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For Forensic Use. Current Trends in Designer Drugs

Bert Toivola, Ph.D. Technical Director

STERLING Reference Laboratories Tacoma, Washington

For Forensic Use. TRIVIA QUESTION

What Seinfeld character failed a drug test due to poppy seed consumption?

For Forensic Use. AGENDA

• Brief History of Designer Drugs • Spice – His tory – Pharmacology – Legal Status – Analysis • Bath Salts

For Forensic Use. A Brief History of Designer Drugs

Designer Drugs:

“drugs w hihhich are crea td(ted (or mar ktdifthketed, if they had already existed) to get around existing drug laws (CSA) usually by modifying the molecular structure of existing drugs to varying degrees”

For Forensic Use. A Brief History of Designer Drugs

What the heck does that mean?

Methamppyhetamine Ecstasy

For Forensic Use. A Brief History of Designer Drugs

Desi gner D rugs: 1920 s – 1930s

ƒ first International Opium Convention (1912)

ƒ second International Opium Symposium (1925)

For Forensic Use. A Brief History of Designer Drugs second International Opium Convention ƒ held in 1925, Geneva, Switzerland

ƒ Specifically banned diacetyl ester of morphine (heroin)

ƒ also included controls over cannabis (“Indian Hemp”)

ƒ Appearance shortly thereafter of alternative esters including: 9 Dibenzoylmorphine 9 Acetyyylpropionylmorphine

ƒ League of Nations (1930) extends control to other analogues

For Forensic Use. A Brief History of Designer Drugs

Designer Drugs: 1960s – 1970s

ƒ Introduction of a number of synthetic hallucinogens (modifications of LSD and PCP)

ƒ DOM/STP (“Serenity, Tranquility, Peace”)

ƒ Little scope to prosecute people over drug analogues

ƒ United States v. Sand, 1973

ƒ ALD-52 (acetylamide of LSD)

For Forensic Use. A Brief History of Designer Drugs

Controlled Substances Act - CSA ()(1970)

ƒ Title II of Comprehensive Drug Abuse Prevention and Control Act of 1970

ƒ Scheduled Drugs – I, II, III, IV, V

For Forensic Use. A Brief History of Designer Drugs

Controlled Substances Act - CSA ()(1970) ƒ Schedule I – heroin, psylocibin, LSD, marijuana, MDMA, PCP

ƒ Sch edul e II – cocaine , me thado n e, ox ycodon e, mooprphin e methamphetamine, amphetamine

ƒ Schedule III – buprenorphine, hydrocodone, marinol

ƒ Schedule IV – benzodiazepines (Valium, Xanax), Z-drugs, (Zolpidem, Zopiclone)

ƒ Schedule V – antitussives with small amounts of codeine, pyrovalerone

ƒ Federal Analogue Act (1986)

For Forensic Use. A Brief History of Designer Drugs

Desigggner Drugs: 1980s – early 1990s ƒ Modern use of term “designer drug” coined in 1980s

ƒ Ecstasy (MDMA)

ƒ “Fake” heroin sold on black market based on fentanyl or meperidine

ƒ Fentanyl analogues sold as China White

For Forensic Use. A Brief History of Designer Drugs

Anabolic Steroids

For Forensic Use. For Forensic Use. SPICE

This is your grandmother’s Parsley, Sage, Rosemary and Thyme

For Forensic Use. SPICE

This is not your grandmother’s PlParsley, Sage, Rosemary an dThd Thyme

For Forensic Use. SPICE and BATH SALTS Calls to Poison Control Centers Calls to Poison Control Centers • SPICE – 2010 2,915 calls – 2011 (July 31) 3,787 calls

• BATH SALTS – 2010 303 calls – 2011 ((y)July 31) 4,137 calls

American Association of Poison Control Centers, July 31 2011

For Forensic Use. SPICE: HISTORY

• 2004 First appearance on the Internet • 2004 First Appearance in Europe • 2008 Wide Spread use in Europe • 2008 First Appearance in United States • 2008 First Analysis of SPICE at University of Freiburg • 2009 Wide Appearance in United States • 2009 First inquiry Fall 2009 • 2010 Laboratory Testing of Spice Available • 2011 Temporary Ban by DEA

For Forensic Use. SPICE:

Nola Gold Botanical Incense • Bay Bean • Siberian Motherwort • Marshmellow • Stevia Leaf • Leonotis leonurus • Blue Lotus • Passion Leaf • Aroma Essence • Damiana •JWH _ 018 •JWH _ 073 NOT FOR HUMAN CONSUMPTION

For Forensic Use. SPICE: ¨9-THC and HU - 210

¨9 -Tetrahydrocannabinol HU - 210

For Forensic Use. SPICE: Synthetic Cannabinoids

• Hebrew University – HU 210 anti-inflammatory – HU 211 anesthetic – HU 243 – HU 308 – HU 331

• Pfizer Pharmaceutical – CP 47,497 analgesic – CP 55,490

For Forensic Use. SPICE: Synthetic Cannabinoids

• Alexandros Makriyannis – AM 2201 – AM 694 – AM 2232

• Sterling-Winthrop Pharmaceutical – WIN 55,512

For Forensic Use. SPICE: Synthetic Cannabinoids

• John W. Huffman,Ph.D., Clemson Univ. – JWH – 007 – JWH – 015 – JWH – 018 – JWH – 019 – JWH – 073 – JWH – 081 – JWH – 122 – JWH – 200 – JWH – 250 – JWH – 251 – JWH – 398

For Forensic Use. SPICE: Synthetic Cannabinoids

• John W . Huffman , Ph. D., Clemson Univ. – Made first synthetic cannabinoid in 1995

– Published formula for JWH – 018 in Bioorganic and Medicinal Chemistry

– Noticed by “underground” Chemists in 2008

– Synthesized over 400 synthetic cannabinoids, none patented

– Retired in 2008

For Forensic Use. SPICE

When asked if he felt any responsibility that he made the drug………

“you can’t be responsible for what idiots are going to do.” JhJohn WHffW. Huffman, Ph PhD.D. Professor, Emeritus January 26, 2011 Chemistry Department Chemical & Engineering News Clemson University

For Forensic Use. SPICE: Preparation

Botanical Material Herbal Incense • Synthetic cannabinoids sppyrayed on herbs, allowed to dry • Residual solvent • No qua lity con tro l • Batches inconsistent • Expensive compared to marijuana • Caveat emptor

For Forensic Use. SPICE: Where to Buy?

• Internet • “Head” Shops/Alternative medicine stores • “Conveni ence” St ores • Magazines • (800) phone ordering services • Ebay • Individual distributors

For Forensic Use. SPICE: Where to Buy?

For Forensic Use. SPICE: Where to Buy?

For Forensic Use. SPICE: Where to Buy?

For Forensic Use. SPICE: Where to Buy?

For Forensic Use. SPICE:DoItYourselfSPICE: Do It Yourself

For Forensic Use. SPICE: Public Menace

Seattle – December 2010 • Defendant noticed slumped over steering wheel of car • 1997 Subaru side-swipes a parked car • Goes airborne • Strikes three pedestrians; no deaths • Crashes into a produce truck • Admits to smoking K2 prior to accident • Charged with vehicular assault • Plead not guilty

For Forensic Use. SPICE: Public Menace

Des Moines – June 2010 • Young man – David Rozga • Graduation party celebration • Smoked K2 • Hallucinations • Extreme anxiety • Commits suicide

For Forensic Use. SPICE: Pharmacology

CB Receptors:

For Forensic Use. SPICE: Pharmacology

• Cannabinoid Receptors

•CB1 – Central Nervous System • Sensory Perception • Motor Control • Cognition • Emotions – Lunggy, Liver, Kidney

•CB2 – Immune System

For Forensic Use. SPICE: Pharmacology

Pharmacological Effects of Synthetic Cannabinoids ƒ HU-210 ƒ CP 47,497 ƒ JWH-018 ƒ JWH-073 ƒ Etc…………

All act as THC agonists

For Forensic Use. SPICE: Pharmacology

• Euphoria (“ high” ) similar to Marijuana • Relaxation • Altered state of consciousness • Distortion of sensory experiences • Impaired motor control • Increased reaction time • Decreased cognition •NOeffect on appetite

For Forensic Use. SPICE: Adverse Side Effects

• Elevated Blood Pressure • Increased Heart Rate • Hyperventilation • Anxiety and Agitation • PiParanoia • Seizures • Vomiting • Death (unsubstantiated media reports)

For Forensic Use. SPICE: Legal Status in U. S. States

• Some or all Synthetic Cannabinoids Banned Alabama Arkansas Georgia Illinois Iowa Kansas Kentucky Louisiana Michigan Missouri Nevada New Hampshire New Mexico Oklahoma Oregon Tennessee Utah Washington West Virginia

For Forensic Use. SPICE: Legal Status U. S. Military

• Banned in All Branches of Military – U.S. Army – USU.S. AirForceAir Force – U.S. Coast Guard – U. S. Marine Corps – U.S. Navy

For Forensic Use. SPICE: Legal Status U. S. Federal

DEPARTMENT OF JUSTICE March 1, 2011 Drug Enforcement Administration 21 CFR Part 1308 [Docket No. DEA-345F] Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into Schedule I AGENCY: Drug Enforcement Administration (DEA), U.S. Department of Justice. ACTION: Final order. **************************************************************************************************************************************** SUMMARY:

The Administrator of the Drug Enforcement Administration (DEA) is issuing this final order to temporarily (CSA) pursuant to the temporary scheduling provisions. The substances are 1-pentyl-3-(1- naphthoyl)indole (JWH-018), 1-butyl-3-(1-naphthoyl)indole (JWH-073), 1- [2-(4- morpholinyl)ethyl]-3-(1-naphthoyl)indole (JWH-200), 5-(1,1- dimethylheptyl)-2-[(1R,3S)-3-hydroxycyclohexyl]- phenol (CP-47,497), and 5-(1,1-dimethyloctyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol (cannabicyclohexanol; CP- 47,497 C8 homologue). This action is based on a finding by the Administrator that the placement of these syyypynthetic cannabinoids into Schedule I of the CSA is necessary to avoid an imminent hazard to the public safety. As a result of this order, the full effect of the CSA and its implementing regulations including criminal, civil and administrative penalties, sanctions and regulatory controls of Schedule I substances will be imposed on the manufacture, distribution, possession, importation, and exportation of these synthetic cannabinoids.

For Forensic Use. SPICE: Legal Status U. S. Federal

• Schedule Status November 24, 2010 DEA published in FdFedera lRl Reg itister itinten ttt to pl ace five synthetic cannabinoids on Schedule 1 of CSA. March 1, 2011- Final rule published. STATUS: Schedule I – illegal • Temporary

For Forensic Use. Spice: Five Banned Compounds

JWH - 018 JWH - 073 JWH - 200

9 CP 47,497 CP 47,497 C8 Homolog ¨ -THC Cannabicylohexonal

For Forensic Use. For Forensic Use. SPICE: Laboratory Testing

• Synthetic Cannabinoids not detected in THC screening immunoassays or THC confirmatory GC/MS testing. • Immunoassays not available. • On-Site screening tests not available. • LC/MS/MS technology available. •Few l abs perf orm testin g. • Expensive $30 - $100 per sample

For Forensic Use. SPICE: LC/MC/MS INSTRUMENT

Sampling Mass Spectrometer Data Processing and Chromatography

For Forensic Use. SPICE: JWH – 018 METABOLISM

MW 341

MW 358MW 358 MW 372 MW 374

For Forensic Use. SPICE: Laboratory Testing

• STERLING Reference Laboratories (Tacoma, WA)

• National Medical Services (Willow Grove, PA)

• Dominion Diagnostics (North Kingstown, RI)

• MedTox (St. Paul, MN)

• NorChem (Flagstaff, AR)

• ElSohly Laboratory (Oxford, MS)

• Redwood Toxicology Laboratory (Santa Rosa, CA)

• AIT (Indianapolis, IN)

For Forensic Use. SPICE: Prevalence

• No national statistics

• Louisiana: – 9 clients “pre-selected” based upon suspicion – 7 tested positive

• STERLING Reference Laboratories – 2215 donor specimens tested (11/10 – 08/11) – 354 tested positive (16.0%)

For Forensic Use. SPICE: The Wild , Wild West

• Parent drug not detected in urine • Metabolites must be measured • Pure met ab olit es are now becom ing available as calibrators • Internal Standards available • Detection windows unknown • No standardized urine cut-off levels

For Forensic Use. SPICE: ANALYSIS

• Future of Spice Testing – More compounds to be tested as SPICE formula evolves – New metabolites • Alternative Matrix – Blood • Measure Parent Drug – Oral Fluid • Measure Parent Drug – Hair • Enhanced Window of Detection

For Forensic Use. Labrat2.jpg

For Forensic Use. Bath Salts – Real or Memorex?

For Forensic Use. The Real Stuff

• Epsom salts or sea salt, or both • Baking soda • 12t1 or 2 teaspoons of glycerin (optional) • Essential oils – mandarin orangg,e, lavender, sandlewood and patchouli

For Forensic Use. DESIGNER DRUGS: BATH SALTS

For Forensic Use. DESIGNER DRUGS: BATH SALTS

For Forensic Use. CATHINONES

• Fresh leaves chewed or consumed as tea • Originated in Ethiopia • Causes release of dopamine from brain areas • Sale of Khat legal in - ™ Australia by permit ™ Oman ™ Yemen ™ United Kingdom

For Forensic Use. CATHINONES - Effects

• Mild euphoria and excitement • Talkative, unrealistic, emotionally unstable • Constipation • Anorectic • Manic behaviors • Drowsy hallucinations

For Forensic Use. SYNTHETIC CATHINONES

4-Methylmethcathinone Methylenedioxypyrovalerone Mephedrone MDPV 4-MMC

Methedrone Methy lone 4-Methoxymethcathinone

For Forensic Use. SYNTHETIC CATHINONES

• Arctic blasting station • Euphoria • Atomi c • HHiurricane ch hliarlie • Bayou revitalisant • Ivory wave (9) •Blaze • Ivory wave ultra • Blitz • Kush blitz • Blue moon • Lady bubbles • Blue silk • Legal • Bohemian bath salts • Love potion 69 • Bolivian bath salts • Moon dust • Dr. booga shooga • Night cap • Cloud 9 (73) • NRG-1 • Cloud 10 • Q concentrated • Columbian odorizer • Red dove • Cotton cloud •Resin • Dream • Scar face •Dynamite • Serenity • Super clean stain remover • White diamonds • White cloud • White Lightening (24)

For Forensic Use. Mephedrone

• Meow Meow, 4-MMC, MCAT • First synthesized in 1929 • The Hive we bs ite (2003)

“I’ve been bored over the last couple of days and had a few fun reagents laying around” before going on the describe that after taking it he had a “fantastic sense of well-being that I haven’t got from any drug before except my beloved Ecstasy” • Tablets or powders • Effects similar to XTC, cocaine, methamphetamine

For Forensic Use. Mephedrone

• Available for sale on internet in 2007 • By 2010 prevalent in most of Europe • Began to repl ace MDMA in Ecs tacy • Illegal in in EU in late 2010 • In USA considered an “analogue”

For Forensic Use. Components of “Bath Salts”

White Lightening Mephedrone White Lightening MDPV Zoom MDPV Energizing aromatherapy powder MDPV and caffeine Euphoria Methylone and caffeine Cotton Cloud Mephedrone, Methlone and MDPV Cloud 9 Methylone and MDPV BiflBayou ivory flower MhdMephedrone Cloud 10 MDPV White Dove Methylone Dynamite Methylone Dynamite “plus” MDPV White China MDPV and unknown compound Snow Day Methylone and MDPV

Clinical experience with and analytical confirmation of “ bath salts” and “ legal highs” (synthetic cathinones) in the United States, Spiller, et al, Clinical Toxicology, (2011), 49

For Forensic Use. Methedrone

For Forensic Use. MDPV

• Component of Ivory Wave • Four times the potency of Ritalin • Stimulant properties • Usually snorted – similar to cocaine • Extremely addictive • No history of FDA approved medical use • Currently popular in Europe, UK and Australia • MDPV is “legal”

For Forensic Use. MDPV

For Forensic Use. BATH SALTS: SIDE EFFECTS

For Forensic Use. MDPV

A warehouse full of JWH-018, JWH-073 and MDPV!!!

For Forensic Use. Bath Salts - Methylone

• Originally patented (1996) as anti-depressant • 2004 – appeared in Netherlands as “Explosion” • Advertized as a “room deodorizer” • Reported dosages of 200 mg • Selling for $13 - $20

For Forensic Use. DESIGNER DRUGS: Bath Salts

• Central Nervous System Stimulants • Similar in action to methamphetamine • Thoug ht to be hig hly a ddic tive • MDPV is 5–8x potency of methylphenidate • Available as research chemical in 2007 • Popular in Europe and Australia

For Forensic Use. BATH SALTS: Legal Status

STATES: Controlled in ‰ Alabama ‰ Mississippi ‰ Arkansas ‰ New York ‰ Florida ‰ NthCliNorth Carolina ‰ Georgia ‰ North Dakota ‰ Hawaii ‰ Oregon ‰ Idaho ‰ Illinois ‰ Tennessee ‰ Kansas ‰ Utah ‰ Kentucky ‰ Virginia/West Virginia ‰ Louisiana ‰ Wyoming ‰ Michigan ‰ Washington (04/15/2011)

For Forensic Use. BATH SALTS: Legal Status

Washington State Banned Five Bath Salts -April 15, 2011 • MDPV • Mephedrone • Methylone •Butylone • 4-Fluoromethcathinone (Flephedrone)

For Forensic Use. BATH SALTS: Legal Status

FEDERAL STATUS DEA “Dispose of Bath Salts” Sept 8, 2011 DEA announces intent to place Bath Salts on Schedule 1 of CSA.

MDPV

Mephedrone

Methylone

For Forensic Use. BATH SALTS: Adverse Side Effects

• Elevated Heart Rate and Blood Pressure • Anxiety and agitation • Hallucinations • Extreme Paranoia • DlDelus ions • Seizures • Nausea and Vomiting • Death

For Forensic Use. BATH SALTS: ANALYSIS

• Bath Salts are not detected in Amphetamine Screening Immunoassays or Confirmatory GC/MS assays • Immunoassays not available. • RidORapid On-Site Tes ts no t ava ila ble • LC- or GC/MS assays available for MDPV and Mephedrone •Methylone, flephedrone, butylone and others

For Forensic Use. Bath Salts – Laboratory Testing

• STERLING Reference Laboratories (,)(Tacoma, WA)

• National Medical Services (Willow Grove, PA)

• Redwood Toxicology Laboratory (Santa Rosa, CA)

• Others?

For Forensic Use. SPICE and BATH SALTS

• FUTURE OF DESIGNER DRUGS • They are here to stay. • The problem will get worse long before it gets better. DEMAND = SUPPLY • Analytical Labs Will Always Lag Behind the Synthetic Chemists

For Forensic Use. TRIVIA QUESTION

What Seinfeld character failed a drug test due to poppy seed consumption?

For Forensic Use. Acknowledgements

Dr. Dan Baker

For Forensic Use. For Forensic Use.