DEA/OD/ODE page 1 of 40 January 2014 Q uinolin
- 8 - yl 1
- pentyl
- 1 H - indole
- 3 - carboxylate (PB
- 22 ; QUPIC ), quinolin
- 8 - yl 1
- (5
- fluoropentyl)
- 1 H - indole
- 3 - carboxylate (5
- fluoro
- PB - 22 ; 5 F - PB - 22 ) , N - (1
- amino
- 3 - methyl
- 1 - oxobutan
- 2 - yl)
- 1 - (4
- fluorobenzyl)
- 1 H - indazole
- 3 - carboxamide (AB
- FUBINACA) and N - (1
- amino
- 3,3 - dimethyl
- 1 - oxobutan
- 2 - yl)
- 1 - pentyl
- 1 H - indazole
3 - carboxamide (ADB
- PINACA)

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

January 2014
Introduction
Since 2009 , there has been a marked increase in law enforcement encounters of synthetic cannabinoids in the United States (U.S.)

. T hese substances are being encountered on the designer drug market , laced on plant material and being abused for their psychoactive properties. Both law enforcement and public health reports demonstrate a sustained abuse of synthetic cannabinoids and this abuse is having a negative impact on communities. Clinical reports demonstrate that the abuse of synthetic cannabinoid designer drug products can result in toxicity (Gunderson et al., 2012 ; Hermanns

- Clausen et al., 2013 ; Fantegrossi et al., 2013 ; Konstrand et al., 2013 ). Synthetic cannabinoids are a large family of compounds that are functionally (biologically) similar to THC, the main active ingredient in marijuana. Synthetic cannabinoids, however, are not organic but are chemicals created in a laboratory. Two of the sy nthetic cannabinoids currently controlled (CP

- 47,497 and cannabicyclohexanol) were first synthesized in the early 1980’s for research purposes in the investigation of the cannabinoid system. JWH

- 018, JWH

- 073, and JWH

- 200 (all controlled under the Syntheti c Drug Abuse Prevention Act of 2012) were synthesized in the mid

- 1990s and studied to further advance the understanding of drug

- receptor interactions regarding the cannabinoid system. Synthesized as research tools, no other known legitimate uses have been identified for these five synthetic cannabinoids.DEA/OD/ODE page 2 of 40 January 2014 According to forensic laboratory reports, the initial appearance of synthetic cannabinoids in herbal incense products in the U.S. occurred in November 2008 when U.S. Customs and Border Protection (CBP) fi rst encountered products using brand names such as “Spice.” Prior to appearing on the U.S. market, synthetic cannabinoids were marketed in herbal incense products in several European countries. After experiencing numerous health

- related incidents, some E uropean countries banned these products/chemicals. According to CBP, a number of the synthetic cannabinoids appeared to originate from foreign sources. Detailed chemical analyses by the Drug Enforcement Administration ( DEA ) and other agencies have found synthetic cannabinoids applied on plant material in herbal incense products marketed to the general public. Product analyses have found variations in both the type of synthetic cannabinoid and the amount of the substance found on the plant material.
The vast majority of cannabinoids are manufactured in Asia by foreign chemists who are not bound by any manufacturing requirements or quality control standards. The bulk products are smuggled into the United States typically as misbranded imports. These chem icals are generally found in powder form or are dissolved in solvents, such as acetone, before being applied to the plant material comprising the “herbal incense” products. After local distributors apply the drug to the leafy material, they package it for retail distribution, ignoring any control mechanisms to prevent contamination or to ensure a consistent, uniform concentration of drug in each package. According to Internet discussion boards and law enforcement encounters, spraying or mixing the synthet ic cannabinoids on plant material provides a vehicle for the most common route of administration

- smoking (using a pipe, a water pipe, or rolling the drug

- spiked plant material in cigarette papers). They are sold under hundreds of different brand names, in cluding “Spice,” “K2,” “Blaze,” “Red X Dawn,” “Paradise,” “Demon,” “Black Magic,” “Spike,” “Mr. Nice Guy,” “Ninja,” “Zohai,” “Dream,” “Genie,” “Sence,” “Smoke,” “Skunk,” “Serenity,” “Yucatan,” “Fire,” and “Crazy Clown.” Law enforcement personnel have enco untered dosage form and packaging operations in residential neighborhoods, garages, and warehouses. Throughout this process, there is no concern for preventing contamination of the product, consistent dosage, or the adverse health consequences that may oc cur from ingesting the drug. As proposed in scientific literature, the risk of adverse health effects is further increased by the fact that similar products vary in the composition and concentration of synthetic cannabinoids applied on the plant material.DEA/OD/ODE page 3 of 40 January 2014 The designer drug products laced with synthetic cannabinoids are often being sold under the guise of ‘ herbal incense ’, ‘potpourri’ , etc. under various product names and routinely 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 I nternet , in head shops, or sold in convenie nce stores. There is an incorrect assumption that these products are safe (Fattore and Fratta, 2011 ; McGuinness and Newell, 2012 ) and further, that mislabeling of these products as ‘ not for human consumption ’ is a legal defense against prosecution

. Research has shown that even after various synthetic cannabinoids are subjected to control measures, producers of thes e products attempt to circumvent the law , thus making intervention measures particularly challenging (Cottencin et al., 2013)

. These substances have no accepted medical use in the U.S. and have been reported to produce adverse health effects in humans while having a negative effect on communities

. Acute and c hronic abuse of synthetic cannabinoids in general ha ve been linked to adverse health effects including signs of addiction and withdrawal ( Zimmermann et al., 2009 ; Muller et al., 2010 ) , numerous reports of emergency room admissions resulting from the ir abuse (Forrester et al., 201 1; Hermanns

- Clausen et al., 2013 , SAMHSA, 2012 ) and death (Patton et al., 2013; Law Enforcement/Toxicology correspondence)

. Psychiatric case reports have been reported in the scientific literature detailing the harms of synthetic cannabinoid abuse and psychoses (Oluwabusi et al.,2012; Peglow et al., 2012: Thomas et al., 2012 )

. The European Monitoring Center for Drugs and Dru g Addiction (EMCDDA) published 84 reports regarding synthetic cannabinoids from January through May 2013, up from 30 reports in 2012 and 9 in 2009 (Cottencin et al., 2013; EMCDDA, 2013). In 2011 and again in 2013, the DEA emergency scheduled a variety of synthetic cannabinoids including JWH

- 018, JWH

- 073, JWH

- 200, CP

- 47,497, and CP

- 47,497 C8 ( temporarily scheduled on March 1, 2011 at 76 FR 11075 , and later placed in s chedule I by Section 1152 of Food and Drug Administration Safety and Innovation Act (FDASIA ), Pub. L. 112

- 144, on July 9, 2012 ) and UR

- 144, XLR 11 and AKB

- 48 ( temporarily scheduled on May 16, 2013 at 78 FR 28735 ) to protect the public health and safety. Section 1152 of the FDASIA amended the Controlled Substances Act ( CSA ) by placing cannabimimetic agents and 26 specific substances (including 15 synthetic cannabinoids, 2 synthetic cathinones, and 9 phenethylamines of the 2C

- series) in s chedule I. UR

- 144, XLR11, and AKB48 were not included among the 15 specific named synthetic cannabin oids, did not fall under the definition of cannabimimetic agents under FDASIA,DEA/OD/ODE page 4 of 40 January 2014

and were emergency scheduled on May 16, 2013. Although s eizures of JWH

- 018, JWH

073, JWH

- 200, CP

- 47,497, and CP

- 47,497 C8 showed a decline shortly after the se drugs we re scheduled, new synthetic cannabinoids began to emerge on the designer drug market. This new generation of synthetic cannabinoids, including UR

- 144, XLR11 , and AKB48 quickly became the new drugs of choice in the synthetic marketplace, reaching total sei zure levels higher than JWH

- 018, JWH

- 073, JWH

- 200, CP

- 47,497, and CP

- 47,497 C8 combined. M ore recently law enforcement has been encountering another generation of synthetic cannabinoids including quinolin

- 8

- yl 1

- pentyl

- 1 H

- indole

3

- carboxylate (PB

- 22 ; QUPIC ) , quinolin

- 8

- yl 1

- (5

- fluoropentyl)

- 1 H

- indole

- 3

- carboxylate (5

- Fluoro

- PB

- 22 ; 5 F

- PB

- 22) , N

- (1

- amino

- 3

- methyl

- 1

- oxobutan

- 2

- yl)

- 1

- (4

- fluorobenzyl)

- 1 H

- indazole

- 3

- carboxamide (AB

- FUBINACA ) and N

- (1

- amino

- 3,3

- dimethyl

- 1

- oxobutan

- 2

- yl)

- 1

- pentyl

- 1 H

- indazole

- 3

- carboxamide (ADB

- PINACA)

.
P B

- 22 and 5 F

- PB

- 22 are synth etic cannabinoids (Figure 1) that have pharmacological effects similar to the s chedule I hallucinogen delta

- 9

- tetrahydrocannabinol (Δ 9

- THC). P B

- 22 and 5 F

- PB

- 22 were not reported in the scientific literature prior to their appearance on the illicit drug market. A report from March 2013 identified PB

- 22 as a component of dried plant material obtained via the I nternet between July 2012 and January 2013 in J apan (Uchiyama et al., 2013). According to the System to Retrieve Information from Drug Evidence (STRIDE 1 ) data, there are 211 reports for PB

- 22 and 168 reports for 5F

- PB

- 22 from January 1 through December 31 , 2013 (Query date: January 22, 2014 ) . During the same time period, the National Forensic Laboratory Information System (NFLIS 2 ) registered 2,612 reports containing these synthetic cannabinoids (PB

- 22

– 1,318 reports; 5F

- PB

- 22

– 1,294 reports) in 29 states (Query date: January 22, 2014 )

. In addition, five death s have been reported involving the use of 5F

- PB

- 22 (see factor 6).

AB

- FUBINACA is also a synthetic cannabinoid (Figure 1 ) that has pharmacological effects similar to the s chedule I hallucinogen delta

- 9

- tetrahydrocannabinol (Δ9

- THC). First appearing in a 2009 patent filed by the pharmaceutical manufacturer Pfizer (Bu chler et al., 2009), AB

- FUBINACA was most recently reported in the scientific literatu re as a component of so - called “ herbal products ” purchased via the I nternet in July 2012 (Uchiyama et al., 2012). T here are 74 reports involving AB

- FUBINACA in STRIDE and 822 reports in NFLIS from January 1 through December 31, 2013 (Query date: January 22, 201 4 )

.

1 STRIDE is a database of drug exhibits sent to DEA laboratories for analysis. Exhibits from the database are from the DEA, other federal agencies, and low enforcement agencies. 2 NFLIS is a national drug forensic laboratory reporting system that systemat ically collects results from drug chemistry analyses conducted by state and local forensic laboratories across the country.DEA/OD/ODE page 5 of 40 January 2014 ADB

- PINACA was first encountered in the United States following reports of serious adverse events in Georgia on August 23, 2013. Reports of ADB

- PINACA were not found in the scientific literature prior to its emergence on the designer drug mar ket. The Georgia Bureau of Investigation (GBI) reported on September 12, 2013 that ADB

PINACA, was detected in “herbal incense” products sold under the brand name “Crazy Clown.” It was later confirmed by the Centers for Disease Control and Prevention (CD C) as the substance responsible for severe adverse events in at least 22 persons who consumed the product (CDC, 2013b) . In addition, o n August 30, 2013, the Colorado Department of Public Health and Environment (CDPHE) was notified by several hospitals of an increase in the number of patients visiting their emergency departments (EDs) with altered mental status after using synthetic marijuana (Appendix 2) . On September 8, 2013, CDPHE, with the assistance of CDC, began an epidemiologic investigation whereby 221 cases of severe illness due to ingestion of a synthetic cannabinoid were identified (CDC, 2013c) . Those that presented at emergency rooms in the Denver, Colorado area around September 1, 2013 had symptoms similar to those found in the August 2013 Georgia incident. Laboratory analysis of samples from the Colorado incident confirmed that the substance abused in the “herbal incense” products was ADB

- PINACA. T here are 40 reports involving ADB

- PINACA in NFLIS from January 1 through December 31, 2013 ( Query date: January 22, 201 4 ). No STRIDE results involving ADB

- PINACA were identified. With no legitimate medical use and limited safety or toxicological information , these substances ( P B

- 22, 5 F

- PB

- 22 , AB

- FUBINACA and ADB

- PINACA ) have emerged on the designer drug market and are being abused for their psychoactive properties. PB

- 22, 5F

- PB

- 22 , AB

- FUBINACA and ADB

- PINACA were also not included among the 15 specific named synthetic cannabinoids under FDASIA , and d o not fall under the definition of cannabimimetic agents as provided under FDASIA

. To protect the public health and safety, the DEA intends to temporar il y place P B

- 22, 5 F

- PB

- 22 , AB

- FUBINACA , and ADB

- PINACA in s chedule I of the CSA

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

- 22, 5F

- PB

- 22 , AB

- FUBINACA and ADB

- PINACA

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

- (6).DEA/OD/ODE page 6 of 40 January 2014 Figure 1 . Chemical Structures

PB

- 22 and 5 F

- PB

- 22 belong to the aminoalkylindole structural class where previous studies have focused primarily on varying the indole nitrogen (1

- position) and 3

- position substituents. PB

- 22 and 5F

- PB

- 22, similar to JWH

- 018 and AM

- 2201 respectively , a re substance s representative of the aminoalkylindole structural class. Aminoalkylindoles are known to exhibit typical cannabinoid pharmacology in vivo (D’Ambra et al., 1992; Compton et al., 1992). For example, 5F

- PB

- 22 is structurally related to AM

- 2201 and it differs by having 8

- quinolinyloxyl replacing the naphthalene group of AM

- 2201. The indole core became a framework for continued investigations with the early work by Sterling

- Winthrop that led to pravadoline and WIN

- 55212

- 2 (D’Ambra et al., 1992). Several other research groups expanded this investigation of structure activity relationships pertaining to this structural class, most notably the laboratories of Huffman and co

- workers and Makriyannis and co

- workers (Huffman, 2009 ; Makriyannis and Liu, 2003 ). The scientific and patent literature details the further modification of the aminoalkylindole structural class with specific substitutions at the 3

- position of the indole core structure to incorporate aromatic and non

- aromatic ring systems.

AB

- FUBINACA is classified as a pentyl indazole and has been reported in the literature as a cannabinoid agonist (Buchler et al., 2009; Uchiyama et al., 2013)

. AB

- FUBINACA shares structural features with the s chedule I substance AKB48. Both AB

F UBINACA and AKB48 are based on the same indazole core structure where the 1

- and 3

- positions of the indazole ring system are substituted. The 1

- position of AB

- FUBINACA is substituted with a para

- fluorobenzyl group. The 3

- position of AB

- FUBINACA, like AKB48, is substituted with an amide linker. In AB

- FUBINACA the nitrogen atom (N) ofDEA/OD/ODE page 7 of 40 January 2014

this linker is further substituted with an acyclic alkyl amide, named 1

- amino

- 3

- methyl

- 1

- oxobutan

- 2

- yl.

A DB

- PINACA is classified as a pentyl indazole and was first report ed online by the GBI following analysis of an herbal incense product called “Crazy Clown” in September of 2013. Consumption of ADB

- PINACA resulted in multiple emergency room visits in Georgia and Colorado. A DB

- PINACA shares structural features with the s chedule I substance AKB48 ( s chedule I)

. There have been no published reports regarding its pharmacological properties. Synthetic Cannabinoids
Q uinolin
- 8 - yl 1
- pentyl
- 1 H - indole
- 3 - carboxylate (PB
- 22 ; QUPIC ) Studies evaluating the pharmacological effects of PB

- 22 in humans and laboratory animals have not been reported in the scientific literature. A study conducted by contract researchers of the National Institute on Drug Abuse (NIDA) and indicated that PB

- 22 binds to and acts as an agonist at the CB1 receptor (NIDA, 2013a; NIDA, 2013b). PB

- 22 , and JWH

- 018 , a schedule I substance, are both based on the same indole core structure where the 1

- position of the indole ring system is substituted with an alkyl group in both structures

. This alkyl group for both PB

- 22 and JWH

- 018 is a five carbon unit chain, known as a pentyl group. Both PB

- 22 and JWH

- 018 are substituted at the 3

- position with a carbonyl linker to a fused aromatic ring system. In PB

- 22 there is an additional oxyg en atom between the carbonyl group and the fused ring system. In both substances, the fused aromatic ring systems are based on ten atoms connected to each other in the same manner. In PB

- 22 , one of these ten atoms is a nitrogen atom whereas in JWH

- 018, t he ring system is carbon

based. Both fused rings in PB

- 22 and JWH

- 018 are aromatic, being of the same chemical classification.
Q uinolin
- 8 - yl 1
- (5
- fluoropentyl)
- 1 H - indole
- 3 - carboxylate (5 F - PB - 22 ) Studies evaluating the pharmacological effects of 5F

- PB

- 22 in humans and laboratory animals have not been reported in the scientific literature. A study conducted by contract researchers of NIDA indicated that 5F

- PB

- 22 binds to and acts as an agonist at t he CB1 receptor (NIDA, 2013c; NIDA, 2013d). 5F

- PB

- 22 is structurally similar to the s chedule I substance AM2201. Both 5F

- PB

- 22 and AM

- 2201 are based on the same indole core structure where the 1

- position of the indole ring system is substituted with the same fluoroalkyl group in both structures. This fluoroalkyl groupDEA/OD/ODE page 8 of 40 January 2014

for both 5F

- PB

- 22 and AM

- 2201 is a five carbon unit chain, known as a pentyl group with a fluorine atom present on the terminal carbon atom. Both 5F

- PB

- 22 and AM

- 2201 are substituted at the 3

- position with a carbonyl linker to a fused aromatic ring system. In 5F

- PB

- 22 there is an additional oxygen atom between the carbonyl group and the fused ring system. In both substances, the fused aromatic rin g systems are based on ten atoms connected to each other in the same manner. In 5F

- PB

- 22 , one of these ten atoms is a nitrogen atom whereas in AM

- 2201, the ring system is carbon

- based. Both fused rings in 5F

- PB

- 22 and AM

- 2201 are aromatic, being of t he s ame chemical classification.

N - (1
- amino
- 3 - methyl
- 1 - oxobutan
- 2 - yl)
- 1 - (4
- fluorobenzyl)
- 1 H - indazole
- 3 - carboxamide (AB
- FUBINACA ).

AB

- FUBINACA shares structural features with s chedule I substances such as AKB48. Both AB

- FUBINACA and AKB48 are based on the same indazole core structure where the 1

- and 3

- positions of the indazole ring system are substituted. The 1

- position of AB

- FUBINACA is substituted with a para

- fluorobenzyl group. The 3

- position of AB

FUBINACA, like AKB48, is substituted with an amide linker. In AB

- FUBINACA the nitrogen atom (N) of this linker is further substituted with an acyclic alkyl amide, named 1

- amino

- 3

- methyl

- 1

- oxobutan

- 2

- yl. A patent submitted by Pfizer in 2009 demonstrates that AB

- FU BINACA has a high affinity and functions as an agonist to the CB1 receptor (Buchler et al., 2009)

. A study conducted by contract researchers NIDA indicated that AB

- FUBINACA also binds to and is an agonist at the CB1 receptor (NIDA, 2013e; NIDA, 2013f ).

N - (1
- amino
- 3,3 - dimethyl
- 1 - oxobutan
- 2 - yl)
- 1 - pentyl
- 1 H - indazole
- 3 - carboxamide (ADB
PINACA)

ADB

- PINACA shares structural features with the s chedule I substance AKB48. ADB

- PINACA and AKB48 are based on the indazole core structure and are substituted on the 1

- and 3

- positions of their core indazole ring system. Structurally, ABD

- PINACA and AKB48 are the same with one exception. AKB48 has an adamantly group attached through an amide linkage to its indazole core. Th e only difference between AKB48 and ADP

- PINACA is that the adamantly group is replaced with a 1

- amino

- 3,3

- dimethyl

- 1

- oxobutan

- 2

- yl group (ADB) to form ADP

- PINACA.DEA/OD/ODE page 9 of 40 January 2014 In v itro Binding at CB1 Function at CB1 PB - 22 K i – 0.73 nM a EC 50 – 2.47 nM b 5F - PB - 22 K i – 0.27 nM c EC 50 – 0.95 nM d AB - F UBINACA K i – 0.9 nM e K i – 0.79 nM f EC 50 – 23.2 nM e EC 50 – 3.0 nM g ADB - PINACA n/a n/a

a NIDA, 2013a b NIDA, 2013b
c NIDA, 2013c d NIDA, 2013d
e Buchler et al., 2009 f NIDA, 2013e g NIDA, 2013f n/a

– not available Table 1. In v itro binding data for PB
- 22, 5F - PB - 22, AB - FUBINACA and ADB
- PINACA

Factor 4. Its history and current pattern of abuse Synthetic cannabinoids were first reported in the U.S. in a November 2008 encounter, where a shipment of ‘Spice’ was seized and analyzed by CBP in Dayton, Ohio. A round the same time, in December 2008, JWH

- 018 and cannabicyclohexanol were identified by German fore nsic laboratories ( 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 )

. Since the initial identification of JWH

- 018 ( November 2008), many additional synthetic cannabinoids have been found applied on plant material and enco untered as designer drug products ( Auwarter et al., 2009 ; DEA, 2009 ) . The popularity of these cannabinoids and their asso ciated products appears to have increased since January 2010 in the U.S. 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 I nternet 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 theirDEA/OD/ODE page 10 of 40 January 2014

reputation as potent herbal intoxicants has been suggested to contribute to 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 the ir method of manufacture and 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. , 1992; Wile y et al., 1998 ; Weibelhaus et al., 2012 ) . Smoking mixtures of these substances abused for the purpose of achieving 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. Distinct pharmacological properties and metabolism of synthetic cannabinoids have been suggested to contribute to the observed toxicity associated with the abuse of synthetic cannabinoids (Fantegrossi et al., 2013). Numer ous states, local jurisdictions, and the international community have also controlled these substances. Synthetic cannabinoids have been developed over the last 30 years as tools for investigat ing the cannabinoid system ( Weissman et al., 1982; Huffman et al., 1996; Huffman et al., 1999 )

. The majority of the substances encountered on the illicit market have not been tested beyond preliminary pre

- clinical laboratory screens before clandestine operators applied them on plant material (Lewin et al., 2013). It is extremely concerning that 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 ) and are marketed directly to adolescents ( ONDCP, 2011 ) . 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 , numerou s other synthetic cannabinoids have been id entified as product adulterants and law enforcement has seized bulk amounts of these substances

. The first synthetic cannabinoid s identified as being abused included JWH

- 018, JWH

- 200, JWH

- 073, CP

- 47,497 , and CP

- 47,497 C8 homologue, followed s hortly thereafter by new generations of synthetic cannabinoids including drugs such as AM2201 and JWH

- 200, and eventually UR

- 144, XLR11 , and AKB48. Since the emergence of PB

- 22, 5F

- PB

- 22 , and AB

- FUBINACA, NFLIS has detailed 2,612 reports from forensic laboratories identifying PB

- 22 and 5F

- PB

- 22 , 822 reports involving AB

- FUBINACA and 40 reports involving ADB

- PINACA in drug related reports for a period from January 1 through December 31, 2013

. In addition, STRIDE has 211 reports in volving PB

- 22 , 168 reports involving 5F

- PB

- 22 and 74 reports involving AB

- FUBINACA during the same time period.DEA/OD/ODE page 11 of 40 January 2014 These synthetic cannabinoid products are marketed directly to adolescents and youth which appear to be the primary abusers o f synthetic cannab inoids and synthetic cannabinoid

- containing products

. This is supported by law enforcement encounters and reports from emergency rooms (SAMHSA, 2012 3 ; Fattore and Fratta, 2011; Vandrey et al., 2012); however, all age groups have been reported by media 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 addition, the majority (59%) of emergency department visits of patients aged 12 to 2 9 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 , includin g 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 a, 2013b, 2013c ; NFLIS, 2013; STRIDE, 2013)

. Numerous herbal incense products have been found to contain one or more synthetic c annabinoid ( s ) ( PB

- 22, 5F

- PB

- 22 , AB

- FUBINACA , and/or ADB

- PINACA ) lac ed on plant material (Appendi x 2 ). 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 )

. The appeal of these highly dangerous substances to adolescents and young adults is particularly concer n ing (Oluwabasi et al., 2012 ; Durand et al., 2013 ). 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%

3 SAMHSA (the Substance Abuse and Mental Health Services Administration) 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.DEA/OD/ODE page 12 of 40 January 2014

in forensic psychiatric cent ers based on their sampling . U.S. Drug Courts 4 have 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 the DEA). According to recent testimony given by t he Deputy Direct or of the Office of National Drug Control Policy (ONDCP) to the U.S. Senate Caucus on International Narcotics Control (September 25, 2013), current drug testing misses significant populations of synthetic cannabinoid use rs . In an example described in his testimony, a study found that in a sample of men 30 years old or younger within the District of Columbia parole and probation system, 39 percent of those who cleanly passed a traditional drug screen tested positive for synth etic cannabinoids 5

. The study continued that between one

- quarter and one

- third of young men who were tested in the Washington, D.C. criminal justice system had positive test results for synthetic cannabinoids, regardless of whether they had failed or pass ed a traditional drug screen 6

. In addition to the characterized psychoses, driv ers with driving impairment have been encountered with confirmed presence of synthetic cannabinoid in their systems (Yeakel and Logan, 2013).
The Monitoring the Future (MTF) 7 Report for 2012 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., 201 3 )

. F or the first time, synthetic cannabinoid use in 8 th and 10 th graders was measured, with annual prevalence rates being 4.4% and 8.8% respectively. The Monitoring the Future Report for 2013 detailed that there has been a recent decline in the use of synthet ic cannabinoids, decreasing from 11.3% in 2012 to 7.9% in 2013 (Johnston et al., 2014).
Summary Recently , law enforcement has been encountering PB

- 22, 5F

- PB

- 22 , and AB

- FUBINACA in increasing numbers. There have also been reports of abuse of

4 Drug courts 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. 5 Office of National Drug Control Policy. Community Drug Early Warning System: The CDEWS Pilot Project, 13. September 13, 2013. 6 Id . p. vi. 7 MTF is a national survey conducted by the Institute for Social Research at the University of Michigan under a grant from the NIDA that tracks drug use trends among American ado lescents in the 8 th , 10 th , and 12 th grades.DEA/OD/ODE page 13 of 40 January 2014

ADB

- PINACA in Georgia and Colorado. 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. PB

- 22, 5F

- PB

- 22 , AB

- FUBINACA , and ADB

- PINACA , similar to the previously scheduled synthetic cannabinoids (DEA, 2012 ; DEA, 2013 ) , have been seized alone and /or 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 Recently, increased exposure incidents have been documented by poison control centers in the U.S. as the abuse of synthetic cannabinoids has been associated with both acute and long

- term public health and safety concerns. From January through December 201 3, according to STRIDE there were 211 reports involving PB

- 22; 168 reports involving 5F

- PB

- 22; and 74 reports involving AB

- FUBINACA (Quer y date: January 22, 2014). From January through December 2013, NFLIS registered 1,318 reports containing PB

- 22 in 2 9 states (Arkansas, Arizona, Colorado, Connecticut, Florida, Georgia, Hawaii, Iowa, Kansas, Kentucky, Louisiana, Maryland, Minnesota, Missouri, North Dakota, Nebraska, New Hampshire, New Jersey, New Mexico, Ohio, Oklahoma, Oregon, Pennsylvania, South Carol ina, Texas, Utah, Virginia, Wisconsin , and Wyoming); 1,294 reports containing 5F

- PB

- 22 in 29 states (Arkansas, Arizona, California, Colorado, Connecticut, Florida, Georgia, Iowa, Indiana, Kansas, Kentucky, Louisiana, Minnesota, Missouri, North Dakota, New Hampshire, New Jersey, New Mexico, Nevada, Ohio, Oregon, Pennsylvania, South Carolina, Tennessee, Texas, Utah, Virginia, Wisconsin , and Wyoming); 822 reports containing AB

- FUBINACA in 21 states (Arizona, Colorado, Connecticut, Florida, Georgia, Iowa, Indi ana, Kansas, Louisiana, Minnesota, Missouri, North Dakota, New Hampshire, New Jersey, Nevada, Ohio, Oklahoma, Pennsylvania, South Carolina, Texas , and Wisconsin); and 40 reports containing ADB

- PINACA in three states (Colorado, Georgia , and Wisconsin) (Quer y date: January 22, 2014). No reports in NFLIS or STRIDE were identified for PB

- 22 or 5F

- PB

- 22 prior to January 2013. No reports in NFLIS or STRIDE were identified for AB

- FUBINACA prior to June 2013 or for ADB

- PINACA prior to August 2013.
AD B

- PINACA was first encountered in the U.S. following reports of serious adverse events in G eorgia and Colorado on August 23, 2013. Reports of ADB

- PINACA were not found in the scientific literature prior to its emergence on the designer drug market

. The Georgia Bureau of Investigation (GBI) reported on September 12, 2013 that ADB

- PINACA, was detected in “herbal incense” products sold under the brand name “Crazy Clown .” It was later confirmed by the Centers for Disease Control and Prevention (CDC) as the substance responsible for severe adverse events in at least 22 persons whoDEA/OD/ODE page 14 of 40 January 2014

consumed the product (CDC, 2013b) . In addition, On August 30, 2013, the Colorado Department of Public Health and Environment (CDPHE) was notified by several hospitals of an increas e in the number of patients visiting their emergency departments (EDs) with altered mental status after using synthetic marijuana (Appendix 2) . On September 8, 2013, CDPHE, with the assistance of CDC, began an epidemiologic investigation whereby 221 cas es of severe illness due to ingestion of a synthetic cannabinoid were identified (CDC, 2013c) . Those that presented at emergency rooms in the Denver, Colorado area around September 1, 2013 had symptoms similar to those found in the August 2013 Georgia inc ident. Laboratory analysis of samples from the Colorado incident confirmed that the substance abused in the “herbal incense” products was ADB

- PINACA.
The American Association of Poison Control Centers (AAPCC) reported receiving i n excess of 5,200 exposure calls in 2012 corresponding to products purportedly applied with synthetic cannabinoids , although the data provided does not generally include biological sample testing that would confirm which cannabinoids the user was exposed to
. 8 In addition, the AAPCC has reported over 2,639 calls regarding synthetic cannabinoids from January to December of 2013. A majority of exposure incidents in both 2012 and 2013 resulted in individuals seeking medical attention at health care facilities. Chronic abuse o f 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 involv ing 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 )

.

8 The content of this report does not necessarily reflect the opinions or conclusions of the American Association of Poison Control Centers. The American Association of Poison Control C enters (AAPCC; http://www.aapcc.org ) maintains the national database of information logged by the 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 ingestion, 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 subs tance(s).DEA/OD/ODE page 15 of 40 January 2014 Synthetic cannabinoids and the associated products are sold over the Internet and found to be abused by diverse populations. Since synthetic cannabinoids were never intended for human consumpt ion, 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 al., 2009 )

. In addition, the chronic abuse of products laced with synthetic cannabinoids has been linked to addiction and withdrawal (Vardakou et al., 2010). The increased abuse of these synthetic cannabinoids in the U.S. is supported by an increasing number of encounters by law enforcement. T here has been a significant increase in availability, trafficking and abuse of PB

- 22, 5F

- PB

- 22 , AB

- FUBINACA , and ADB

- PINACA throughout the U.S. since January 2013 , evident from the increasing number of encounters reported by forensic laboratories (NFLIS da ta). In addition, laboratory confirmations of novel cannabinoids such as ADB

- PINACA have resulted in serious illness and adverse effects following consumption in Georgia and Colorado. Due to the previous scheduling action s of various synthetic cannabinoi ds ( emergency scheduling of JWH

- 018, JWH

- 200, JWH

- 073, CP

47, 497 , and CP

- 47,497 C8 homologue, March 1, 2011 ; permanent scheduling of JWH

- 018, JWH

- 200, JWH

- 073, CP

- 47,497 , and CP

- 47,497 C8 homologue in addition to others under FDASIA, July 9, 2012 ; emergency scheduling of UR

- 144, XLR11 , and AKB48, May 16, 2013 ) , law enforcement has been encountering n ew synthetic cannabinoids including PB

- 22, 5F

PB

- 22 , AB

- FUBINACA , and ADB

- PINACA

.

0 5000 10000 15000 20000 25000 30000

2010 2011 

## Emergency Department Visits Involving Synthetic Cannabinoids*DEA/OD/ODE page 16 of 40 January 2014

Figure 2 . Emergency department visits involving synthetic cannabinoids (SAMHSA, 2013). Synthetic cannabinoid d ata 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

- h our EDs in the U.S. 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 potential ly laced with synthetic cannabinoids that have resulted in visits to emergency departments. Follow ing legislative control of JWH

- 018, JWH

- 200, JWH

- 073, CP

- 47,497 , and CP

- 47,497 C8 , by FDASIA in July of 2012 and the emergency scheduling of UR

- 144, XLR11 , a nd AKB48 in May 2013, law enforcement has begun encountering novel synthetic cannabinoids including PB

- 22, 5F

- PB

- 22 , AB

- FUBINACA , and ADB

- PINACA

.
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 privat e organizations. Detailed product analyses describe variations in the amount and synthetic cannabinoid laced on the plant material even within samplings of the same product ( Hudson et al., 2010 ) . These unknowns pr esent a significant risk or danger to the abusing individuals ( 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 roo ms in response to the abuse of synthetic cannabinoids include vomiting, anxiety, agitation, irritability, seizures, hallucinations, tachycardia, elevated blood pressure, and loss of consciousness ( Forrester et al., 2011; Cohen et al., 2012 ; Harris and Brown, 2013; Hermanns

- Clausen et al., 2013 ; Zawilska and Wojcieszak, 2013 ) (see reports from state health departments and poison centers including AAPCC, Appendix 1). A 12

- month study conducted in 2012 demonstrated that out of 950 self

- reported users, 2.4% repor ted having a medical emergency requiring treatment resulting from a combination of panic, anxiety, paranoia , and breathing difficulties (Winstock and Barratt, 2013). DataDEA/OD/ODE page 17 of 40 January 2014

from this study also demonstrated that recent users who reported seeking emergency treatment were significantly younger than those who did not report seeking treatment (Winstock and Barratt, 2013). These data correspond to figures reported by SAMSHA, which demonstrates that youth, specifically those aged 12 to 17 years old, comprise a l arge percentage of users requiring emergency medical attention (Figure 3.)

Figure 3. Age
- related emergency department visits involving synthetic cannabinoids and marijuana (SAMHSA, 2012). 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., 1992; 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 )

. S imilar products have been found to vary in the amount and type of synthetic 0 5 10 15 20 25 30 35

Aged 12-17 Aged 18-20 Aged 21-24 Aged 25-29 Synthetic Cannabinoids Marrijuana 

## Age Related Synthetic Cannabinoid and Marijuana
- Related Emergency Department (ED)

Visits
- 2010DEA/OD/ODE page 18 of 40 January 2014

cannabino id laced on t he plant material, w hich could be one explanation for the n umerous emergency department admissions that have been connected to these substances ( Vardakou et al., 2010; Vearrier and Osterhoudt, 2010 ; Schneir et al., 2011 ; Fattore and Fratta, 2011 ) . Health warnings have been issued by numerous state public health departments (Appendix 1) and poison control centers describing adverse health effects associated with smoking (inhaling) these products including agitation, vomiting, tach ycardia, elevated blood pressure, seizures, hallucinations , and non

- responsivenes s . The earliest reported detection of PB

- 22 was via Finnish Customs (Tulli) in Helsinki who intercepted a consignment of 54 kilograms en route from China to Russia on October 27, 2012. Finland notified the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) on November 20, 2012 9

. From January through November 2013, CBP reported the following seizures with most shipments originating in China and intended f or destinations within the U .S. : PB

- 22

– 25 seizures involving 69.6 kg; 5F

- PB

- 22

– 23 seizures involving 32.9 kg; and AB

- FUBINACA

– 9 seizures involving 16.1 kg (Appendix 2) 10

. The DEA has reported multiple encounters of large quantities of PB

- 22, 5F

- PB

- 22 , and/or AB

- FUBINACA that have been confirmed by forensic laboratories (STRIDE). In addition, a report sent to the DEA from the Mansfield Division of Police Forensic Science Laboratory in Mansfield, Ohio has confirmed the presence of PB

- 22 (1 7 cases) or 5F

- PB

- 22 (6 cases) from January through May of 2013 11

. This report included incident/investigative public narratives that included physical symptoms and observations of users. Excerpts from these reports with laboratory confirmation of either PB

- 22 or 5F

- PB

- 22 are detailed below.

PB - 22 1) Subject was unable to stand, and when trying to stand, he kept falling down. Subject was lethargic and could not speak clearly. Subject transported to medical facility.
5F - PB - 22 1) After smoking “spice” all day, subject began vomiting and having convulsions. Subject was unconscious when law enforcement arrived, was not responding , but was breathing. Subject would be comatose one minute and then would become violent the next. Medic s restrained the subject’s legs and were working on

9 Correspondence from EMCDDA to the Drug and Chemical Control (ODEC) Unit of the DEA 02 / 01/2013

. 10 Correspondence from CBP to ODEC, DEA

. 11 Correspondence from Mansfield Division of Police Forensic Science Laboratory to ODEC, DEA 06/13 /2013

.DEA/OD/ODE page 19 of 40 January 2014 restraining the subject’s arms when the subject appeared to start hallucinating. The subject began screaming and tried to get off of the stretcher several times. The subject began to scream that “he ha d to shoot him to save his cousin”. The subject appeared to be looking into the corner of the ceiling. Subject referred to medical facility. 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 a l., 2010 )

. From July through November 2013, five death s ha ve been reported involving 5F

- PB

- 22. A 17 year old male’s cause of death was listed by the medical examiner as “5F

PB

- 22 intoxication 12

. ” Autopsy findings of an 18 year old male reported as a fatal cardiac arrhythmia and/or fatal seizure in association with 5F

- PB

- 22 use 13

. In addition, a toxicology laboratory is currently gathering additional information for three separate postmortem toxicological investigation s in which 5F

- PB

- 22 has been identified in blood and quantitatively measured 14

. As mentioned above, there are reported instances of emergency department admissions in associat ion with the abuse of PB

- 22 and 5F

- PB

- 22

. There is no accepted medical use of these substances in the U.S

.
In late August 2013, local law enforcement in Brunswick, G eorgi a reported that 22 users presented to emergency departments with sever e adverse reactions after the consumption of a synthetic product called “Crazy Clown”. Adver se effects included the inability to stand, foaming at the mouth, violence towards police and paramedics , and memory lapse. The substance responsible for these effects was later identified by the GBI as ADB

- PINACA. Days later in early September 2013, ove r 200 patients presented to emergency departments in Colorado after have adverse reactions to a synthetic product labeled as “Black Mamba” (Appendix 2)

. Adverse effects included having no gag reflex, inability to breathe on their own, hallucinations , and psychotic episodes as described by nurses and attending physicians. The substance in these episodes was also identified as ADB

- PINACA. The CSA (21 U.S.C. 811(h)(4) requires the Deputy Administrator to notify the Secretary of the Department of Healt h and Human Services (HHS) of his intention to temporarily place a substance into S chedule I of the CSA. 15 The Deputy Administrator

12 Co rrespondence from Law Enforcement to ODEC, DEA , 09/10/2013 13 Correspondence from Law Enforcement to ODEC, DEA, 11/12/2013 14 Correspondence from Private Toxicology Laboratory to ODEC, DEA, 11/18/2013 15 The Secretary of HHS has delegated to the Assistant Secretary for HHS the authority to make domestic drug scheduling recommendations. As set forth in a memorandum of understanding entered into by HHS, the FDA, and NIDA, FDA acts as the lead agency within HHS in carrying out the Secretary’s scheduling responsibilities under the CSA, with the concurrence of NIDA. 50 FR 9518.DEA/OD/ODE page 20 of 40 January 2014

transmitted notice of his intent to place PB

- 22, 5F

- PB

- 22, AB

- FUBINACA, and ADB

- PINACA in schedule I on a temporary basis to the Assistant Secretary by letter dated November 7, 2013. The Assistant Secretary responded to this notice by letter dated January 27, 2014 , and advised that based on review by the Food and Drug Administration (FDA), there are currently no investigational new drug applications or approved new drug applications for PB

- 22, 5F

- PB

- 22, AB

- FUBINACA, or ADB

- PINACA. The Assistant Secretary also stated that HHS has no objection to the temporary placement of PB

- 22, 5F

- PB

- 22, AB

- FUBINACA, or AD B

- PINACA into schedule I of the CSA. The DEA has taken into consideration the Assistant Secretary’s comments. As PB

- 22 , 5F

- PB

- 22, AB

- FUBINACA, or ADB

- PINACA are not currently listed in any schedule under the CSA, and as no exemptions or approvals are in effect for PB

- 22, 5F

- PB

- 22, AB

- FUBINACA, or ADB

- PINACA under Section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355), the DEA believes that the conditions of 21 U.S.C. 811(h)(1) have been satisfied. Any additional comments submitted by the Assistant Secretary in response to this notification shall also be taken into consideration before a final order is published. 21 U.S.C. 811(h)(4).
Conclusion of 3 - Factor Analysis After a careful review of the scientific literature, Factors 4, 5, and 6, NFLIS, STRIDE, and other law enforcement data and sources of information, it is evident that PB

- 22, 5F

- PB

- 22 , AB

- FUBINACA and ADB

- PINACA are trafficked and abused and pose an imminent hazard to public safety

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

- 22, 5F

- PB

- 22 , AB

- FUBINACA , and ADB

- PINACA indicated that these substances , including their salts, isomers, and salts of isomers, pose an imminent hazard to public safety and health, have high potential for abuse, have no currently accepted medical use in treatment in the U.S. , and lack accepted safety for use under medical supervision.DEA/OD/ODE page 21 of 40 January 2014 R eferences Atwood BK, Huffman J, Straiker A, Mackie K (2010)

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DEA (2012) Schedules of Controlled Substances: Placement of 1

- Butyl

- 3

- (1

- naphthoyl)indole (JWH

- 073), 1

- pentyl

- 3

- (1

- naphtoyl)indole (JWH

- 018), 1

- [2

- (4

- morpholinyl)ethyl]

- 3

- (1

- naphthoyl)indole (JWH

- 200), 5

- (1,1

- dimethylheptyl)

- 2

- (3

- hydroxycyclohexyl)

- phenol (CP

- 47,497), and 5

- (1,1

- dimethyloctyl)

- 2

- (3

- hydroxycyclohexyl)

- phenol (cannabicyclohexanol and CP

- 47,497 C8 homologue) into Schedule I : Backgr ound, Data, and Analysis: Eight Factors Determinative of Control and Findings Pursuant to 21 U.S.C. 812(b). DEA (2013) 1

- pentyl

- 3

- (2,2,3,3

- tetramethylcyclopropoyl)indole (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): Background Information and Evaluation of ‘Three Factor Analysis’ (Factors 4, 5 and 6) for Temporary Scheduling. 78 FR 28735. Dresen S, Ferreiros N, Putz M, Westphal F, Z immermann R, Auwarter V (2010)

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. How globalization and market innovation challenge how we think about and respond to drug use: 'Spice' a case study. Addiction 105:951

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Gunderson EW, Haughey HM, Ait

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. Use of high

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. Design, synthesis and pharmacology of cannabimimetic indoles. Bioorg anic and Med icinal Chem istry Letters 4:563

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. Synthesis and pharmacology of a very potent cannabinoid lacking a phenolic hydroxyl with high affinity for the CB2 receptor. J ournal of Med icinal Chem istry 39(20):387 5

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Konstrand R, Roman M, Andersson M, Eklund A (2013). Toxi cological findings of synthetic cannabinoids in reacreational users. Journal of Analytical Toxicology 37(8):534

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. Spice: a never ending story? Forensic S cience I nternational 191:58

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M akriyannis A and Liu, Q. (2003)

. Heteroindanes: A new class of potent cannabimimetic ligands (patent). WO 03/035005 A2. McGuinness TM, Newell D (2012). Risky recreation: synthetic cannabinoids have dangerous effects. Journal of Psychosocial Nursing and Mental Health Se rvices 50(8): 16

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. The synthetic cannabinoid Spice as a trigger for an acute exacerbation of cannabis

induced recurrent psychotic episodes. Schizophrenia R esearch 118:309

- 310. NIDA (2013 a ). Cannabinoid, CB1 (h) Cannabanoid, CB1 (h) Testing Profile and IC50/Ki Determination. TDP# PB

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- 8

- 8877: July 23, 2013. NIDA (2013b). Cannabinoid, CB1 (h) Agonist Cellular/Functional Assay. TDP# PB

- 22. NIDA Contract N01D A

- 8

- 8877: August 1, 2013. NIDA (2013c ). Cannabinoid, CB1 (h) Cannabanoid, CB1 (h) Testing Profile and IC50/Ki Determination. TDP# 5F

- PB

- 22. NIDA Contract N01DA

- 8

- 8877: July 23, 2013. NIDA (2013d). Cannabinoid, CB1 (h) Agonist Cellular/Functional Assay. T DP# 5F

- PB

- 22. NIDA Contract N01DA

- 8

- 8877: August 1, 2013. NIDA (2013e ). Cannabinoid, CB1 (h) Cannabanoid, CB1 (h) Testing Profile and IC50 /Ki Determination. TDP# AB

- FUBINACA . NID A Contract N01DA

- 8

- 8877: September 9 , 2013. NIDA (2013f ). Cannabinoid, CB1 (h) Agonist Cellular /Functional Assay. TDP# AB

FUBINACA . NIDA Contract N01DA

- 8

- 8877: September 25, 2013

. NFLIS (2013)

. National Forensice Laboratory Information System. Drug Enforcement Administration.DEA/OD/ODE page 25 of 40 January 2014

Oluwabusi OO, Lobach L, Akhtar U, Youngman B, Ambrosini (2012). Synthetic cannabinoi

- induced psychosis: t wo adolescent cases. Journal of Child and Adolescent Psychopharmacology 22(5):393

- 395.
ONDCP (Office of National Drug Control Policy) , 2011. Synthetic Marijuana. Patton AL, Chimalakonda KC, Moran CL, McCain KR, Radominska

- Pandya A, James LP, Kokes C, Moran JH (2013). K2 Toxicity: Fatal Case of Psychiatric Complications Following AM2201 Exposure. J orunal of Forensic Sci ence . 58(6):1676

- 80

. Peglow S, Buchner J, Briscoe G. (2012). Synthetic can nabinoid psychosis in previously nonpsychotic patient. American Journal of Addiction 21(3):287

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- Related Emergency Department Visits. Rockville, MD: Center for Behavioral Health Statistics and Quality. Schifano F, Corzazza, O., Deluca, P., Davey, Z., Di Furia, L., Farre, M., Flesland, L., Mannonen, M., Pagani, S., Peltoniemi, T., Pezzolesi, C., Scherbaum, N., Siemann, H., Skutle, A., Torrens, M., Van der Kreeft, P. (2009) Psychoactive drug or mystical incense? Overview of online available information on Spice products. International Journal of Culture and Mental Health 2:137

- 144. Schneir AB, Cullen J, Ly BT (2011) "Spice" girls: synthetic cannabinoid intoxication. The Journal of E mergency M edicine 40:296

- 299. Sharma SK, Jia G, Lown JW (2001) Novel cyclopropylindole conjugates and dimers: synthesis and anti

- cancer evaluation. Current M edicinal C hemistry Anti

- C ancer A gents 1:27

- 45. Sobolevsky T, Prasolov I, Rodchenkov G (2012) Detection of urinary metabolites of AM

2201 and UR

- 144, two novel synthetic cannabinoids. Drug T esting and A nalysis Epub ahead of print.
STRIDE (2013) System to Retrieve Information from Drug Evidence. Drug Enforcement Administration.DEA/OD/ODE page 26 of 40 January 2014

Thomas S, Bliss S, Malik M (2012). Suicidal ideation and self

- harm following K2 use. Journal of Oklahoma State Medical Association 105(11):430

- 433. Uchiyama N, Matsuda S, Kawamura M, Kikura

- Hanajiri R, Goda Y (2013) Two new - type cannabimimetic quinolinyl carboxylates, QUPIC and QUCHIC, two new cannabimimetic carboxamide derivatives, ADB

- FUBINACA and ADBICA, and five synthetic cannabinoids detected with a thiophene derivative a

- PVT and an opioid receptor agonist AH

- 7921 i dentified in illegal products. Forensic Toxicology, Published online: March 15. Uchiyama N, Kawamura M, Kikura

- Hanajiri R, Goda Y (2012b) URB

- 754: A new class of designer drug and 12 synthetic cannabinoids detected in illegal products. Forensic S cience I n ternational 227(1

- 3):21

- 32

. Uchiyama N, Kawamura M., Kikura

- Hanajiri, R., Goda, Y. (2012a) Identification of two new - type synthetic cannabinoids, N

- (1

- adamantyl)

- 1

- pentyl

- 1H

- indazole

- 3

- carboxamide (APICA) and N

- (1

- adamantyl)

- 1

- pentyl

- 1H

- indazole

- 3

- carboxa mide (APINACA), and detection of five synthetic cannabinoids, AM

- 1220, AM

- 2233, AM

- 1241, CB

- 13 (CRA

- 13), and AM

- 1248, as designer drugs in illegal products. Forensic Toxicol ogy 30:114

- 125. Uchiyama N, Kikura

- Hanajiri R, Ogata J, Goda Y (2010) Chemical analysis of synthetic cannabinoids as designer drugs in herbal products. Forensic S cience I nternational 198:31

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- 241. Vardakou I, Pistos C, Spiliopoulou C (2010)

. Spice drugs as a new trend: mode of action, identification and legislation. Toxicology L etters 197:157

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. A teenager with agitation: higher than she should have climbed. Pediatric E mergency C are 26:462

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- 323. Weissman A, Milne GM, Melvin LS, Jr. (1982)

. Cannabimimetic activity from CP

- 47,497, a derivative of 3

- phenylcyclohexanol. The Journal of P harmacology and E xperimental T her apeutics 223:516

- 523. Wells DL, Ott CA (2011)

. The "new" marijuana. The Annals of P harmacotherapy 45:414

- 417.DEA/OD/ODE page 27 of 40 January 2014

Wiley JL, Compton DR, Dai D, Lainton JA, Phillips M, Huffman JW, Martin BR (1998)

. Structure

- activity relationships of indole

- and pyrrole

- deriv ed cannabinoids. The Journal of P harmacology and E xperimental T herapeutics 285:995

- 1004. Winnstock AR, Barratt MJ. (2013)

. The 12

- month prevalence and natrue of advers e experiences resulting in emergency medical prsentations associated with the use of synthetic cannabinoid products. Hum an Psychopharm acology: Clin ical and Exp erminetal 28:390

- 393. Yeakel JK, Logan BK (2013). Blood synthetic cannabinoid concentrations in cases of suspected impaired driving. Journal of Analytical Toxicology 37(8):547

- 551. Zawilska JB, Wojcieszak J (2013). Spice/K2 drugs

– more than innocent subsitutes for marijuana. Internation Journal of Neuropsychopharmacology, epub ahead of print.
Z immermann US, Winkelmann PR, Pilhatsch M, Nees JA, Spanagel R, Schulz K (2009)

. Withdrawal phenomena and dependence syndrome after the consumption of "spice gold". Deutsches Arzteblatt I nternational 106:464

- 467.DEA/OD/ODE page 28 of 40 January 2014

Appendix 1 Public Health 1. The Substance Abuse and Mental Health Services Administration (SA MHSA) reported that in 2010, an estimated 11,406 emergency department visits involved a synthetic cannabinoid product. 2. SAMHSA reported that in 2011, an estimated 28,531 emergency department visits involved a synthetic cannabinoid product, a 2.5 times increase over the 2010 estimated visits. 3. 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 leve l 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. 4. Monitoring the Future study results for 2013 (released 12/18/2013 ) state that use of synt hetic marijuana amongst 12th graders fell from 11.3% in 2012 to 7.9% in 2013

. 5. Health effects from the drug can be life

- threatening and can include: a. Severe agitation and anxiety. b. Fast, racing heartbeat and higher blood pressure. c. Nausea and vomiting. d. Muscle spasms, seizures, and tremors. e. Intense hallucinations and psychotic episodes. f. Suicidal and other harmful thoughts and/or actions. g. http://www.aapcc.org/alerts/synthetic

- marijuana/ 6. ...these substances are among the worst they have ever seen. People high on these drugs can get very agitated and violent, exhibit psychosis and severe behavior changes, and have harmed themselves and others. Some have been admitted to psychiatric hospit als and have experience continued neurological and psychological effects (News Release

– American Associ ation of Poison Control Centers: AAP CC Issues Statement on the Synt hetic Drug Abuse Prevention Act , July 11, 2012 )

. Poison Control Centers

1. March 24 AAPC C Press Release. As of March 24, 2010, 112 exposure calls had been received since 2009 regarding synthetic cannabinoids and associated products, including 59 exposure calls since March 1, 2010, according to the National Poison Data System ( NPDS )

. 2. July 23, 2010 AAPCC Press Release. As of July 23, 2010, 761 exposure calls had been received regarding synthetic cannabinoids and associated products according to NPDS.DEA/OD/ODE page 29 of 40 January 2014 3. August 20, 2010 AAPCC Press Release. As of August 20, 2010, 1,057 exposure calls had been rec eived regarding synthetic cannabinoids and associated products according to NPDS. 4. September 27, 2010 AAPCC Press Release. As of September 27, 2010, 1,503 exposure calls had been received regarding synthetic cannabinoids and associated products according t o NPDS. 5. November 3, 2010 AAPCC Press Release. As of November 3, 2010, 1,966 exposure calls have been received by poison centers regarding products purported to contain synthetic cannabinoids according to NPDS. Calls have been received in 48 states and th e District of Columbia. 6. November 22, 2010 AAPCC Press Release . As of November 22, 2010, poison centers have reported 2,304 exposure calls regarding products purported to contain synthetic cannabinoids according to NPDS. Poison centers have received expos ure calls 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 exposure calls this year alone. As of December 21, 2010, poison centers have reported 2,752 exposure calls about the products according to NPDS. 8. January 18, 2011 AAPCC Press Release. As of January 18, 2011, U.S. poison centers have received more than 3,000 exposure calls regarding products purported to contain synthetic cannabinoi ds. In 2010, poison centers reported 2,867 exposure calls. As of January 18, 2011, U.S. poison centers have reported 217 exposure calls for 2011. 9. February 3, 2011, AAPCC Press Release. As of February 3, 2011, U.S. poison centers have reported 385 exposu re calls for 2011. 10. February 10, 2011, AAPCC Press Release. Synthetic marijuana products have spurred more than 3,000 exposure calls to U.S. poison centers since 2010. 11. February 24, 2011, AAPCC Press Release. As of February 24, 2011, U.S. poison centers ha ve reported 706 exposure calls for 2011. The total number of calls since 2010 is more than 3,500 exposure calls. 12. April 20, 2011, AAPCC Press Release. Synthetic marijuana products have spurred more than 4,500 exposure 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 exposure calls related to synthetic marijuana and bath salts. In 2011, the number jumped to more than 13,000. Sixty percent of these case s involved patients 25 and younger.DEA/OD/ODE page 30 of 40 January 2014 14. November 28, 2011, AAPCC Press Release. Poison center data provides vital information leading to the DEA ban of synthetic drugs. 15. February 16, 2012, AAPCC Press Release. American Association of Poison Control Centers jo ins the Office of National Drug Control Policy Working Group in address ing the dangers o f synthetic drugs. 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 De cember 31 , 2012 , poison center s nationwide have received 5,200 exposure calls regarding exposure to synthetic cannabinoids. 19. Fro m January 1, 2013 through December , 2013 , poison center s nationwide have received 2,639 exposure 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 ( www .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 D angers of Synthetic Marijuana , March 18, 2010 (www.cadca.org)DEA/OD/ODE page 31 of 40 January 2014

Table 3. NFLIS – State and Local Forensic Laborato ry Reports (Quer y date: January 22, 2014 )

2010 2011 2012 2013 Total Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 † JWH - 018; JWH - 073; JWH - 200; CP - 47,497 CP 47,497 C8 homologue 138 413 670 1 , 197 1 , 515 997 661 542 427 354 228 144 102 87 74 1 7 7,566

UR - 144; XLR11; AKB48 1* 0 0 0 0 0 0 50 569 3,308 6,238 4,957 6,079 5,955 3,119 1,002 31,278
PB - 22 0 0 0 0 0 0 0 0 0 0 0 0 223 445 475 175 1,318 5F - PB - 22 0 0 0 0 0 0 0 0 0 0 0 0 102 4 27 573 192 1, 294
AB FUBINACA 0 0 0 0 0 0 0 0 0 0 0 0 0 22 396 404 822
ADB PINACA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 38 2 40 *Encounter confirmed in March 2012; † = data are incomplete for fourth quarter 2013, still being reported

.DEA/OD/ODE page 32 of 40 January 2014

Table 4. ST RIDE Records (January through November * (Quer y date: January 22, 2014 ):

NUMBER OF RECORDS PB - 22 211 5F - PB - 22 168 AB - FUBINACA 74 ADB - PINACA 0
* No reports identified in STRIDE regarding PB

- 22 or 5F

- PB

- 22 prior to February 2013. No reports of AB

- FUBINACA prior to J une 2013.DEA/OD/ODE page 33 of 40 January 2014

Appendix 2
T able 5. Reports from ADB
- PINACA overdoses ( August – September 2013)* Location Substance Identified Packet Label Remarks Denver, CO ADB

- PINACA Crazy Clown Pineapple Express Non e

Denver, CO ADB

- PINACA Crazy Clown Two males passed out in a vehicle; both became extremely ill; drive r placed on life support

Denver, CO ADB

- PINACA AM

- HI

- C; Atomic Bomb; Black Mamba Single vehicle

accident, driver passed out while driving and collided with a tree
Denver, CO ADB

- PINACA Dead Man Walking User became ill after

using subs tance and required hospitalization

Denver, CO ADB

- PINACA Unknown User wa s found slumped over the wheel o f a vehicle in the middle of an intersection

Denver, CO ADB

- PINACA Mamba Male and female user found passed out in backyard; female vomited over herself; male became combative and required restraints

Denver, CO ADB

- PINACA Mamba User had minimal vitals upon EMS arrival; required use of a respirator at hospital; user collapsed following single puff from a rolled cigarette of “Mamba”DEA/OD/ODE page 34 of 40 January 2014

Denver, CO ADB

- PINACA Mamba Two juveniles required hospitalization after smoking mamba; one juvenile found stumbling down the street * Communication from Aurora Police Department to the DEA (12/18/2013) T able 6 . Reports from Customs and Border Prote ction Laboratory (January – November 2013)
Date of Detention Identified

Substance(s) Detained at Originated from Destination TOTAL WEIGHT

1/29/2013 PB

- 22 FedEx Anchorage, AK China Fort Lauderdale, FL 15 kg

1/29/2013 PB

- 22 FedEx Anchorage, AK China Fort Lauderdale, FL 15 kg 2/8/2013 PB

- 22 San Francisco Intl Mail China Richardson, TX 2 kg 2/13/2013 PB

- 22 San Francisco Intl Mail China San Dimas, CA 2 kg 2/28/2013 PB

- 22 San Francisco Intl Mail China Newman Lake, WA 300

grams 2/28/2013 PB

- 22 San Francisco Intl Mail China Newman Lake, WA 300

grams 2/28/2013 PB

- 22 San Francisco Intl Mail China Arlington, TX 100 grams 3/6/2013 PB

- 22 San Francisco Intl Mail China Tulsa, OK 2 kg

3/13/2013 PB

- 22 FedEx Anchorage, AK China South Charleston, WV 3.5 kg

3/22/2013 5

- fluoro

- PB

- 22 FedEx Anchorage, AK China Columbia, MO 3.5 kg 4/4/2013 PB

- 22 San Francisco Intl Mail China Phoenix, AZ 200 gramsDEA/OD/ODE page 35 of 40 January 2014

4/4/2013 PB

- 22 San Francisco Intl Mail China Temecula, CA 2 kg 4/4/2013 PB

- 22 San Francisco Intl Mail China Columbia, MO 2 kg 4/4/2013 PB

- 22 San Francisco Intl Mail China Columbia, MO 2 kg 4/4/2013 PB

- 22 San Francisco Intl Mail China Walnut, CA 2 kg 4/12/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Phoenix, AZ unknown 4/19/2013 PB

- 22 San Francisco Intl Mail China Sprints, LA 100 grams 5/6/2013 PB

- 22 San Francisco Intl Mail China Decatur, IL 100 grams 5/16/2013 PB

- 22 San Francisco Intl Mail China Las Cruces, NM 1 gram 5/18/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail Hong Kong Las Vegas, NV 500 grams 5/31/2013 5

- fluoro

- PB

- 22 FedEx Anchorage, AK China Las Cruces, NM 1 kg 6/13/2013 PB

- 22 San Francisco Intl Mail China Coeur D'Alene, ID 500

grams 6/13/2013 PB

- 22 San Francisco Intl Mail China Baytown, TX 1 kg 6/25/2013 PB

- 22 San Francisco Intl Mail Hong Kong Salt Lake City, UT 5 kg 6/25/2013 PB

- 22 San Francisco Intl Mail China Houston, TX 2 kg 6/25/2013 PB

- 22 San Francisco Intl Mail China Chatsworth, CA 1 kg 6/25/2013 PB

- 22 San Francisco Intl Mail China Katy, TX 3 kg 6/27/2013 5

- fluoro

- PB

- 22 FedEx Anchorage, AK China Las Vegas, NV 3 kg 6/29/2013 5

- fluoro

- PB

- 22 FedEx Anchorage, AK China Puerto Rico 2.8 kg 7/5/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Pahrump, NV 1 kgDEA/OD/ODE page 36 of 40 January 2014

7/5/2013 PB

- 22 San Francisco Intl Mail China Tacoma, WA 3 kg 7/8/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Las Vegas, NV 2 kg 7/8/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Las Vegas, NV 2 kg 7/10/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Anchorage, AK 1 kg 7/17/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Las Cruces, NM 300

grams 7/17/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Independence, LA 700

grams 7/17/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Independence, LA 700

grams 7/17/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Independence, LA 2.5 kg 8/8/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Houston, TX 3 kg 8/15/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Ogden, UT 500 grams 8/22/2013 PB

- 22 San Francisco Intl Mail China Elizabeth, NJ 5.5 kg 9/4/2013 5

- fluoro

- PB

- 22 FedEx Anchorage, AK China Tulsa, OK 2.3 kg 9/5/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Baton Rouge, LA 50 grams 10/3/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail unknown unknown 1.3 kg 10/9/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Bremerton, WA 2 kg 10/9/2013 AB

- FUBINACA San Francisco Intl Mail China Houston, TX 5 kg 10/24/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Casper, WY 800 grams 10/24/2013 5

- fluoro

- PB

- 22 San Francisco Intl Mail China Bremerton, WA 2 kg 10/24/2013 AB

- FUBINACA San Francisco Intl Mail China Houston, TX 4 kgDEA/OD/ODE page 37 of 40 January 2014

10/24/2013 AB

- FUBINACA San Francisco Intl Mail China Anderson, SC 10 grams 10/31/2013 AB

- FUBINACA San Francisco Intl Mail China Austin, TX 5 grams 11/7/2013 AB

- FUBINACA San Francisco Intl Mail China Metairie, LA 100 grams 11/7/2013 AB

- FUBINACA San Francisco Intl Mail China Canyon Country, CA 2 kg 11/7/2013 AB

- FUBINACA San Francisco Intl Mail China Canoga Park, CA 3 kg 11/7/2013 AB

- FUBINACA San Francisco Intl Mail China Canyon Country, CA 2 kg 11/7/2013 AB

- FUBINACA San Francisco Intl Mail China Mchenny, IL 5 grams

Table 7 . DEA Sample Laboratory Results

Date Label Flavor/ Characteristic Confirmed

Substance Lab Notes

5/2/2013 Dr. Feelgood Kush PB

- 22 South Central 2g packet, mad

scientist holding green bottle
5/2/2013 Dr. Feelgood Chronic Hypnotic PB

- 22 South Central 2g packet, mad

scientist holding green bottle
6/6/2013 Scorpion

King PB

- 22 Northeast Plastic vial, picture of scorpion 6/6/2013 Newer

Diesel PB

- 22 Northeast Plastic vial, gold crown
6/6/2013 Black PB

- 22 Northeast Plastic vial, scary eyes on label 6/6/2013 Dead Man PB

- 22 Northeast Plastic vial 6/6/2013 Aloha PB

- 22 Northeast Plastic vial 6/6/2013 El diablo PB

- 22 Northeast Plastic vial

6/10/2013 Caution PB

- 22 Northeast 3g, Orange packet, biohazard symbol 6/10/2013 California PB

- 22 Northeast Packet, greenDEA/OD/ODE page 38 of 40 January 2014 Dreams and white marijuana leaf on front
6/10/2013 Kush PB

- 22, XLR11 Northeast 11g, green sparkle writing, black packet 6/14/2013 Demon Child Kush PB

- 22, 5F

PB

- 22 Western 2g packet, skull on front

6/14/2013 Red Eye Jack PB

- 22 Western 3g, Jack (from playing cards) on front with red eye 6/14/2013 Demon Child Blueberry Thrill PB

- 22, 5F

PB

- 22 Western 5g packet, skull on front

6/14/2013 Biohazard Original PB

- 22 Western 2g packet, brown background, biohazard symbol on front

6/14/2013 Game

Master Original PB

- 22, XLR11 Western 1g packet, Man with numbers coming from head, blue background

6/17/2013 OMG Next Gen PB

- 22 Northeast 4g packet, dwarf, psychedelic colors

8/26/2013 Wonderland Kush PB

- 22, 5F

PB

- 22 Western 2g packet, red mushrooms growing over a dock and pond

8/26/2013 Joker Chronic Hypnotic 5F

- PB

- 22 Western 5g black packet, evil clown face on front, aromatic therapy

8/26/2013 Vato Locos Melon Mamba PB

- 22, 5F

PB

- 22 Western 2g black packet, three guys in suits (green, purple, red), also comes in larger packet
8/26/2013 Hysteria

Black Melon Mamba;

Strawberry PB

- 22, 5F

PB

- 22 Western 2g black packet, XXX, red triangle pattern 8/26/2013 WTF PB

- 22 Western 1.5 and 2.5 gDEA/OD/ODE page 39 of 40 January 2014 black packet, Fidel Castro w/no toilet paper on front

8/26/2013 El Diablo PB

- 22 Western Small plastic vial, black lid, red and black label
8/26/2013 Fallen Angel Kush; Chronic Hypnotic PB

- 22, 5F

PB

- 22 Western 5g black packet, woman on fire on front
8/26/2013 Devils

Advocate Kush PB

- 22, 5F

PB

- 22 Western 5g black packet, skull with horns, fire behind

8/26/2013 Black

Mamba PB

- 22 Western Clear plastic vial with black lid, red sticker on topDEA/OD/ODE page 40 of 40 January 2014