Mind and Body/Opinion

Entering the Fourth Wave of the overdose epidemic

A surge in overdoses is being driven by dangerous contaminants such as “tranq” being added to the illicit drug supply

Photo courtesy of School of Public Health at Brown University

Adina Badea, Claire Macon and Alexandra Collins from Brown University are members of the testRI research team, featured in a story written by Abdullah Shihipar, "Brown researchers aim to save lives by testing illicit drugs for secret, often deadly ingredients."

By Ian Knowles
Posted 8/22/22
A fourth wave of drug overdoses is being driven by a surge in new additives to the illicit drug supply in Rhode Island.
What are the opportunities to restrict the supply of contaminants to the illicit drug supply entering Rhode Island? How can harm reduction activities adopt and adapt to the new contaminants of the illicit drug supply? Does the R.I. Attorney General need to become involved in strategizing new approaches to opioid abatement, focused on increasing use of adulterants in the illicit drug supply? What kinds of shared resources can be developed between other New England states to develop new strategies to respond the Fourth Wave of overdoses?
The next governor will be faced with numerous public health questions, focused on the response by schools and by workplaces to whether or not to re-institute mask mandates, despite the growing number of residents who have been vaccinated and boosted. The news that Gov. McKee tested positive for the coronavirus on Sunday, Aug. 21, will bring a whole new level of scrutiny to government policies regarding how to provide protection to vulnerable populations – including those residents who are immuno-compromised.
The health workforce issues continue to be a problem for the delivery of health care services across the state. In addition, the health industry sector needs to ramp up its testing to be able to identify and recommend treatment for the preponderance of Long COVID in Rhode Island.


PROVIDENCE – We now appear to be caught in the Fourth Wave of the 32nd year of the national opioid overdose epidemic.

• The First Wave began with a marked increase in overdose deaths involving prescription opioids.

• The Second Wave began with rapid increases in overdose deaths involving heroin.

• The state’s response, started in 2012 with the Drug Overdose Prevention and Rescue Coalition, convened by the R.I. Department of Health, and enhanced in 2015 by the Governor’s Overdose Prevention and Intervention Task Force, led to a marginal decrease in the fatality rate from 2017-2019.

However, the fatality rate precipitously increased in 2020 and continues to rise, reaching an all-time high of 436 deaths in 2021.

• This increase coincided with the massive infiltration of fentanyl into the illicit drug supply – the Third Wave.

This Third Wave caught us by surprise. It shouldn’t have. In March 2015, the Drug Enforcement Administration issued a nationwide alert identifying fentanyl as a threat to public health and safety.

No effective response yet
We have not yet developed an effective response to combat the Third Wave.

And now, we have the looming specter of a Fourth Wave - an illicit drug supply that is increasingly contaminated (‘cut’) with a wide range of dangerous constituents. There is sufficient state and national warning of the Fourth Wave.

Our response time cannot be as extended as was our response to fentanyl.

There is important initial Rhode Island data from TestRI, a project and study that includes the analysis of user-supplied illicit street drugs. The study is led by researchers at Brown, one of whom is Alexandra Collins, an assistant professor of epidemiology at Brown’s School of Public Health.

“The drug supply across the U.S. is continuing to change rapidly, and it has left a lot of unknowns [that are often deadly],” Dr. Collins said. “While there are regional differences, supply contents remain very complex and comprised of a range of synthetic and novel psychoactive substances that can really increase overdose risk.”

At least 50 cutting agents found in RI’s illicit drug supply
The initial two months of analysis of samples sold as heroin, fentanyl, cocaine, and methamphetamine has found the presence of at least 50 cutting agents in the Rhode Island supply.

They include substances that the FDA has taken off the market as long ago as 1983, and substances that can potentiate the effect of opioids. [The days when heroin was more safely cut with lactose and quinine and cocaine with lidocaine and benzocaine are long gone].

Some of those more dangerous adulterants that are common in the Rhode Island supply include:

  Xylazine [‘tranq’] is a long-acting veterinary sedative. It is not an opioid.

We have received ample warning about the increase of Xylazine contamination in the illicit opioid market supply. The practice has been common in Philadelphia for about 20 years and is now spreading, particularly to the Northeast.

There was a large spike in the use of Xylazine in Philadelphia in 2019, and a recent Health Alert from the Philadelphia Health Commissioner’s office said that: “In 2021, 91 percent of samples of purported of heroin or fentanyl from Philadelphia also contained xylazine, making it the most common adulterant in the drug supply.”

As fentanyl/heroin have rapid onset and short duration of effect, Xylazine, a powerful veterinary sedative, is being used to extend the effect. It has the potential, by itself, to cause an overdose.

Xylazine is not a scheduled substance. As it is a veterinary drug, there is an ample supply of the diverted pharmaceutical grade substance. And, of course, the main concern is that Naloxone does not have reversal efficacy for Xylazine.

• Phenacetin is an analgesic that was banned by the FDA in 1983. Its chronic use was associated with hemolytic anemia and renal failure. It is a common cutting agent.

• Levamisol is a veterinary drug used to treat parasitic infections in animals, is a prevalent adulterant in cocaine, depletes the white blood cells, and is described having the potential to be highly toxic in humans.

• Alprazolam [Xanax] is a short acting benzodiazepine that can itself cause overdose. The risk is higher when used with opioids [or alcohol].

• Gabapentin is an anticonvulsant that is also commonly used to treat nerve pain. If used with opioids, there is a potentiating sedative effect.

• Ketamine [‘Special K’] is medically used as an anesthetic, for acute pain management, and to treat depression. Its effect is described as similar to PCP and is illicitly used for its hallucinogenic effects. It is known as a ‘date rape’ drug as it induces dissociative anesthesia, a trance-like state, and amnesia.

• Fentanyl analogs are synthetics that illicitly manufactured and pose a significant risk because the effects are not predictable.

For example, para-fluorofentanyl, common in the Rhode Island supply, is less potent than fentanyl, but the risk is high because the therapeutic index is smaller. This means that there is a narrower range between the dose to get effects and the dose that can cause overdose.

There are presently more than 200 Fentanyl analogs or derivatives. The present limitation with the fentanyl test strips that we distribute as a critical harm reduction tool is that are not able to detect every type of fentanyl. [This does not imply that the test strips should not be used. They definitely should be, but in conjunction with other harm reduction strategies such as test dosing, and never using alone.]

Consistent findings
The TestRI findings are consistent with national findings presented at a JCOIN webinar last month. [The Justice Community Opioid Innovation Network is a program within the National Institutes of Health].

Their 2020-2021 information includes:

• In New Hampshire, there are typically 18-22 different compounds in the illicit drug supply that included Acetyl Fentanyl, Gabapentin, Levamisole, and Xylazine.

• In Vermont’s opioid and cocaine samples, 54 percent of the opioid and cocaine samples contained 9 or more constituents.

Since 2018, more than 30 novel opioids have been introduced to the streets. These include ‘Nitazenes’ – a new class of opioids. Nitazene compounds are described as 1.5 to 40 times more potent than Fentanyl.

In April, the Ohio Attorney General issued a warning that Nitazene is being found as a diluent in Fentanyl, Tramadol, Cocaine, Heroin, Methamphetamine, and PCP analogs.

Clear and present dangers
It is clear that the major driver of the state’s increased overdose fatality rate continues to be the contaminated and poisoned illicit drug supply.

It is clear that the trend is not simply continued fentanyl contamination. The changing composition of our street drugs has resulted in a more complex and an even more dangerous product.

One of the main points of the JCOIN findings is that in addition to the increased overdose risks with the new products, there is now the danger of a new set of chronic health problems, due to the side effects of common adulterants such as phenacetin and levamisol.

We have not been able to address the fentanyl contamination. We are not presently positioned to address the effects from a Fourth Wave. We have not directly addressed the drug supply itself.

The strategies and planning, from the initial CDC recommendations over 20 years ago, to the most recent recommendations of our Rhode Island Opioid Settlement Committee, have focused on managing the results of the epidemic.

We seem to continue to assume that the strategies of the failed War on Drugs are sufficient to deal with the illicit drug supply. They are not.

Editor’s Note: Part Two will re-introduce some long-standing but ignored strategies to directly address the drug supply.

Ian Knowles is the program director at RICARES. He is a frequent contributor to ConvergenceRI.

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