Understanding Abused Drugs Testing Results

By: Paul L. Cary Toxicology Laboratory

University of Missouri

Presented by: Vinnie Happ Redwood Toxicology Laboratory,

An Alere group of companies.

Designer Drugs SPICE/K2, BATH SALTS, ETC.

PROBLEMS POSED BY

September 19, 2010 CCAPPOAP

The Story of Designer Drugs

Designer Drugs:

drugs, which are created (or reformulated, if the drug already existed) to get around existing drug laws (CSA), usually by modifying the molecular structures of existing drugs to varying degrees

Designer Drugs:

designer drug was first coined by law enforcement in the 1980s

second International Opium Convention in 1925 which specifically banned alternative esters of morphine

1960s - 1970s, new synthetic hallucinogens (modifications of LSD & PCP)

1980s - 1990s, design of MDMA (ecstasy) & methcathinone

2000 - 2005, derivatives of psilocybin & mescaline - anabolic steroid

What Drives the Production Designer Drugs ?

consumer preferences

law enforcement control

Spice/K2 and Synthetic Cannabinoids

What’s in these incense products?

Listed Ingredients in Spice Canavalia rosea: commonly known as beach bean or bay bean - vine

found in tropical and subtropical beach dunes

Nymphaea caerulea: also known as Blue Egyptian water lily

Scutellaria nana: perennial herb also known as Dwarf skullcap

Pedicularis densiflora: known commonly as Indian warrior - a perennial herb

Leonotis leonurus: also known as Lion's Tail and Wild Dagga - a perennial shrub native to southern Africa

Zornia latifolia: is a perennial herb

Nelumbo nucifera: known by a number of names including Indian Lotus, or simply Lotus - aquatic perennial commonly found in China

Leonurus sibiricus: commonly called Honeyweed or Siberian motherwort, herbaceous plant native to Asia

vanilla

honey

Preparation of the incense :

botanicals are sprayed with liquid preparations of:

HU-210

HU-211

CP 47,497

JWH-018

JWH-073

JWH-250

JWH-081

JWH-210

JWH-200

And many more

Synthetic cannabinoids are not Salvia divinorum.

Salvia divinorum is a

psychoactive plant which can induce dissociative effects.

Where can these incense products be

purchased?

Sources of Incense Products:

head shops/alternative medicine stores / convenience stores

internet/on-line sources (2004)

1-(800) phone ordering services

individual distributors

What s the story behind these synthetic THC

chemicals?

Origins of Synthetic Cannabinoids

HU-210 & HU-211 - synthesized at Hebrew University, Israel in 1988. HU-210 is an anti-inflammatory; HU-211 as an anesthetic

CP 47,497 - developed by Pfizer in 1980 as an analgesic (pain reliever)

JWH-018 & JWH-073 - synthesized by a researcher at Clemson (1995) for use in THC receptor research - John W. Huffman

more than 100 different synthetic cannabinoids have been created

Synthetic Cannabinoids Timeline:

first appearance on the Internet 2004

Europe was original target market

by 2008 widespread in Europe

University Hospital Freiburg, Germany first analysis of incense, late in 2008

2008 introduced into US

widespread in US by late 2008 - 2009

first email Spring 2009

first urine metabolite laboratory test available mid 2010 by Redwood Toxicology Lab

Synthetic Cannabinoids act as THC agonists

-An agonist is a chemical that binds to a receptor

and triggers a response – often mimicking the action of a naturally occurring substance.

Receptor

Drug (agonist)

Why Designer Drugs Work

Brain Receptors

Natural Neurotransmitters

noradrenaline

dopamine

Designer Chemists Trick Brain

Dopamine MDMA

Why Change the Key?

• prolong the effect of the drug • increase the potency of the drug • select the desired effect • make the drug more difficult to detect • avoid patent infringement • make an illegal drug legal

Drug

CB Receptors:

CB1 and CB2

CB1 receptor influence mainly the brain (central nervous system, CNS), but there are also effects expressed in the lungs, liver and kidneys

CB2 receptor effects mainly the immune system and in certain stem cells

CB Receptors:

Smoking Cannabinoids

BG: motor control, learning

Hippo: memory, spatial navigation

CB: cognitive functions - attention, language, emotions

What does CB1 receptor control?

Pharmacological Effects of Synthetic Cannabinoids are Similar to THC increase heart rate & blood pressure

altered state of consciousness

mild euphoria and relaxation

perceptual alterations (time distortion)

intensification of sensory experiences

pronounced cognitive effects

impaired short-term memory

reduction in motor skill acuity

increase in reaction times

Dependence Syndrome Similar to Marijuana

Reported Effects of Synthetic Cannabinoids are Different to THC

production inconsistencies

herbal incense blends are harsher to inhale

effect on appetite is non-existent

increased restlessness & aggressive behavior

herbal incense produces a shorter high (perceptual alterations & sensory effects are limited)

doesn t mix well with alcohol (hangovers)

incense costs more than marijuana

Prevalence of Synthetic THC? No national statistics

Louisiana: 9 clients pre-selected based upon suspicion

7 tested positive

Columbia MO: 17 clients pre-selected based upon suspicion

12 tested positive / 5 self-admissions

Pennsylvania:

Confirmed use in Bucks, Lehigh, Lancaster Counties

National Lab Drug Test Data (Redwood Toxicology Lab): 16.5% average positivity rate

(Treatment and/or via court order samples)

National Statistics for Synthetic THC

American Association of Poison Control Centers has reported:

All of 2009 13 cases

First half of 2010 567 cases in 41 states

4000% increase

As of July 31, 2011 4,137 reported exposures to bath salts

Can synthetic THC chemicals be detected by

drug testing?

Drug Testing:

NO on-site, rapid, instant tests

NO laboratory-based screening tests

Five laboratories employing LC/MS/MS technology

$25- $50 per sample

National Laboratory Statistics for “Synthetic Marijuana” Test Redwood Toxicology Laboratory began testing JWH-018, JWH-073

and their metabolites in July 2010.

Over 50,000 urine samples analyzed; primarily from treatment and drug court programs around the nation.

Alarming overall positivity rate of 18%.

Redwood also developed a Saliva based test that confirms presence of JWH-018, JWH-073 and JWH-250 in oral fluid.

Redwood analyzed over 600 samples with a positivity rate of 15%.

Information confirms popularity of these products.

Issues of Concern

What synthetic compounds (or metabolites) are being tested by these laboratories?

no standardized urine cutoff levels

no standardized methods (LC/MS/MS)

tests detect metabolites

no independent quality control materials

no proficiency testing

detection window unknown

Detection Window ???

testing for metabolites

educated guess - same as real marijuana

many labs advertising up to 72 hours

confounding issue - differing cutoff levels

fact is - we don t know!

A New Designer Drug – Bath Salts

Bath Salts: The term bath salts refers to a range of water-

soluble products designed to be added to a bath. They are said to improve cleaning, improve the experience of bathing, serve as a vehicle for cosmetic agents, and some even claim medical benefits. Bath salts have been developed which mimic the properties of natural mineral baths or hot springs.

Sold Under the Names:

Ivory Wave

Ivory Pure

Ivory Coast

Purple Wave

Vanilla Sky

Health Hazard?

What s in Bath Salts:

Methylenedioxypyrovalerone (MDPV) is a psychoactive drug with stimulant properties which acts as both a norepinephrine & dopamine reuptake inhibitor (NDRI).

MDPV has four times the potency of Ritalin

MDPV - no history of FDA approved medical use

sold since 2007 as a research chemical

MDPV:

currently popular in Europe, UK & Australia

is usually snorted - similar to cocaine

considered extremely addictive

adverse medical/psychiatric ramifications

no on-site or screening drug tests

designer drug chemically similar to cathinone

first synthesized in 1929

amphetamine-like properties

powerful synthetic stimulant

rediscovered by synthetic chemists in 2003

widespread in Europe, Australia, US

Methylmethcathinone (Mephedrone)

reformulation of cathinone, a chemical found in the

khat plant of Eastern Africa

khat existence traced to 15th C. Ethiopia

grown in Somalia, Yemen, Kenya, Ethiopia

khat is banned in the U.S.

Mephedrone

Pharmacological Effects of Bath Salts : increase heart rate & blood pressure

pupil dilation

hyperactivity, arousal & over stimulation

increased energy & motivation

euphoria - agitation

dizziness

nausea

breathing difficulties

diminished perception of the requirement for food and sleep

Can Bath Salts be Detected by Drug

Testing?

Drug Testing:

NO on-site, rapid, instant tests

NO laboratory-based screening tests

laboratories employing LC/MS/MS technology

unknowns regarding this testing

cutoff levels

detection times

standardized testing procedures

National Laboratory Statistics for “Bath Salt” Test Redwood Toxicology Laboratory began testing designer stimulants

in January 2011.

As of May, over 2,000 urine specimens received from treatment and drug court programs nationwide have been analyzed.

So far, 8% of the specimens analyzed were found to be positive for one or more designer stimulant substance.

88% of the positive specimens detected MDPV

33% of the positive specimens detected Methylone

Mephedrone was found in 5 specimens, Butylone in 2, TFMPP and BZP in one specimen each.

Clearly MDPV and Methylone are the cause of greatest immediate concern.

The Next Wave?

2C-E Nicknamed "Europa"

synthesized in 1970 s -1980 s

psychedelic phenethylamine

taken orally

powerful hallucinogenic effects

high can last 6- 12 hours

sold through European sources

one death reported in MN on March 11, 2011

2C-E Nicknamed "Europa" synthesized by Alexander Shulgin

popularized MDMA (Ecstasy)

PIHKAL book (1991)

2C-I another phenethylamine available

2C-E is chemically related to other 2C phenethylamines

exact legal status is unclear - 2C-B banned under CSA

What s the legal status of synthetic

cannabinoids and stimulants?

Legal Status of Synthetics with the (DEA)

March 1, 2011, the DEA, issued final notice to temporarily place five (5) synthetic cannabinoids into the Controlled Substances Act (CSA) for at least one year

synthetic cannabinoids treated as Schedule 1 drugs

a drug that has a high potential for abuse

a drug that has no currently accepted medical use in treatment in the United States

there is a lack of accepted safety for use of the drug under medical supervision

September 7, 2011 — DEA Moves to Emergency Control Synthetic Stimulants. Ban to cover: Mephedrone , MDPV and Methylone

Legal Status of Synthetic Cannabinoids /Stimulants (DEA)

DEA took action - imminent hazard to the public safety

imposes criminal sanctions and regulatory controls of Schedule I substances under the CSA

covers the manufacture, distribution, possession, importation, and exportation

Ramifications of DEA Action:

eliminate the commercial distribution of synthetic cannabinoids

drive synthetic cannabinoids underground

limit their availability

impact on criminal justice - wait and see?

States Banning Bath Salts : Control status typically features MDPV and/or Mephedrone

Louisiana

North Dakota

Florida

New Jersey

Pennsylvania

Washington

Kansas

Arkansas

New Mexico

Idaho

Oregon

Tennessee

West Virginia

Wisconsin

Virginia

Wyoming

Missouri

Kentucky

Hawaii

Mississippi

Alabama

Michigan

Georgia

Oklahoma

Utah

Legal Status of Synthetics in (PA)

Senate Bill 1006

Signed into law June 23, took effect on August 22, 2011

Bans eight (8) synthetic cannabinoids and their analogues along with salvia divinorum

Bans six (6) synthetic stimulants including MDPV, Mephedrone and Methylone

Amendment 7 was added that includes language barring all chemicals that are similar to the substances found in bath salts, synthetic cannabinoids and 2C

PA’s Act 7 of 2011 The following substances are added to PA Department of Health’s Schedule I effective August

22, 2011, under Act 7 of 2011 (Senate Bill 1006), and are thus illegal under the Controlled Substance, Drug, Device and Cosmetic Act (35 P.S. 780-101 et seq.):

“Salvia” Salvia Divinorum Salvinorin A Divinorin A “Synthetic Cannabinoids” CP 47,497 and Homologues, 2-[(1R, 3S)-3-Hydroxycyclohexyl]-5-(2-

Methyloctan-2-yl)phenol. HU-210, [(6AR, 10AR)-9-(Hydroxymethyl)-6,6-Dimethyl-3-(2-methyloctan-2-

yl)6A,7,10,10A-Tetrahydrobenzo[C]Chromen-1-ol)] HU-211, (Dexanabinol, (6AS,10AS)-9-(Hydroxymethyl)-6,6-Dimethyl-3-(2-

Methyloctan-2-yl)-6a,7,10,10A Tetrahydrobenzo[C]Chromen-1-ol) JWH-018, 1-Pentyl-3-(1-Naphthoyl)indole JWH-019, 1-Hexyl-3-(1-Naphthoyl)indole JWH-073, 1-Butyl-3-(1-Naphthoyl)indole JWH-200, (1-(2-Morpholin-4-ylethyl)indol-3-yl)-naphthalen-1-ylmethanone

Act 7 of 2011 “Bath Salts” 3,4-Methylenedioxymethcathinone (methylone) 3,4-Methylenedioxypyrovalerone (MDPV) 4-Methylmethcathinone (Mephedrone) 4-Methoxymethcathinone 4-Fluoromethcathinone 3-Fluoromethcathinone

Act 7 of 2011

“Phenethylamines” 2-(2,5-Dimethoxy-4-ethylphenyl) ethanamine (2C-E) 2-(2,5-Dimethoxy-4-methylphenyl) ethanamine (2C-D) 2-(4-Chloro-2,5-dimethoxyphenyl) ethanamine (2C-C) 2-(4-Iodo-2,5 dimethoxyphenyl) ethanamine (2C-I) 2-[4-(Ethylthio)-2,5-dimethoxyphenyl] ethanamine (2C-T-2) 2-[4-(Isopropylthio)-2,5-dimethoxyphenyl] ethanamine (2C-T-4) 2-(2,5-Dimethoxyphenyl) ethanamine (2C-H) 2-(2,5-Dimethoxy-4-nitro-phenyl) ethanamine (2C-N) 2-(2,5-Dimethoxy-4-(N)-propylphenyl) ethanamine (2C-P)

Is the Legislation having an impact??

Associated Press article

PepsiCo 3Q profit climbs on snack, beverage sales

By SARAH SKIDMORE , 10.12.11, 12:27 PM EDT

Are There Control Strategies Other Than

Testing?

Alternative Control Strategies:

community supervision

search & seizure -(probation/client contract)

car, home, possessions

Court s Response: place specific synthetic cannabinoid

prohibition in your client contract

establish a certain testing date - inform client population

establish sanction severity

select participants for testing where there are indications of herbal incense use

identify positive participants in court & sanction openly to enhance deterrent effect

provide opportunity for participants to self-report

Client Prohibition Guidance:

Any and all designer drugs that can be purchased legally, over the counter without a physician s prescription are strictly prohibited.

Any and all “smoking mixtures (other than products specifically designated to contain only tobacco) are strictly prohibited.

Any and all products sold or marketed under false pretenses with the warning “Not for Human Consumption are strictly prohibited.

Designer Drug Evolutionary Path

Plant to Designer Drug

Plant Natural Drug(s)

Synthetic Drug(s)

Designer Drug(s)

Ma Huang

Chinese herb

(ephedra sinica)

ephedrine & pseudo- ephedrine (natural stimulants)

amphetamine & meth-

amphetamine developed in

the early 1900 s

MDMA (Ecstasy)

Plant to Designer Drug

Plant Natural Drug(s)

Synthetic Drug(s)

Designer Drug(s)

Cannabis sativa

(marijuana)

delta - 9 tetrahydro-cannabinol

(THC)

Dronabinol & Marinol

HU, CP & JWH

synthetic cannabinoids

(JWH-018, HU-211,

CP-49,497)

Plant to Designer Drug

Plant Natural Drug(s)

Synthetic Drug(s)

Designer Drug(s)

Khat

(catha edulis)

cathinone (natural

stimulant)

phenyl-propanolamine

(PPA - weight loss drug)

methcathinone synthesized in 1928 in Soviet

Union (antidepressant)

mephedrone (methylmeth-cathinone)

one of the bath salt

constituents

Designer Drugs: designer drugs are here to stay

similar evolutionary patterns

testing will nearly always lag behind

legal controls will be challenging and delayed

BE PROACTIVE!

build community supervision/expand search & seizure efforts

design client contract specifically address designer drugs

Presented by: Vinnie Happ Redwood Toxicology Laboratory,

An Alere group of companies.

vhapp@redwoodtoxicology.com

By: Paul L. Cary Toxicology Laboratory

University of Missouri

carypl@health.missouri.edu

Thank you for your time.