relieve pain. They’re not, according to the Center for Behavioral Statistics and Quality Report, taking them to get high. However, once dependent on and subsequently addicted to opioids, it’s almost impossible to overcome the compulsion to use these potent narcotics without professional detox and subsequent behavioral therapy and other treatment modalities.

As a study published in 2019 in the International Journal of Geriatric Psychiatry points out, prescription opioids and benzodiazepine misuse is associated with suicidal ideation in older adults. According to the study findings, although 2.2 percent of older adults in the U.S. who were not engaged in opioid or benzodiazepine misuse reported suicidal thoughts, 25.4 percent of those who misused both said they endorsed such suicidality. A report from the New England Journal of Medicine found that opioids were linked to a doubling of suicides and overdoses since 2000.

Prescription opioids include natural , semisynthetic opioids (including oxycodone and hydrocodone), methadone, synthetic opioids other than methadone (including fentanyl, fentanyl analogs, and tramadol),

And, further complicating an already serious situation, misusing opioids in combination with benzodiazepine and Z-drug misuse can lead to fatal overdoses. A 2019 study reported in Sleep looked at co-usage of benzodiazepines and opioids in the U.S. and noted that the “progressive increases in these two forms of psychoactive medication polypharmacy is concerning, given that these drug use patterns are associated with increased risk for serious adverse outcomes.”

The Dangers of Polydrug Addiction

Addiction to opiate narcotics can co-occur with addiction to benzodiazepines and Z-drugs. This is called polydrug addiction. The danger is that even with legitimate prescriptions for painkillers, anxiety and sleep medications, tolerance, dependence and addiction can result. Using all three classes of drugs simultaneously not only increases the risk of addiction, it also escalates the risk of overdose and death.

Anyone who is abusing, misusing or is addicted to benzos, opioids and/or Z-drugs is advised to seek professional help to safely detox and wean off use through counseling and other behavioral therapies.


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Benzos, Opioids and Z-Drugs: Deadly Combos

Suzanne Kane

Suzanne Kane is a Los Angeles-based writer, blogger and editor. Passionate about helping others live a vibrant and purposeful life, she writes daily for her website, She is a regular contributor to Psych Central. You can reach her at [email protected].

APA Reference
Kane, S. (2019). Benzos, Opioids and Z-Drugs: Deadly Combos. Psych Central. Retrieved on August 13, 2020, from
Scientifically Reviewed
Last updated: 23 Jan 2019 (Originally: 23 Jan 2019)
Last reviewed: By a member of our scientific advisory board on 23 Jan 2019
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