The “Fourth Wave” of the Opioid Epidemic Is Upon Us

The fourth wave of the opioid epidemic is upon us

Plus: Powerful pot’s connection to addiction and psychosis, and sleep’s role in relapse prevention

By Mark Mravic

The apparent leveling-off of opioid fatality numbers in recent months may have given rise to some optimism, but a new study out of Northwestern University paints a much grimmer picture of where the opioid epidemic stands and where it’s headed.

Also this week, a study that finds correlations between cannabis potency and serious mental health problems, and the importance of undisturbed REM sleep in preventing relapse.

From Jama Network:
“Explosive” Growth in Overdose Deaths, Everywhere

Studying geographic trends in opioid overdose deaths from 1999 to 2020, researchers at Northwestern found that, for the first time, both opioid fatality rates and the acceleration of those rates are converging at record numbers across all regions of the U.S. The result, they say, is a “fourth wave” of overdose deaths that the study’s lead author says will be “worse than it’s ever been before.”

Three previous overlapping waves of opioid deaths—the first driven by prescription painkillers beginning around 2000, the second by a rise in heroin use starting in the late 2000s and the third from the influx of synthetic opioids such as fentanyl in the mid-2010s—had distinct geographic profiles, the authors found. In the first wave, death rates were higher in urban counties but accelerated faster in rural areas. The second wave was concentrated in urban areas. The third wave impacted both rural and urban areas, but in a non-linear fashion.

“Not only is the death rate from [opioids] at an all-time high, but the acceleration of that death rate signals explosive exponential growth that is even larger than an already historic high.”

—Lori Post, Northwestern University

The authors’ proposed “fourth wave,” which corresponded with the onset of the COVID-19 pandemic, has been made more lethal than previous waves through the mixing of powerful synthetic opioids with stimulants such as cocaine and methamphetamine, complicating the treatment of overdoses. Most worrisome is that, unlike in past waves, fatality numbers and rates of increase are pointing up—way up—across all types of communities in the U.S.

“I’m sounding the alarm because, for the first time, there is a convergence and escalation of acceleration rates for every type of rural and urban county,” corresponding author Lori Post, PhD, of Northwestern’s Feinberg School of Medicine, said in a release. “Not only is the death rate from [opioids] at an all-time high, but the acceleration of that death rate signals explosive exponential growth that is even larger than an already historic high.” That, Post said, is “going to mean mass death.”

The authors say policymakers must closely examine available resources and treatment needs in differing communities, particularly because urban outreach and treatment approaches may not work in rural areas. “The only path forward,” Post said, “is to increase awareness to prevent opioid use disorders and to provide medication-assisted treatment that is culturally appropriate and non-stigmatizing” in all communities.   

From The Lancet:
High-Potency Cannabis Linked to Addiction and Psychosis

As marijuana grows in acceptance, it’s also getting stronger. That’s cause for significant concern, according to the results of the first systematic review of research literature on the association of cannabis potency with mental health and addiction. Analyzing 20 studies on the subject, the review’s authors found that the higher the potency of a cannabis product—defined by the concentration of THC, the psychoactive compound that creates a high—the more likely it is to cause psychosis (characterized by a loss of contact with reality, such as hearing voices and having delusions) and cannabis use disorder (CUD).

The authors write, “The use of higher potency cannabis, compared with lower potency cannabis, is associated with an increased risk of psychosis, and this risk is higher in people who use cannabis daily. Higher potency cannabis use has also been associated with an earlier onset of psychosis, more symptoms of psychosis, and an increased risk of relapse. … Use of higher potency cannabis was also consistently associated with an increased risk of CUD, recent cannabis use problems, and severity of cannabis dependence.”

“The findings support recommendations to discourage the use of higher potency cannabis products for low-risk use.“

—study in The Lancet

THC concentrations have been increasing worldwide in recent years, the authors note. In the U.S. and Europe, potency has more than doubled over the past decade, aided by the growing legal market, mostly unregulated, that has driven the development of new products such as concentrated extracts. And while legal marijuana sellers might provide potency information for their products, street weed doesn’t typically come with labels.

“The findings support recommendations to discourage the use of higher potency cannabis products for low-risk use,” the authors write. “This recommendation should be incorporated into education tools and in the management of cannabis use in clinical settings. Policymakers should carefully consider cannabis potency when regulating cannabis in legal markets, such as through limits or taxes based on THC concentration.”

From Biological Psychiatry:
Links Between Sleep Disturbances and Relapse

Yanhua Huang

Could a good night’s sleep be a key to avoiding relapse? A new study from the University of Pittsburgh provides insight into the interplay between rapid eye movement (REM) sleep and drug-seeking behavior—and offers the potential for sleep therapies that reduce relapse risk. “Previously there was a notion that poor sleep may worsen drug craving and relapse,” said lead author Yanhua Huang, PhD, “and we now offer a more granular view on the specific sleep features to be considered for potential biomarkers for predicting relapse.”

Huang and her colleagues trained rats to self-administer cocaine, and then withheld the drug, putting the rodents into withdrawal. When cocaine-associated cues were re-introduced, the rats developed “craving incubation”—an increased drive to take the drug—and showed REM sleep disturbances. Researchers then warmed the rats’ beds to improve their REM sleep continuity, and saw a lessening of the drug-seeking behavior. They also found that activating melanin-concentrating hormone-producing (MCH) neurons, which regulate REM sleep, decreased the craving.

“The results have important implications,” Huang said in a release. “For example, when treating relapse, it is important to pay attention to REM sleep improvement, complementary to current practice focusing on non-REM sleep interventions. Additionally, we have identified the important roles of MCH neurons in this regulation. This will provide the rationale for testing potential drugs in the future.”

Photo: Matt Paul Catalano