Spice K2 and OtherSpice K2 and OtherSpice, K2 and Other Spice, K2 and Other Synthetic Synthetic CannabinoidsCannabinoids

AADCP - Specialty Court Conference

Douglas Kramer – TASC, Inc

AADCP Specialty Court Conference

Herbal IncenseHerbal IncenseHerbal Incense Herbal Incense

Sold in head shops or online Sold in head shops or online as an incense product as an incense product

Herbs and botanicals Herbs and botanicals treated with synthetictreated with syntheticcannabinoid chemicalscannabinoid chemicalscannabinoid chemicalscannabinoid chemicals

Many varieties/scentsMany varieties/scents

Labeled “Not for Human Labeled “Not for Human Consumption”Consumption”

Herbal IncenseHerbal IncenseHerbal Incense Herbal Incense

Variety of Products AvailableVariety of Products Available

Spice, K2, Smoke, Yucatan Spice, K2, Smoke, Yucatan p , , ,p , , ,Fire, Hush, GenieFire, Hush, Genie

Single Use or Bulk ProductSingle Use or Bulk ProductSingle Use or Bulk ProductSingle Use or Bulk Product

Sold Loose or in joint formSold Loose or in joint form

Aromatic HerbsAromatic HerbsAromatic HerbsAromatic HerbsCanavaliaCanavalia maritimamaritima, , NymphaeaNymphaea caeruleacaerulea, , ScutellariaScutellaria nananana, ,

PedicularisPedicularis densifloradensiflora, , LeonotisLeonotis leonurusleonurus, , ZorniaZornia latifolialatifolia, , N l bN l b ifif LL ibi iibi i NelumboNelumbo nuciferanucifera , , LeonurusLeonurus sibiricussibiricus… many more.… many more.

Herbal EffectsHerbal EffectsHerbal EffectsHerbal Effects

Most of the herbal components have very little Most of the herbal components have very little psychoactive effects, although some traditional psychoactive effects, although some traditional herbalists may disagree. At most, they:herbalists may disagree. At most, they:herbalists may disagree. At most, they:herbalists may disagree. At most, they:

Add color and flavorAdd color and flavor May have mild relaxing propertiesMay have mild relaxing properties Decrease blood pressureDecrease blood pressure Reduce inflammationReduce inflammation Reduce inflammationReduce inflammation Induce mild euphoria Induce mild euphoria

S h i th hi h i f ?So where is the high coming from?

Drug DiscoveryDrug DiscoveryDrug DiscoveryDrug Discovery

Intense psychoactive properties were being Intense psychoactive properties were being reported, but with little verification.reported, but with little verification.

In late 2008, forensic analyses conducted in In late 2008, forensic analyses conducted in Europe identified JWHEurope identified JWH--018 as a psychoactive 018 as a psychoactive ing edient in man of these p od ctsing edient in man of these p od ctsingredient in many of these products.ingredient in many of these products.

JWHJWH--018: synthetic cannabinoid synthesized in 018: synthetic cannabinoid synthesized in y yy y1995 for experimental purposes.1995 for experimental purposes.

Cannabis OverviewCannabis OverviewCannabis OverviewCannabis Overview

Used for more than 4000 years for euphoric and Used for more than 4000 years for euphoric and therapeutic effectstherapeutic effects

Most commonly abused drug in the world. Most commonly abused drug in the world.

Roughly 4% of the world's adult population (162Roughly 4% of the world's adult population (162 million million people) use cannabis annually, and about 0.6% people) use cannabis annually, and about 0.6% (22.5(22.5 million) use it on a daily basismillion) use it on a daily basis(22.5(22.5 million) use it on a daily basismillion) use it on a daily basis

CannabisCannabisCannabisCannabis

Contains:Contains:

>450 chemicals >450 chemicals >60>60--90 different 90 different cannabinoidscannabinoids

99--Tetrathydrocannabinol (THC)Tetrathydrocannabinol (THC)Main psychoactive ingredient of marijuanaMain psychoactive ingredient of marijuanaMain psychoactive ingredient of marijuanaMain psychoactive ingredient of marijuana

CannabisCannabisCannabisCannabis

THC content in marijuana varies THC content in marijuana varies –– typically 2typically 2--5% 5% in cannabis, but much higher has been foundin cannabis, but much higher has been found

Marijuana users may experience stimulant, Marijuana users may experience stimulant, depressant, and/or hallucinogenic propertiesdepressant, and/or hallucinogenic propertiesdepressant, and/or hallucinogenic propertiesdepressant, and/or hallucinogenic properties

Most commonly used for hallucinogenic effectsMost commonly used for hallucinogenic effects

Most individuals sMost individuals selfelf--titratetitrate their THC intaketheir THC intake

CannabisCannabisCannabisCannabis

Most common Medicinal Uses:Most common Medicinal Uses:

R li f f d itiR li f f d iti Relief from nausea and vomitingRelief from nausea and vomiting

Stimulation of hunger Stimulation of hunger Stimulation of hunger Stimulation of hunger

General analgesic effects (pain reliever)General analgesic effects (pain reliever)

Lowered intraocular eye pressure Lowered intraocular eye pressure

What areWhat are CannabinoidsCannabinoids??What are What are CannabinoidsCannabinoids??

Class of chemicals that have similar structure Class of chemicals that have similar structure and/or activity that mimic:and/or activity that mimic:

PhytocannabinoidsPhytocannabinoids (found in cannabis plants)(found in cannabis plants)•• Natural, herbal, classicalNatural, herbal, classicalNatural, herbal, classicalNatural, herbal, classical

EndocannabinoidsEndocannabinoids•• (found in CNS and immune systems of animals)(found in CNS and immune systems of animals)

Cannabinoid FunctionsCannabinoid FunctionsCannabinoid FunctionsCannabinoid Functions

What are the What are the EndocannabinoidEndocannabinoid functions?functions?

Signaling molecules (Lipid messengers) that are Signaling molecules (Lipid messengers) that are released from cells to bind to nearby cell released from cells to bind to nearby cell receptors.receptors.receptors.receptors.

Signaling is retrograde (reverse direction Signaling is retrograde (reverse direction postsynaticpostsynatic to to presynapticpresynaptic neurons)neurons)

Cannabinoid ReceptorsCannabinoid ReceptorsCannabinoid ReceptorsCannabinoid Receptors

A l b f C bi id RA l b f C bi id RAt least two subtypes of Cannabinoid Receptors:At least two subtypes of Cannabinoid Receptors:

CBCB Receptor Receptor CBCB11 Receptor Receptor

Found throughout the peripheral and CNS systemsFound throughout the peripheral and CNS systemsFound throughout the peripheral and CNS systemsFound throughout the peripheral and CNS systems

CBCB22 Receptor Receptor

Found throughout the peripheral nervous system Found throughout the peripheral nervous system d i t d ith th i td i t d ith th i tand associated with the immune systemand associated with the immune system

SyntheticSynthetic CannabinoidsCannabinoidsSynthetic Synthetic CannabinoidsCannabinoids

Four Groups of Synthetic Four Groups of Synthetic CannabinoidsCannabinoids::

THC Analogue (classical)THC Analogue (classical) THC Analogue (classical)THC Analogue (classical)

NonNon--classical classical –– CyclohexylphenylCyclohexylphenyl (CP) series(CP) seriesy y p yy y p y ( )( )

AminoalkylindolesAminoalkylindoles –– (JWH compounds)(JWH compounds)

Other Other –– Fatty Acid AmidesFatty Acid Amides

Synthetic Cannabinoid AgonistsSynthetic Cannabinoid AgonistsSynthetic Cannabinoid AgonistsSynthetic Cannabinoid Agonists

M t M t f llf ll CBCB & CB& CB t i tt i tMost are Most are fullfull CBCB11 & CB& CB22 receptor agonistsreceptor agonists

Originally investigated for medicinal purposes:Originally investigated for medicinal purposes:Originally investigated for medicinal purposes:Originally investigated for medicinal purposes:

AnalgesicsAnalgesics

Weight managementWeight management

Control of NauseaControl of Nausea

Smoking cessationSmoking cessation Smoking cessationSmoking cessation

Cannabinoid AgonistsCannabinoid Agonists

THC AnaloguesTHC Analogues

HUHU--210,210, HUHU--211, HU211, HU--243,243, HUHU--308, HU308, HU--320, HU320, HU--331,331, HUHU--336, HU336, HU--345345

Raphael Raphael MechoulamMechoulam

Hebrew UniversityHebrew University

Cannabinoid AgonistsCannabinoid Agonists

CyclohexylphenylCyclohexylphenyl (CP) Series(CP) Series

Pfizer PharmaceuticalPfizer PharmaceuticalPfizer PharmaceuticalPfizer Pharmaceutical

CP 47 497 CP 55 940CP 47 497 CP 55 940CP 47,497, CP 55,940,CP 47,497, CP 55,940,CP 47,497 CP 47,497 –– (C8), (C8), CP 50,556CP 50,556--1, CP 55,2441, CP 55,244

Cannabinoid AgonistsCannabinoid Agonists

AminoalylindolesAminoalylindoles

Over 470 analoguesOver 470 analoguesOver 470 analoguesOver 470 analoguesJWHJWH--015, JWH015, JWH--018, JWH018, JWH--019, 019, JWHJWH--073, JWH073, JWH--081, JWH081, JWH--122, 122, JWHJWH 133 JWH133 JWH 147 JWH147 JWH 171 171 JWHJWH--133, JWH133, JWH--147, JWH147, JWH--171, 171, JWHJWH--210, JWH210, JWH--250, JWH250, JWH--398398

John John W HuffmanW HuffmanJohn John W.HuffmanW.Huffman

Clemson UniversityClemson University

Synthetic Cannabinoid AgonistsSynthetic Cannabinoid AgonistsJWH-018 JWH-073 CP 47,497 JWH-250

Synthetic Cannabinoid AgonistsSynthetic Cannabinoid Agonists

Spice Gold 20 mg/g 11 mg/g

Spice Diamond 17 0.07

Spice Maxx 17 19

Spice Silver 9 16Spice Silver 9 16

Space 10

K2 Blonde 12 13

K2 Standard 9 9

K2 Cit 10 10K2 Citron 10 10

K2 Summit 11 9

K2 Blue 15

K2 Pink 11 14

K2 Latte 16 0.28

K2 Mint 19 0.30

K2 Silver 8 16

Herbal Blends 2-36 1-17 Table Data Compiled by NMS Labs

Adverse EffectsAdverse EffectsAdverse EffectsAdverse EffectsPhysiological Effectsy g

Raised blood pressure and heart rate Bloodshot eyes Swaying Slurred speech

Anxiety, Agitation Paranoia and Hallucinations

Psychological Effects

Paranoia and Hallucinations Seizures and convulsions Short-term memory loss Time dilation

Adverse EffectsAdverse EffectsAdverse EffectsAdverse EffectsJWH-018 Initial Trials

Statistically significant, dose-dependent, region-specific decreases in cannabinoid binding observed in all brain

d f ll d d fregions examined following 4 and 14 days of treatment.

The pattern of CB1 receptor down-regulation was similar to that observed in adults treated with cannabinoids; however, that observed in adults treated with cannabinoids; however, the magnitude of down-regulation was smaller in adolescents.

Thi d d t i j il This reduced compensatory response in juveniles may contribute to some acute behavioral effects, the pharmacological cross-tolerance and the long-lasting, adverse psychological consequences of cannabinoid p y g qexposure during adolescence.

A Case of DependenceA Case of DependenceA Case of DependenceA Case of Dependence20-year old patient reported that he had smoked "Spice Gold" daily for 8 months.

He developed tolerance and rapidly increased the dose to 3g per day. He felt a continuous desire for the drug and kept on using it despite the development of persistent cognitive impairment. p p g p

Urinary drug screens were negative on admission to the hospital, as they were again on discharge.

On hospital days 4–7, he developed inner unrest, drug craving, nocturnal nightmares, profuse sweating, nausea, tremor, and headache.

His blood pressure was elevated for two days, with a maximal value of 180/90 p y ,mm Hg accompanied by a heart rate of 125/min.

The patient stated that he had experienced a similar syndrome a few weeks earlier during a phase of abstinence owing to a short supply, and that it had g p g pp y,quickly subsided after he had started consuming "Spice" once again.

Federally Banned Cannabinoids (March 2011)Federally Banned Cannabinoids (March 2011)

JWH-018

9-THC

JWH-073

JWH-200CP-47,497

Cannabicyclohexanol

Additional AZ Banned Cannabinoids (Feb 2011)Additional AZ Banned Cannabinoids (Feb 2011)

HU-210

9-THC

HU-210

JWH-015

JWH-250

JWH-019 JWH-398

Analysis by LC/MS/MSAnalysis by LC/MS/MSAnalysis by LC/MS/MSAnalysis by LC/MS/MS

DetectionDetectionDetectionDetection Most compounds are not detected by drug screening testsMost compounds are not detected by drug screening tests Most compounds are not detected by drug screening testsMost compounds are not detected by drug screening tests

Detection period roughly 24Detection period roughly 24--72 hours in urine72 hours in urine•• Only metabolites are detected in urineOnly metabolites are detected in urine•• Only metabolites are detected in urineOnly metabolites are detected in urine•• Typically JWH metabolites analyzed due to availability of standards Typically JWH metabolites analyzed due to availability of standards

Approximately 8Approximately 8--48 hours in blood and oral fluid48 hours in blood and oral fluid Approximately 8Approximately 8 48 hours in blood and oral fluid48 hours in blood and oral fluid•• Parent drug detectedParent drug detected

Advanced testing methodology utilizedAdvanced testing methodology utilized Advanced testing methodology utilizedAdvanced testing methodology utilized

•• Liquid Liquid ChromatographyuChromatographyu/Tandem Mass Spectrometry (LC/Tandem Mass Spectrometry (LC--MS/MS)MS/MS)

ChallengesChallengesChallengesChallenges

Hundreds of potential compounds can be used in themanufacturing process of Spice products

Limited number of banned chemicals on the books

Moving target – Spice industry responds to the bans,g g p y p ,Laboratories must respond in kind

Lack of complete understanding of metabolism

Lack of certified metabolite standards (getting better)

Promising Synthetic Promising Synthetic CannabinoidsCannabinoids

9-THC HU-210*

JWH-133JWH 133WIN 55,212

* Banned in AZ

Drug Development:Drug Development: RimonabantRimonabantDrug Development: Drug Development: RimonabantRimonabant

(SR141716) Antiobesity drug(SR141716) Antiobesity drug Antagonist of CB1 receptor -Possible use to mediate CB1 cannabinoidpharmacodynamics by blockade of agonists

• Decrease in heart rate (BPM)

• Reduced cannabis effects of 40-75% inReduced cannabis effects of 40 75% in single dose or multiple small dosing

• No significant cannabis withdrawl

• No clinical adverse effects

RimonabantRimonabant (cont’d)(cont’d)RimonabantRimonabant (cont d)(cont d)First CB1 Receptor antagonist on the market, used in conjunction with diet and exercise for weight loss. g

Other Uses:• Assisted in smoking cessation therapy

• Addiction reduced cocaine-seeking responses by 2 of 3 most common triggers in relapse (priming and cues)

• Possible reduction of ethanol and opiate-seeking behaviorp g

• Hypothetically could improve short-term memory (in rats)

• Blocks psychoactive and cardiovascular effects of THC without p yaffecting the pharmocokinetics

FDA supported its use for obesity in 2006 but never was brought to market after f l d f b h ffailure to demonstrate safety by the manufacturer.

Benefits deemed no longer outweighing the risks – pulled in 2009

Bath Salts and OtherBath Salts and OtherBath Salts and Other Bath Salts and Other StmulantsStmulants

17th National TASC Conference on Drugs & Crime

Douglas Kramer – TASC, Inc. - Arizona

Bath SaltsBath SaltsBath SaltsBath Salts

Sold in head shops, Sold in head shops, gas stations and online gas stations and online

Psychoactive / DissociativePsychoactive / Dissociative

Illegal in many statesIllegal in many statesIllegal in many statesIllegal in many states

Highly addictive and Highly addictive and dangerousdangerousgg

Snorted, but can be smoked, Snorted, but can be smoked, taken orally or injectedtaken orally or injected

Bath SaltsBath SaltsBath SaltsBath Salts

4MMC, Meow4MMC, Meow--meow, MC, MTV,meow, MC, MTV,MM--CAT, Bounce, Plant Food CAT, Bounce, Plant Food

$30$30--90 / gram 90 / gram -- talctalc--likelike

Usually made in China / AsiaUsually made in China / Asia

Pixie Dust, Ivory Wave, Ocean, Pixie Dust, Ivory Wave, Ocean, Charge Plus, White Lightning, Charge Plus, White Lightning, g , g g,g , g g,White Girl, Scarface, Hurricane White Girl, Scarface, Hurricane Charlie, Vanilla Sky, Charlie, Vanilla Sky, BonzaiBonzai,,Grow, Blue Silk, Grow, Blue Silk, LoveyLovey DoveyDovey, ,, , yy yy

Bath Salt EffectsBath Salt EffectsBath Salt EffectsBath Salt Effects Effects last 2 Effects last 2 -- 4 hours 4 hours

Feelings of euphoria Feelings of euphoria -- Increased alertnessIncreased alertness

Dilated pupilsDilated pupils

Slurred speech, Inability to stop talkingSlurred speech, Inability to stop talkingp , y p gp , y p g

Increased heart rateIncreased heart rate

Both decreased and/or increased sexual function/desireBoth decreased and/or increased sexual function/desire

Negative EffectsNegative EffectsNegative EffectsNegative Effects

Physical: Physical: Physical: Physical: CNS stimulantCNS stimulant Increase BP and heart rateIncrease BP and heart rate Chest pain, heart attack, strokeChest pain, heart attack, stroke InfertilityInfertility

Psychological: Psychological: Delusions, paranoia, psychosisDelusions, paranoia, psychosis Personality disordersPersonality disorders Personality disordersPersonality disorders Depression when not using Depression when not using –– as long as several weeksas long as several weeks

After effects such as tachycardia, hypertension, and mildAfter effects such as tachycardia, hypertension, and mildstimulation lasting from 6 stimulation lasting from 6 -- 8 hours8 hours

Chemical CompositionChemical CompositionChemical CompositionChemical Composition

MephedroneMephedrone -- 44--methylmethcathinone (4methylmethcathinone (4--MMC)MMC)

AKA: AKA: MephMeph drone MCAT drone MCATAKA: AKA: MephMeph, drone, MCAT, drone, MCAT

Originally developed in 1929 Originally developed in 1929 -- recently “rediscovered” recently “rediscovered”

Analogue to other controlled substancesAnalogue to other controlled substances

Sold as plant food or bath salts Sold as plant food or bath salts –– not for human not for human consumptionconsumption

Chemical CompositionChemical CompositionChemical CompositionChemical Composition

MDPV (3,4MDPV (3,4--methylenedioxypyrovalerone)methylenedioxypyrovalerone)

AKA: MDPK Magic Super Coke MTV and PVAKA: MDPK Magic Super Coke MTV and PVAKA: MDPK, Magic, Super Coke, MTV and PVAKA: MDPK, Magic, Super Coke, MTV and PV

Originally developed in the 60’s for chronic fatigue andOriginally developed in the 60’s for chronic fatigue andappetite suppression. appetite suppression.

Abuse and dependence a problem with a compulsive desire Abuse and dependence a problem with a compulsive desire to continuously reto continuously re--dosedose

Similar in structure to MDMA, but more of a stimulant Similar in structure to MDMA, but more of a stimulant

Only has mild Only has mild empathogenicempathogenic or or entactogenicentactogenic propertiesproperties

High Addiction PotentialHigh Addiction PotentialHigh Addiction PotentialHigh Addiction Potential

Abuse and dependence a problem with a compulsive desire Abuse and dependence a problem with a compulsive desire to continuously reto continuously re--dosedose

Some are constantly chase that first highSome are constantly chase that first high

MephedroneMephedrone reduces to 4reduces to 4--methylephedrine methylephedrine -- a known a known MephedroneMephedrone reduces to 4reduces to 4 methylephedrine methylephedrine a known a known CardiotoxicCardiotoxic compoundcompound

Crushing chest pain Crushing chest pain –– common common redosingredosing the cause?the cause? Crushing chest pain Crushing chest pain common common redosingredosing the cause?the cause?

Other StimulantsOther StimulantsOther StimulantsOther Stimulants

CathinoneCathinone

Found in the shrub Found in the shrub Catha Catha edulisedulis ((KhatKhat) ) Found in the shrub Found in the shrub Catha Catha edulisedulis ((KhatKhat) )

Part of the Middle East culturePart of the Middle East culture

Stimulant typically extracted from Stimulant typically extracted from chewing fresh leaveschewing fresh leaves

Other StimulantsOther StimulantsOther StimulantsOther Stimulants

MethcathinoneMethcathinone

First synthesized in 1928First synthesized in 1928 First synthesized in 1928First synthesized in 1928

It was used in the Soviet Union during the 1930s and It was used in the Soviet Union during the 1930s and 1940s as an anti1940s as an anti depressant depressant 1940s as an anti1940s as an anti--depressant. depressant.

Since the 1960s, Since the 1960s, methcathinonemethcathinone has been used as a has been used as a recreational drug in the (former) Soviet Unionrecreational drug in the (former) Soviet Unionrecreational drug in the (former) Soviet Union.recreational drug in the (former) Soviet Union.

Stimulant StructuresStimulant Structures

CathinoneMethcathinoneMephedrone

MDPV MDMAMDPV MDMA

DetectionDetectionDetectionDetection Most compounds are not detected by drug screening testsMost compounds are not detected by drug screening tests Most compounds are not detected by drug screening testsMost compounds are not detected by drug screening tests

Detection period roughly 24Detection period roughly 24--72 hours in urine72 hours in urine

AnalyteAnalyte--specific methodologies are usedspecific methodologies are used

G Ch t h /M S t t (GCMS)G Ch t h /M S t t (GCMS)•• Gas Chromatography/Mass Spectrometry (GCMS)Gas Chromatography/Mass Spectrometry (GCMS)•• Liquid Liquid ChromatographyuChromatographyu/Tandem Mass Spectrometry (LC/Tandem Mass Spectrometry (LC--MS/MS)MS/MS)

Specialized Stimulants Panel should include:Specialized Stimulants Panel should include: Specialized Stimulants Panel should include:Specialized Stimulants Panel should include:•• Amphetamine / MethamphetamineAmphetamine / Methamphetamine•• MDA / MDMAMDA / MDMA•• CathinoneCathinone / / MethcathinoneMethcathinoneCat o eCat o e // et cat o eet cat o e•• MephedroneMephedrone / MDPV/ MDPV

TASC, Inc. 2008TASC, Inc. 2008

Questions and CommentaryQuestions and Commentary

Thank You!Thank You!

Presentation: www.tascaz.org/NTASC2011

Doug Kramer: (602) 257-7588 x189g ( )

dkramer@tascaz.org

www.tascaz.org

SalviaSalviaSalviaSalvia

Active constituent Active constituent -- SavinorinSavinorin AA

Most potent naturallyMost potent naturallyp yp yoccurring hallucinogenoccurring hallucinogen

Rapid high in 1Rapid high in 1--5 minutes5 minutesRapid high in 1Rapid high in 1 5 minutes5 minutes

Tapers off 5Tapers off 5--10 minutes10 minutes

Return to “baseline” in Return to “baseline” in 2020--30 minutes30 minutes