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Home , Dibutylone, Phenibut

UR Recovery Center of Excellence

Synthetic , Other Substances, and

HRSA Rural Communities Response Program (RCORP) Rural Center of Excellence in Substance Use Disorder October 16, 2020 UR Medicine Recovery Center of Excellence: Service Area

• Partnering with 23 counties in Appalachian KY, OH, NY, and WV • Support and resources for rural communities across the U.S.

2 UR Medicine Recovery Center of Excellence Reducing morbidity, mortality & other harmful effects of substance use disorder (SUD)—particularly from synthetic opioids—by combining CDC evidence-based practices1 with emerging best practices from Appalachian partners to provide new rural-focused resources and hands-on technical assistance

Primary Academic Care MOUD Behavioral Detailing Provision Distribution Telemedicine Health of MOUD Bridge Assessment Program Officer ED & SUD Treatment Ecosystem of Behavioral Provider Recovery Health Partnership Care Manager in Primary Care

3 Synthetic Opioids, Other Substances, and Stimulants

1. Understand synthetic opioids as drivers of opioid overdose mortality

2. Understand the next wave of use

3. Learn about resources for understanding new trends in drug use and novel psychoactive substances (NPS)

4 The Overdose Epidemic

Source: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. (Last reviewed 2020, March 19). Understanding the epidemic.

5 The Overdose Epidemic & COVID-19

• The sense of connection fostered in recovery programs can be an important factor in promoting recovery from . Connection with others becomes difficult when people are advised to stay home, wear masks, and practice physical distancing. Many states have already reported increases in opioid overdose.2

• Overdose Detection Mapping Application Program (ODMAP) is a syndromic surveillance system that provides near real-time suspected overdose data nationally.

• In the time following 3/19/20, 62% of participating counties experienced an increase in overdose submissions with an observed 18% increase in suspected overdose submissions.3

Source for figure: ODMAP. Cited in Washington Post (2020, July 1).

6 Synthetic Opioids as Drivers of Opioid Overdose Deaths

Source: CDC. (Last reviewed 2020, March 19). Opioid data analysis and resources.

7 Synthetic Opioids

 In 2018, 67% of opioid-related deaths involved synthetic opioids.4

 Making naloxone available for opioid overdose reversal is one of the CDC evidence-based practices.5

 “Higher doses of naloxone are needed in the synthetic opioid era.”6

Source for figure: CDC. (Last reviewed 2020, March 19). Opioid data analysis and resources.

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Source for figures: CDC. (Last reviewed 2020, March 19). Synthetic opioid overdose data.

9 Fentanyl Analogs & Novel Synthetic Opioids

• Fentanyl, alfentanil, remifentanil, sufentanyl— used in anesthesia

• Carfentanil—used in large animal anesthesia; the most potent approved opioid drug • 10,000x more potent than • 30-100x more potent than fentanyl

• MANY other fentanyl analogs7,8

• Other novel synthetic opioids • U-47700, U-48800, U-50488, U-51754, W-18

• Isotonitazene—reported in U.S. in 20199

Source for figure: U.S. Drug Enforcement Administration. (2019). National drug threat assessment, p. 11.

10 Stimulant Use: The Next Wave? Overdose Deaths Involving Stimulants Have Increased

Rates of overdose deaths involving synthetic opioids other than , , and psychostimulants with abuse potential (e.g. ) all increased from 2017 to 2018.10 • deaths involving synthetic opioids increased by 10%, from 9.0 per 100,000 in 2017 to 9.9 in 2018. • Deaths involving cocaine more than tripled (from 1.4 to 4.5). • Deaths involving psychostimulants increased nearly five-fold (from 0.8 to 3.9).

Keep in mind that there are no FDA-approved for stimulant use disorder.

11 Opioids Driving Increase in Cocaine-Involved Overdose

• Data suggest that the increase in cocaine-involved overdose deaths from 2015 to 2018 was driven by opioids.

• The increase in cocaine overdose deaths from 2015 to 2018 was mirrored by a corresponding increase in the rate of overdose deaths involving both cocaine and fentanyl.

• During this time period, we also saw a substantial increase in the rate of overdose deaths involving cocaine and fentanyl, without . Cocaine overdose deaths involving fentanyl but no heroin, are a proxy for deaths where fentanyl might have been present in the cocaine product. Source for figure: NDEWS. (2020). New York City SCS Drug Use Patterns & Trends, p. 8.

12 Methamphetamine 2015-2018

• During 2015–2018, an estimated 1.6 million U.S. adults aged ≥18 years, on average, reported past-year methamphetamine use.

• 52.9% had a methamphetamine use disorder.

• 22.3% reported injecting methamphetamine within the past year.

• Co-occurring substance use and mental illness were common among those who used methamphetamine within the past year.11 Source for figure: National Surveys on Drug Use and Health. 2015-2018, using 2010 U.S. Census-based population estimates. Cited in Jones et al. (2020).

13 Methamphetamine & Overdose in the West

Source: NCHS National Vital Statistics System. Cited in AP News (2019, October 25).

14 Removals of Methamphetamine by State in Kilograms, 2018

Source: DEA. (2019). 2019 National drug threat assessment, p. 44.

15 New Trends in Drug Use and Other Novel Psychoactive Substances (NPS)

• New NPS being reported each year, and the market for these substances changes from year to year. • Synthetic (K2, Spice) • Synthetic (“”)

• Drug trends and fads: which ones are a real problem, and which are hype or urban legend?

• How can we follow and make sense of NPS and other drug trends?

16 Resources for Understanding New Trends in Drug Use and Novel Psychoactive Substances (NPS)

• CDC: Center for Disease Control

• SAMHSA: & Mental Health Services Administration—NSDUH, TIPS

• NDEWS: National Drug Early Warning System

• DEA: Drug Enforcement Administration

• NFLIS: National Forensic Laboratory Information System

• ODMAP: Overdose Detection Mapping Application Program

• MTF: the Future

• NIDA: National Institute on Drug Abuse—DrugFacts series

17 NDEWS: National Drug Early Warning System

• Funded by NIDA

• Currently involves Univ. of Florida, NYU & Florida Atlantic University

• Subscribe to NDEWS Weekly Briefings

Source for figure: About NDEWS. (Accessed 2020, October 2.)

18 NDEWS Web Monitoring

“AP-238 is a derivative of Bucinnazine (AP-237, 1- butyryl-4-cinnamyl-piperazine), which has been used clinically in China and is currently listed for purchase on popular web-based drug marketplaces. AP-238 was recognized as a potentially relevant drug keyword through algorithmic monitoring of communities dedicated to drug discussion on the social media platform Reddit. Mentions of ‘AP-238’ in the past 18 months across ~70 drug-oriented subreddit communities were quantified and aggregated by month to obtain a relative metric of discussion over time.” Source: NDEWS Weekly Briefing, Issue 5. (2020, September 25).

19 International Resources

• WHO: World Health Organization

• UNODC: United Nations Office on Drugs and Crime

• EMCDDA: European Monitoring Centre for Drugs and Drug

20 Most Commonly Reported Synthetic Cannabinoids

• National Forensic Laboratory Information System (NFLIS), part of the DEA

• 5F-MDMB-PICA=methyl 2-(1-(5- fluoropentyl)-1H-indole-3- carboxamido)-3,3- dimethylbutanoate

Source: DEA, National Forensic Laboratory Information System. (2020). NFLIS-Drug 2019 Annual Report, p. 18.

21 Synthetic Cannabinoids: Number of Exposure Calls to the American Association of Poison Control Centers for Synthetic Cannabinoids, 2010-2018

Source: DEA. (2019). 2019 National drug threat assessment, p. 94.

22 Synthetic Cathinones

• Stimulant properties, usually sold as pills or capsules, but can also be smoked or snorted

• In 2017, there were 10,693 reports of synthetic cathinones to NFLIS, a 36% increase over the 7,879 reports in 2016.

• The most frequently reported synthetic in 2017 was N-ethylpentylone at 60.49%.

• The second most common synthetic cathinone was dibutylone at 10.9%.

• DEA published a temporary scheduling order controlling N-ethylpentylone. in Schedule I of the Controlled Substances Act (CSA) in August 2018. Dibutylone is a positional isomer of , a Schedule I substance and thus is in Schedule I of the CSA.12

23 Other Drug Use Trends

• Phenibut

•

• Social media “challenges”

24 Phenibut

• β-phenyl-γ-aminobutyric acid (a GABA Number of human exposure cases related to phenibut use reported to poison centers, by year—National Poison Data receptor ) System, , January 2009–December 2019

• Drug developed in in the 1960s for use as an antianxiety with cognitive enhancement properties

• Available online and in health stores

• Adverse consequences of overuse: , respiratory , withdrawal symptoms13 Source for figure: Graves et al. (2020).

25 There are many sides to use

1. Hallucinogen use disorder

2. Spiritual uses for some hallucinogens

3. Research on potential medical use

26 Hallucinogen Use Disorder

DSM-5 divides hallucinogen use into 2 categories:

1. Use Disorder: Phencyclidine and phencyclidine-like compounds (, cyclohexamine, dizocilipine)

2. Other Hallucinogen Use Disorder

Hallucinogen persisting perception disorder

27 Hallucinogens: Spiritual Use

• Psychonaut: a person who uses altered states to gain deeper insight and spiritual experiences

• : psychoactive substances used in a spiritual context

• Psychedelics: , mushrooms, LSD, DMT, PCP, MDMA

• : ketamine, , , salvia,

28 Hallucinogens—Resurgence of Research14

• Ketamine

• Used in anesthesia • Esketamine

• 2019—approved for treatment of severe treatment-resistant depression

• Nasal spray given in a medical office, works immediately

• Targets glutamate receptor • Psilocybin

• Possible treatment for depression

• FDA gave it “breakthrough therapy status” in 2018 to allow for clinical trials for treatment- resistant depression

29 Social Media “Challenges”

• “Benadryl () Challenge”

• FDA issued warning 9/24/20

30 Summary

1. Synthetic opioids are drivers of opioid overdose mortality.

2. Overdoses connected with stimulant use have increased.

3. There are many good resources for understanding new trends in drug use and novel psychoactive substances (NPS).

31 We look forward to your input and questions!

UR Medicine Recovery Center of Excellence Technical Assistance Center • Phone: 1-844-263-8762 (1-844-COE-URMC) • Email: [email protected] Website: recoverycenterofexcellence.org Twitter: @URMC_Recovery

This HRSA RCORP RCOE program is supported by the Health Resources & Services Administration (HRSA) of the US Department of Health & Human Services (HHS) as part of an award totaling $9.1M with 0% financed with non- governmental sources.

The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement by HRSA, HHS or the US Government.

32 References

1. Centers for Disease Control and Prevention (CDC). (2018). Evidence-based strategies for preventing opioid overdose: What’s working in the United States. 2. American Medical Association. (Updated 2020, September 8). Reports of increases in opioid-related overdose and other concerns during COVID pandemic. Advocacy Resource Center Issue Brief. 3. Alter, A., Yeager, C. (2020 June). COVID-19 impact on U.S. national overdose crisis. ODMAP Report. 4. Wilson, N., Kariisa, M., Seth, P., Smith, H., Davis, N.L. (2020). Drug and opioid-involved overdose deaths—United States, 2017–2018. Morbidity and Mortality Weekly Report, 69(11), 290–297. 5. CDC. (2018). 6. Moss, R.B., Carlo, D.J. (2019). Higher doses of naloxone are needed in the synthetic opioid era. Substance Abuse Treatment, Prevention, and Policy, 14(6). 7. U.S. Drug Enforcement Administration (DEA). (2019). 2019 National drug threat assessment. 8. O’Donnell, J.K., Halpin, J., Mattson, C.L., Goldberger, B.A., Gladden, R.M. (2017). Deaths involving fentanyl, fentanyl analogs, and U-47700—10 states, July-December 2016. Morbidity and Mortality Weekly Report, 66(43), 1197–1202. 9. Center for Forensic Science Research and Education. (2019 November). Potent synthetic opioid—isotonitazine—recently identified in Midwestern United States. CFSRE Public Health Alert. 10. Hedegaard, H., Miniño, A.M., Warner, M. (2020). Drug overdose deaths in the United States, 1999–2018. NCHS Data Brief, 356. 11. Jones, C.M., Compton, W.M., Mustaquim, D. (2020). Patterns and characteristics of methamphetamine use among adults—United States, 2015–2018. Morbidity and Mortality Weekly Report, 69(12), 317–323. 12. DEA. (2019), p. 94. 13. Graves J.M., Dilley J., Kubsad, S., Liebelt, E. (2020). Notes from the field: Phenibut exposures reported to poison centers—United States, 2009–2019. Morbidity and Mortality Weekly Report, 69(35), 1227–1228. 14. Garcia-Romeu, A., Kersgaard, B., Addy, P.H. (2016). Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology, 24(4), 229-268.

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