The Overwhelming Driver: Synthetic Opioids
The United States continues to grapple with a severe drug overdose crisis, and the data points overwhelmingly to one category of substances as the main culprit: synthetic opioids [1.2.7]. In 2023, nearly 76% of all overdose deaths involved an opioid, and of those, a staggering 92% involved synthetic opioids other than methadone, which is primarily illegally manufactured fentanyl (IMF) [1.4.1]. This means that about 69% of all drug overdose deaths in 2023 were linked to IMF [1.2.1]. Fentanyl is a potent synthetic opioid, estimated to be 80-100 times stronger than morphine [1.2.5]. Its prevalence has reshaped the landscape of the overdose epidemic, which has evolved through several waves, from prescription opioids to heroin, and now to this potent synthetic substance [1.5.3].
The Rise of Polysubstance Overdoses
A critical and growing dimension of the overdose crisis is the involvement of multiple drugs, known as polysubstance use [1.2.1, 1.6.8]. Many individuals who die from an overdose have more than one type of drug in their system, which can have unpredictable and synergistic effects, dramatically increasing the risk of death [1.5.3, 1.6.8]. Data from 2023 shows that 47% of drug overdose deaths involved both opioids and stimulants [1.4.1].
Common Drug Combinations
- Opioids and Stimulants: The combination of opioids (especially fentanyl) with stimulants like cocaine and methamphetamine is increasingly common [1.4.2]. In 2023, about 33% of all overdose deaths involved psychostimulants (like methamphetamine) and 28% involved cocaine [1.2.1]. The number of deaths involving both stimulants and IMF is the main driver of the increase in stimulant-related fatalities [1.4.2].
- Opioids and Benzodiazepines: This combination is also a significant contributor to overdose deaths. In 2023, there were 10,870 overdose deaths involving benzodiazepines, and nearly 70% of those also involved IMF [1.4.2].
- Fentanyl as an Adulterant: A particularly dangerous aspect of the current crisis is that fentanyl is often added to other illicit drugs like heroin, cocaine, and counterfeit prescription pills, frequently without the user's knowledge [1.5.3, 1.5.6]. This means a person may consume a fatal dose of fentanyl while believing they are using a different substance.
- Xylazine ('Tranq'): The emergence of xylazine, a veterinary tranquilizer not approved for human use, has added another layer of complexity. Often found mixed with fentanyl, this combination is known as "tranq dope" [1.5.8]. Xylazine is a central nervous system depressant that can cause dangerously low breathing and heart rate. Crucially, the opioid-reversal medication naloxone does not work on xylazine's effects, although it is still recommended for use in any suspected overdose because of the high likelihood of opioid co-involvement [1.5.8].
Comparison of Substances in Overdose Deaths
| Drug Category | Involvement in 2023 Overdose Deaths | Key Characteristics & Trends | Citation(s) |
|---|---|---|---|
| Synthetic Opioids (e.g., Fentanyl) | ~69% of all deaths | 80-100 times stronger than morphine. The primary driver of the overdose crisis. Often mixed with other drugs. | [1.2.1, 1.2.5] |
| Psychostimulants (e.g., Methamphetamine) | ~33% of all deaths | Deaths have risen sharply, often in combination with fentanyl. | [1.2.1, 1.4.2] |
| Cocaine | ~28% of all deaths | Deaths continue to increase, largely driven by co-involvement with IMF. | [1.4.1, 1.4.2] |
| Prescription Opioids | ~12% of all deaths (13,026 deaths) | No longer the main driver, but many deaths involving them also involve IMF. | [1.4.2, 1.5.2] |
| Heroin | ~4% of all deaths (3,984 deaths) | Deaths have decreased significantly, but a high proportion of remaining heroin deaths also involve fentanyl. | [1.2.1, 1.4.2] |
| Benzodiazepines | ~10% of all deaths (10,870 deaths) | Nearly 70% of these deaths also involved IMF. | [1.4.2] |
Key Risk Factors
Several factors increase an individual's risk of a drug overdose. A primary risk is a history of a substance use disorder [1.5.6]. Another critical risk factor is a reduced tolerance, which can occur after a period of abstinence, such as after detoxification or release from incarceration [1.5.2, 1.5.6]. Using drugs alone is also a major risk, as there is no one present to call for help or administer life-saving measures like naloxone [1.2.3]. Mixing drugs, particularly with other central nervous system depressants like alcohol or benzodiazepines, significantly elevates the risk of a fatal outcome [1.2.3, 1.5.6].
Conclusion
In conclusion, the answer to 'What are the majority of drug overdoses caused by?' is unequivocally synthetic opioids, with illegally manufactured fentanyl at the epicenter of the crisis [1.4.1]. This is compounded by the rising trend of polysubstance use, where fentanyl is frequently and lethally combined with stimulants like cocaine and methamphetamine, as well as other depressants [1.4.1, 1.6.1]. The contamination of the illicit drug supply with fentanyl means that even users of non-opioid drugs are at high risk. Addressing this public health emergency requires a multi-faceted approach that includes robust prevention, widespread access to treatment for substance use disorders, and harm reduction strategies like the distribution of the opioid overdose reversal drug, naloxone [1.5.6].
