New research from Dr Joseph Friedman and Dr Chelsea L Shover highlights important changes in the drugs implicated in overdose deaths in North America – from the prescription drugs that characterised deaths in the early 2000s, to the fentanyl mixed with stimulants that have become a prominent feature of deaths since 2015.

Fentanyl is a synthetic opioid, which is reportedly “50–100 times more potent than morphine”. Fentanyl has featured in a lot of media coverage about the opioid epidemic in the past decade due to being associated with a spike in deaths in the United States and being mixed with other illicit drugs. However, research from Dr Joseph Friedman and Dr Chelsea L Shover, published in the journal Addiction, suggests that the current opioid epidemic in North America is bigger than the story of fentanyl. They say the ‘fourth wave’ that we are now witnessing is due to a combination of fentanyl and stimulants, which have been termed ‘poly-substance deaths’.

One, two, three, four

The rate of overdose deaths in the US has been steadily rising over the past four decades. The common denominator is opioids – a class of drugs that “activate an area of nerve cells in the brain and body called opioid receptors that block pain signals between the brain and the body”. Opioids include heroin, oxycodone, dihydrocodeine, morphine, fentanyl, and tramadol. While their effects can be experienced as positive, for example, increased confidence, feeling invincible, relief from pain, and euphoria, the use of opioids can have adverse consequences, including respiratory depression, which is the cause of many drug-related deaths.

The types of opioids implicated in drug deaths have changed over time. Scholars have described the pattern using the metaphor of ‘waves’. The first wave of overdose deaths was in the late 1990s or early 2000s, when there was a rise in deaths involving prescription opioids. The second wave began in 2010 and was linked to an increase in heroin-related deaths. The third wave began in 2013, with a shift to deaths involving fentanyl. And then, the fourth wave began in 2015 with a rise in deaths involving fentanyl combined with stimulants.

The risks of opioids + stimulants

Stimulants are a class of drugs that “increase the activity of the central nervous system”. The Drugs Wheel lists some of the effects of stimulants as increased energy, increased heart rate, euphoria, paranoia, anxiety, and sexual arousal.

The co-use of fentanyl and stimulants may be due to people desiring the combined effects of both types of drugs, or it may be due to people consuming them together unintentionally (e.g. if cocaine has been cut with fentanyl before being sold or shared).

There are several risks of using stimulants at the same time as opioids, for example:

• Stimulants can cause your body to use more oxygen, while heroin can slow your breathing rate – a combination that can increase your risk of experiencing respiratory depression.
• The effects of stimulants and opioids might seem to cancel each other out, leading people to take more of each of the substances, and potentially take too much (leading to an overdose).

Geographical differences

Friedman and Shover found that virtually all states in the US experienced an increase in the proportion of fentanyl deaths involving stimulants between 2015 and 2021; the proportion of overdose deaths involving both classes of drugs rose from under one per cent in 2010 to 32% in 2021. By 2021, however, there were large differences between states in the number of deaths involving fentanyl and stimulants.

“There are now two basic archetypes of states in the United States with respect to overdose death rates: (a) states where fentanyl and cocaine co-use predominates; and (b) states where fentanyl and methamphetamine co-use predominates, with surprisingly little overlap between these two groups.” Friedman and Shover (Addiction, 2023)

The states with the highest proportions of deaths involving fentanyl and stimulants were Alaska (66%), West Virginia (60%), Rhode Island (59%), Hawaii (59%), and California (58%), and the states with the lowest proportions were New Hampshire (22%), Nebraska (30%), and Wyoming (31%).

In the Northeast, the main stimulant was cocaine. Among states in the West region, it was methamphetamine. And the Midwest and South saw a more mixed profile, with both methamphetamine and cocaine.

‘More sought-after and commonplace’

According to Friedman and Shover, ethnographic and qualitative research suggests that the characteristics of fentanyl might be making poly-substance use “more sought-after and commonplace”. For example, the shorter duration of fentanyl (compared with heroin) might cause people to seek out other substances that could prolong the onset of withdrawal symptoms, increase euphoria, or improve energy levels.

Monitoring poly-substance deaths is challenging. Some much-relied-upon datasets in the US were not designed to track the prevalence of “complex sets of drug co-involvement in overdose deaths”. Furthermore, not all substances (especially novel substances) are tested for in autopsy toxicology investigations. The landscape has changed quite rapidly in the past decade. And as Friedman and Shover say, “even the most current results may simply represent snapshots of shifting dynamics that will soon change”.

by Natalie Davies

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