There were more than 93,000 reported overdose deaths in 2020—a 30% increase from 2019 and more than any previous year in U.S. history.1 In 2021, we surpassed this tragic milestone. While fentanyl is a leading factor in recent trends, stimulant-related deaths have also increased dramatically. Research shows that stimulant-related deaths are often attributed to severe cardiovascular and cerebrovascular dysfunction,2,3,4 including sudden cardiac death,5 myocardial infarction, and cerebrovascular infarction.6
While acute toxicity contributes to stimulant-related deaths, decades of research suggest a more complex dynamic. Chronic conditions such as hypertension, atherosclerosis, structural heart disease (e.g., cardiomyopathy), and electrical conduction disorders are often driven by stimulant use, and contribute to cardiovascular and cerebrovascular events.7 People who die from acute stimulant toxicity have higher rates of pre-existing cardiovascular disease (CVD) compared to those who die from opioid overdose or injuries.6 Moreover, CVD is often undiagnosed in this population. In fact, silent CVD progression is frequently pronounced in people who use cocaine regularly, many of whom remain asymptomatic until presenting to an emergency department with an acute event.8 In addition, the consequences of silent progression may be exacerbated in low-income individuals for whom CVD is more prevalent and health-care is less consistent.9,10,11,12 A recent study among unsheltered and unstably housed women found that those who co-used cocaine and alcohol had higher levels of cardiac injury, even after adjusting for CVD risk factors.13 Those who used cocaine were also seven times as likely to have white matter hyperintensities compared to those who did not.14
On average, people who use stimulants self-report more than one acute toxicity event per year (defined as taking enough of a stimulant to feel so sick or scared that one’s life may be in danger).15 Many consider symptoms of stimulant toxicity, such as chest tightness, a “normal” part of the experience,16 implying that cardiovascular symptoms in the setting of drug use often occur over long periods of time and may be difficult to separate from stimulant-related toxicity. Almost two-thirds of acute stimulant toxicity deaths in 2019 were among people over age 40, while most opioid overdose deaths occurred in younger individuals between 25 and 34.17
In contrast to death from acute opioid toxicity, which can readily occur even with first-time use, we hypothesize based on the existing evidence that death from acute stimulant toxicity is often an outcome of long-term, cumulative exposure.