Lethal Drug Combinations

Taking a drug concurrently with another drug—legal or illicit—can lead to drugs interacting with each other. These interactions can produce unintended consequences that are, at times, dangerous or even deadly.

Prescription drugs typically warn of known interactions on labels or in the instructions for use. Alcohol, recreational marijuana and illicit drugs, however, do not come with labels warning users.

Here are a few of the most common, and most dangerous, combinations of intoxicating substances.

Dangerous Drug Combinations with Alcohol

Alcohol is the most widely used drug in the U.S. In 2018, 55.3% of adults over the age of 18 used alcohol in the past month, according to the National Survey on Drug Use and Health.1

  • Dangers of Mixing Alcohol with Benzodiazepines, Barbiturates, and Prescription Sleep Aids: Alcohol is a central nervous system (CNS) depressant. It shares similar characteristics with other CNS depressants that like barbiturates and benzodiazepines and works synergistically to enhance their sedative effects.2 Approximately 1 in 5 people who misuse alcohol also misuse benzodiazepines.3 Combining the two can lead to a life-threatening overdose. Alcohol has an additive effect on psychomotor impairment with prescription sleep aids like Ambien (zolpidem). It also increases the risks of “sleep driving” and other complex behaviors (e.g., making and eating food, sleepwalking, etc.) sometimes associated with Ambien use.4
  • Dangers of Mixing Alcohol with Opioids: Alcohol enhances the effects opioids have on the central nervous system, such as drowsiness, sedation and decreased motor skills. Concurrent use of opioids and alcohol significantly increases the risk of respiratory depression and death.5 It’s estimated that approximately 1 in 5 prescription opioid deaths also involve alcohol.5
  • Dangers of Mixing Alcohol with Cocaine, Methamphetamine and MDMA (i.e., Molly or Ecstasy): Concurrent use of alcohol with cocaine, methamphetamine and ecstasy is very high.6 Alcohol enhances the feelings of euphoria experienced with these substances while at the same time having a detrimental effect on the brain and puts increased stress on the body’s cardiovascular system.Concurrent use of methamphetamine and alcohol tempers the detrimental effects on performance and sleep compared to each drug alone, however, it may also exacerbate methamphetamine-induced impairments in learning and spatial memory.6,7 Concurrent use of alcohol and cocaine produces cocaethylene, a metabolite that extends the effects of cocaine use but is also associated with seizures, liver damage, and compromised functioning of the immune system.8,9 Use of cocaine and alcohol also negatively impacts performance in neurobehavioral tests of intelligence, memory and verbal learning.Alcohol extends the duration of euphoria experienced with MDMA while limiting the sedative effect of alcohol, however, concurrent use negatively impacts learning and memory and is also associated with heightened feels of anxiety.6
  • Dangers of Mixing Alcohol with Prescription stimulants (i.e., Adderall): Medications like Adderall or Ritalin are important drugs to help people with attention deficit-hyperactivity disorder (ADHD), but they are widely abused by college students in part because of a misconception of their efficacy as study drugs or performance enhancers.10 Concurrent use of Ritalin (methylphenidate) and alcohol produces ethylphenidate, a potentially deadly metabolite. Some may use alcohol and prescription stimulants in an effort to mute some of the subjectively unpleasant effects of the other but at the same time put themselves at increased risk of detrimental effects on their body’s cardiovascular system.11 College students who misuse alcohol and prescription stimulants also report lower grade point averages, have higher rates of substance use and experience other adverse consequences vs. students who drink alcohol but do not misuse prescription stimulants.12
  • Dangers of Mixing Alcohol with Caffeine: Combining caffeine and alcohol is discouraged by both the U.S. Food and Drug Administration and Centers for Disease Control and Prevention. Caffeine masks the depressant effects of alcohol, making drinkers feel more alert than they are. This may lead to greater impairment increasing the risk of alcohol-caused harm (e.g., motor vehicle crashes, binge drinking, or alcohol poisoning).13,14

Dangerous Drug Combinations with Opioids

Opioid drugs, from Vicodin and other prescribed painkillers to heroin, are among the most abused drugs in the United States. The opioid abuse epidemic has been linked to pharmaceutical companies misleading healthcare providers and patients about the addictive potential of opioid painkillers.15 When prescriptions run out, people who have become addicted often turn to other means to acquire the drugs, including illicit sources, where they may be exposed to heroin or stronger drugs like fentanyl.

Aside from alcohol, opioids are often mixed with:

  • Dangers of Mixing Opioids with Benzodiazepines: More than 30 percent of overdoses involving opioids also involve benzodiazepines.16 Both benzodiazepines and opioids are CNS depressants, so they enhance each other’s effects, including inhibiting motor control and respiration, increasing the likelihood of death.17 Benzodiazepine and pharmaceutical opioids are the most common cause of mortality from polysubstance overdose.8
  • Dangers of Mixing Opioids with Cocaine: A speedballis an intentional combination of heroin and cocaine. Concurrent use helps to alleviate heroin withdrawal symptoms. It’s a highly dangerous combination and those who use both drugs experience problems with depression and anxiety vs. those who just use cocaine alone.18
  • Dangers of Mixing Opioids with Fentanyl and other opioids: Combining different types of prescription opioids with one another or with heroin can dramatically increase the risk of overdose and death. In 2016, synthetic opioids, (primarily illegal fentanyl) passed prescription opioids as the most common drugs involved in overdose deaths in the United States.19 With recent reports of fentanyl contaminating illicit narcotics (including heroin) and the ongoing opioid addiction epidemic, this problem is becoming more pronounced.20

Other Dangerous Drug Combinations

  • Dangers of Mixing Club drugs: MDMA (ecstasy, Molly), PCP, ketamine, and other club drugs are dangerous on their own. However, these substances are often taken together, with alcohol or with marijuana.21 Because they are manufactured drugs, they are often misrepresented, mixed with adulterants, or another substitute is substituted altogether.21 All of these things result in a high risk of overdose or unanticipated consequences and potential health risks.21
  • Dangers of Mixing Marijuana and other drugs: Although many states have legalized marijuana for both recreational and medical purposes, it still can be dangerous—especially when mixed with other drugs. When marijuana is taken concurrently with alcohol, the alcohol increases the absorption of THC—the psychoactive ingredient in marijuana—which enhances the high.8 Marijuana use has also been associated with drug-seeking behavior in people who are predisposed to addictive behavior,2 and the concurrent use of marijuana and other substances may contribute to the development of psychosis, particularly in adolescents.22

Combining Drugs Accidentally and Polydrug Abuse

There are several reasons people may combine both legal and illicit drugs, risking negative—potentially deadly—side effects. Combining intoxicating substances occurs frequently, often by accident or unintentionally, so it is important to pay attention to warning labels on prescription medications and know when combining drugs might have additive effects that could lead to accidental overdose.23,24

In some instances, illicit drugs are sold with adulterants, which can include other intoxicating substances as well as filler substances including other drugs—such as heroin that’s laced with fentanyl.25,26 When a person abusing one type of drug does not know they are ingesting a different substance, it heightens the risk of overdose because they do not know how much they are consuming.8,25

Polydrug abuse is unfortunately common among people who have developed a substance use disorder as well as for those who struggle with a co-occurring mental health disorder.27-29

It’s never too late to reach out for help. Call us today at to learn more about drug rehab treatment in Texas.


  1. Center for Behavioral Health Statistics and Quality. (2019). Results from the 2018 National Survey on Drug Use and Health: Detailed Tables.Substance Abuse and Mental Health Services Administration, Rockville, MD.
  2. Weathermon, R., & Crabb, D. W. (1999). Alcohol and medication interactions. Alcohol Research & Health: The journal of the National Institute on Alcohol Abuse and Alcoholism, 23(1), 40–54.
  3. Schmitz A. (2016). Benzodiazepine use, misuse, and abuse: A reviewThe Mental Health Clinician, 6(3), 120–126.
  4. Food and Drug Administration. (2008). Ambien (zolpidem tartrate).
  5. Esser, M. B., Guy, G. P., Jr, Zhang, K., & Brewer, R. D. (2019). Binge Drinking and Prescription Opioid Misuse in the U.S., 2012-2014American Journal of Preventive Medicine, 57(2), 197–208.
  6. Althobaiti, Y. S., & Sari, Y. (2016). Alcohol Interactions with Psychostimulants: An Overview of Animal and Human StudiesJournal of Addiction Research & Therapy, 7(3), 281.
  7. Vaghef, L., Babri, S., & Vahed, M. M. (2014). The Effect of Escalating Dose, Multiple Binge Methamphetamine Regimen and Alcohol Combination on Spatial Memory and Oxidative Stress Markers in Rat Brain. Journal of Alcoholism & Drug Dependence, 2(3):159.
  8. Miller, S. C., Fiellin, D. A., Rosenthal, R. N., & Saitz, R. (2019). The ASAM Principles of Addiction Medicine, Sixth Edition. Philadelphia: Wolters Kluwer.
  9. Andrews, P. (1997). Cocaethylene toxicity. Journal of Addictive Diseases, 16(3):75-84.
  10. National Institute on Drug Abuse. (2018). Prescription Stimulants.
  11. National Institute on Drug Abuse for Teens. (2019). What are Prescription Stimulants (Amphetamines)?
  12. Egan, K. L., Reboussin, B. A., Blocker, J. N., Wolfson, M., & Sutfin, E. L. (2013). Simultaneous use of non-medical ADHD prescription stimulants and alcohol among undergraduate students. Drug and Alcohol Dependence, 131(1-2), 71–77.
  13. Centers for Disease Control and Prevention. (2018). Fact Sheets – Alcohol and Caffeine.
  14. Dietary Guidelines 2015-2020. (2015). Appendix 9: Alcohol.
  15. National Institute on Drug Abuse. (2019). Opioid Overdose Crisis.
  16. National Institute on Drug Abuse. (2018). Benzodiazepines and Opioids.
  17. Afzal, A., & Kiyatkin E.A. (2019). Interactions of benzodiazepines with heroin: Respiratory depression, temperature effects, and behavior. Neuropharmacology, 158:107677.
  18. Bamsey, R. (2017). Polydrug Use: Prevalence, Predictors, Pharmacology and Psychopharmacology. The Yale Review of Undergraduate Research in Psychology, 7, 20–24.
  19. National Institute on Drug Abuse. (2018). Fentanyl and Other Synthetic Opioids Drug Overdose Deaths.
  20. National Institute on Drug Abuse. (2018). Nearly half of opioid-related overdose deaths involve fentanyl.
  21. Gahlinger, P.M. (2004). Club Drugs: MDMA, Gamma-Hydroxybutyrate (GHB), Rohypnol, and Ketamine. American Family Physician, 69(11):2619–2627.
  22. Jones, J. D., Calkins, M. E., Scott, J. C., Bach, E. C., & Gur, R. E. (2017). Cannabis Use, Polysubstance Use, and Psychosis Spectrum Symptoms in a Community-Based Sample of U.S. YouthThe Journal of Adolescent Health : Official publication of the Society for Adolescent Medicine60(6), 653–659.
  23. Calcaterra, S., Glanz, J., & Binswanger, I. A. (2013). National trends in pharmaceutical opioid related overdose deaths compared to other substance related overdose deaths: 1999-2009Drug and Alcohol Dependence, 131(3), 263–270.
  24. Coffin, P. O., Galea, S., Ahern, J., Leon, A. C., Vlahov, D., & Tardiff, K. (2003). Opiates, cocaine and alcohol combinations in accidental drug overdose deaths in New York City, 1990-98Addiction, 98(6), 739–747.
  25. Griswold, M. K., Chai, P. R., Krotulski, A. J., Friscia, M., Chapman, B., Boyer, E. W., … Babu, K. M. (2018). Self-identification of nonpharmaceutical fentanyl exposure following heroin overdoseClinical Toxicology (Philadelphia, Pa.), 56(1), 37–42.
  26. Enos, G.A. (2017). Opioid adulterants now affecting cocaine supply. Addiction Professional.
  27. National Institute on Drug Abuse. (2018). Common Comorbidities with Substance Use Disorders.
  28. Flynn, P. M., & Brown, B. S. (2008). Co-occurring disorders in substance abuse treatment: issues and prospectsJournal of Substance Abuse Treatment, 34(1), 36–47.
  29. Timko, C., Ilgen, M., Haverfield, M., Shelley, A., & Breland, J. Y. (2017). Polysubstance use by psychiatry inpatients with co-occurring mental health and substance use disordersDrug and Alcohol Dependence, 180, 319–322.
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