2019 - ncmedsoc.org...E-cig puff: 0.5 to 15.4 mg Salt Lake County Health Dept Tested amount of nicotine in 153 vape juices All from local vape / tobacco shops Content of Nicotine varied:

This continuing medical education activity is jointly provided by the North Carolina Society of Pathologists and

Southern Regional Area Health Education Center

NORTH CAROLINA SOCIETY OF PATHOLOGISTS

FRIDAY AND SATURDAY, APRIL 12-13, 2019GRANDOVER RESORT, GREENSBORO, NC

2019 ANNUAL

MEETING

FOCUS ON GASTROINTESTINAL PATHOLOGY

FRIDAY HANDOUTS

1

Update on e-Cigarettes

Drew A. MacGregor, MD, FCCP

Departments of Anesthesiology & Medicine

Wake Forest University School of Medicine

E-cigs: is the smoke clearing?

Disclosures

No financial disclosures at all

Personal: both parents smoked like chimneysMother until she died

Father into mid 60s

Huge exposure to second hand smoke

2

Objectives

Review the mechanics of e-cigs & vapes

Potential benefits of e-cigs

Considerable new data of Risks of e-cigs

Review FDA regulations

Where to go from here

So what are e-cigs & vapes?

History

Cigarettes came to be around 1865Washington Duke in Raleigh rolled and sold to

soldiers at the end of the civil war

First cigarette making machine 1881Could make 120,000 per day !

Tobaccoville, NC factory (Reynolds)Produces 350 Million cigarettes per day

3

MAY I ASSUME….

Tobacco-based cigarettes kill peopleNicotine is just one drug

>20,000 toxins formed by burning tobacco

Over 400,000 people die each year in America due to direct toxic effects from cigarettes

No FDA regulation

Tobacco products largely exempt from any regulation, except in those rare circumstances where manufacturers made explicit health claims

June 22, 2009 – Obama signed into law the “Family Smoking Prevention and Tobacco Control Act” allowing the FDA to regulate manufacturing, marketing and sales

What if we don’t use tobacco?

Water-based flavorings

Superheated vapor

Just Steam instead of smoke

Gotta be healthier right??

Electronic Nicotine Delivery SystemsENDS

4

“Not Appealing to Minors”

E-cigs and vapes ARE marketed to kidsAnd that results in SALES !

MAY I ASSUME….

5

6

A researcher, paid predominately by e-cig and vaping manufacturers, might present misleading or incomplete information?

MAY I ASSUME….

The Fight is On

7

Interesting tidbit

First concept patent by Gilbert in 1963Failed because smoking tobacco was considered

“safe” and more “enjoyable”

E-cig invented in 2003 by Hon Lik – a Beijing pharmacist and 3 ppd smokerFather died of lung cancer

What are PG and VG? In simple terms, PG and VG are the odourless liquids

that are combined with flavour and nicotine to create e-juice. They produce vapour when heated, which allow them to be inhaled. The two fluids have a different consistency to each other, and also have a slightly different taste. They have distinct mouth and throat sensations when vaped. Most modern e-liquid uses a combination of the two fluids, though the ratio can vary dramatically. Some vaping set-ups can only work with a certain level of PG and VG. Choosing the wrong PG/VG ratio can put first-timers off so be careful to choose the right level for your equipment.

Interesting facts….

Nicotine vaporizes at about 290C

Coils in e-cigs & vapes reach 500-800CLots of science:“juice” cooling of coil

Inflow air temp and rate

“dry residue” on coilsTry to minimize

Vehicle for the nicotine “e-juice”Propylene glycol (PG)

Vegetable glycerine (VG)

8

How much nicotine?

Tobacco cigarette puff: 1.54 to 2.60 mg

E-cig puff: 0.5 to 15.4 mg

Salt Lake County Health Dept

Tested amount of nicotine in 153 vape juicesAll from local vape / tobacco shops

Content of Nicotine varied:88% less than listed on label

840% more than listed on label

61% varied by more than 10% of label

Other studies creating regulation that will require testing of “Harmful and Potentially Harmful Constituents” - HPHCs

Are We Ready?

9

In this unregulated, exponentially expanding growth industry, we cannot be certain of what is contained in the e-cigs and vapesAnd, what happens when we burn these

chemicals at very high temperatures

And, what the short and long-term effects of these chemical might be

MAY I ASSUME….

E-cigs might be good

Claim by manufacturer: “e-cigs are between 100 and 1,000 times less dangerous”WHO demands recant – no evidence to support

3,500 users questioned (online questionnaire)79% of people who had quit tobacco cigs felt

they would relapse without e-cigs

Another email study 31% were tobacco free at 6 months

66% reported fewer daily tobacco cigarettes

(n=216)

2009

Lawsuit filed fought FDA’s authority to claim that ENDS meet the definition of a combination drug-device product under the Federal Food, Drug and Cosmetic Act.

FDA’s Division of Pharmaceutical AnalysisDetected diethylene glycol and carcinogens,

including nitrosamines in e-cigs.

July 22, 2009 ENDS regulation begins

10

Comparison to Hook You

Toxic Organic Compounds

Just the First Layer

Are We Learning?

11

Conclusion: Because of the associations between diacetyland bronchiolitis obliterans and other severe respiratory

diseases observed in workers, urgent action is recommended to further evaluate this potentially widespread exposure via flavored e-cigarettes

Finally (2016), the FDA Enters

But what does the FDA do?

Main focus is to prevent e-cigs in kids18 year old age limit initiated

Gives manufacturers 2 years to submit tobacco product applicationAnd the FDA has 1 year to review

The FDA is “exploring (if e-cigs are safer than tobacco cigarettes) with respect to tobacco regulation”

12

What the FDA has NOT DONE

Found evidence that e-cigs help you quit

Found evidence that e-cigs are safer

Determined if regulation will decrease use by those under age 18

Created any list of the potentially toxic compoundsIn the juice itself

Produced by heating the juice

Where to go from here

Wide open researchUnlimited chemicals and “additives”

Toxicity studies ongoing

Variables are almost unlimitedTemp

Solutions

Solvents

Residues

They probably are “SAFER”

Nitrosamines and heavy metals lower0.02 – 10% as high as in tobacco cigarettes

Glycols and other solventsSlightly higher than patches and other NDSs

Known toxicity with ingestion, but don’t know about inhalation toxicity

DiacetylIn 51 of nearly 7,000 flavorings tested

Associated with “popcorn lung”

13

Public Health England 2015

Encourages medical licensing as nicotine replacement therapy, stating, “vaping is 95% safer than smoking” and “can help people to quit smoking and reducing their cigarette consumption, even among those not intending to quit and rejecting other support”

Conclusions: No Doubts

No doubt e-cigs are safer than tobacco

No doubt e-cigs are under-regulatedAmount of nicotine

Toxins in juices

Ability to manipulate juices

Purity of components

Electrical components (batteries/chargers)

No doubt e-cigs are marketed to kids

Conclusions: Little Doubt

Starting e-cigs increases rate of smokingEspecially with kids

Vapes/e-cigs create carcinogenic compounds and have inadequately defined risks

Using e-cigs decreases use of tobacco

Using e-cigs can help people quit smoking

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Conclusions: Unknown

Long-term effects of components:Nicotine

Metals

HPHCsFlavorings

Vegetable glycerin, Propylene glycol

Risks of vapes & e-cigs vs not using at all

Benefits of vapes & e-cigs over cigarettesActual changes in long term consequences???

Even for Beginners

If you want to hear more….

https://www.nbcnews.com/think/video/inside-the-heated-battle-over-juul-creating-teen-addicts-or-saving-lives-1336027715694

1

FORENSIC CONSEQUENCES OF VAPING

SANDRA C. BISHOP-FREEMAN, PH.D. F-ABFT

DEPUTY CHIEF TOXICOLOGIST

NORTH CAROLINA SOCIETY OF PATHOLOGISTS

ANNUAL MEETING APRIL 12TH , 2019

Image from: http://www.vapor-news.com/2016/06/22/understanding-popularity-vaping-culture/

1

OVERVIEW

• VAPING EVOLUTION

• SMOKERS, CELEBRITIES, CHILDREN

• LIQUIDS OTHER THAN NICOTINE

• VAPING INJURIES

• EXPLOSIONS AND BURNS

• VAPING TOXICITY

• CONCENTRATED NICOTINE IN A VIAL

• ACCIDENTAL INGESTIONS

• SUICIDAL INGESTIONS 2

VAPING EVOLUTIONWHO?

Is history Repeating Itself?

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2

CELEBRITIES AND RISE IN VAPING POPULARITY

https://www.youtube.com/watch?v=pJ7_J74GPj0

23 million likes on FB, 10 million Twitter followers

https://www.theverge.com/2016/2/2/10901260/leonardo-dicaprio-vaping-trouble-american-lung-association

October 2010Actress Katherine Heigl is arguably the most responsible for bringing vaping into the public eye by openly vaping on live television during an interview with David Letterman. She claims the vape has really helped her get off of cigarettes.

February 2016

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• AS THE DOGS SNIFFED THE LUGGAGE AND THE BUS, THE AGENTS “WENT THROUGH EVERY

LITTLE THING,” ETHERIDGE RECALLS. EVENTUALLY, ONE DOG POKED ITS NOSE INTO HER BAG.

“I HAD SOME CANNABIS OIL, ACTUALLY A VAPE PEN, IN MY TOILETRY CASE AND THEY

FOUND IT. THEY DIDN’T GET MUCH, IT WAS A SMALL AMOUNT.”

https://variety.com/2017/music/news/melissa-etheridge-arrest-marijuana-canada-border-vape-pen-1202591722/

5

• COUGH, DIFFICULTY BREATHING THAT WAS WORSENING BY THE MINUTE

• SUDDEN STABBING PAINS IN THE CHEST WITH EVERY INHALATION AND EXHALATION.

• SHE NEEDED TUBES INSERTED ON BOTH SIDES OF HER CHEST TO DRAIN FLUID FROM HER

LUNGS.

• HER DOCTORS DIAGNOSED HYPERSENSITIVITY PNEUMONITIS, SOMETIMES CALLED

WET LUNG, AN INFLAMMATION OF THE LUNGS DUE TO AN ALLERGIC REACTION TO

CHEMICALS OR DUST

https://www.cnn.com/2018/05/17/health/case-study-teen-vaping-wet-lung/index.html

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3

• “KIDS WERE CONGREGATING IN THE BATHROOMS, SO WE’D HAVE KIDS IN A

STALL, 5 OR 6 KIDS AT A TIME IN A STALL.

• HE LOCKED CERTAIN BATHROOMS AND CAME UP WITH SIGN IN AND SIGN

OUT SHEETS AS A WAY FOR HIM TO DETECT A PATTERN ON WHEN STUDENTS

WOULD GO VAPING.

• “I WOULD HATE TO LOSE A GENERATION OF KIDS WHILE WE’RE WAITING

FOR THE RESEARCH."

https://fox61.com/2018/09/24/high-school-principal-develops-strategy-to-tackle-students-vaping-in-school/

7

OCME CASE- ASTHMA

8

VAPING EVOLUTIONWHAT?

Flavored Water, Flavored nicotine, CBD OIL, “CBD OIL” (A.K.A Synthetic Cannabinods), THC OILs (More popular than we think!)

Other Substances…….Alcohol, Vitamins, Illicit drugs……FENTANYL!!9

4

VAPING SHOPS: GREENSBORO, NC

10

IS NON-NICOTINE E-LIQUID JUST “WATER VAPOR”?

• NO!

• NICOTINE FREE E-LIQUID EXISTS

• BUT…….

• CONTAINS CARBONYLS, VOCS, AND METALS

AND OVERALL HAVE FEWER CHEMICALS THAN CONVENTIONAL CIGARETTES.

• HOWEVER…….

• THREE OF THE FLAVORING CHEMICALS — CINNAMALDEHYDE, O-VANILLIN AND PENTANEDIONE — ALL CAUSED CYTOTOXICITY OR CELL DEATH.

• IT'S YET TO BE DECIDED IF VAPING IS SAFE, OR IF CERTAIN FLAVORS ARE DEFINITELY MORE DANGEROUS THAN OTHERS. BUT YOU SHOULD STILL PROCEED WITH CAUTION.

https://www.bustle.com/p/these-are-the-7-most-toxic-vaping-flavors-according-to-science-9432319

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WHO IS THE REAL TARGET?

THE FDA AND THE FEDERAL TRADE COMMISSION WENT

AFTER 13 MAKERS/SELLERS OF LIQUIDS THAT LOOK LIKE

JUICE BOXES, CANDY, OR COOKIES.

Coffee Candy Cola Fruit Belgian waffle

https://www.washingtonexaminer.com/policy/healthcare/fda-warns-companies-about-enticing-kids-with-e-cigarette-flavors

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5

SAFE TO EAT, SAFE TO INHALE???

• FDA REGULATES FOOD ADDITIVES BASED ON:

• HISTORICAL USE, CARCINOGENICITY, ORAL TOXICITY IN ANIMALS

• GENERALLY RECOGNIZED AS SAFE (GRAS) IS A DESIGNATION

THAT A CHEMICAL OR SUBSTANCE ADDED TO FOOD IS

CONSIDERED SAFE

• WORST CASE: MICROWAVE POPCORN BUTTER

FLAVORING DIACETYL

• SAFE TO EAT, DANGEROUS TO LUNGS

• BUT THIS IS ALSO FOUND IN TRADITIONAL CIGARETTES……..WE

STILL NEED MORE RESEARCH13

Megan Cartwright, Ph.D. Student in ToxicologyEmail: [email protected]

ADVANCED VAPING (FROM THE EXPERTS)

• THE VAST MAJORITY OF VAPERS USE E-LIQUIDS, BUT OTHER COMMON

MATERIALS INCLUDE WAXY CONCENTRATES AND DRY HERBS.

• DIFFERENT VAPORIZERS SUPPORT THE VAPING OF DIFFERENT MATERIALS.

• E-LIQUIDS VAPORIZERS HAVE A CARTRIDGE OR TANK

• DRY HERB VAPORIZER WILL HAVE A HEATING CHAMBER

Image from: https://vapingdaily.com/what-is-vaping/

14

MORE THAN JUST NICOTINE

15

6

VAPING ALCOHOL

• WHEN YOU DRINK ALCOHOL, IT IS

ABSORBED THROUGH THE BODY OVER-TIME

• WHEN YOU VAPE ALCOHOL, IT GOES

DIRECTLY INTO YOUR BLOODSTREAM

• RAPID RUSH OF ALCOHOL TO THE BRAIN

16

WHAT ELSE EXACTLY IS BEING VAPED?

• VITAMINS• "VAPING VITAMINS IS AN ALTERNATIVE METHOD OF

SUPPLEMENTING VITAMINS," THE COMPANY SAYS ON ITS WEBSITE.

"WE RECOMMEND IT TO THOSE WHO ARE LOOKING FOR A NEW

WAY OUTSIDE OF TAKING VITAMIN PILLS."

• VITACIG® A,B,C,E &COQ10 (UBIDACENONE)

• HERBS• ENERGY BOOST, LOVE, RELAX

• WORMWOOD, DAMINA, PASSIONFLOWER, CARUABA BARK, CATNIP,

MACA ROOT, POPPY

• CIALIS• 20 MG/ML OF E-LIQUID

• BY SMOKING, IMPROVE YOUR SEXUAL CAPACITY!

17

DABBING: VAPING THC

• CONCENTRATED DOSES OF CANNABIS MADE BY EXTRACTING CHEMICALS FROM THE PLANT, USING SOLVENTS LIKE BUTANE TO HEAT IT UP. YOU ARE LEFT WITH A WAXY, HONEY-LOOKING PASTE THAT YOU PUT INTO AN E-CIGARETTE, WHICH THEN PRODUCES SMOKE THAT YOU INHALE.

• DAB DOSES ARE EXTREMELY HIGH, BETWEEN 40% AND 80% THC.

THIS IS DEFINITELY NOT THE ROUTE TO GO FOR A FIRST TIME USER!!!

• DABS, ALSO KNOWN AS BUTANE HASH OIL (BHO) — WHICH ARE SOMETIMES CALLED "BUDDER," "HONEYCOMB" OR "EARWAX"

• DUE TO THE USE OF BUTANE IN THE CREATION OF THE DAB WHICH IS WELL DOCUMENTED AS OFTEN CAUSING EXPLOSIONS, THERE IS A REAL RISK HERE OF HARMING YOURSELF.

https://herb.co/marijuana/news/dabbing-vaping-edibles-best

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7

WHAT DO DABBING TOOLS LOOK LIKE?

Shatter Image: https://www.cannabis.info/en/blog/what-is-dabbing-is-it-good-or-bad

Cannabis Shatter is a type of BHO with a glass-like texture that usually breaks or Shatters when it’s dropped (as the name suggests).

Tools Image: https://www.leafly.com/news/cannabis-101/how-to-dab-cannabis-concentrates

1. Extract 2. Water Pipe3. Nail 4. Dome5. Torch 6. Dabber

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https://www.nytimes.com/2015/01/13/health/with-the-e-joint-the-smoke-clears-.html

Image from: https://cannabis.net/dispensaries/monterey-bay-alternative-medicine/menu/juju-joints-disposable-vape-pen-500-mg

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• FOR A RESEARCH LETTER PUBLISHED IN JAMA PEDIATRICS ON MONDAY, RESEARCHERS

ANALYZED 2016 NATIONAL YOUTH TOBACCO SURVEY RESULTS OF MORE THAN 20,000

STUDENTS. THEY FOUND THAT 8.9 PERCENT OF THOSE SURVEYED SAID THEY HAD SMOKED

CANNABIS IN E-CIGARETTES. MALE STUDENTS WERE MORE LIKELY TO REPORT CANNABIS USE.

• AMONG THOSE WHO REPORTED VAPING, NEARLY 1 IN 3 HIGH SCHOOL STUDENTS AND

ABOUT 1 IN 4 MIDDLE SCHOOL STUDENTS REPORTED USING CANNABIS IN THE DEVICES.

https://www.usatoday.com/story/news/nation-now/2018/09/18/students-vaping-marijuana-cannabis-jama-study/1343495002/

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https://www.deseretnews.com/article/900040111/park-city-9th-grader-hospitalized-after-smoking-thc-from-vape-pen-school-officials-say.html

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• HEALTH OFFICIALS ARE INVESTIGATING MORE THAN 30 REPORTS SINCE DECEMBER OF ER PATIENTS WITH SERIOUS SYMPTOMS INCLUDING ALTERED MENTAL STATES, HALLUCINATIONS, SEIZURES, LOSS OF CONSCIOUSNESS AND RAPID HEARTBEATS.

• “PEOPLE SHOULD BE AWARE THAT PRODUCTS LABELED AS CBD OIL MIGHT CONTAIN OTHER SUBSTANCES,” SAID STATE HEALTH DIRECTOR BETSEY TILSON, MD, MPH. “THE SYMPTOMS WE ARE SEEING THAT RESULT IN THESE EMERGENCY DEPARTMENT VISITS ARE NOT TYPICAL FOR CBD OIL USE.”

• NO DEATHS HAVE BEEN REPORTED, AND HEALTH OFFICIALS HAVE NOT LINKED A SPECIFIC BRAND OR SOURCE WITH THE ER VISITS.

• SIMILAR CBD OIL-RELATED SYMPTOMS HAVE BEEN REPORTED AT MEDICAL FACILITIES AT FORT BRAGG AND CAMP LEJEUNE, WHERE MILITARY HEALTH AUTHORITIES HAVE ALSO RAISED CONCERNS.

http://www.charlotteobserver.com/news/local/article203727924.html

23

http://www.wbtv.com/story/37776246/recent-cases-involving-vaping-of-synthetic-marijuana-address-dangers/

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9

• TRADITIONAL SMOKED SPICE/K2 LOOKS LIKE NATURAL MARIJUANA.

• THE ACTIVE INGREDIENTS ARE SPRAYED ONTO THE PLANT MATERIAL.

• THE MOST POPULAR BRANDS SOLD TODAY ARE SPICE AND K2, BUT SPICE

IS SOLD UNDER MORE THAN 600 NAMES INCLUDING MOJO, SCOOBY SNAX, BLACK

MAMBA AND ANNIHILATION.

• VAPING THE LIQUID FORM OF SYNTHETIC MARIJUANA IS A FAST-RISING TREND,

REPLACING SMOKING.

INTRODUCTION TO SPICE/K2

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• SPICE AND K2 MAY CONTAIN ONE OF MANY SYNTHETIC

CANNABINOIDS (SC) SUCH AS JWH-018, JWH-073, JWH-200,

AM-2201 UR-144, XLR-11, AKB4, CANNABICYCLOHEXANOL

AND AB-CHMINACA, AB-PINACA OR AB-FUBINACA.

• SC HAPPENS TO FIT INTO THE SAME RECEPTORS THAT THC

LATCHES ONTO IN THE BRAIN, HOWEVER, SOME ARE 100X

STRONGER THAN THC.

• NEGATIVE SIDE EFFECTS INCLUDE HIGH BLOOD PRESSURE,

BLURRED VISION, HEART ATTACK, VOMITING, SEIZURES,

HALLUCINATIONS, AND SEVERE ANXIETY AND PARANOIA.

DEATHS HAVE ALSO BEEN ASSOCIATED WITH USE OF THE

DRUG.

INTRODUCTION TO SPICE/K2

26

• BRODIFACOUM (BDF) IS AN ANTICOAGULANT FOUND IN RODENT BAIT AND IS

COMMONLY USED AS A HOUSEHOLD RODENTICIDE.

• IT IS KNOWN AS A SUPERWARFARIN, WITH UP TO 100 TIMES THE POTENCY OF WARFARIN

AND A HALF-LIFE OF AT LEAST 16 DAYS COMPARED WITH 40 HOURS IN WARFARIN.

• AS OF APRIL 27, 2018, THE ILLINOIS DEPARTMENT OF PUBLIC HEALTH (IDPH) HAS RECEIVED

REPORTS OF 156 CASES, INCLUDING 4 DEATHS, DUE TO BDF COAGULOPATHY LINKED TO K2.

• LABORATORY TESTING CONFIRMED BRODIFACOUM EXPOSURE (LACING OF RECREATIONAL

DRUGS) IN AT LEAST 60 OF THESE PATIENTS.

https://emergency.cdc.gov/han/han00410.asp

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10

https://www.ncdhhs.gov/news/press-releases/dhhs-carolinas-poison-center-investigating-case-severe-bleeding-potentially

Brodifacoum is a highly lethal 4-hydroxycoumarin vitamin K antagonist anticoagulant poison. In recent years, it has become one of the world's most widely used pesticides. It is typically used as a rodenticide.

28

• NOT GENERALLY ASSOCIATED WITH VAPING, BUT IT IS CONNECTED TO SYNTHETIC

CANNABINOIDS

• THE NC OCME TOXICOLOGY LABORATORY HAS A QUALITATIVE METHOD FOR THE

DETERMINATION OF BRODIFACOUM, BROMADIOLONE, DIFENACOUM, AND WARFARIN.

• AT THIS TIME, ONLY CASES CONSISTENT WITH COAGULOPATHY SHOULD BE

INVESTIGATED FOR RODENTICIDES.

NC OCME AND “SPICE OF DEATH”

Image from: https://www.rehabcenter.net/fake-marijuana-rat-poison/

29

• THIS STUDY CHARACTERIZED COMMERCIALLY AVAILABLE E-LIQUIDS WITH NO ADVERTISED CONTENT.

• DESIGNER DRUGS SUCH AS MDMB-FUBINACA CAN BE FOUND IN COMMERCIALLY AVAILABLE ELECTRONIC CIGARETTE PRODUCTS.

• THIS DRUG WAS DEMONSTRATED TO AEROSOLIZE AND, THEREFORE, HAS THE POTENTIAL FOR RESPIRATORY DELIVERY.

30

11

RECENT 5F-ADB DETECTION IN MULTIPLE U.S. MILITARY SPECIMENS BY THE DOD NEW AND EMERGING DRUGS SURVEILLANCE PROGRAM

• RELATED TO THE PRODUCT BLACK MAGIC SMOKE

• THE SPECIAL FORENSIC TOXICOLOGY DRUG TESTING LABORATORY

DETECTED 28 URINE SPECIMENS THAT CONTAINED 5F-ADB METABOLITE

• WITH A 2.8% PREVALENCE RATE FOR A SPECIFIC LOCATION. NO

OTHER SYNTHETIC CANNABINOIDS WERE PRESENT

SOFT Meeting 2018 MN S50 by Lynn M. Wagner AFME, Dover AFB, DE

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5F-ADB VS. THC

• ‘super-strength’ synthetic cannabinoids

• K2, Spice, and similar drugs are often referred to as fake marijuana, which can entice people to try it. But what people don’t realize is that these synthetic products contain chemicals that are much more potent than THC

• 5F-AMB and 5F-ADB are 90 and 300 times, respectively, more potent than THC as full agonists for the human CB1 receptor

• Cases present with psychomotor agitation, confusion, anxiety and psychosis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486620/pdf/11419_2017_Article_369.pdf

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• FROM A PUBLIC HEALTH PERSPECTIVE, CONCERNS OF LACK OF DATA ON RISKS RELATED TO VAPING RECREATIONAL DRUGS WARRANT ATTENTION

• A CULTURE OF VAPING IS EMERGING THAT INCLUDES THE PERCEIVED POSITIVE ATTRIBUTES OF VAPING CANNABIS AND THE MARKETING OF VAPING DEVICES NOT JUST FOR NICOTINE USE.

• THIS NOVEL CULTURE COULD INCREASE THE PREVALENCE OF USE; DECREASE THE AGE OFONSET OF USE AND LEAD TO MORE PROBLEMATIC USE OF CANNABIS AND OTHER RECREATIONAL DRUGS VIA VAPING DEVICES.

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12

• UNKNOWN POSTMORTEM

TOXICOLOGY RESULTS

• BUT, THIS IS A SCARY POSSIBILITY!

https://nypost.com/2017/07/03/man-dies-after-vaping-liquid-fentanyl/34

• MY PREDICTION:

WE WILL BE SEEING

MORE AND MORE AND

MORE OF THIS

https://www.mlive.com/news/flint/2019/02/4-lapeer-students-hospitalized-after-ingesting-unknown-substance-in-vape-pen.html

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VAPING EXPLOSIONS AND BURNS

36

13

https://www.fda.gov/TobaccoProducts/Labeling/ProductsIngredientsComponents/ucm539362.htm

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EXAMPLES OF VAPING INJURIES IN THE NEWS

• IN 2015, A 29-YEAR-OLD COLORADO MAN WAS SMOKING AN E-CIGARETTE WHEN IT

EXPLODED IN FACE, BREAKING HIS NECK, SHATTERING HIS TEETH, FRACTURING HIS

FACE, AND BURNING HIS MOUTH, ACCORDING TO CBS NEWS.

• A 15-YEAR-OLD CALIFORNIA BOY LOST A HALF DOZEN TEETH IN 2016 WHEN HIS

ELECTRONIC CIGARETTE EXPLODED IN HIS MOUTH, ACCORDING TO THE PRESS

DEMOCRAT. CBS NEWS REPORTED IN FEBRUARY THAT A LITHIUM ION BATTERY USED TO

POWER A VAPE PEN WAS BLAMED FOR A JAN. 30 FIRE AT DENVER INTERNATIONAL

AIRPORT.

https://www.cbsnews.com/news/man-seriously-injured-by-e-cigarette-explosion/

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INJURIES FROM EXPLOSIONS

Explosions in pants pockets

Explosions in face/mouth39

14

40

https://www.wyff4.com/article/vape-explodes-leaving-man-with-serious-facial-injuries-officials-say/22566760

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https://www.cbs17.com/news/north-carolina-news/fight-over-vaping-device-at-nc-party-triggers-stabbing-teen-seriously-wounded/1574392684

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15

https://www.nytimes.com/2018/05/16/us/man-killed-vape-explosion.html

Image: https://www.youtube.com/watch?v=h1D4jIsB_T0

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SUMMARY OF FORENSIC EVIDENCE

VIALS OF E-LIQUIDS AND/OR MYSTERIOUS AROMAE-CIGARETTES OFTEN DON'T SMELL BAD; HOWEVER, MOST E-LIQUIDS HAVE FLAVORS IN THEM THAT USUALLY SMELL LIKE CANDY, MINT, VANILLA, FRUIT, ETC.

UNFAMILIAR HANDHELD GADGETSE-CIGARETTES COME IN VARIOUS SHAPES. THE MOST COMMON ONES RESEMBLE A PEN. IF YOU COME ACROSS A PEN THAT ISN'T A PEN OR OTHER UNFAMILIAR GADGET, BE AWARE THAT IT COULD BE A VAPORIZER. LOOK FOR HOLES ON EACH END.

BATTERIES AND CHARGERSVAPERS NEED TO CHARGE THEIR VAPORIZERS ON A REGULAR BASIS. WHILE SOME E-CIGS CAN BE CHARGED WITH A USB CABLE, MOST OF THE POWERFUL E-CIGS LIKE BOX MODS SUPPORT 18650 BATTERIES. IF YOU SEE UNFAMILIAR BATTERIES, TAKE A LOOK AROUND AND YOU MIGHT FIND A VAPING DEVICE.

METALLIC WIRES AND COTTON WICKSIF YOU FIND ORGANIC COTTON, EMPTY PLASTIC VIALS OR THIN METALLIC COILS, THIS IS YET ANOTHER RED FLAG.

DISCARDED ATOMIZERSTHE ATOMIZERS ARE A VITAL PART OF E-CIGS AS THEY TURN E-JUICE INTO VAPOR. HOWEVER, AFTER A WHILE USUALLY BURN OUT. IF YOU COME ACROSS A DISCARDED ATOMIZER IN THE TRASH CAN, IT'S A PRETTY CLEAR INDICATION OF VAPING.

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VAPING INGESTIONS AND TOXICITY

45

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NICOTINE HISTORY

• FOR CENTURIES, GARDENERS HAVE USED HOME-MADE MIXTURES OF TOBACCO AND

WATER AS A NATURAL PESTICIDE TO KILL INSECT PESTS

• THE SMOKING OF PIPES AND CIGARS SPREAD QUICKLY THROUGHOUT THE 1600S.

• IN 1828, WILHELM HEINRICH POSSELT, A DOCTOR, AND KARL LUDWIG REINMANN, A

CHEMIST, BOTH FROM GERMANY, FIRST ISOLATED NICOTINE FROM THE TOBACCO

PLANT AND IDENTIFIED IT AS A POISON.

• NICOTINE IS ISOLATED FROM THE TOBACCO PLANT NICOTIANA TABACUM AND

SUSTAINS TOBACCO ADDITION

• THE TOBACCO INDUSTRY EXPLODED IN 1880 WHEN A MACHINE WAS FIRST

PATENTED TO MASS-PRODUCE PAPER CIGARETTES.

Images from: https://www.medicalnewstoday.com/articles/240820.php

Nicotiana tabacum comes from the nightshade family

46

NICOTINE ADME

• NICOTINE CAN BE RAPIDLY ABSORBED THROUGH THE SKIN, ALVEOLI, OR OROPHARYNGEAL MUCOSA,

AS WELL AS THROUGH THE GASTROINTESTINAL MUCOSA AFTER INHALATION, INGESTION, OR DERMAL

CONTACT

• UPON ENTERING THE ARTERIAL CIRCULATION, NICOTINE QUICKLY MOVES TO THE BRAIN AND IS

SUBSEQUENTLY TRANSFORMED INTO TO A NUMBER OF METABOLITES.

• QUANTITATIVELY, THE MOST IMPORTANT METABOLITE OF NICOTINE IS COTININE. IN HUMANS,

ABOUT 70–80% OF NICOTINE IS CONVERTED TO COTININE.

NC OCME TOX CAN DETECT BOTH NICOTINE AND COTININE IN SCREENING METHODS47

NICOTINE TOXICITY

• LOW NICOTINE DOSES STIMULATE THE NEURAL AND CARDIOVASCULAR SYSTEMS

• AWAKENING EFFECT WITH INCREASED HEART RATE AND BLOOD PRESSURE

• HIGH DOSES SUPPRESS THE VITAL SYSTEMS

• BURNING SENSATION IN THE MOUTH AND THROAT, NAUSEA, VOMITING, ABDOMINAL PAIN,

HEADACHE, CONFUSION, DIZZINESS, WEAKNESS, MIOSIS, URINATION AND DEFECATION.

• INGESTION OF HIGHER DOSES LEADS TO ARRHYTHMIAS, BRADYCARDIA, CONVULSIONS,

COMA, RESPIRATORY FAILURE, RAPID PROGRESSION TO HYPOTENSION, AND DEATH

• A LETHAL DOSE OF NICOTINE HAS BEEN ESTIMATED TO BE AS LESS AS 40MG IN ADULTS AND 1

MG/KG IN CHILDREN. HOWEVER, IT IS RECOMMENDED THAT CHILDREN WHO HAVE INGESTED

0.2 MG/KG OR MORE OF NICOTINE BE SEEN BY A PROFESSIONAL48

17

• ELI JAMES "EJ" HOTALING, WHO WOULD HAVE TURNED 2 ON MAY 17, IS THE FIRST CHILD IN THE COUNTRY TO DIE FROM ACCIDENTALLY SWALLOWING THE TOXIC INGREDIENT IN ELECTRONIC CIGARETTES, ACCORDING TO THE AMERICAN ACADEMY OF PEDIATRICS.

• UNCAPPED BOTTLE CONTAINING A NICOTINE SOLUTION ON A LOW TABLE IN THE DINING ROOM

• IT WAS LABELLED HEARTLAND VAPES, 100 MILLIGRAMS, POLICE SAID. THE COMPANY, BASED OUT OF OKLAHOMA CITY, IS A DISTRIBUTOR AND MANUFACTURER OFELIQUIDS AND INGREDIENTS. ON THE COMPANY'S WEBSITE, CHILDPROOF CAPS FOR BROWN, GLASS BOTTLES LIKE THE ONE DESCRIBED BY POLICE ARE AVAILABLE FOR SALE SEPARATELY FROM THE INGREDIENTS AND CONTAINERS.

https://www.timesunion.com/news/article/Case-closed-in-Fort-Plain-liquid-nicotine-death-6195411.php

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• 24-YR-OLD F, UNRESPONSIVE, PULSELESS

• SUICIDE NOTE

• PARTIALLY INGESTED BOTTLE OF WHISKEY, 2 EMPTY 15ML VIALS OF CONCENTRATED NICOTINE (100 MG/ML, ALL PRESCRIPTION MEDS HAD APPROPRIATE PILL COUNTS

• BP 74/53 PULSE 106 BPM, RESPIRATION 14 BREATHS/MINUTE, PUPILS FIXED AND DILATED

• MYOCLONIC JERKING, ABSENCE OF CORNEAL, GAG, AND COUGH REFLEXES

• TOX: PLASMA NICOTINE AND COTININE > 1,000 NG/ML

• E-LIQUID BOTTLES WERE NOT TESTED

• DIED 3 DAYS POST-INGESTION

50

• 32-YEAR-OLD MALE ADMITTED TO THE HOSPITAL FOLLOWING CARDIAC ARREST

• INGESTED NICOTINE-CONTAINING E-LIQUID WHILE UNDER THE INFLUENCE OF ALCOHOL.

• HE WAS DESCRIBED AS AGITATED, AND COLLAPSED WITHIN 1 H OF INGESTION OF THE NICOTINE LIQUID.

• HE WAS SHOWN TO HAVE SUFFERED BRAIN HYPOXIA, ATTRIBUTED TO PROLONGED CARDIOPULMONARY RESUSCITATION.

• DRANK APPROXIMATELY 20ML FROM A BOTTLE CONTAINING 72MG/ML NICOTINE LIQUID, LEADING TO A TOTAL INGESTION OF 1440 MG

• A SERUM SAMPLE TAKEN 24 H AFTER COLLAPSE CONTAINED NICOTINE AT A CONCENTRATION OF 1600 NG/ML OF NICOTINE.

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18

• NO REGULATIONS REGARDING CHILDPROOF BOTTLING AND PACKAGING OR WARNING SIGNS ON LIQUID NICOTINE PRODUCTS

• PARENTS OF CHILD PROVIDED 5ML OF LIQUID NICOTINE MISTAKING IT FOR COLD MEDICINE (CONCENTRATION: 10 MG/ML)

• WHEN THE EMERGENCY MEDICAL TECHNICIANS ARRIVED, SHE WAS FOUND TO HAVE PULSELESS ELECTRICAL ACTIVITY. SPONTANEOUS CIRCULATION WAS RESTORED AFTER APPROXIMATELY 40 MINUTES OF CARDIOPULMONARY RESUSCITATION.

• THE COTININE LEVEL IN HER URINE WAS 1,716 NG/ML.

• DESPITE INTENSIVE SUPPORTIVE CARE, SEVERE ANOXIC BRAIN INJURY WAS FOUND ON COMPUTED TOMOGRAPHY AND THE CHILD ULTIMATELY DIED.

• THIS FATALITY HIGHLIGHTS THE NEED FOR PUBLIC HEALTH EFFORTS TO MINIMIZE SUCH ACCIDENTS.52

PUBLIC HEALTH RISK OR BENEFIT?

• "WE ARE FORTUNATE TO KNOW THE RISKS OF CIGARETTE

SMOKING, BASED ON DECADES OF EPIDEMIOLOGICAL RESEARCH."

WARNER SAID. "IT COULD TAKE YEARS BEFORE WE KNOW THE

FULL HEALTH IMPACT OF VAPING, IF INDEED WE EVER WILL.

https://www.wxyz.com/news/vaping-has-potential-to-benefit-public-health-university-of-michigan-study-says

53

Image: http://www.vividsmoke.com/

The ONLY thing that belongs in your lungs is fresh clean air. Everything else is going to have some negative effects on your lungs and your overall health. Try to get healthy!

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1

Postmortem Forensic Toxicology:An Update on North Carolina’s Opioid Crisis prescription opioids to heroin to fentanyl

Sandra C. Bishop‐Freeman, Ph.D. F‐ABFTNC OCME Deputy Chief Toxicologist

NORTH CAROLINA SOCIETY OF PATHOLOGISTSAnnual Meeting April 12th , 2019

1

Training Outline

1. Office of the Chief Medical Examiner Toxicology Laboratory

2. Dramatic Increases in overdose deaths with heroin and non‐pharmaceutical grade fentanyl

3. Upward trends for stimulants used in combination with illicit opioids 

4. Emerging illicit drug combinations: unknown powders, counterfeit mimic tablets 

These views are my own and do not reflect the views of the State of North Carolina or any other agency I have worked for in the past!

‐Sandra C. Bishop‐Freeman, Ph.D. F‐ABFT

2

Introduction

• The opioid epidemic explosion is a public health crisis.

• This presentation is filled with facts from the state of North Carolina.

• The certification of opioid deaths has risen significantly in the past few years.

http://www.cnn.com/2016/05/10/health/fentanyl‐new‐heroin‐deadlier/index.html

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2

Image: https://carolinapublicpress.org/wp‐content/uploads/2014/12/Screen‐Shot‐2014‐12‐01‐at‐8.38.42‐AM.png

http://www.pewtrusts.org/en/research‐and‐analysis/blogs/stateline/2017/07/06/opioid‐overdose‐deaths‐swamp‐medical‐examiners

http://wncn.com/2017/11/15/opioid‐epidemic‐taxes‐nc‐medical‐examiners‐2/

4

When does OCME get involved? 

• “Upon the death of any person resulting from violence, poisoning, accident, suicide, or homicide; occurring suddenly when the deceased had been in apparent good health or when unattended by a physician; occurring in a jail, prison, correctional institute, or in police custody; or occurring under any suspicious, unusual or unnatural circumstance, the medical examiner of the county in which the deceased is found shall be notified…” N.C. General Statutes § 130A‐383

5

1. North Carolina Office of the Chief Medical Examiner 

Forensic Toxicology Laboratory

6

3

Organizational Chart

Chief Toxicologist Vacant

Evidence Tech Valerie Durham

Forensic Chemist II (3)

(3)

Supervisor Erin Hensel

Chem Tech III (2)

QA/QC ChemistMarc Feaster

Forensic Chemist I (4)

Deputy Chief Toxicologist Sandra Bishop, Ph.D. F-ABFTToxicologist

Justin Brower, Ph.D.

Toxicology for the entire state of North Carolina: 16.5 lab employees

We are an American Board of Forensic Toxicology (ABFT) accredited laboratory

Admin Kara Palmer

Drug & alcohol case certification

Alcohol certification

OPIS GrantChem II CDC

OPIS GrantChem I CDC

Part-time Admin Vacant

7

8

When does Toxicology get involved?Most Common Types of Cases

• Known Cause of Death (traumatic homicide or suicide, MVA)

▫ Volatile Test only: Turn around time: ~2‐3 days

•Unknown Cause of Death (potential overdoses)

▫ Drug Testing for licit/illicit substances: Turn around time: varies

“Typical” known drugs: ~20 working days when fully staffed Cocaine, Methadone, Heroin, Fentanyl, SSRIs, Cough/cold meds, etc.

Unknown drugs, new street drugs…….longer! In‐house method must be validatedOutside testing an option IF it and $ exists!

4

NC OCME Toxicology TestingUnknown Cause of Death: “Full Tox Testing”

• Screening Test▫ Presumptive presence or absence of a drug Currently, we do not use Immunoassay‐based techniques at our lab 

• Confirmation Test▫ Quantitative assay Generates concentration or amount found in specimen Known calibrators and controls

▫ Tests for specific drugs/metabolites

Central Blood

Peripheral Blood

Liver

Urine

Vitreous Humor, Gastric Contents, Brain, Muscle, Hair, “Fluid,” Physical Evidence

Clinical vs. Forensic Toxicology

• Clinical tests are being used for diagnosis or treatment.▫ Results are only presumptive and qualitative▫ Typically in urine (which is historical in nature)

• Forensic toxicology results are done with the purpose of being used as evidence in legal proceedings, and have a number of stringent requirements because of that purpose.▫ Results are quantitative, screening and confirmation is the gold standard▫ Analysis may need to occur in a variety of specimens within one decedent

2. Dramatic Increases in overdose deaths with heroin and non‐pharmaceutical grade fentanyl

Pain, addiction, trafficking 

Pills  Heroin Fentanyl Fentalogs

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5

• Postmortem Interpretation is the most challenging▫ Elevated due to overuse or drug‐drug interactions?

▫ Tolerance will play a huge role 

• Medication history is crucial when concentrations are in the upper normal or “in‐between” range▫ The NC Controlled Substances Reporting System (CSRS)

▫ Current prescription info (what, how much, what is left)

• Scene Evidence and recent behavior also could be a deciding factor▫ Other prescription or over‐the‐counter meds?

The Opioid‐dependent Chronic Pain Patient

Example• Oxycodone ER tablets

• 10 mg orally BID

• 60 pills• 10 remaining

• Prescribed 6 days ago• Belonged to decedent

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Opioid/Benzodiazepine Combo Death

NC OCME data on deaths involving benzodiazepines in combination with opioids

▫ Physicians should check the Controlled Substances Reporting System (CSRS) to verify that patients aren’t taking a prescription opioid before prescribing a benzodiazepine.

NC OCME data on gabapentin‐related deaths

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1000%    in heroin‐related deaths from 2010‐2017

Heroin currently supplemented with fentanyl or fentalogs (fentanyl analogs)

Data set for 2018 is not complete, nowhere back to numbers from early 2010s

Rise in Heroin Deaths 

15

6

Opioids 101: Classification by structure/function

• Natural Opium Alkaloids

▫ Morphine

▫ Codeine▫ Thebaine• Semi‐Synthetic Opioids

▫ Heroin▫ Hydrocodone/Hydromorphone

▫ Oxycodone/Oxymorphone

• (Synthetic Opioids)▫ Fentanyl

https://www.opiates.com/wp‐content/uploads/2016/02/Various‐Opioid‐Molecules.jpg

morphine

16

Opium Poppy to Fentanyl

• Fentanyls are often mixed in with heroin

▫ users may or may not know what they are buying

• Why are cook‐book fentanyls now popular???

• The cost‐efficiencies production

• Most obviously, hiding a kitchen sink‐based lab is much easier than hiding a field of plants. 

• Fentanyl is much cheaper to make than heroin

• Exponentially more potent

http://theprovince.com/feature/from‐opium‐to‐fentanyl‐how‐did‐we‐get‐here

https://www.businessinsider.com/the‐us‐cant‐seem‐to‐cut‐back‐afghanistans‐opium‐production‐2018‐6

17

It’s not personal, it’s just business

• China and Mexico are key

• Synthetic drugs and precursor chemicals that skirt the government’s regulations, often selling their products over the internet

• Illicitly Manufactured Fentanyl (IMF) is often combined with or substituted for heroin, or it is pressed into counterfeit pills.

http://www.insightcrime.org/news‐briefs/mexico‐china‐are‐key‐nodes‐in‐fentanyl‐trade‐dea

Illicit Drug Trafficking makes money

18

7

Fentanyl

Comparing fentanyl and synthetic analogues ▫ New drugs, new methods, more deaths

a) Pharmaceutical Grade Fentanyl (prescription‐based)

b) Non‐pharmaceutical Grade Fentanyl (street fentanyl)

c) Fentanyl analogues

Potency/Dose will vary!

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Rise in Fentanyl Deaths 

• 460%  in fentanyl related deaths from ‘10‐’17

• 210%  from ‘15‐’17

• Data set for 2018 is not complete.

20

YEAR 1st 2nd 3rd 4th 5th

2000 Methadone Cocaine Morphine Oxycodone Ethanol

2001 Methadone Cocaine Oxycodone Morphine Heroin

2002 Methadone Cocaine Oxycodone Morphine  Heroin

2003 Methadone Cocaine Morphine Oxycodone Heroin

2004 Methadone Cocaine Morphine Oxycodone Fentanyl

2005 Cocaine Methadone Hydrocodone Oxycodone Fentanyl

2006 Methadone Cocaine Oxycodone Fentanyl Morphine

2007 Methadone Cocaine Oxycodone Fentanyl Morphine

2008 Methadone Oxycodone Cocaine Fentanyl Morphine

2009 Methadone Oxycodone Cocaine Fentanyl Morphine

2010 Methadone Oxycodone Cocaine Fentanyl Morphine

2011 Methadone Oxycodone Cocaine Oxymorphone Fentanyl

2012 Cocaine Oxycodone Methadone Heroin Fentanyl

2013 Oxycodone Methadone Heroin Cocaine Oxymorphone

2014 Heroin Cocaine Oxycodone Fentanyl Methadone

2015 Heroin Cocaine Oxycodone Fentanyl Oxymorphone

2016 Cocaine Fentanyl Heroin Oxycodone Fentanyl Analogues

Top Five drugs 

in Poisoning Deaths by Year

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8

Quick Case Study: NC OCME: Multidrug toxicity 

Case Study: LC Expanded Screen (LC/ion‐trap MS, Orbitrap)

Presumptive Positive for 6‐MAM, morphine, Oxycodone, Clonazepam Metabolite, Furanylfentanyl,4‐ANPP and below quantitation (BQL) codeine and hydromorphone 

NC OCME Certified Toxicology Report

9

Heroin/Fentanyl/Analogs : MIXTURES

Heroin is often supplemented with varying amounts of fentanyl and/or fentanyl analogues, which explains the increasing numbers of cases positive for both.

87 170 201 287401

573 547137

118 101160

211

390657

7

31

153

599

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2010 2011 2012 2013 2014 2015 2016 2017

Heroin Fentanyl Fentalogs •Huge rise in fentalogs•Most are new and unscheduled at federal and state levels• Little known about▫ Activity▫ Toxicity

2014‐mid 2017 Data:Fentanyl Analogues in North Carolina

AnalyteDate of Death

Total CasesFirst Case Last Case

Acetyl fentanyl 1/19/2014 present 63

Furanyl fentanyl 9/11/2015 present 469

Butyryl fentanyl 11/12/2015 present 3

2‐Fluorofentanyl 5/16/2016 9/10/2016 11

Fluoroisobutyryl fentanyl 7/5/2016 present 63

Acryl fentanyl 7/9/2016 5/2/2017 7

Carfentanil 11/24/2016 present 30

THF Fentanyl 1/18/2017 1/18/2017 1

Methoxyacetyl fentanyl 4/13/2017 present 54

Cyclopropyl fentanyl 5/17/2017 present 141

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0

2

4

6

8

10

Oct‐16 Nov‐16 Jan‐17 Mar‐17 Apr‐17 Jun‐17 Aug‐17

NC OCME Carfentanil

• Carfentanil is considered 100x the potency of fentanyl

• “The side effect of carfentanil is death” 

• 52 confirmed and quantitated cases in our OCME Database Oct 2016‐2018

• No cases so far in 2019 

10

3. Upward trends for stimulants used in combination with illicit opioids 

Recent data from NC OCME

28

Increase in Cocaine found in addition to Fentanyl

• “We’re seeing a dangerous trend of drug dealers and cartels cutting various drugs with fentanyl and increasingly it’s a recipe for death”

• It’s quite possible that this is happening way up stream over the head of dealers

• “Nobody wants to kill off their customer.” 

• At NC OCME, 35.6% of fentanyl/analogue‐related deaths also involved cocaine in 2017, compared to 30.6% in 2016.

29

• Meth served as an opioid substitute, provided a synergistic high (i.e., the roller coaster effect), and balanced out the effects of opioids so one could function “normally”

• Helped alleviate opioid withdrawal symptoms, most likely 

because of their dual action on dopamine reward systems in the brain 

• Methamphetamine‐related deaths increased by 1178.6% from 2010 to 2018 at NC OCME

30

11

4. Emerging illicit drug combinations: unknown powders, counterfeit mimic tablets, miscellaneous substances

New drugs, new methods, even more deaths

Synthetic drugs can be altered at a molecular level such that they fall outside current legal definitions of prohibited substances. Sometimes called either “legal highs” or “new psychoactive substances”.

31

https://www.nbcnews.com/news/us‐news/pills‐found‐prince‐s‐estate‐contained‐fentanyl‐official‐says‐n635861

https://www.washingtonpost.com/news/arts‐and‐entertainment/wp/2016/08/22/prince‐might‐have‐been‐the‐victim‐of‐a‐counterfeit‐pill‐problem‐sweeping‐the‐nation/?utm_term=.b8a8e6ae7058

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• CathinonesMimics methamphetamine and MDMA

• Synthetic OpioidsMimics effects of morphine, oxy, heroin

• Synthetic Cannabinoids (Spice, K2)Mimics marijuana

NPS (New/Novel Psychoactive Substances)

Drug Class 2011 2012 2013 2014 2015 2016 2017

Fentanyl Analogues 0 0 0 1 3 4 3

Other Opioids 0 0 2 0 0 1 2

Designer Benzodiazepines 0 0 0 0 1 2 1

Cathinones (“bath salts”) 5 9 1 1 1 5 2

Limitations: If we don’t know what we are looking for we MIGHTmiss something. 

Formerly known as “research chemicals”, “bath salts”, “plant food”, “analogs”

U‐47700, U‐49900, U‐51754

etizolam, diclazepam

**Free Samples!

33

12

Speaking of endless possibilities……..

An oxycodone mimic tablet contained 20 different drugs: “a mixture of fentanyl; fluoroisobutyrylfentanyl; butyrylfentanyl; methamphetamine; chloroethcathinone; alpha‐PPP; deschloroketamine; cocaine; levamisole; caffeine; lidocaine; carbamazepine; TH‐PVP; U‐47700; 4‐ANPP; diclazepam; flubromazepam; etizolam; deschloroetizolam; and dibutylone. The predominant compound was flubromazepam.

OC/40 Mimic Tablets (Actually Containing 20 Different Drugs) in Imperial Beach, San Diego County, California

Opioid Replacements

• ”Natural Highs” opioid replacements are still dangerous ▫ Imodium

▫ Mitragynine (Kratom) 

▫ Poppy seed tea

• Self‐Medicating Withdrawal Symptoms▫ Ibogaine▫ Kambo

• When all else fails, where I can I find drugs at 3 a.m.?▫ Grocery Stores, Pharmacies, etc. 

35

• The recommended daily adult dosage is between 4‐16 mg per day• Users seeking an opioid‐like high from this drug reportedly take it inexcess of 200 mg per dose!!! 

• Often seen with diphenhydramine and omeprazole (P‐gp inhibition) • Mid‐2012 to early 2015: 19 cases where loperamide was implicated in COD• Estimate for 2017 is 24 cases• Estimate for 2018 is 22 cases• This is problem is NOT going away!!

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Synthetic Cannabinoids

• THC and metabolites are not currently analyzed in the NC OCME Tox Lab

• ‘super‐strength’ Select synthetic cannabinoids are recently added to our menu.

• K2, Spice, and similar drugs are often referred to as fake marijuana, which can entice people to try it. 

• 5F‐AMB and 5F‐ADB are 90 and 300 times, respectively, more potent than THC as full agonists for the human CB1 receptor 

• Patients may present with psychomotor agitation, confusion, anxiety and psychosis.

THC vs. 5F‐ADB

Infant and Toddlers Exposed to Potent Opioids

• “One Pill Can Kill”• Cases were presented at the American Academy of Forensic Sciences meeting• We have had several potent opioid cases in North Carolina including pills such as oxycodone, oxymorphone, prescriptions like methadone and fentanyl patches and illicit drugs such as heroin, fentanyl, and fentalogs including carfentanil

• This is problem is getting worse!!

[email protected]

919‐743‐9026 (desk)

Resource for: Pharmacology of drugs Drug‐drug interactionsEmerging drug trends Laboratory drug detection 

NC OCME Epidemiologist: Alison Miller [email protected]

http://www.acmt.net/_Library/Fentanyl_Position/Fentanyl_PPE_Emergency_Responders_.pdf

Link to Emergency Responder Fentanyl Information: