What Is Opioid Overdose?

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Opioids are analgesic drugs used to treat acute and chronic pain. They can be prescribed as therapeutic agents for pain symptoms, such as morphine, but they can also be found as illicit substances e.g., heroin.1 An opioid overdose occurs when a person consumes higher concentrations of these drugs than their body can tolerate or when opioids are combined with other substances, leading to devastating effects potentially including death. This happens when opioids overstimulate specific brain regions responsible for regulating respiration (breathing in and out), leading to respiratory depression, which, if not treated promptly, can be fatal.2

You may be familiar with the opioid overdose epidemic in the U.S. which involves high addiction and mortality rates, but what has been the situation in Europe over the last few decades? Opioid overdose rates in Europe present a more favourable outlook, with a decline in the prescription of opioid medicines. Even if opioid overdose is not prevalent in European countries, specialists remain observant and cautious of potentially dangerous trends.3

Opioid overdose caused approximately 150,000 deaths worldwide in 2019, with rates increasing yearly.4 According to the 2023 European drug report, an estimated 1 million people engaged in high-risk opioid use in 2021, with 74% of cases resulting in fatal overdoses.5 Opioid overdose rates can be linked to various factors:6

  • The overprescription of opioids, especially in the U.S., due to local decentralised healthcare access regulations and misuse of prescribed opioids
  • Illicit use of street drugs, such as heroin and morphine, contributing to 2.34 per 100,000 deaths in England in 2020
  • The use of synthetic opioids, specifically fentanyl, which is a 50 times more potent opioid than heroin and 100 times more potent than morphine

Understanding how opioids work in the human body and the factors associated with this opioid crisis is important not only for understanding the potentially disastrous effects of opioids but also for knowing how to respond in case of witnessing such an emergency.

Understanding opioids

Origins and types of opioids

Opioids constitute a wide class of medications originally deriving from the plant Papaver somniferum, also referred to as opium poppy. This plant contains naturally occurring alkaloids known as opiates, forming the basis for natural and synthetic derivatives with pharmacological action. Opioids are categorised according to their chemical structures and origin:7

  • Naturally derived opioids or opiates: Directly extracted from the plant or isolated from different plant parts. Examples include opium, morphine, and codeine
  • Semisynthetic derivatives: Acquired through mild chemical processing or by combining natural opioids with laboratory-made adjuvants. Heroin, hydrocodone, oxycodone, and buprenorphine fall into this category
  • Synthetic derivatives: Entirely human-made to mimic the actions of natural opioids. Examples include fentanyl, methadone, and tramadol

Mechanism of action

Opioids act by modifying the human body’s opioid system, which is responsible for regulating pain, emotions, respiration, and other physiological responses. They bind to and activate various opioid receptors present throughout the central and peripheral nervous system. The activation of these receptors triggers in-built signalling pathways, resulting in the pharmacological effects of opioids.8

The adverse effects of opioid use are linked to the tolerance built after repetitive administration of these drugs. Prolonged use of opioids such as morphine, one of the most widely prescribed analgesic drugs, can result in decreased effects over time. To achieve the best drug efficacy, the dose may be increased, potentially resulting in tolerance, addiction, and the risk of opioid overdose.8

While opioids are correlated with multiple adverse effects, respiratory depression poses the most serious consequence of an opioid overdose. Specific opioid receptors are in control of the normal respiratory rate, and excessive activation can disrupt automated neuronal responses, potentially resulting in hypoventilation (inadequate breathing) and death.8

Factors contributing to opioid overdose 

  • Misuse or prolonged use of prescribed opioids (e.g., oxycodone, methadone, morphine), or use without professional supervision, can lead to tolerance, addiction, and opioid overdose4
  • Use of illicit synthetic opioids or street drugs, such as fentanyl and heroin, poses a significant risk for overdose4
  • Having a history of substance use and combining opioids with other substances or medications, including alcohol, benzodiazepines, barbiturates, anaesthetics, or certain pain medications increases the likelihood of overdose4
  • Using opioids following an extended time of abstinence can be risky. Changes in the body’s tolerance may result in overdose when high doses are consumed4
  • Health conditions like HIV, mental illnesses, liver and lung diseases have all been linked to opioid overdose4
  • Older individuals, males and those with low socioeconomic status are associated with a higher risk of opioid overdose

Signs and symptoms of opioid overdose

Image source: Recognise the signs of opioid overdose by Tokatli MR. Icon sourcesI-VIII

Individuals experiencing an opioid overdose present specific signs and recognising them could potentially save a person’s life. These signs comprise the “opioid overdose triad” and include:9

  • Unresponsiveness or unconsciousness: Individuals in opioid overdose are often unable to speak or be awakened
  • Pinpoint pupils: Pupil shrinkage to a very small size
  • Respiratory depression: Individuals with acute opioid poisoning present slowed, shallow, or stopped breathing

Additional symptoms include:10

  • Limp body
  • Purple or blue lips or fingernails
  • Pale, cold, or clammy skin
  • Choking or gurgling sounds

Emergency response

The primary intervention for opioid overdose is naloxone, a semisynthetic opioid receptor antagonist. Naloxone competes with opioids by binding and deactivating the opioid receptors, reversing analgesia but more importantly respiratory depression. It functions as an exclusive antidote for opioid overdose. This means it has a remarkably high safety profile as it remains clinically inert in the absence of opioids. However, if other substances are contributing to the overdose in combination with opioids, naloxone loses its efficacy. Depending on the route of administration it can act within minutes but is also rapidly eliminated. This means that individuals in opioid overdose may experience recurring respiratory depression, necessitating multiple naloxone doses. Therefore, calling 999 for further assistance is crucial.11

Naloxone is available in three different formulations: as injectable liquid administered intravenously, intramuscularly, or subcutaneously. These can be in the form of prefilled auto-injection devices or as an intranasal spray.12

While emergency personnel routinely administer naloxone and provide resuscitation in incidences of opioid overdose, clear guidelines for bystanders are vital to saving lives. In recent years, several European countries have introduced specific guidelines for the correct use of naloxone outside healthcare facilities. Implementing take-home naloxone kits and providing educational and training programs to the community are fundamental techniques suggested by the World Health Organization to address this emergency.12,13 

How to respond if you believe a person is overdosing on opioids

Image source: Emergency response guide by Tokatli MR. Icon sourcesIX-XIII

If you act promptly by following a few proper steps, you can save a person's life:14

  1. Check for vital signs: Monitor their breathing, heartbeat, and alertness. Shout their name, rub your knuckles on their chest, or pinch them. Try to interact with the person and keep them awake. DO NOT forcibly try to wake them by slapping, using cold water, making them vomit, or injecting substances other than naloxone.
  2. Call for help: Emergency personnel should intervene as soon as possible. They may give you instructions over the phone to first aid until rescue arrives.
  3. Administer naloxone if available: Naloxone typically acts in 2-3 minutes but has a short duration, and multiple doses might be needed.
  4. Initiate compressions: If the person remains unresponsive, initiate CPR and continue while waiting for naloxone to act.
  5. Wait and monitor: Do not leave the person alone until help arrives. Continuous monitoring is crucial even if they revive, as overdose symptoms may reoccur. If you need to leave, place them in the ‘recovery position’ on their side. Although not life-threatening, opioid withdrawal symptoms may appear, including fast heart rate, body aches, and diarrhoea. It is best to seek medical assistance by transporting the person to an emergency room.

Prevention strategies

Individuals using opioids and those close to them should be aware of these preventive strategies to avert the occurrence of a dreadful overdose event: 4,15

  • Follow your doctor's advice: Take prescribed opioids as consulted by your practitioner without personalising doses or altering their frequency. If you are hesitant, consult an expert for more information
  • Do not mix substances: Avoid combining opioids with other substances like illicit drugs, alcohol, sleeping pills, benzodiazepines, barbiturates, or certain analgesic drugs. Always inform you doctor about the medication you take
  • Avoid sharing medications: Do not take another person’s medications nor split yours. Pharmacological treatment is tailored to the needs and tolerance of each individual
  • Secure storage: Keep opioids in a safe place, away from children or pets. If unused, make sure to dispose of them properly
  • Seek support: Recovery support groups are available in multiple communities, providing valuable encouragement. Pharmaceutical agents, such as methadone, may be also be advised by your practitioner to manage symptoms of withdrawals and cravings


In conclusion, opioid overdose is a critical consequence arising from the overconsumption of prescribed or illicit opioid drugs and the combination of different substances. While opioids provide highly effective pain relief, they can cause tolerance and dependence. Addiction and high-risk use of opioids can be associated with overprescription, the expansion of synthesising illicit drugs, personal choices and mental health.

Opioid overdose is a medical emergency that demands attention on a global, community, and individual level, irrespective of its prevalence rates. Rapid emergency response is crucial for saving lives. At-home naloxone kits, training programs for emergency actions, educational initiatives for prevention and opioid treatment programs are imperative approaches that your community may have available to help combat this situation. Collectively addressing the challenges of opioid overdose and other crises are essential steps towards a safer and healthier future.


  1. Reeves KC, Shah N, Muñoz B, Atwood BK. Opioid receptor-mediated regulation of neurotransmission in the brain. Front Mol Neurosci. 2022 Jun 15;15:919773. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242007/
  2. Schiller EY, Goyal A, Mechanic OJ. Opioid overdose. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. Available from: http://www.ncbi.nlm.nih.gov/books/NBK470415/
  3. van Amsterdam J, Pierce M, van den Brink W. Is europe facing an emerging opioid crisis comparable to the u. S.? Therapeutic Drug Monitoring. 2021 Feb;43(1):42. Available from: https://journals.lww.com/drug-monitoring/abstract/2021/02000/is_europe_facing_an_emerging_opioid_crisis.6.aspx
  4. Opioid overdose [Internet]. [cited 2023 Nov 24]. Available from: https://www.who.int/news-room/fact-sheets/detail/opioid-overdose
  5. European Monitoring Centre for Drugs and Drug Addiction. European drug report 2023 [Internet]. LU: Publications Office; 2023 [cited 2023 Nov 24]. (European drug report ... (Online)). Available from: https://data.europa.eu/doi/10.2810/161905
  6. Roberts AO, Richards GC. Is England facing an opioid epidemic? Br J Pain. 2023 Jun;17(3):320–4. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278447/
  7. Opioids. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Available from: http://www.ncbi.nlm.nih.gov/books/NBK547864/
  8. Paul AK, Smith CM, Rahmatullah M, Nissapatorn V, Wilairatana P, Spetea M, et al. Opioid analgesia and opioid-induced adverse effects: a review. Pharmaceuticals. 2021 Nov;14(11):1091. Available from: https://www.mdpi.com/1424-8247/14/11/1091
  9. American Addiction Centers [Internet]. [cited 2023 Nov 24]. Opioid overdose signs, symptoms & treatment. Available from: https://americanaddictioncenters.org/prescription-drugs/opiate-overdose
  10. Save a life from prescription opioid overdose | rx awareness | cdc injury center [Internet]. 2020 [cited 2023 Nov 24]. Available from: https://www.cdc.gov/rxawareness/prevent/index.html
  11. Britch SC, Walsh SL. Treatment of opioid overdose: current approaches and recent advances. Psychopharmacology (Berl). 2022;239(7):2063–81. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986509/
  12. Preventing fatal overdoses: a systematic review of the effectiveness of take-home naloxone | www.emcdda.europa.eu [Internet]. [cited 2023 Nov 24]. Available from: https://www.emcdda.europa.eu/publications/emcdda-papers/naloxone-effectiveness_en
  13. Take-home naloxone – topic overview | www.emcdda.europa.eu [Internet]. [cited 2023 Nov 22]. Available from: https://www.emcdda.europa.eu/publications/topic-overviews/take-home-naloxone_en
  14. Opioid overdose prevention toolkit | SAMHSA publications and digital products [Internet]. [cited 2023 Nov 24]. Available from: https://store.samhsa.gov/product/Opioid-Overdose-Prevention-Toolkit/SMA18-4742
  15. Preventing, Recognizing, and Treating Opioid Overdose | SAMHSA [Internet]. [cited 2023 Nov 23]. Available from: https://www.samhsa.gov/medications-substance-use-disorders/medications-counseling-related-conditions/opioid-overdose

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Maria Raza Tokatli

Master's degree, Pharmacy, University of Rome Tor Vergata

Master's degree holder in pharmacy and licensed pharmacist in Italy with a diverse background in medical writing, research, and entrepreneurship. Advocating for personalised approaches in medicine, and an AI enthusiast committed to enhancing health awareness and accessibility. Intrigued by the pursuit of expanding knowledge, actively staying updated on new insights in the pharmaceutical and technological fields.

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