America’s Decades-Long Overdose Crisis and the Radical Transformation of the Illicit Drug Market: Implications for Public Health

Jon E. Zibbell, PhD Senior Scientist RTI International Atlanta, GA

August 11, 2021 Faculty Disclosure

I have no financial disclosures to declare.

2 Educational Need/Practice Gap

• Educational Need: Drug-related health outcomes and overdose deaths will continue to occur in Kentucky and throughout the United States based upon the current overdose crisis and illicit drug market. Many of these harms could be avoided if there were more interventions and awareness programs put in place by local, state, and federal organizations.

• Practice Gap: Organizations will have to work together at the local, state, and federal level to effectively address the current overdose crisis in Kentucky and the United States.

3 Objectives

• Learn how the illicit drug market is serving as a social determinant of health with the capacity to influence individual drug preferences, consumption patterns, and health outcomes.

• Understand the pharmacologic effects associated with a changing drug supply and its impact on consumers' drug use behavior, overdose risk, and quality of life.

• Discover how people who use illicit drugs are responding to the rapidly changing illicit drug supply while attempting to navigate volatile and unregulated illicit drug markets more safely.

4 Expected Outcome

Learners will have a better understanding of the current illicit drug market and the implications for public health agencies throughout the United States.

5 Drug Overdose Deaths in the United States 900,000 Drug Overdose Deaths since 1999

4X as many opioid deaths in 2014 as 2000

CDC, MMWR, January 2016 30% Increase from 2019 (81,000)

CDC, National Virus Surveillance System (NVSS) 7 https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm Drugs Involved in OD Deaths, U.S., 2000-2016 Drugs Involved in OD Deaths, U.S., 2000-2016*

4th Wave 1st Wave: Prescription Opioids Illicit Stimulants

2018 Deaths Cocaine=14,666 Meth = 12,092 (90% w/ IMF)

2nd Wave: Heroin 3rd Wave: Illicit Fentanyl

*NYT Interactive, 09/02/2017, National Center for Health Statistics Drug OD Deaths Involving Cocaine, US, 2003-2017

CDC, MMWR, 05.03.19 Drug OD Deaths Involving Psychostimulants, US, 2003-2017 Drug OD Deaths Involving Psychostimulants, US, 2003-2017

CDC, MMWR, 05.03.19 Percentage of Drug OD Deaths Involving 10 Most-Common Combinations of Opioids and Stimulants by Fentanyl, Jan-June 2019

CDC-Vital Signs, MMWR; 09.04.20 Data Source: CDC, SUDORS Sharp Increase in Fentanyl and Fentanyl Analogs, 2015-2017

➢ 2015: 524 Fentanyl Law Enforcement Exhibits ➢ 524 fentanyl ➢ 160 fentanyl analogs (4 distinct analogs) ➢ 8 exhibits of 4-ANPP (fentanyl precursor chemical) ➢ 2016: 877 Fentanyl Law Enforcement Exhibits ➢ 877 fentanyl ➢ 409 fentanyl analogs (15 distinct analogs) ➢ ~60% of substance were seized and reported for the first time

➢ 2017: 1873 Fentanyl Law Enforcement Exhibits ➢ 1873 fentanyl ➢ 952 fentanyl analogs* (17 distinct analogs) ➢ ~117% increase in identification from 2016-2017 ➢ 7 substance seized and identified for the first time ➢ 81 exhibits of 4-ANPP (fentanyl precursor chemical)

*Fentanyl; Furanyl fentanyl; U-47700; ANPP; 4-FiBF; Carfentanil; Acetylfentanyl; Cyclopropylfentanyl; Methoxyacetylfentanyl; Acryl fentanyl; Butyryl fentanyl; 3-Methylfentanyl; THF Fentanyl; U-49900; 12 Benzylfentanyl; U-48800; 2-Thiofuranyl fentanyl B. †Jill Head, Supervisory Chemist, Special Testing and Research Laboratory, DEA. Exhibits seized 01/01/2017 through 12/31/2017. Data retrieved 01/08/2018. Opioid OD Deaths & Law Enforcement Exhibits of Heroin, Fentanyl & Carfentanil Ohio, 2014-2017

❖Fentanyl seizures were significantly associated with OD deaths (x2=3528; P<.001)

❖Every additional fentanyl seizure was associated with 0.58 increase in deaths (95% CI, 0.41-0.74; P<.001)

Zibbell et al., 2020, JAMA Net Op Local Trends in North Carolina

14 Fentanyl Overdose Response and Community Engagement (FORCE) Study

➢ 3-year NIH-funded study ➢ Ethnographic Investigation of the fentanyl risk environment ➢ Illicit drug market drug use behavior health outcomes ➢Ethnographic Methods • Participant observation • In situ conversations • Semi-structured interviews ➢ How did PWID come to recognize the heroin market was changing to IMF? ➢ How did fentanyl impact drug use behavior and health outcomes? ➢ What strategies did PWID employ in response to fentanyl?

15 Respondents identified four, main changes associated with the introduction of fentanyl to the illicit opioid market:

Physical Physical Sensations Appearance

Drug Consumption Preferences Techniques

Duhart Clarke, Kral, & Zibbell, in press FORCE Study Physical Sensations Associated with Fentanyl (compared to heroin)

❖ More rapid onset o The “rush” “Yeah, it’s warm . . . If you o Warmth in face and/or limbs o ‘Pins and needles’ do too much, it’s like a o Dizziness massive rush, and then it’s o Chest tightening/shortness of breath almost like a panic state.” ❖ Shorter duration of effect (male, 34) o Much shorter high (5-30 minutes) “I did this little sprinkle of o no “legs” o Increased injection frequency fentanyl and it just put me o Shorter high but longer time to withdrawal (upwards of 12 hrs) out. And I’ve never nodded out on dope.” (male, 33) ❖ Heavier sedation o Unpredictable and uncontrollable o More akin to bouts of sleepiness than traditional heroin ‘nod’ o Fear of sudden attacks of sleep (e.g., narcolepsy) o Contributing to increased use of cocaine/crack and methamphetamine

Duhart Clarke, Kral, & Zibbell, under review FORCE Study Physical Appearance of Illicit Opioids

Heroin Products ❖ COLOR o Heroin is mostly brown(ish) o Fentanyl can be white, off-white, tan, light brown, and several pastel colors (pink, purple)

❖ TEXTURE o Heroin: chunky; rocky Fentanyl Products o Fentanyl: fine, crystal-like powder

❖ TASTE o Heroin: bitter o Fentanyl: sweet, pharmaceutical

Duhart Clarke, Kral, & Zibbell, 2021, under review FORCE Study Heroin Adulterated with Fentanyl—Massachusetts

Photo: Zibbell Baltimore’s “Scramble” Heroin

Photo: Dan Ciccarone Solo Fentanyl Product (No Heroin)—Massachusetts

Photo: Zibbell “Heroin” product—North Carolina

Photo: Zibbell “Gray Death” in Atlanta

Photo: Zibbell Fentanyl Sold as Pink “Heroin” (North Carolina)

Photo: Zibbell ‘Tar’ Heroin—North Carolina

25 Photo; Zibbell Counterfeit Oxycontin Containing IMF Cocaine and Fentanyl—North Carolina

Photo: Zibbell Methamphetamine—North Carolina Photo: Zibbell Drug Preferences & Combinations

❖ Preferences vary for heroin vs. fentanyl “Heroin’s my drug of o Market availability influences individual drug preferences o Heroin and Fentanyl vs. Fentanyl-only choice. These days the o Drug preference vary by age meth I do to counteract o Fentanyl’s market dominance limits choice of using one or the other the sedation.” (male, 36) ❖ Increased co-use of illicit opioids & stimulants o Response to fentanyl’s heavy sedation “Fentanyl is so strong that o Supply and consumption of illicit stimulants vary by urbanicity if I were just doing it by itself, I couldn’t get my ❖ Increased use of Gabapentin head out of my lap. I don’t o To potentiate opioid effect (non-medical use) want to be just zonked o To treat withdrawal symptoms (medical use) out.” (male, 47) o Increasing evidence of physical dependence akin to benzodiazepines (GABA receptors) o Increased prescribing / increased diversion (low street price evidence of high prevalence)

Duhart Clarke, Kral, & Zibbell, under review FORCE Study From the perspective of people who use illicit stimulants…

➢I think people are using more meth to counteract the fentanyl because it’s going to wake you up more. People are, you know, doing meth now with their heroin to counteract the fentanyl (Female, 35).

➢Heroin’s my drug of choice, so that would be what I would fiend for. These days, the meth I do to counteract the, you know, sedation, and, well, just because it’s there... (Male, 36).

➢Well, I do the meth if I’m sick and can’t find no heroin (Male, 44)

➢I just don’t do this fentanyl by itself. . . . What I’m doing is so strong that if I were just doing it by itself, that I couldn’t probably get my head out of my lap and deal with my day. I don’t want to be just zonked out, ya know, so I do meth to help that (Male, 47).

Duhart Clarke & Zibbell, in press Health Impacts of Changes in Drug Use Behavior

➢ More frequent injections with fentanyl ❑ Increased risk for: • Bacterial Infections (abscesses) • Infectious Disease (HIV/HCV/Endocarditis) • Drug Overdose “The fact that I have to ➢ Changing routes of administration inject more is tearing my o From injecting to insufflation or combinations thereof veins up. It’s harder to ➢ Increased illicit stimulant use find places to shoot; my o Introduction of cardiac risk legs now swell because o Combination of cardiac and respiratory strain when co-using opioids I’m using the veins in my o Development of multiple SUDs in individuals legs.” (female, 44) ➢ OD prevention strategies o Tester shots o Slower plunger pushes o Not using alone o Buying from same seller(s) o Using SSPs o Having naloxone ‘at the ready’

Duhart Clarke, Kral, & Zibbell, under review FORCE Study A Rapidly Changing Risk Environment

➢ Most consumers are unaware of the purity and potency of street-purchased, illicitly-made opioids…and increasingly concerned about IMF-adulterated cocaine and methamphetamine

➢ Continued flow of fentanyl and fentanyl analogs into America’s illicit drug supply has created an unpredictable and lethal risk environment.

➢ Changes in drug use behavior and injection frequency bode ill for OD and infectious disease prevention and SUD treatment

➢ The increasing presence of fentanyl in cocaine and methamphetamine is cause for concern, with supplier-intent and patterns of adulteration broadly misunderstood.

➢ The presence of toxic diluents, adulterants, and ‘cut’ are presenting acute health and overdose risks for PWID ➢ Isotonitazene (Benzimidazole-derived opioids) ➢ Xylazine (clonidine analog; used medically for animal sedation) ➢ Skin ulcers; limb skin lesions; physical deterioration

32 Public Health Challenges: Overdose

➢The combination of product diversity and market unpredictability presents the greatest risk for accidental overdose because it significantly impedes consumers’ ability to recognize and adapt to discernable market fluctuations

➢IMFs are increasingly detected in non-opioid drugs like cocaine and methamphetamine but also counterfeit prescription medications like Xanax, Percocet, and Oxycontin ➢ Fentanyl adulteration of non-opioid drugs has the effect of expanding the fentanyl risk environment to stimulant consumers and pill sniffers, most of whom are opioid naïve (i.e., no tolerance)

➢Systematic, public health testing of illicit drug products is the most viable means for identifying, monitoring, and tracking current or emerging substances. This is particularly relevant given the sharp increase in novel psychoactive substances (NPS) entering the U.S. o Fentanyl Test Strips o Community-based drug checking with portable infrared and spectrometry machines o Near real time surveillance at the local level is urgently needed o Include people who use drugs in community-based research as subject matter experts (SMEs) Beyond OD: Health Outcomes Associated with Injection Drug Use CDC’s 2016 National HIV Vulnerability Assessment

Van Handel et al. Jour of AIDS, 2017 CDC Report on Hepatitis C and Opioid Injection

Zibbell et al., 2018, Am Jour Pub Hth HIV Outbreaks Have Been Occurring among PWID in the U.S.

Provided by Judith Feinberg, MD Injection Drug Use Linked to Increased Incidence of Endocarditis (2010-2015)

J Am Coll Cardiol, 2019 Skin and Soft Tissue Infections CDC, MMWR, June 8, 2016 Substance Use Disorders (SUDs)

➢Polydrug and polypharmacy use is contributing to multiple SUDs in individuals who use drugs, particularly among those using different drug classes ➢People who regularly consume illicit stimulants, illicit opioids, and sedatives can have concurrent SUDs: ▪ Stimulant Use Disorder ▪ Opioid Use Disorder ▪ Benzodiazepine Use Disorder ▪ How do we treat people with multiple SUDs? ▪ What are the implications of growing stimulant use among people currently on OUD treatment?

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Thank you!

Jon E. Zibbell RTI International [email protected]

www.rti.org

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