DEA/OD/ODE page 1 of 39 May 08, 2013 1

- pentyl

- 3

- (2,2,3,3

- tetramethylcyclopropoyl)indole (UR

- 144),
1

- (5

- fluoro

- pentyl)

- 3

- (2,2,3,3

- tetramethylcyclopropoyl)in dole (5

- fluoro

- UR

- 144;
XLR11 ) and N

- (1

- adamantyl)

- 1

- pentyl

- 1H

- indazole

- 3

- c arboxamide (APINACA, AKB48 )

Background Information and Evaluation of ‘ Three Factor Analysis ’ (Factor s 4, 5 and 6) for T emporary S cheduling

Drug and Chemical Evaluation Section, Office of Diversion Control, Drug Enforcement Administration, Washington
, DC 20537

May 2013

Introduction

Since 2009 , there has been a marked increase in th e law enforcement encounters of various synthetic cannabinoids in the United States

. Both law enforcement and public health reports suggest the sustained popularity of these substances i n the designer drug market, most commonly abused as plant material adulterants. The se associated products are often being sold as incense and lab eled ‘not for human consumption ’

. Additionally, the se products are mark eted as a ‘legal high ’ or

‘ legal alternative to marijuana’ and are readily available over the internet, in head shops, or sold in convenie nce stores.

These substances have no accepted medical use in the United States and have been reported to produce adverse effects in humans. Chronic abuse of synthetic cannabinoids in general ha s been linked to adverse health effects including signs of addiction and withdrawal ( Zimmermann et al., 2009 ; Muller et al., 2010 ) , as well as numerous reports of emergency room admissions resulting from the ir abuse (Forrester et al., 201 1; Hermanns

- Clausen et al., 2013 , SAMHSA, 2012 )

.

1

- pentyl

- 3

- (2,2,3,3

- tetramethylcyclopropoyl)indo le (UR

- 144), 1

- (5

- fluoro

- pentyl)

- 3

- (2,2,3,3

- tetramethylcyclopropoyl)indole (5

- fluoro

- UR

- 144; XLR11 ) and N

- (1

- adamantyl)

- 1

- pentyl

- 1H

- indazole

- 3

- carboxamide (APINACA, AKB48 ) are synthetic cannabinoids (Figure 1) and are pharmacologically similar to the Schedule I hallucinogen delta

- 9

- tetrahydrocannabinol (Δ 9

- THC). UR

- 144 was first developed as a research tool by Abbott laboratories ( Frost et al., 2010). XLR11 and AKB48 were not designed as research tools, however began showing up in seizures in 201 1

. F rom January 2010 through April 3 , 2013 according to the System to Retrieve Information on Drug EvidenceDEA/OD/ODE page 2 of 39 May 08, 2013 (STRIDE 1 ) data, there are 1,510 reports involving 1 79 cases for UR

- 144, 1,194 reports involving 186 cases for XLR11 and 112 reports involving 40 cases for AKB48. From January 2010 to March 2013 , the National Forensic Laboratory Information System (NFLIS 2 ) registered 14,831 reports containing these synthe tic cannabinoids (UR

- 144

– 5,465 reports; XLR11

– 8,837 reports; AKB48

– 529 reports) in at least 32 states. No reports regarding UR

- 144, XLR11 or AKB48 were reported in NFLIS prior to March of
2010

.

For the period January 2010 through March 2013, NFLIS and STRIDE reports for the three synthetic cannabinoids UR

- 144, XLR11, and AKB48 (16,014 t otal reports) exceeded the number of reports for the five synthetic cannabinoids JWH

- 018, JWH

- 073,
JWH

- 200, CP

- 47,497, and CP

- 47,497 C8 (7,555 total reports). JWH

- 018, JWH

- 200, JWH

073, CP

- 47,497 and CP

- 47,497 C8 homologue were temporarily scheduled on Ma rch 1, 2011, and later placed in Schedule I by Section 1152 of Food and Drug Administration Safety and Innovation Act (FDASIA), Pub. L. 112

- 144, on July 9, 2012. Section 1152 of the FDASIA amended the CSA by placing cannabimimetic agents and 26 specific

s ubstances (including 15 synthetic cannabinoids, 2 synthetic cathinones, and 9 phenethylamines of the 2C

- series) in Schedule I. UR

- 144, XLR11, and AKB48 were not included among the 15 specific named synthetic cannabinoids, and do not fall under the definit ion of cannabimimetic agents, under FDASIA.

With no legitimate medical use and limited pharmacological information , these substances (UR

- 144, XLR11 and AKB48 ) have emerged on the designer drug market and are being abused for their psychoactive properties. To protect the public health and safety, the Drug Enforcement Administration (DEA) intends to temporar il y place UR

- 144,
XLR11 and AKB48 in S chedule I of the C ontrolled Substances Act (CSA)

. With respect to finding an imminent hazard to the public safety
, DEA has considered the factors required under the CSA for the temporary scheduling of UR

- 144, XLR11 and AKB48

. 21 U.S.C. 811(h)(3) and 811(c)(4)

- (6).

1 STRIDE, a DEA database which compiles information on exhibits analyzed in DEA laboratories.
2 NFLIS, a DEA database which compiles information on exhibits analyzed in state and local laboratories.DEA/OD/ODE page 3 of 39 May 08, 2013 N N N H O

A K B

- 4 8 N O

U R

- 1 4 4 N O

X L R

- 1 1

F

Figure 1 . Chemical Structures

UR

- 144 and XLR11 are classified as cyclopropylindoles, a class of compounds that have previously been investigated due to their possible cytotoxic, anti

- cancer or a nti

- HIV potentials ( Wang et al., 1996
, Milbank et al., 1999
, Sharma et al., 2001
, Choi and Ma,
2010 , Hassam, 2012 ) as well as their affinity for cannabinoi d receptors ( Frost et al.,
2010 )

. Currently available data for UR

- 144 include binding ( Frost et al., 2010 , Perkin Elmer , 2013 a ; RTI, 2013 ) locomotor (Elsken et al., 2013 a ) and drug discrimination (RTI, 2013) data (Table 1)

. Similarly
, currently available data for XLR11 include binding and drug discrimination data (RTI, 2013), a functional assay test ( Perkin Elmer et al., 2013) and locomotor data (Elsken et al, 2013 b ; Table 1 ). AKB48 is classified as a pentyl indazole and has been repor ted in the literature as a cannabinoid agonist ( Uchiyama,
2012a , Uchiyama et al., 2012b )

. To date, AKB48 has been evaluated in in vitro binding and functional assay s and in locomotor study (Elsken et al., 2013 c , Perkin Elmer, 2013 c ; Table 1 ).

Synthetic Cannabinoids

1

- pentyl

- 3

- (2,2,3,3

- tetramethylcyclopropoyl)indole (UR

- 144)

UR

- 144 has been shown to bind to both the CB1 and CB2 receptors ( Frost et al.,
2010 ; RTI, 2013 )

. A study conducted by contract researchers of the National Institute on Drug Abuse (NIDA ) and of the DEA indicated that UR

- 144 is an agonist at CB1 and CB2 receptors ( Perkin Elmer , 2013 a ; RTI, 2013 )

. UR

- 144 ( ED 50 = 7.1 μmol/kg ) has been shownDEA/OD/ODE page 4 of 39 May 08, 2013 to be THC

- like in d rug discrimination studies (RTI, 2013). A NIDA study evaluating locomotor effects of UR

- 144 concluded that treatment with UR

- 144 resulted in both time

- and dose

dependent depression of locomotor activity following 10 and 30 mg/kg (Elsken et al.,
2013 a ). UR

- 144 is chemically similar to other Schedule I substances such as JWH

- 018 and
AM

- 2201

. These substances ( UR

- 144 , AM

- 2201 and JWH

- 018 ) share the same core indole structure with substitutions at the 1 a nd 3 positions of this fused bi cyclic ring system. They bind to CB1 receptors, and are substances representative of the aminoalkylindole structural class. Numerous substances of the a minoalkylindole class have been shown to exhibit typical cannabinoid pharmacology in vivo ( D'Ambra et al., 1992 ; Compton et al., 1992a )

.

1

- (5

- fluoro

- pentyl)

- 3

- (2,2,3,3

- tetramethylcyclopropoyl)indole (5

- fluoro

- UR

- 144; XLR11 )

XLR11 was first identified in 2012 as an ingredient in synthetic cannabis smoking blends. XLR11 , similar to JWH

- 018, is a substance representative of the aminoalkylindole structural class. Numerous substances of the aminoalkylindole class are known to exhibit CB1 cannabinoid pharmacology in vivo ( D'Ambra et al., 1992
, Compton et al., 1992a )

. The cyclopro pylindole XLR11 , also known as 5

- fluoro

- UR

- 144, closely resembles UR

- 144 in that it retains the identical core structure. A fluorine group is added to the end of the side chain attached to the 1

- position of the indole core. While XLR11 shows structural similarity to UR

- 144, JWH

- 018, AM

- 2201, A

- 796,260 and
A

- 834,735, it was not listed in any patent or scientific literature alongside these compounds and does not appear to have been produced by Abbott Laboratories. The

structure

- activity relationship infor mation indicates that the substitution of a fluoride atom on the terminal position of the five carbon alkyl chain (pentyl) (Example AM

- 2201
vs. JWH

- 018) is well

- tolerated. Thu s, it is anticipated that the substitution of a fluoride atom on the alkyl chain of UR

- 144 , as is the case with XLR11 , would retain similar binding affinity for the CB1 receptor. Structure

- activity relationship studies indicate that indole derivatives substituted with an alkyl group at the indole

- 1 position retain activity at the can nabinoid receptors ( Huffman, 1994 ; Wiley et al., 1998
, Aung et al., 2000 ) and replacement of the naphthyl group by a tetramethylcyclopropyl also retains activity at the cannabinoi d receptors ( Frost et al., 2010 )

. XLR11 , similar to JWH

- 018, has the above

- mentioned substitutions at the indole

- 1 and indole

- 3 positions.

XLR11 has been shown to bind to both the CB1 and CB2 receptors (RTI, 2013 )

. A study conducted by contract researchers of the National Institute on Drug Abuse (NIDA) and of the DEA indicated that XLR11 is an agonist at CB1 and CB2 receptors ( Perkin Elmer , 2013 b ; RTI, 2013 ). XLR11 ( ED 50 = 3.3 μmol/kg ) has been shown to be THC

- lik e in d rug discrimination studies (RTI, 2013). A study by the contract researchers of the NIDADEA/OD/ODE page 5 of 39 May 08, 2013 found that XLR11 (10 and 30 mg/kg) suppresses locomotor activity in both time

- and dose

- dependent manner (Elsken et al., 2013 b ). A report by the Centers for Dis ease Control and Prevention (CDC) in February of 2013 described 16 patients that presented to emergency depar tments with nausea, vomiting
, abdominal pain and acute kidney injury following smoking of synthetic cannabinoids (CDC , 2013)

. Of these 16 patients, toxicological analysis of product samples and clinical specimens identified XLR11 or its metabolite in 7 of the 16 patients.

N

- (1

- adamantyl)

- 1

- pentyl

- 1H

- indazole

- 3

- carboxamide (APINACA, AKB48 )

The pentyl indazole AKB48 , also referre d to as APINACA, is expected have a potent affinity for both the CB1 and CB2 receptors based upon data that show confirmed analogs of AKB48 , differing only by the addition of a functional group (Cl

- , I

or CN

- group substituted for the terminal methyl of the pentyl moiety) have a very high affinity for the cannabinoid receptors. Three compounds referred to as analogs for
AKB48 had reported K i values of 1.7, 0.6 and 2.3 nM for the CB1 receptor ( Makriyannis,
2003 ) ( Uchiyama, 2012a )

. AKB48 has been shown to bind to both the CB1 and CB2 receptors (RTI, 2013; Uchimaya et al., 2012b )

. A study conducted by contract researchers of the National Institute on Drug Abuse (NIDA) indicated that AKB48 is an agonist at CB1 receptors ( Perkin Elmer , 2013 c ). F irst identified in Japan in March of 2012 as an ingredient in synthetic cannabis smoking blends ( Uchiyama et al., 201 2b )
, AKB48 closely resembles cannabinoid compounds outlined in patent WO 2003/0 35005 ( Makriyannis, 2003 )

. AKB48 is structurally similar to JWH

- 018 with AKB48 containing a pentyl chain on the indazole

- 1 position. A drug discrimination study demonstrated that
JWH

- 018 fully substitute s for THC at 3 mg/kg (Jarbe et al., 2011). JWH

- 018 was also reported to suppress th e locomotor activity of rats with greater significance and for longer duration than Δ 9

- THC ( Uchiyama et al., 2012c ) , suggesting that AKB48 may have cannabimimetic activity similar to that of JWH

- 018 ( Uchiyama, 2012a )

. A s tudy by the contract researchers of NIDA found that AKB48 (3 to 30 mg/kg) reduces locomotor activity in both time

- and dose

- dependent manner ( Elsken et al., 2013 c ).DEA/OD/ODE page 6 of 39 May 08, 2013 Table 1 . Summary of Available Pharmacology Data for UR

- 144, XLR11 and
AKB48

In vivo In vitro

Binding at CB1 Function at CB1 Locomotor Activity (8

- hr session) THC Drug Discrimination

UR

- 144 K i = 28.9 nM A

K i = 150 nM I Agonist
EC 50 = 1295
nM B Depressed (ID 50 =7.8 mg/kg) F Full Substitution

( ED 50 = 7.1 μmol/kg A )
XLR11 K i = 24.2 nM A Agonist
EC 50 = 359 nM C Depressed (ID 50 =10.3

mg/kg) G Full Substitution

( ED 50 = 3.3 μmol/kg A )
AKB48 K i = 304.5 nM D Agonist
EC 50 = 585 nM E Depressed (ID 50 =2.2 mg/kg) H NC

A RTI International, 2013

B Perkin Elmer , 2013 a
C Perkin Elmer, 2013b

D Perkin Elmer, 2013c

E Perkin Elmer, 2013d

F Elsken et al., 2013 a
G Elsken et al., 2013 b

H Elsken et al., 2013 c
I Frost et al., 2010
NC

– not completed

Factor 4. Its history and current pattern of abuse

Synthetic cannabinoids were first reported in the United States in a December 2008 encounter, where a shipment of ‘Spice’ was seized and analyzed by U.S. Customs and Border Patrol in Dayton, Ohio. Additionally around the same time, in December 2008, JWH

018 and cannabicyclohexanol were identified by German fore nsic laborat ories ( EMCDDA,
2009 ) . It has been stated that there is a belief that these substances existed and were abused some time pr ior to their identification ( Psychonaut Web Mapping Research Group,
2009 )

.DEA/OD/ODE page 7 of 39 May 08, 2013 Since the initial identification of JWH

- 018 (December 2008), many additional synthetic cannabinoids have been found laced on related products ( Auwarter et al., 2009
, DEA, 2009 ) . The popularity of these cannabimimetic substances and their associated products appea rs to have increased since January 2010 in the United States based on seizure exhibits and media reports. This trend appears to mirror those expe rienced in Europe since 2008 ( EMCDDA, 2009 )

. Synthetic cannabinoids are being encountered in most regions of the U.S. with the substances found as adulterants on plant material or being abused alone as self

- reported o n internet discussion boards ( Atwood et al., 2010 )

.

Data gathered from published studies, supplemented by discussions on Internet discussion websites and personal communications demonstrate that these products are being abused mainly by smoking for their psychoactive properties. The adulterated products are marketed as ‘legal’ alternatives to marijuana. This characterization and their reputation as potent herbal intoxicants increased their popularity ( Lindigkeit et al., 2009 )

. These substances alone or laced on plant material have the potential to be more harmful than cannabis due to their method of manufacture a nd the potency of the substances. Several synthetic cannabinoids have been shown to display higher potency in vitro and in
vivo when compared to Δ 9

- THC ( Compton et al., 1992a
, Wiley et al., 1998 ) . Smoking mixtures of these substances abused for the purpose of achievin g intoxication have resulted in numerous emergency room visits and calls to poison control centers. Abuse of these synthetic cannabinoids and their products has been characterized with both acute and long term public health and safety issues. Numerous st ates, local jurisdictions, and the international community have also controlled these substances.

Synthetic cannabinoids have been developed over the last 30 years to be used as tools for investigat ing the cannabinoid system ( Weissman et al., 1982; Huffman et al., 1996; Huffman et al., 1999 ) . Subsequently, these substances have been identified as adulterants in numerous retail products ( Auwarter et al., 2009
, EMCDDA, 2009 , Lindigkeit et al., 2009
, Dresen et al., 2010
, Hudson et al., 2010
, Uchiyama et al., 2010
, Uchiyama,
2012a , Uchiyama et al., 2012b ) . JWH

- 018 was the first synthetic cannabinoid to be identified as a product adulterant in Germany in 2008 . This substance was initially synthesized as a research tool to investigate the cannabinoid system ( Huffman, 1994
, Wiley et al., 1998 )

. Since then
, numerous other synthetic cannabinoids including UR

- 144,
XLR11 and AKB48 have been id entified as product adulterants and b ulk seizures have occurred by law enforcement. NFLIS details over 13,956 reports from forensic laboratories identifying UR

- 144, XLR11 and AKB48 in drug related reports for a period from March 2010

to April 03 , 2013

. In addition, STRIDE has 2,816 reports involving UR

- 144, XLR11 and
AKB48 from January 2009 through April 03 , 2013.DEA/OD/ODE page 8 of 39 May 08, 2013 Youth appear to be the primary abusers o f synthetic cannabinoids and synthetic cannabinoid

- containing products
, as supported by law enforcement encounters and reports from emergency rooms (SAMHSA, 2012) 3 ; however, all age groups have been discussed in media reports as abusing these substances and related products. For patien ts between the ages of 12

- 29, 75 % of emergency department visits in 2010 involved synt hetic cannabinoids . In additi on, the majority (59%) of emergency department visits of patients aged 12 to 29 did not involve any other substance. Of the remaining 41% of individuals, the most frequently abused substance in combination with synthetic cannabinoids was marijuana (17%), pharmaceuticals (17%) and alcohol (13%) (SAMHSA, 2012)

. Individuals including minors are purchasing synthetic cannabinoids from Internet websites, gas stations, convenience stores, and head shops. These substances and laced products are commonly marketed as ‘legal highs’ with a disclaimer of ‘not for human consumption ’

. As detailed in reports, law enforcement and public health officials are encountering the abuse of these substances (CDC , 2013, NFLIS, 2013, STRIDE, 2013)

.

Numerous herbal incense product s have been found to contain one or more synthetic cannabinoid ( s ) (UR

- 144, XLR11 and/or AKB48 ) lac ed on plant material (Appendix 1 ). There is no known explanation for the addition of these synthetic cannabinoids to plant material being marketed as herbal incense, other than for their psychoactive properties ( Lindigkeit et al., 2009 ) . The psychoactive properties are directly linked to the synthetic cannabinoids laced on the plant material sold as retail products ( Auwarter et al., 2009
, EMCDDA, 2009 , Atwood et al., 2010 )

. To lace the plant material, the s ynthetic cannabinoids are generally dissolved in a solvent and sprayed on the plant material or the plant material is soaked in a solution of the dissolved substance ( Vardakou et al., 2010
, Wells and Ott, 2011 )

. Two research articles propose that the packaging is professional and in conspicuous (unlabeled) , targeting young people, poss ibly eager to use cannabis, but who are afraid of the judicial consequences and/or association with illicit drugs ( Lindigkeit et al., 2009
, Schifano, 2009 )

.

Dresen and colleagues ( Dresen et al., 2010 ) found that synthetic cannabinoids are being abused by individuals in drug treatment centers with a positive rate of 63 .3% in forensic psychiatric cent ers based on their sampling . U.S. Drug Courts 4 have

3 SAMHSA is a branch of the U.S. Department of Health and Human Services. It is charged with improving the quality and availability of prevention, treatment, and rehabilitative services in order to reduce illness, death, disability, and cost to society resulting from substance abuse and mental illnesses.
4 Drug c ourts were developed to achieve a reduction in recidivism and substance abuse among nonviolent, substance abusing offenders by increasing their likelihood for successful rehabilitation through early, continuous, and intense judicially supervised treatment, mandatory periodic drug testing, and the use of appropriate sanctions and other rehabilitation services. Drug courts analyze specimens from participants for new and existing drugs of abuse.DEA/OD/ODE page 9 of 39 May 08, 2013 communicated concerns related to the abuse of synthetic cannabinoids and a response rate of greater than 30% by juveniles subject to routine drug screens from a sampling ( information communicated to DEA).

As part of the Monitoring the Future (MTF) 5 Report for 2012, some of the most important findings were presented in a press release on December 19, 2012. In this press release, the MTF study detailed that while synthetic cannabinoid use has remained level in 12 th graders at 11.3%, “the fact that its prevalence rate has remained high despite federal and state efforts to reduce its use is troublesome” (Johnston et al., 2012). For the fir st time, synthetic cannabinoid use in 8 th and 10 th graders was measured, with annual prevalence rates being 4.4% and 8.8% respectively.

Summary Recently
, law enforcement has been encountering UR

- 144, XLR11 and AKB48 and their products in increasing numbers. Synthetic cannabinoids and their associated products are available over the Internet or found to be sold in gas stations, convenience stores, and tobacco and head shops. UR

- 144, XLR11 and AKB48 , similar to the previously scheduled synthetic cannabinoids (DEA, 2012)
, have been seized alone and spiked on products that are marketed as herbal incense and promoted as legal alternatives to marijuana.

Factor 5. The scope, duration, and significance of abuse

NFLIS, a n ational database capturing data from forensic laboratories, has reported 14,831 reports ( January 2010 to March 2013) related to UR

- 144, XLR11 and
AKB48 from various s tates including, Alaska, Alabama, Arkansas, California, Colorado, Florida, Georgia, Iowa, Indiana, Illinois, Kansas, Kentucky, Louisiana, Maryland, Minnesota, Missouri, New Hampshire, New Jersey, New Mexico, North Dakota, Nebraska, Nevada, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Utah, Virginia , Wisconsin and Wyomin g (query date: May 6 , 2013)

. STRIDE has 2,816 reports involving UR

- 144, XLR11 and /or AKB48 from January 2010 through April 3 , 2013 (query date: April 04 , 2013)

. Recently, increased exposure incidents have been documented by poison control centers in the United States as the abuse of synthetic cannabinoids has been associated with both acute and long

- term public health and safety concerns. From January 1 through December 31 , 2012 , the American Association of Poison Control Centers (AAPCC) ha s reported receiving an excess of 5,200 exposure

5 MTF is a national survey conducted by the Institute for Social Research at the University of Michigan under a grant from the National Institute on Drug Abuse (NIDA) that tracks drug use trends among American adolescents in the 8 th , 10 th , and 12 th grades.DEA/OD/ODE page 10 of 39 May 08, 2013 calls corresponding to products purportedly laced with synthetic cannabinoids , although the data provided does not generally include biological sample testing that would confirm which cann abinoids the user was exposed to 6

. In addition, AAPCC has reported over 400 calls regarding synthetic cannabinoids through February of 2013. A majority of exposure incidents resulted in seeking medical attention at health care facilities. Chronic abuse of synthetic cannabinoids ha s been linked to signs of addiction and withdrawal similar to that experienced with cannabis abuse ( Zimmermann et al., 2009
, Muller et al., 2010
, Vardakou et al., 2010 ) . Additionally, tolerance to these drugs may develop fairly rapid ly with larger doses being required to achieve the desired effect ( EMCDDA, 2009 )

. In 2010, the Substance Abuse and Mental Health Services Administration (SAMHSA) reported 11,406 emergency department visits involved a synthetic cannabinoid product. In 2011, SAMHSA reported the number of emergency department visits involving a synthetic cannabinoid product had increased 2.5 times to 28, 531 (SAMHSA, 2013) (Figure 2 )

.

Synthetic cannabinoids and the associated products are sold over the Internet and found to be abused by diverse po pulations. Since synthetic cannabinoids were never intended for human consumption, minimal information exists as to the health implications resulting from exposure to these substances ( Griffiths et al., 2010
, Vardakou et al., 2010 )

. The scientific literature and reports received by DEA suggest that tolerance and dependence to synthetic cannabinoids may develop ( Zimmermann et a l., 2009 )

.

The increased abuse of these synthetic cannabinoids in the United States is supported by an increasing number of encounters by law enforcement. Over the past year, in the United States, there has been a significant increase in availability, trafficking an d abuse of UR

- 144, XLR11 and AKB48 , evident from the increasing number of encounters reported by forensic laboratories (NFLIS data). The initial indication of the evidence of abuse of AKB48 appeared in 2011 upon identification in products, with evidence o f abuse of
UR

- 144 and XLR11 appearing in 2012. Due to the previous temporary scheduling action of the five synthetic cannabinoids (JWH

- 018, JWH

- 200, JWH

- 073, CP

- 47,497 and CP

- 47,497 C8

6 The content of this report does not necessarily reflect the o pinions or conclusions of the American Association of Poison Control Centers. The American Association of Poison Control centers (AAPCC; http://www.aapcc.org ) maintains the national database of information logged by th e country’s 57 Poison Control Centers (PCCs). Case records in this database are from self

- reported calls: they reflect only information provided when the public or healthcare professionals report an actual or potential exposure to a substance (e.g. an ing estion, inhalation, or topical exposure, etc.), or request information/educational materials. Exposures do not necessarily represent a poisoning or overdose. The AAPCC is not able to completely verify the accuracy of every report made to member centers. Additional exposures may go unreported to PCCs and data referenced from the AAPCC should not be construed to represent the complete incidence of national exposures to any substance(s).DEA/OD/ODE page 11 of 39 May 08, 2013 homologue [cannabicyclohexanol], March 1, 2011) , followed by the SDAPA (July 9, 2012) which permanently place d these initial five substances into Schedule I but also controlled a number of additional substances, manufacturers and users of synthetic cannabinoids then

turn ed to new synthetic cannabinoids, namely UR

- 144, XLR11 and AKB48

.

Figure 2 . Emergency department visits involving synthetic cannabinoids (SAMHSA, 2013). Data were not collected prior to 2010. *Estimates of ED visits are based on a representative sample of non

- Federal, general, short

- stay hospitals with 24

- hour EDs in the U.S.

P roduct analyses have yielded important information regarding these synthetic substances. Smoking mixtures sold in Russia have been analyzed and found to contain
UR

- 144 along with other compounds, including J WH

- 018 ( Sobolevsky et al., 2012 )

. AKB48 , UR

- 144 and XLR11 have also been identified in designer drugs currently b eing sold in Japan ( Uchiyama, 2012a
, Uchiyama et al., 2012b ) . The chronic abuse of products laced with synthetic cannabinoids has been linked to addiction and withdrawal ( Vardakou et al., 2010 )

.

Summary

The abuse of synthetic cannabinoids is characterized in the scientific literature and by law enforcement encounters with reported adverse health effects. Numerous calls have been received by poison control centers regarding the abuse of products 0 5000 10000 15000 20000 25000 30000

2010 2011 

## Emergency Department Visits Involving Synthetic Cannabinoids*DEA/OD/ODE page 12 of 39 May 08, 2013 potential ly laced with synthetic cannabinoids that have resulted in visits to emergency departments. Following the SDAPA in July of 2012, new generations of synthetic cannabinoids including UR

- 144, XLR11 and AKB48 increasingly replaced those cannabinoids that were placed into Schedule I of the CSA.

Factor 6. What, if any, risk there is to the public health

Law enforcement, military, and public health officials have reported exposure incidents that demonstrate the dangers associated with abuse of synthetic cannabinoids to both the individual abusers and other affected individuals since these substances were never intended for human use. Warnings regarding the dangers associated with abuse of synthetic cannabinoid s and their products have been issued by numerous state public health departments and poison control centers and private organizations. Detailed product analyses describe variations in the amount and synthetic cannabinoid laced on the plant material even within samplings of the sa me product ( Hudson et al., 2010 ) . These unknowns
pr esent a significant risk or danger to the abusing ind ividuals ( Auwarter et al., 2009
, Hudson et al., 2010 )

. Wells and Ott stated concern regarding the possibility of serotonin syndrome related to synthetic cannabinoids of the indole structural class due to the similarity to
serotonin ( Wells and Ott, 2011 )

. Some of the common clinical effects reported in
emergency rooms in response to the abuse of synthetic cannabinoids include vomiting, anxiety, agitation, irritability, seizures, hallucinations, tachycardia, elevated blood pressure, and loss of consciousness ( Harris and Brown, 2013; Hermanns

- Clausen et al., 2012; Forrester et al., 2011; Cohen et al., 2012 ) (see reports from state health departments and poison centers including AAPCC, Appendix 1).

By sharing pharmac ological similarities with the S chedule I substances ( Δ 9

- THC and
JWH

- 018 )
, synthetic cannabinoids pose a risk to the abuser ( Weissman et al., 1982
, Compton et al., 1992a
, Wiley et al., 1998 ) , and t he chronic abuse of products laced with synthetic cannabinoids has been linked to addiction and withdrawal ( Vardakou et al.,
2010 )

. Submissions to DEA laboratories from January 2012 through April 03, 2013 have documented over 150 distinct packaging examples containing mixture s of UR

- 144, XLR11 and/or AKB48

. S imilar products have been found to vary in the amount and type of synthetic cannabino id laced on the plant material, which could by one explanation for the

n umerous emergency department admissions that have been connected to these substances ( Vearrier and O sterhoudt, 2010
, Schneir et al., 2011 )

. In 2010, 11, 406 emergency department visits involved a synthetic cannabinoid produ ct (SAMHSA, 2012). In 2011, SAMHSA reported the number of emergency department visits involving a synthetic cannabinoid product had increased 2.5 times to 28,531 (SAMHSA, 2013)

. HealthDEA/OD/ODE page 13 of 39 May 08, 2013 warnings have been issued by numerous state public health departments and poison control centers describing adverse health effects associated with smoking (inhaling) these products including, agitation, vomiting, tachycardia, elevated blood pressure, seizures, hallucinations and non

- responsiveness (Appendix 1).

Due to in creasing trends in this newer generation of synthetic cannabinoids, UR

144 and XLR11 have been added to the toxicological panel (i.e. a list of synthetic cannabinoids commonly tested for) from two major laboratories. NM S Laboratories (Willow Grove, PA ) re

- analyzed 46 blood samples collected in July 2012. These samples had been positive for a synthetic drug compound, but were originally not tested for UR

144 or XLR11 . Upon re

- analysis, 27/46 (58 %) we re positive for UR

- 144 and 14/46 (30 %) were positive for XLR11 7

. An additional 28 samples collected in December 2012 were analyzed using NMS Laboratories new scope which includes UR

- 144 and XLR11 testing. Results from these 28 samples demonstrated 8/28 (28%) positivity for UR

- 144 and 12/28 (44%) positivity for XLR11 8

. Redwood Laboratories (Santa Rosa, CA) has also recently added UR

- 144 and XLR11 to their toxicological panel. From January through June 2012, Redwood Laboratories reported between 6.5

– 9.7% positivity for synthetic cannabinoids, not including UR

- 144 or XLR11 9 . These levels diminished in the subsequent 6 months between July and December 2012, falling from 8.0 % in July 2012 to a low of 2.8% positivity in December 2012. Using a new panel, Redwood Laboratories re

- analyzed 300 randomly chosen sam ples from December 2012, and found the positivity results climb to 16% (39/300 for UR

- 144 and/or XLR11 alone) for all synthetic cannabinoids tested when including UR

- 144 and XLR11 in the panel where tests without UR

- 144 and XLR11 showed only 2.8 % positivi ty ( Table 2 ) 10

. Th ese data suggest newer non

- controlled synthetic cannabinoids are being abused , specifically UR

- 144 and XLR11

. A third company, Premier Integrity Solutions (Russell Springs, KY), supplies the toxicological services for the state of Kentucky’s drug court program. Data provided by the court coordinator for the state of Kentucky demonstrated that there were 310 drug tests for synthetic cannabinoids dating from July 1, 2012 through December 20, 2012. Of these 310 drug tests, 24 were pos itive for synthetic cannabinoids, with 19/24 showing positivity for UR

- 144 or one of its metabolite 11 , 12 . No testing for XLR11 was reported.

7 Correspondence from NMS Laboratories to ODEC, DEA 12/31/2012 8 Corr espondence from NMS Laboratories to ODEC, DEA 12/20/2012 9 Correspondence from Redwood Laboratories to ODEC, DEA 01/07/2013 10 Correspondence from Redwood Laboratories to ODEC, DEA 01/07/2013 11 Correspondence from Kentucky Court System to ODEC, DEA 12/20/20 12 12 Correspondence from Kentucky Court System to ODEC, DEA 12/21/2012)DEA/OD/ODE page 14 of 39 May 08, 2013 Table 2 . Synthetic Cannabinoid Testing by Redwood Laboratories Percent Positivity Synthetic Cannabinoids a (Excluding UR

- 144/ XLR11 ) Synthetic Cannabinoids b (Including UR

- 144/ XLR11 ) December 2012 2.8 % 16 %

a 238/8118 total samples tested by Redwood Laboratories in December 2012

b 39/300 randomly selected samples by Redwood Laboratories from December 2012

Since abusers obtain these drugs through unknown sources, purity of these drugs is
uncertain
, thus posing significant adverse health risk to these users ( EMCDDA, 2009 , Dresen et al., 2010 )

. As mentioned above, there are reported instances of emergency department admissions i n associat ion with the abuse of these THC

- like substances . There is no accepted medical use of these substances in the United States.

In February 2013, the CDC published a report describing unexplained cases of acute kidney injury in 16 patients, all of whom had reported recent smoking of synthetic cannabinoids. Upon further investigation, it was determined that of the 16 patients, 7 of the subjects had smoked substances that were positive for XLR11 or its metabolite. Cases were reported from Wyoming (4 cases), Rhode Island (1 case), New York (2 cases), Oregon (6 cases), Kansas (1 case) and O klahoma (2 cases) (CDC , 2013).

According to a letter from Assistant Secretary of Health Howard Koh of the Department of Health and Human Services (dated March 14, 2013, see attached), the Food and Drug Administration has reported there are currently no approved drug applications and no investigationa l new drug applications for UR

- 144, XLR11 or AKB48. The Department of Health and Human Services has no objection as to DEA’s plan to temporarily place UR

144, XLR11 and AKB48 into Schedule I of the CSA.

Conclusion of 3

- Factor Analysis

After a careful re view of the scientific literature, Factors 4, 5, and 6, NFLIS, STRIDE, and other law enforcement data and sources of information, it is evident that UR

- 144,
XLR11 , and AKB48 are trafficked and abused and pose a significant public health risk. These drugs have become popular among drug abusers due to their THC

- like effects and pharmacological similarity to JWH

- 018.

DEA has considered the three criteria for placing a substance into Schedule I of the CSA (21 U.S.C. 812). The data available and reviewed for UR

- 144, XLR11 , and AKB48DEA/OD/ODE page 15 of 39 May 08, 2013 indicated that these substances , including their salts, isomers, and salts of isomers, pose an imminent hazard to public safety and health, have no currently accepted medical use in treatment in the United States, and lack accepted safety for use under medical supervision.DEA/OD/ODE page 16 of 39 May 08, 2013 R eferences

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Public Health
1. The Substance Abuse and Mental Health Services Administration (SAMHSA) reported that in 2010, and estimated 11,406 emergency department visits involved a synthetic cannabinoid product. 2. Monitoring the Future study results for 2012 (released 12/19/2012) state that for the second year of reporting, use of synthetic marijuana amongst 12 th graders held level at 11.3%. Study authors stated that while a leveling was encouraging, the high prevalence rate despite federal and state efforts to reduce its use was troublesome. 3. State of Kentucky Drug Court reported that out of 24 positive tests for synthetic cannabinoids from September 2012 through December 2012, 19 of these tests were positive for UR

- 144. ( XLR11 and AKB48 were not tested in these samples) 4. NMS laboratories re

- evaluated 50 blood samples originally tested in July 2012 that were negative for synthetic cannabinoids. After further screening in December 2012 f or UR

- 144 and XLR11 , 27/50 samples tested positive for UR

- 144 and 14/50 samples tested positive for XLR11

. 5. NMS laboratories evaluated 28 new blood samples in December 2012 using a new platform that included testing for UR

- 144 and XLR11 . 8/29 samples tested positive for UR

- 144 and 12/28 samples tested positive for XLR11

. 6. Redwood laboratories used a newly validated method to re

- test samples in December 2012 for UR

- 144 and XLR11 . Of the 300 randomly chosen samples that were originally negative for synthetic ca nnabinoids, 39/300 were found to contain metabolites of either UR

- 144 and/or XLR11

. 7. DEA laboratories have reported over 144 individual spice products that tested positive for UR

- 144, XLR11 and/or AKB48 ranging from November 2012 through January 2013.

Poi son Control Centers

1. March 24 AAPCC Press Release. As of March 24, 2010, 112 calls had been received since 2009 regarding synthetic cannabinoids and associated products, including 59 calls since March 1, 2010, according to NPDS.
2. July 23, 2010 AAPCC Press R elease. As of July 23, 2010, 761 calls had been received regarding synthetic cannabinoids and associated products according
to NPDS.
3. August 20, 2010 AAPCC Press Release. As of August 20, 2010, 1,057 calls had been received regarding synthetic cannabinoids and associated products according to NPDS.DEA/OD/ODE page 22 of 39 May 08, 2013 4. September 27, 2010 AAPCC Press Release. As of September 27, 2010, 1,503 calls had been received regarding synthetic cannabinoids and associated products according to NPDS.
5. November 3, 2010 AAPCC Press Release. A s of November 3, 2010, 1,966 calls have been received by poison centers regarding products purported to contain synthetic cannabinoids according to the National Poison Data System (NPDS). Calls have been received in 48 states and the District of Columbia.
6. November 22, 2010 AAPCC Press Release . As of November 22, 2010, poison centers have reported 2,304 calls regarding products purported to contain synthetic cannabinoids according to the National Poison Data System (NPDS). Poison centers have received cal ls in 49 states and the District of Columbia.
7. December 21, 2010 AAPCC Press Release. As of December 21, 2010, U.S. poison centers have reported receiving more than 2,500 calls this year alone. As of December 21, 2010, poison centers have reported 2,752 c alls about the products according to the National Poison Data System (NPDS).
8. January 18, 2011 AAPCC Press Release. As of January 18, 2011, U.S. poison centers have received more than 3,000 calls regarding products purported to contain synthetic cannabinoi ds. In 2010, poison centers reported 2,867 calls. As of January 18, 2011, U.S. poison centers have reported 217 calls for 2011.
9. February 3, 2011, AAPCC Press Release. As of February 3, 2011, U.S. poison centers have reported 385 calls for 2011.
10. February 10, 2011, AAPCC Press Release. Synthetic marijuana products have spurred more than 3,000 calls to U.S. poison centers since 2010.
11. February 24, 2011, AAPCC Press Release. As of February 24, 2011, U.S. poison centers have reported 706 calls for 2011. The total number of calls since 2010 is more than 3,500 calls.
12. April 20, 2011, AAPCC Press Release. Synthetic marijuana products have spurred more than 4,500 calls to U.S. poison control centers since 2010.
13. July 11, 2012, AAPCC Press Release. In 2010, poison centers nationwide responded to about 3,200 calls related to synthetic marijuana and bath salts. In 2011, the number jumped to more than 13,000. Sixty percent of these cases involved patients 25 and younger.
14. November 28, 2011, AAPCC Press Release. Poison center data provides vital information leading to DEA ban of synthetic drugs.
15. February 16, 2012, AAPCC Press Release. American Association of Poison Control Centers joins the Office of National Drug Control Policy Working Group in address the dangers if sy nthetic drugs.DEA/OD/ODE page 23 of 39 May 08, 2013 16. May 31, 2012, AAPCC Press Release. The AAPCC commends the U.S. Senate for passing a ban of synthetic drugs in SB 3187 and call on the U.S. House of Representatives to include the language in the final version of the bill.
17. July 11, 2012, AAPCC Press Release. AAPCC comment the nation’s policy makers on passage into the law the Synthetic Drug Abuse Prevention Act of
2012.
18. From January 1, 2012 through December 31 , 2012 , poison center s nationwide have received 5,200 calls regarding exposure to synthetic cannabinoids.

Relevant Positions/ Statements by Organizations

A. National Drug Court Institute, Drug Court Practitioner Fact Sheet, Spice, K2 and the Problem of Synthetic Cannabinoids , October 2010, vol. 5, no. 1. ( www.ndci.org )
B. MetroKids, ‘Spice’ Health Warning Issued , April 2010 ( www.metrokids.com )
C. Indiana Prevention Resource Center, Indiana University Bloomington, K2/Spice: A Fake Drug Carr ying a Real Potential for Harm , undated, ( www.drugs.indiana.edu )
D. Prevention First, Fake Marijuana Called Spice or K2 Can Cause Serious Harm to
Teens , April 13, 2010 ( ww w.prevention.org )
E. Saint Louis University, SLU Toxicologist Warning to Parents: Look for Signs of K2
, March 3, 2010 ( www.slu.edu/x35328.xml )
F. Community of Anti

- Drug Coalitions of America, Researchers Warn About Dangers of Synthetic Marijuana , March 18, 2010 (www.cadca.org)DEA/OD/ODE page 24 of 39 May 08, 2013 Table 3. NFLIS

– State and Local Forensic Laboratory Reports (Queried on May 6, 2013)

2010 2011 2012 2013# Total Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 JWH

- 018; JWH

- 073; JWH

- 200; CP

- 47,497 CP

- 47,497 C8

homologue 138 413 670 1196 1515 995 658 526 423 324 213 129 26 7226

UR

- 144; XLR11; AKB48 1* 0 0 0 0 0 0 47 537 3185 5643 3798 1620 14831
*Encounter confirmed in Mar 2012; # = data is incomplete for 2013 Q1, still being reported

Table 4. STRIDE Records ( January 1, 2010 through April 03 , 2013 *# ):

CASES RECORDS
AKB48 40 112

UR

- 144 179 1, 510

XLR11 1 86 1,194

* No reports identified in STRIDE regarding UR

- 144, XLR11 or AKB48 prior to January 2010
# Multiple records in STRIDE contained a combination of AKB48, UR

- 144 or XLR11DEA/OD/ODE page 25 of 39 May 08, 2013 Table 5. DEA Sample Laboratory Results

Date Label Flavor/ Characteristic Confirmed Substance Lab Notes

3/29/2013 Bizarro; Zensence XLR

- 11 Northeast Black packet, purple yellow reversed superman, 1.5 g 3/29/2013 Orgazmo; Zensence XLR

- 11 Northeast Red circle, yellow lightning bolt, 1.5g 3/28/2013 Scooby Snax XLR

- 11, 5

- Cl

UR

- 144 Southwest 10g packet, Tie

dyed front purple/yellow, Scooby doo on front 3/28/2013 Green Giant XLR

- 11 Southwest 3g, green
cartoon on front, orange hair, green packet 3/27/2013 Scooby Snax XLR

- 11 Southwest 4g packet, Tie

dyed front, Scooby doo on front 3/27/2013 Kush 10X Kryptonite XLR

- 11 Southwest 3g, Green lettering on front 3/27/2013 WTF XLR

- 11 Southwest Fidel Castro on toilet, no toilet
paper 3/27/2013 Diablo XLR

- 11 Southwest 3g packet, skull on fire 3/20/2013 Smokin Dragon Potpourri Strawberry XLR

- 11 Southwest Clear plastic vial with green cap, purple/pink dragon on front 3/20/2013 Smokin Dragon Potpourri Pomegranate XLR

- 11, UR

144 Southwest Clear plastic vial with green cap, purple/pink dragon on front 3/20/2013 Smokin Dragon Potpourri Strawberry XLR

- 11 Southwest Clear plastic vial with green cap, purple/pink dragon on front 3/20/2013 Mad Hatter Blueberry XLR

- 11 Northeast 3g packet, blue background,DEA/OD/ODE page 26 of 39 May 08, 2013 Madd Hatter tipping hat 3/15/2013 Puff Hypnotic XLR

- 11, UR

144 Southwest Clear plastic vial with black cap, dragon on front 3/15/2013 Smokin Dragon Potpourri Hypnotic XLR

- 11, UR

144 Southwest Clear plastic vial with red cap, purple/pink dragon on front 3/15/2013 Smokin Dragon Potpourri Pomegranate XLR

- 11, UR

144 Southwest Clear plastic vial with purple cap, purple/pink dragon on front 3/15/2013 Smokin Dragon Potpourri Blueberry XLR

- 11, UR

144 Southwest Clear plastic vial with red cap, purple/pink dragon on front 3/8/2013 Diablo XLR

- 11, 5

- Cl

UR

- 144 Southwest 3g packet, skull on fire 3/6/2013 G

- 20 XLR

- 11 Southwest 4g, G

- 20 on front, black and red packet, Mr. Happy 3/6/2013 G

- 20 XLR

- 11 Southwest G

- 20 on front, black and white writing, Mr. Happy 3/6/2013 Mr. Happy Blueberry XLR

- 11 Southwest Smiley face in yellow, green, red, purple and yellow 3/6/2013 Mr. Happy XLR

- 11 Southwest Smiley face, black and white 3/6/2013 Diablo XLR

- 11 Southwest 3g packet, skull on fire 3/6/2013 Diablo XLR

- 11, UR

144 Southwest 3g packet, skull on fire 3/6/2013 Bizarro; Zensence Lime XLR

- 11 Northeast Black packet, purple yellow reversed superman, 1.5 g 3/5/2013 Everest 12 diff. flavors XLR

- 11 Northeast 3.5 g, gold packet, blue mountains, The highest peak on earth 3/5/2013 Liberty Sweet UR

- 144 Northeast 3g, silverDEA/OD/ODE page 27 of 39 May 08, 2013 Herbal Incense Domination packet, liberty bell on front 3/5/2013 Smokin Dragon Potpourri 4 flavors, 3 strengths XLR

- 11, 5

- Cl

UR

- 144 Northeast Clear plastic vial with red/green/tan
cap, purple/pink dragon on front 3/4/2013 Darkness Purple Haze XLR

- 11, UR

144, 5

- Cl

- UR

144 Northeast 5g, face in shadow, black, packet 3/4/2013 Darkness Purple Haze XLR

- 11, UR

144 Northeast 5g, face in shadow, black, packet 3/4/2013 Mystic Forbidden Fruit XLR

- 11 Northeast 6g, Medusa on front 3/4/2013 WTF XLR

- 11 Northeast Fidel Castro on toilet, no toilet
paper 3/4/2013 Down2Earth Purple Chronic XLR

- 11, UR

144, 5

- Cl

- UR

144 Northeast 10g, multi

color, octopus standing on
green mushrooms,
cartoon 3/4/2013 AK

- 47 Kush XLR

- 11 Northeast 3g packet, red black, silhouette woman holding rifle 2/26/2013 Bizarro; Zensence Cherry XLR

- 11 Northeast Black packet, purple yellow reversed superman, 1.5 g 2/26/2013 Bizarro; Zensence Cherry XLR

- 11 Northeast Black packet, purple yellow reversed superman, 1.5 g 2/26/2013 Bizarro; Zensence Cherry XLR

- 11 Northeast Black packet, purple yellow reversed superman, 1.5 g 2/26/2013 Bizarro; Zensence Lime XLR

- 11 Northeast Black packet, purple yellow reversed superman, 1.5 g 2/25/2013 Syn Swag XLR

- 11 Western Business manDEA/OD/ODE page 28 of 39 May 08, 2013 devil, wings, orange, blue suit black packet 2/25/2013 WTF XLR

- 11 Western Fidel Castro on toilet, no toilet
paper 2/25/2013 Syn Smooth XLR

- 11 Western Purple black packet, devil on front, thumbs
up 2/11/2013 Diablo XLR

- 11, UR

144 Southwest 3g packet, skull on fire

2/7/2013 The Original Cloud Nine XLR11 Southwest 1g packet, light blue, smiling cloud on front

2/7/2013 Diablo XLR11 , UR

144 Southwest 3g packet, skull on fire

2/7/2013 Smokin Dragon Potpourri Blueberry XLR11 Southwest Clear plastic vial with RED cap,

purple/pink dragon on front

1/18/2013 Kaptain Kush Strawberry XLR11 , 5

- Cl

UR

- 144 Southwest Clear plastic vial with red cap, skeleton pirate with K on hat

1/18/2013 Kaptain Kush Kush XLR11 , 5

- Cl

UR

- 144 Southwest Clear plastic vial with green cap, skeleton pirate with K on hat

1/18/2013 Kaptain Kush Hypnotic XLR11 , 5

- Cl

UR

- 144 Southwest Clear plastic vial with red cap, skeleton pirate with K on hat

1/17/2013 Ultra Zombie Matter Halo Dusk XLR11 Western Small glass or plastic jar/container

1/14/2013 Legal Devil Potpourri XLR11 Southwest Clear plastic vial with red cap, X, picture of man/devil on front

1/14/2013 Hi 5 XLR11 Southwest Clear plastic vial, tan cap, green looking shamrock on frontDEA/OD/ODE page 29 of 39 May 08, 2013 1/12/2013 Handy XLR11 Southwest Clear plastic vial with red cap, blue handicap

diagram on front

1/12/2013 Hi5 Potpourri Hi 5 XLR11 Southwest 7g clear plastic vial, tan cap, green looking shamrock on front

1/12/2013 Fly’n High Kush XLR11 Southwest Clear plastic vial with black cap, Bob Marley on front in green

1/12/2013 Fly’n High Strawberry XLR11 Southwest Clear plastic vial with red cap, Bob Marley on

front in red

1/12/2013 Fly’n High Blueberry XLR11 Southwest Clear plastic vial with blue cap, Bob Marley on

front in blue

1/12/2013 Kaptain Kush Blueberry XLR11 Southwest Clear plastic vial with red cap, skeleton pirate with K on hat

1/12/2013 Smokin Dragon Potpourri Cherry XLR11 , UR

144 Southwest Clear plastic vial with green cap,

purple/pink dragon on front

1/11/2013 Luscious Aroma Grape UR

- 144 Northeast Small clear glass or plastic jar/container

1/11/2013 Luscious Aroma Strawberry UR

- 144 Northeast Small clear glass or plastic jar/container

1/11/2013 Ultra Zombie Matter Halo XLR11 Northeast Small glass or plastic jar/container

1/11/2013 Madd Hatter XLR11 , UR

144 Southwest 3g packet, Madd Hatter

with Aces coming from sleeve on front

1/11/2013 Madd Hatter UR

- 144 Southwest 3g packet, Madd Hatter

with AcesDEA/OD/ODE page 30 of 39 May 08, 2013 coming from sleeve on front

1/11/2013 Joker XLR11 Southwest 4g black packet, Joker on front,

face is silver glitter, red lips.

1/11/2013 Scooby Snax XLR11 Southwest 4g packet, Tie

dyed front, Scooby doo on front

1/10/2013 Sin City Watermelon XLR11 Southwest 2g clear vial, Red cap, green plant material

1/10/2013 XLR11 Southwest 1kg silver packet, no

labeling

1/9/2013 M G XLR11 Mid

Atlantic 10g, Snow white dwarf on

front, green package Mr.

Nice Guy

1/8/2013 Sky Bomb XLR11 Northeast 1.25 grams, small glass or plastic jar/container

1/8/2013 Sky Pilot XLR11 Northeast Small packet, fighter pilot with mask on front

1/8/2013 Blue Kush Ltd Edition XLR11 Northeast Small packet, blue lettering with crown on top of SH

1/8/2013 Black Venom XLR11 Northeast Black packet, eyes on front

1/8/2013 Ultra Zombie Matter Halo Dusk XLR11 Northeast Small glass or plastic jar/container 12/14/2012 Ultra Zombie Matter Halo Twilight XLR11 Western Small glass or plastic jar/container 12/14/2012 Ultra Zombie Matter Halo Midnight XLR11 Western Small glass or plastic jar/container 12/13/2012 Mary & Jane XLR11 , UR

144 Southwest Black packet, two naked females onDEA/OD/ODE page 31 of 39 May 08, 2013 front (blonde, brunette kneeling) 12/13/2012 Miami Spice XLR11 , UR

144 Southwest Black packet, picture of Miam i Blvd. on front 12/13/2012 Screamin Demon XLR11 , UR

144 Southwest Black packet, skull in flames on front 12/13/2012 Shockwave XLR11 , UR

144 Southwest Black packet, screaming man with headphones 12/7/2012 Hammer Head XLR11 Northeast Black packet, no weight, white skull with stars

on forehead 12/7/2012 AK

- 47 XLR11 , UR

144 Northeast 3g, silver and yellow, picture

of AK

- 47 on front 12/7/2012 AK

- 47 XLR11 Northeast 3g, silver and red, picture of AK

- 47 on front 12/7/2012 Platinum, Caution XLR11 , UR

144 Northeast 3g, packet has glitter, silver background,

biohazard

symbol 11/30/2012 M G Blueberry XLR11 South Central 12g, Snow white dwarf on

front, green packet , Mr. Nice Guy 11/30/2012 You Only Live Once XLR11 , UR

144 Southwest 3g black packet, red writing 11/30/2012 Demon XLR11 , UR

144 Southwest Orange packet, red word "demon"

behind 11/30/2012 Dank XLR11 , UR

144 Southwest Small plastic vial, Mr. Nice guy smiley with XX eyes 11/20/2012 Aloha...get Lei'd Blueberry XLR11 , UR

144 Mid

Atlantic Small glass or plasticDEA/OD/ODE page 32 of 39 May 08, 2013 jar/container 11/20/2012 Ultra Zombie Matter Halo XLR11 Western Small glass or plastic jar/container 11/20/2012 Ultra Zombie Matter Halo Twilight XLR11 Western Small glass or plastic jar/container 11/20/2012 Ultra Zombie Matter Halo After Dark XLR11 Western Small glass or plastic jar/container 11/16/2012 NOLA Diamond Pot p ourri Hypnotic XLR11 Southwest 3g packets

11/16/2012 XLR11 Southwest White and black bricks of substance 11/15/2012 Relaxinol XLR11 Southwest Mr. Nice Guy, rabbit holding a pocket watch by mushrooms 10/31/2012 AKB48 Southwest 10/31/2012 XLR11 Southwest XLR11 identified in 6/14 substances tested 10/26/2012 AKB48 Southwest 10/25/2012 Sonic Zero; Zensence Blueberry XLR11 Southwest 1.5g long glass vial 10/25/2012 Bizarro; Zensence Strawberry XLR11 Mid

Atlantic 1.5g packet,

reverse superman in purple and

yellow 10/22/2012 Avalanche; Zensence Pineapple XLR11 Western 1.5g packet, snowcapped mountains, light blue 10/22/2012 Neutronium; Zensence XLR11 , UR

144 Western 3.5g packet, black, atom/ele ctrons 10/22/2012 Bizarro; Zensence Cherry XLR11 Western 1.5g packet,

reverse superman in purple and

yellow 10/22/2012 Bizarro; Zensence Blueberry XLR11 Western 1.5g packet,

reverseDEA/OD/ODE page 33 of 39 May 08, 2013 superman in purple and

yellow 10/10/2012 Fly’n High Blueberry XLR11 Henderson PD Nevada 2.09, plastic tube, picture of

Bob Marley 10/10/2012 Lava Extra Strength Strawberry XLR11 , UR

144 Mid

Atlantic Red/black packet, volcano and lava 10/10/2012 Pure Sin XLR11 , UR

144 Mid

Atlantic 3g packet, 3 skulls on front, red barbed wire

on reverse 10/9/2012 XLR11 , UR

144 Southwest Unlabeled small clear glass jar, black cap 10/4/2012 K4 Max UR

- 144 Western 3g, clear packet,
compass on front 10/3/2012 Clown Loyal Original XLR11 Western 2g, black plastic container 10/3/2012 Mad Monkey Strawberry XLR11 , UR

144 Southwest 5g, cartoon monkey on front, reverse

states "Its

LEGAL" 10/3/2012 7H 4:20 XLR11 , UR

144 Southwest 7H combination in multiple circles on label, LEGAL 10/3/2012 Zombie Life XLR11 , UR

144 Southwest 3g packet, tombstone on front, labeled K

and H on top 9/19/2012 Purple Diesel XLR11 , UR

144 Southwest 3g packet, psychedelic front, glitter,

starburst 9/19/2012 Sour Diesel Original XLR11 Southwest Clear small plastic bag 9/19/2012 Diablo Original XLR11 , UR

144 Southwest 3g packet, skull on fire 9/17/2012 Diablo XLR11 , UR

144 Southwest 3g packet, skull on fire 9/17/2012 Wanted XLR11 , UR

144 Southwest 3g packet, Wanted poster, skull andDEA/OD/ODE page 34 of 39 May 08, 2013 crossbones 9/12/2012 XLR11 , UR

144 Southwest

9/12/2012 XLR11 Southwest 9/12/2012 XLR11 , UR

144 Southwest

9/10/2012 Sonic Boom XLR11 , UR

144 Southwest 2g/4g, Wicked LLC, red smoke rising 9/10/2012 Supernova XLR11 Western Small plastic container, blue star in background 9/10/2012 Zombie Matter Halo Acid Rain XLR11 Western 1g, Small plastic container, biohazard symbol in black/yellow 9/10/2012 Zombie Matter Halo Midnight XLR11 Western 1g, Small plastic container, biohazard symbol in black/yellow 9/5/2012 Tiger Shark XLR11 , UR

144 Southwest 4g, picture of tiger shark swimming 9/5/2012 New King Kong XLR11 Southwest 3g, picture of screaming

gorilla 9/5/2012 Atomic XLR11 , UR

144 Southwest 4g, picture of nuclear explosion 9/5/2012 New King Kong XLR11 , UR

144 Southwest 3g, picture of screaming

gorilla 9/4/2012 9mm XXX Blueberry XLR11 Southwest 2g, plastic vial, clear 9/4/2012 Purple Diesel Hydro XLR11 , UR

144 Southwest 3g packet,
psyc he delic front, glitter,

starburst 9/4/2012 7H 4:20 XLR11 , UR

144 Southwest 7H combination in multiple circles on label, LEGAL 8/31/2012 Mr. Happy Original XLR11 , UR

144 Southwest Smiley face in yellow, green,DEA/OD/ODE page 35 of 39 May 08, 2013 red, purple and yellow 8/31/2012 7

- g Smoking Rasta UR

- 144 Southwest Cannabis leaves around small

round vial, metal cap 8/30/2012 XLR11 , UR

144 Southwest Black packet, no labeling 8/30/2012 Bloody Mary Halo XLR11 Western Kneeling woman, halo on head, stone
statue 8/29/2012 Zombie Matter Halo Blackout XLR11 Western 1g, Small plastic container, biohazard symbol in black/yellow 8/29/2012 $25K UR

- 144 Mid

Atlantic 2g white packet, green spiral of smoke 8/29/2012 $25K UR

- 144 Mid

Atlantic 5g silver packet, green spiral of smoke 8/27/2012 Anarchy UR

- 144 Western Small glass jar, black lid, gray

background 8/23/2012 Scooby Snax Second Generation XLR11 , UR

144 Southwest 10g packet with pink background,

glittered Scooby

- Doo 8/23/2012 Mad Monkey XLR11 , UR

144 Southwest 5g, cartoon monkey on front, reverse

states "Its

LEGAL" 8/21/2012 White Widow Da Brand XLR11 , UR

144 Southwest 6cm clear plastic vial, black widow spider on front 8/21/2012 Hayze Hawaiian XLR11 Western 1.5g packet with volcano on

front, white background 8/21/2012 Super Stank Fragrance of Skunk XLR11 Western 2g packet with brown skunk on

front, blackDEA/OD/ODE page 36 of 39 May 08, 2013 background 8/17/2012 Knockout Original XLR11 Southwest Small clear plastic bag 8/17/2012 Purple Diesel 420 XLR11 Southwest 3g packet,
psyc he delic front, glitter,

starburst 8/13/2012 Kosmic Kush XLR11 Southwest 2.5g packet, planet system in brown and black 8/13/2012 New King Kong XLR11 Southwest 3g, picture of screaming

gorilla 8/13/2012 Botanical Potpourri Hydro; 7H XLR11 Southwest Skulls with horns, 7H and

red/yellow

flames 7/27/2012 Sonic Boom UR

- 144 Northeast 2g/4g, Wicked LLC, red smoke rising 7/23/2012 Hysteria Black Mr. Bubble XLR11 , UR

144 Western 5g, black packet, red lines on back 7/23/2012 Hysteria Black Joocy Fruit XLR11 , UR

144 Western 5g, black packet, red lines on back 7/23/2012 Black Sabbath Groovy Grape XLR11 Western

7/20/2012 Hayze Hawaiian

Ultra UR

- 144 Western 1.5g packet with volcano on

front, white background 7/19/2012 Joker XLR11 , UR

144 Southeast 4g black packet, Joker face from Batman 7/19/2012 Mind Trip XLR11 , UR

144 Southeast 4g packet, skull with glitter

around 7/19/2012 Out World UR

- 144 Southeast 4g packet, upside down city, XXX sun, moon, cloud 7/13/2012 Express Barely Legal XLR11 Southeast 3g red packet, cartoon young

girl, roller

skates, foodDEA/OD/ODE page 37 of 39 May 08, 2013 tray 7/13/2012 Barely Legal High Octane Apple UR

- 144 Southeast 1g packet, checkered flag, young girl with
gas pump 7/13/2012 Barely In XLR11 Southeast 1g red packet, crying schoolgirl, Mr. Nice guy behind, chalkboard 7/13/2012 Mad Hatter/Cloud 9 Second Generation XLR11 , UR

144 Southeast 10g, cartoon of mad hatter

7/13/2012 Kick Ass UR

- 144 Southeast 3g, ninja on front 7/11/2012 XLR11 , UR

144 Henderson PD Nevada 1.52g

7/11/2012 UR

- 144 Henderson PD Nevada 0.14g

7/5/2012 Relaxinol LE UR

- 144 Southeast 1g, Mr. Nice guy, black

packet 7/3/2012 Mr. Nice Guy Strawberry XLR11 , UR

144 Southeast 1g, red strawberry 6/25/2012 Vesuvius South Pacific XLR11 Western 3g packet, clouds over

mountain 6/25/2012 Vesuvius Sex XLR11 Western 3g packet, clouds over

mountain 6/25/2012 Vesuvius Sexy XLR11 Western 3g packet, pink smoke strands, white background 6/18/2012 Hayze Hawaiian

Ultra XLR11 Western 1.5g packet with volcano on

front, white background 6/5/2012 Dead Man Walking UR

- 144 Northeast Clear vial, black cap, white label

with skeleton 6/5/2012 Sam Pie UR

- 144 Northeast Clear vial, black cap, bl ack label WARNING notDEA/OD/ODE page 38 of 39 May 08, 2013 for hum.

c onsump. 6/5/2012 Fire Extreme UR

- 144 Northeast Clear vial, black cap, black label 6/1/2012 Vesuvius Sky XLR11 Western 3g packet, clouds over

mountain 6/1/2012 Vesuvius Eruption XLR11 Western 3g packet, clouds over

mountain 6/1/2012 Vesuvius Huckle Berry XLR11 Western 1g, Small white plastic container 6/1/2012 Vesuvius South Pacific XLR11 Western 1g, Small white plastic container 6/1/2012 Vesuvius Carnival XLR11 Western 1g, Small white plastic container 5/22/2012 Green Cobra Hypnotic XLR11 Northeast 1.5g packet, cartoon of cobra snake 5/22/2012 Super Kush Honeysuckle XLR11 Northeast 1.5g packet, black background 4/27/2012 Black Mamba DP UR

- 144 Northeast Clear vial, black cap, black label 4/27/2012 Mr. Spice Green UR

- 144 Northeast Clear vial, black cap, green label

with cartoon

man 4/27/2012 Magic Man UR

- 144 Northeast 1.5g clear packet, white

label, red skeleton, green
star 4/18/2012 Mary Janes Private Reserve UR

- 144 Southwest Clear vials, gold label or print on

vial, woman side profile various colors

(gold, blue, purple, pink, red writing on

gold label)DEA/OD/ODE page 39 of 39 May 08, 2013