Epidemiology

Opioid use disorder and overdose is a growing concern worldwide.[3]​​

In the UK, a total of 2551 drug poisoning deaths in 2023 involved opioids, which represented nearly half of all drug poisoning deaths (46.8%; increasing to 60.7% once deaths that had no drug type recorded were excluded). This was 12.8% higher than in 2022 (2261 deaths).[4]

In the US, provisional data shows overdose deaths involving opioids are decreasing. In 2023, there were an estimated total of 110,037 drug overdose deaths, of which 83,140 involved opioids. In 2024, the estimated total overdose deaths was 80,391, with 53,743 involving opioids. Although these numbers are still very high, this decrease marks the lowest levels of overdose deaths since 2019.​[5]

New synthetic opioids (NSO) emerged on the illicit drug market in the second half of the 2000s and have become increasingly widespread. The most popular and the largest NSO subgroups are high-potency fentanyl and its analogues.[6] During 2016, the rate of synthetic opioid overdose deaths (other than methadone) exceeded those of heroin overdose deaths for the first time in the US (6.2 per 100,000 population vs. 4.9 per 100,000 population, respectively).[7]​ During 2019-2022, US overdose deaths involving illegally manufactured fentanyls more than doubled, from an estimated 35,473 in 2019 to 73,838 in 2022.[8][9] Carfentanil, a fentanyl analogue 100 times more potent than fentanyl, has recently re-emerged in the US drug supply, and was linked to 238 deaths in 2024 (January to June), up from 29 deaths in 2023 (January to June).[10]

Data from public health and law enforcement agencies also indicate widespread adulteration of cocaine with fentanyl and its analogues.[11][12] The mixture of stimulants, such as cocaine and methamphetamines, with fentanyl is driving what experts call the opioid epidemic's ‘fourth wave’. The percent of US overdose deaths involving both fentanyl and stimulants increased from 0.6% in 2010 to 32.3% in 2021. By 2021, stimulants were the most common drug class found in fentanyl-involved overdoses in every state in the US.[13]

The opioid crisis has also become increasingly complicated due to the emergence of comixtures of synthetic opioids with other central nervous system depressants. This includes animal tranquilisers such as xylazine, and more recently, medetomidine, both associated with a growing number of fatalities in the US.[14][15][16][17] From 2019 to 2022, among 21 jurisdictions in the US (including 20 states and the District of Columbia), the monthly percentage of illegally manufactured fentanyl-involved deaths with xylazine detected increased 276%, from 2.9% to 10.9%.[18]

Many non-fentanyl NSOs are now also becoming increasingly prevalent on the illegal drug scene.[6] Nitazenes and nitazene analogues (e.g., benzimidazole opioids) have been found as contaminants in street heroin and cocaine as well as black market vaping liquids and fake prescription drugs purchased online. New forms of nitazenes are emerging, with one believed to be >300 times more potent than morphine and >45 times more than fentanyl.[19][20]​ In the UK, the Office for Health Improvement and Disparities and the National Crime Agency confirmed through laboratory testing that there were 179 deaths involving one or more nitazenes occurring between June 2023 and May 2024.[21]

Recent abstinence, resulting in loss of tolerance (e.g., during incarceration), increases the risk of overdose. Because of this, drug overdose is the most common cause of death of former inmates after prison release; the risk of death in the 2 weeks after release is 12 times that of the general population.[22]

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