Forensic Investigation of K2, Spice, and “Bath Salt” Commercial

Forensic Science International 233 (2013) 416–422

Contents lists available at ScienceDirect

Forensic Science International

jou rnal homepage: www.elsevier.com/locate/forsciint

Forensic investigation of K2, Spice, and ‘‘bath salt’’ commercial

preparations: A three-year study of new designer drug products

containing synthetic cannabinoid, stimulant, and hallucinogenic compounds

a a b b c

Kathryn A. Seely , Amy L. Patton , Cindy L. Moran , Mary L. Womack , Paul L. Prather ,

c d e

William E. Fantegrossi , Anna Radominska-Pandya , Gregory W. Endres ,

b a f g,h

Kermit B. Channell , Nathaniel H. Smith , Keith R. McCain , Laura P. James ,

a,c,

Jeffery H. Moran *

Arkansas Department of Health, Public Health Laboratory, Little Rock, AR 72205, United States

Arkansas State Crime Laboratory, Little Rock, AR 72205, United States

Department of Pharmacology & Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States

Department of Biochemistry, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States

Cayman Chemical Co., Ann Arbor, MI 48108, United States

Department of Pharmacy Practice, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States

Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States

Arkansas Children’s Research Institute, Little Rock, AR 72202, United States

A R T I C L E I N F O A B S T R A C T

Article history: New designer drugs such as K2, Spice, and ‘‘bath salts’’ present a formidable challenge for law

Received 10 July 2013

enforcement and public health ofﬁcials. The following report summarizes a three-year study of 1320 law

Received in revised form 30 September 2013

enforcement cases involving over 3000 products described as vegetable material, powders, capsules,

Accepted 5 October 2013

tablets, blotter paper, or drug paraphernalia. All items were seized in Arkansas from January 2010

Available online 14 October 2013

through December 2012 and submitted to the Arkansas State Crime Laboratory for analysis. The

geographical distribution of these seizures co-localized in areas with higher population, colleges, and

Keywords:

universities. Validated forensic testing procedures conﬁrmed the presence of 26 synthetic cannabinoids,

12 designer stimulants, and 5 hallucinogenic-like drugs regulated by the Synthetic Drug Prevention Act

Bath salts

of 2012 and other state statutes. Analysis of paraphernalia suggests that these drugs are commonly used

Designer drug

Synthetic cannabinoid concomitantly with other drugs of abuse including marijuana, MDMA, and methamphetamine. Exact

Stimulant designer drug compositions were unpredictable and often formulated with multiple agents, but overall,

Hallucinogen the synthetic cannabinoids were signiﬁcantly more prevalent than all the other designer drugs detected.

The synthetic cannabinoids JWH-018, AM2201, JWH-122, JWH-210, and XLR11 were most commonly

detected in green vegetable material and powder products. The designer stimulants methylenediox-

ypyrovalerone (MDPV), 3,4-methylenedioxy-N-methylcathinone (methylone), and a-methylamino-

valerophenone (pentedrone) were commonly detected in tablets, capsules, and powders. Hallucinogenic

drugs were rarely detected, but generally found on blotter paper products. Emerging designer drug

products remain a signiﬁcant problem and continued surveillance is needed to protect public health.

1. Introduction of an intense high, easy accessibility, affordability, and avoidance of

detection in standard drug tests [1]. Perhaps the most prevalent of

The escalating use of designer drugs is likely attributable to such products are purportedly marijuana-like smoking blends

several factors, including the legality of these drugs, the expectation frequently branded as ‘‘K2’’ or ‘‘Spice’’, designer stimulant prepara-

tions of powders generally termed ‘‘bath salts,’’ and various tablets,

or capsules frequently described as ‘‘party pills’’ or ‘‘research

chemicals.’’ A recent Monitoring the Future survey found that one in

* Corresponding author at: Arkansas Department of Health, Public Health

nine high school seniors reported use of K2 or Spice in the previous

Laboratory, 201 South Monroe Street, Little Rock, AR 72205, United States.

year [2,3], and U.S. Poison Control Centers experienced

Tel.: +1 501 661 2826; fax: +1 501 661 2972.

E-mail address: [email protected] (J.H. Moran). an exponential increase in telephone calls regarding synthetic

K.A. Seely et al. / Forensic Science International 233 (2013) 416–422 417

Table 1

List of synthetic cannabinoids, designer stimulants, and new hallucinogen-like compounds searched in the JusticeTrax database. Note that the 2-, 3-, and 4-

ﬂuoromethcathinone compounds are searched together in the database since the methodology used in this study could not separate the speciﬁc isoforms of this compound.

Compound Synonyms CAS Number Formal name Class

2C-B – 66142-81-2 4-Bromo-2,5-dimethoxy- Phenethylamine (2C series)

56281-37-9 (HCl salt) benzeneethanamine

2C-E – 71539-34-9 2,5-Dimethoxy-4- Phenethylamine (2C series)

923013-67-6 (HCl salt) ethylphenethylamine

2C-H – 3600-86-0 2,5-Dimethoxy- Phenethylamine (2C series)

3166-74-3 (HCl salt) benzeneethanamine

2C-I 2,5-Dimethoxy-4- 69587-11-7 4-Iodo-2,5-dimethoxy- Phenethylamine (2C series)

iodophenethylamine 64584-32-3 (HCl salt) benzeneethanamine

2C-T-2 2,5-Dimethoxy-4- 207740-24-7 4-(Ethylthio)-2,5-dimethoxy- Phenethylamine (2C series)

ethylthiophenethylamine 681160-71-4 (HCl salt) benzeneethanamine

3,4-Dimethylmethcathinone 3,4-DMMC 1082110-00-6 1-(3,4-dimethylphenyl)-2- Designer stimulant

1081772-06-6 (HCl salt) (methylamino)-1-propanone (cathinone analog)

4-MEC 4-Methylethcathinone, NRG-1, 1225617-18-4 2-Ethylamino-1-(4- Designer stimulant

NRG-2 1266688-86-1 (HCl salt) methylphenyl)-1-propanone (cathinone analog)

4-MePPP MPPP, MaPPP, NRG-3 28117-80-8 4 -Methyl-a- Designer stimulant

1313393-58-6 (HCl salt) pyrrolidinopropiophenone

4-Methylmethcathinone 4-Methylephedrone, 4-MeMC, 1189805-46-6 2-Methylamino-1-(4- Designer stimulant

Mephedrone, 4-MMC 1189726-22-4 (HCl salt) methylphenyl)-1-propanone (cathinone analog)

25C-NBOMe 2C-C-NBOMe 1227608-02-7 2-(4-Chloro-2,5- Phenethylamine

dimethoxyphenyl)-N-(2- (NBOMe series)

methoxybenzyl)ethanamine

25I-NBOMe 2C-I-NBOMe 919797-19-6 4-Iodo-2,5-dimethoxy-N-[(2- Phenethylamine

1043868-97-8 (HCl salt) methoxyphenyl)methyl]- (NBOMe series)

benzeneethanamine

A-834735 – 895155-57-4 [1-[(Tetrahydro-2H-pyran-4- Synthetic cannabinoid yl)methyl]-1H-indol-3- yl](2233- tetramethylcyclopropyl)-

methanone

a-PVP O-2387, b-ketone-prolintane, 2- 14530-33-7 1-Phenyl-2-(1-pyrrolidinyl)-1- Designer stimulant

(1-pyrrolidinyl)-Valerophenone, 5485-65-4 (HCl salt) pentanone, monohydrochloride (cathinone analog)

a-Pyrrolidinovalerophenone

AKB48 APINACA 1345973-53-6 1-Pentyl-N- Synthetic cannabinoid tricyclo[3.3.1.13,7]dec-1-yl-1H-

indazole-3-carboxamide

AM694 – 335161-03-0 [1-(5-Fluoropentyl)-1H-indol-3- Synthetic cannabinoid

yl](2-iodophenyl)-methanone

AM1248 – 335160-66-2 [1-[(1-Methyl-2- Synthetic c cannabinoid piperidinyl)methyl]-1H-indol-3- yl]tricyclo[3.3.1.13,7]dec-1-yl-

methanone

AM2201 – 335161-24-5 [1-(5-Fluoropentyl)-1H-indol-3- Synthetic cannabinoid

yl]-1-naphthalenyl-methanone

AM2233 – 444912-75-8 (2-Iodophenyl)[1-[(1-methyl-2- Synthetic cannabinoid piperidinyl)methyl]-1H-indol-3-

yl]-methanone

Butylone b-Keto MBDB 802575-11-7 1-(1,3-Benzodioxol-5-yl)-2- Designer stimulant

17762-90-2 (HCl salt) (methylamino)-1-butanone (cathinone analog)

Fluoromethcathinone 2-FMC, 3-FMC, 4-FMC, 447-40-5 1-(2-Fluorophenyl)-2- Designer stimulant

ﬂephedrone 7589-35-7 (HCl salt) (methylamino)propan-1-one, 1- (cathinone analog) (3-ﬂuorophenyl)-2-

(methylamino)propan-1-one, 1- (4-ﬂuorophenyl)-2-

(methylamino)propan-1-one

JWH-007 – 155471-10-6 (2-Methyl-1-pentyl-1H-indol-3- Synthetic cannabinoid

yl)-1-naphthalenyl-methanone

JWH-015 – 155471-08-2 (2-Methyl-1-propyl-1H-indol-3- Synthetic cannabinoid

yl)-1-naphthalenyl-methanone

JWH-019 – 209414-08-4 (1-Hexyl-1H-indol-3-yl)-1- Synthetic cannabinoid

naphthalenyl-methanone

JWH-022 AM2201 N-(4-pentenyl) analog 209414-16-4 1-Naphthalenyl[1-(4-penten-1- Synthetic cannabinoid

yl)-1H-indol-3-yl]-methanone

JWH-073 – 208987-48-8 (1-Butyl-1H-indol-3-yl)-1- Synthetic cannabinoid

naphthalenyl-methanone

JWH-081 – 210179-46-7 (4-Methoxy-1-naphthalenyl)(1- Synthetic cannabinoid pentyl-1H-indol-3-yl)-

methanone

JWH-098 – 316189-74-9 (4-Methoxy-1-naphthalenyl)(2- Synthetic cannabinoid methyl-1-pentyl-1H-indol-3-

yl)-methanone

JWH-122 – 619294-47-2 (4-Methyl-1-naphthalenyl)(1- Synthetic cannabinoid pentyl-1H-indol-3-yl)- methanone

418 K.A. Seely et al. / Forensic Science International 233 (2013) 416–422

Table 1 (Continued )

Compound Synonyms CAS Number Formal name Class

JWH-200 WIN 55,225 103610-04-4 [1-[2-(4-Morpholinyl)ethyl]-1H- Synthetic cannabinoid indol-3-yl]-1-naphthalenyl-

methanone

JWH-201 – 864445-47-6 2-(4-Methoxyphenyl)-1-(1- Synthetic cannabinoid

pentyl-1H-indol-3-yl)-ethanone

JWH-203 – 864445-54-5 2-(2-Chlorophenyl)-1-(1- Synthetic cannabinoid

pentyl-1H-indol-3-yl)-ethanone

JWH-210 – 824959-81-1 (4-Ethyl-1-naphthalenyl)(1- Synthetic cannabinoid pentyl-1H-indol-3-yl)-

methanone

JWH-250 – 864445-43-2 1-(1-Pentyl-1H-indol-3-yl)-2- Synthetic cannabinoid

(2-methoxyphenyl)-ethanone

JWH-251 – 864445-39-6 2-(2-Methylphenyl)-1-(1- Synthetic cannabinoid

pentyl-1H-indol-3-yl)-ethanone

JWH-302 – 864445-45-4 2-(3-Methoxyphenyl)-1-(1- Synthetic cannabinoid

pentyl-1H-indol-3-yl)-ethanone

JWH-398 – 1292765-18-4 (4-Chloronaphthalen-1-yl)(1- Synthetic cannabinoid

pentylindolin-3-yl)-methanone

JWH-018 adamantyl analog AB-001 1345973-49-0 (1s,3s)-Adamantan-1-yl(1- Synthetic cannabinoid pentyl-1H-indol-3-

yl)methanone

JWH-018 adamantyl carboxamide APICA, 2NE1 1345973-50-3 1-Pentyl-N- Synthetic cannabinoid tricyclo[3.3.1.13,7]dec-1-yl-1H-

indole-3-carboxamide

JWH-018 N-(5-chloropentyl) analog – – (1-(5-Chloropentyl)-1H-indol-3- Synthetic cannabinoid

yl)(naphthalen-1-yl)methanone

JWH-122 N-(4-pentyl) analog JWH 022 4-methylnaphthyl – (4-Methylnaphthalen-1-yl)(1- Synthetic cannabinoid

analog MAM2201 N-(4- (pent-4-en-1-yl)-1H-indol-3-

pentenyl) analog yl)methanone

MAM2201 JWH 122 N-(5-ﬂuoropentyl) 1354631-24-5 [1-(5-Fluoropentyl)-1H-indol-3- Synthetic cannabinoid

analog AM2201 4- yl](4-methyl-1-naphthalenyl)-

methylnaphthyl analog methanone

0 0 0 0

MDPPP 3 ,4 -MDPPP 3 ,4 -MD-a-PPP 783241-66-7 1-(1,3-Benzodioxol-5-yl)-2-(1- Designer stimulant

24698-57-5 (HCl salt) pyrrolidinyl)-1-propanone, (cathinone analog)

monohydrochloride

MDPV Methylenedioxy pyrovalerone 687603-66-3 1-(1,3-Benzodioxol-5-yl)-2-(1- Designer stimulant

24622-62-6 (HCl salt) pyrrolidinyl)-1-pentanone (cathinone analog)

Methylone 3,4-Methylenedioxy-N- 186028-79-5 1-(1,3-Benzodioxol-5-yl)-2- Designer stimulant

methylcathinone bk-MDMA, M1 186028-80-8 (HCl salt) (methylamino)-1-propanone (cathinone analog)

PBP a-Pyrrolidinobutiophenone 13415-82-2 1-Phenyl-2-(1-pyrrolidinyl)-1- Designer stimulant

13415-54-8 (HCl salt) butanone (cathinone analog)

Pentedrone a-Methylamino-valerophenone 879722-57-3 2-(Methylamino)-1-phenyl-1- Designer stimulant

879669-95-1 (HCl salt) pentanone (cathinone analog)

Pentylone bk-Methyl-K, bk-MBDP 698963-77-8 1-(1,3-Benzodioxol-5-yl)-2- Designer stimulant

17763-01-8 (HCl salt) (methylamino)-1-pentanone (cathinone analog)

RCS-4 E-4, BTM-4, OBT-199, SR-19 1345966-78-0 (4-Methoxyphenyl)(1-pentyl- Synthetic cannabinoid

1H-indol-3-yl)methanone

RCS-4 C4 homolog – 1345966-77-9 (4-Methoxyphenyl)(1-butyl-1H- Synthetic cannabinoid

indol-3-yl)-methanone

RCS-8 SR-18, BTM-8 1345970-42-4 1-(1-(2-Cyclohexylethyl)-1H- Synthetic cannabinoid indol-3-yl)-2-(2-

methoxyphenyl)ethanone

UR-144 KM-X1 1199943-44-6 (1-Pentyl-1H-indol-3- Synthetic cannabinoid yl)(2,2,3,3- tetramethylcyclopropyl)-

methanone

UR-144 N-(5-chloropentyl) analog – – (1-(5-Chloropentyl)-1H-indol-3 Synthetic cannabinoid -yl)(2,2,3,3- tetramethylcyclopropyl)

methanone

XLR11 5-Fluoro UR-144 1364933-54-9 (1-(5-Fluoropentyl)-1H-indol-3- Synthetic cannabinoid yl)(2,2,3, 3-tetramethylcyclopropyl)

methanone

(–) None identiﬁed.

The positional isomers of 2-, 3-, or 4-ﬂuoromethcathinone could not be distinguished.

cannabinoids in 2011 compared to 2009 [4,5]. In contrast, only 1.3% manufacture designer drug products into Schedule I of the

of high school seniors reported use of ‘‘bath salts’’ in the previous Controlled Substances Act [6,7]. Less common drugs not speciﬁcally

year, perhaps due to the relatively high perceived risk [2,3]. listed in the statutes, as well as the next generation of emerging

Escalating abuse and evidence demonstrating the toxic nature of drugs, are potentially regulated through structural similarity clauses

these compounds led to regulations and other control measures in in the Synthetic Drug Abuse Prevention Act of 2012 [7,8].

the United States and Europe. In the United States, regulatory actions Thus far, most synthetic cannabinoids identiﬁed in K2 or Spice

resulted in the permanent placement of many of the synthetic products are pharmacologically characterized as agonists

cannabinoids, designer stimulants, and hallucinogens used to at human cannabinoid type I receptors. However, structural

K.A. Seely et al. / Forensic Science International 233 (2013) 416–422 419

differences between synthetic cannabinoids and D -tetrahydro- There are instances where adulterants and other illicit drugs

cannabinol (D -THC), the primary psychoactive constituent in may be identiﬁed during investigations but not reported to

marijuana, lead to these synthetic compounds possessing surveillance programs like the National Forensic Laboratory

increased biological activity [9–12], which may explain neuro- Information System. Thus, the development of an expanded

logical and cardiovascular complications often reported in human surveillance system was required for evaluating the complex

case studies of K2 toxicity [13–17]. In contrast, the pharmacology nature and changing formulations of designer drugs. The surveil-

of the reported ‘‘bath salt’’ designer stimulants is typically lance system used for this study searched the JusticeTrax LIMS for

attributed to active cathinone and/or piperazine constituents designer synthetic cannabinoid, stimulant, and hallucinogen cases

that inhibit the reuptake or stimulate the release of the investigated during the study period. Speciﬁc drugs targeted for

monoamine neurotransmitters [18–20]. Recent in vivo studies this study are provided in Table 1. During the comprehensive,

conﬁrm the stimulant-like effects of the more common consti- manual review of case ﬁles and notes, geographical information as

tuents in ‘‘bath salt’’ preparations [20,21]. The pharmacological well as information about speciﬁc drug formulations, composi-

mechanisms responsible for the hallucinogenic properties of tions, and adulterants were reported.

piperazine, tryptamine, and the phenylethylamine analogs are

less characterized but thought to be mediated through serotonin

3. Results and discussion

5-HT2A receptors [22–24].

Despite the toxicity of these emerging drugs of abuse and recent

A total of 3481 items including vegetable material, tablets/

regulatory efforts, use of synthetic cannabinoids, designer

capsules, blotter paper, powders, and paraphernalia were submit-

stimulants, and new hallucinogenic drugs remains largely

ted to the Arkansas State Crime Laboratory as evidence in 1320

unabated. Drugs are readily available on the internet, and rapidly

cases involving the emerging drugs of abuse listed in Table 1. The

changing formulations and confusing brand names add layers of

geographical distribution of these cases suggests that designer

complexity for forensic and public health investigations. Compre-

drugs co-localize with higher populations, colleges and universi-

hensive surveillance systems are now required to keep track of

ties. The ﬁve counties with the highest prevalence of designer drug

these emerging drugs. This 3-year study reports results obtained

products (Benton, Faulkner, Washington, Sebastian, and Pulaski)

from a designer drug surveillance system designed to investigate

represent 36% of the state population and, with the exception of

composition and prevalence of designer synthetic cannabinoid,

Benton County, are home to multiple large universities [25].

stimulant, and hallucinogen-like drugs seized in the state of

Overall, the number of items containing synthetic cannabinoids

Arkansas from January 2010 through December 2012.

was greater than the number of items containing either designer

stimulants or hallucinogen-like drugs (Fig. 1). While there is

seemingly a large number of potential emerging designer drugs

2. Methods

(Table 1), evaluations show a preference for the synthetic

cannabinoids AM2201, JWH-018, JWH-122, JWH-210, and/or

In 2010, the Arkansas State Crime Laboratory responded to the

XLR11 and the designer stimulants MDPV, methylone, and/or

emergence of new designer drugs in the state by validating forensic

pentedrone (Figs. 2–4). At least one of these eight designer drugs

drug testing methodology. This laboratory provides testing

services to local, state, and federal law enforcement agencies

and receives conﬁscated drugs and paraphernalia obtained

statewide. Conﬁscated items were subjected to accredited forensic

testing utilizing gas chromatography–mass spectrometry (GC–MS)

analytical procedures. GC–MS reference libraries were developed

with analytical reference standards provided by Cayman Chemical

(Ann Arbor, MI) and served as the basis for positive identiﬁcations.

Analytical ﬁndings were documented in case notes and uploaded

to the JusticeTrax (St. Mesa, Arizona) laboratory information

management system (LIMS) as a permanent record.

Fig. 1. Timeline of the number of cases of synthetic cannabinoid and stimulant/ Fig. 2. Histogram illustrating the compounds detected in vegetable material. The

hallucinogen items seized from January 2010 to December 2012. majority of compounds found in these items are synthetic cannabinoids.

420 K.A. Seely et al. / Forensic Science International 233 (2013) 416–422

Fig. 3. Histograms indicating the prevalence of compounds in tablets, capsules, or blotter paper (A) and powders (B).

was detected in over 85% of the tested items, while less than 1% of residues were solids, some liquids were recovered from syringes,

the items contained hallucinogen-like drugs. Speciﬁc drug glass vials and plastic containers. Residue tested from 390 items

formulations were also highly unpredictable. Over 300 unique submitted as paraphernalia primarily contained AM2201 (45% of

drug mixtures were detected in vegetable material, tablets/ items) and D -THC (30% of items) (Fig. 5). Not surprisingly, these

capsules, blotter paper, and/or powders tested as part of this results suggest that users of these designer drug products may

investigation. have a propensity to also use marijuana. The concomitant use of

Review of case notes, personal communications with investi- other designer drugs and/or other drugs of abuse like metham-

gators, and blog reports on drug forums revealed that designer phetamine, cocaine, and MDMA were also noted as part of this

drug products containing dried vegetable material are commonly investigation (Fig. 4).

referred to as either K2 or Spice. Powders, tablets, or capsules were The effects of new policies on speciﬁc designer drug formula-

commonly referred to as ‘‘bath salts’’, ‘‘party pills’’, or ‘‘research tions were investigated since this study occurred during the

chemicals’’ and believed to contain stimulants or hallucinogen-like enactment of several new state and federal regulations. As

drugs. However, this study reveals that these assertions are not reported previously in Europe and the United States [26–28],

consistently accurate. Nearly 2700 items submitted as vegetable the chemical composition of the products containing synthetic

material were found to contain a synthetic cannabinoid, a designer cannabinoids continuously changed during the surveillance

stimulant, D -THC, and/or caffeine (Fig. 2); furthermore, these period. Initially, 100% of the samples assayed contained JWH-

items were often formulated with multiple drugs. Analytical 018 (Fig. 5), but as more stringent regulations were enacted

results from tablets, capsules, blotter paper, and powders were also throughout 2011, the incidence of JWH-018 detection decreased,

complex. Caffeine and the cathinone analog designer stimulant while the structural analogs AM2201, JWH-210, and JWH-122

MDPV were detected in over 80% of the tablets and capsules (Fig. 3, became prevalent. AM2201 is chemically similar to JWH-018 but is

Panel A), while the powders were much more likely to contain halogenated with a ﬂuorine atom on the carbon terminus of the

MDPV, methylone, or pentedrone (Fig. 3, Panel B). For unknown alkyl side chain (Fig. 6). Likewise, JWH-210 and JWH-122 are

reasons, the powders rarely contained caffeine. The hallucinogen- similar in structure to JWH-018 but contain a methyl or ethyl

like phenethylamines (the ‘‘2C’’ and NBOMe series of drugs listed group on the naphthalene group, respectively (Fig. 6). By the end of

in Table 1) were most commonly detected in laced blotter paper, 2012, the prevalence of AM2201, JWH-210, and JWH-122

presumably to mimic LSD preparations. None of the tablets, decreased, likely as a result of stringent structural analog

capsules, or blotter paper seized contained a synthetic cannabi- regulations, but the number of products containing the synthetic

noid, but several of the powders contained the synthetic cannabinoid XLR11 increased (Fig. 5). XLR11 is a relatively

cannabinoids JWH-122, JWH-210, AM2201, and JWH-018 N-(5- unknown and structurally distinct cannabinoid compound con-

chloropentyl) analog (Fig. 3, Panel B). taining a tetramethylcyclopropyl functional group not present in

Paraphernalia seized in cases suspected of involving designer any of the previously described aminoalkylindoles, like JWH-018

drugs were evaluated as a way to provide information on the (Fig. 6).

potential concurrent abuse of drugs. Paraphernalia included Unlike the synthetic cannabinoid compounds, the most

residue collected from smoking devices and pipes, plastic bags abundant designer stimulant and hallucinogen-like drugs detected

and containers, foil packets, spoons, and cards. Although most during the study period did not trend with the introduction of new

K.A. Seely et al. / Forensic Science International 233 (2013) 416–422 421

Fig. 4. Histogram of the compounds detected in paraphernalia, including smoking

devices, residues from packaging, and liquids in syringes and vials.

Fig. 6. Structures of D -THC (delta-9 tetrahydrocannabinol), JWH-122 (4-methyl-1-

naphthyl)-(1-pentylindol-3-yl)methanone, JWH-018 (1-pentyl-3-(1-naphthoyl)indole,

JWH-210 ((4-ethyl-1-naphthalenyl)(1-pentyl-1H-indol-3-yl)-methanone), AM2201

(1-(5-ﬂuoropentyl)-3-(1-naphthoyl)indole, and XLR11 ((1-(5-ﬂuoropentyl)-1H-indol-

3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone) (A). Structures of cathinone (b-

ketoamphetamine), MDPV (methylenedioxypyrovalerone), methylone (3,4-methylene

dioxy-N-methylcathinone), and pentedrone (a-methylamino-valerophenone) (B).

molecule, which is a Schedule I compound in the United States, and

importantly, are all Schedule I compounds themselves, either

explicitly or implicitly under analog clauses of the Synthetic Drug

Abuse Prevention Act of 2012. Prevalence and trends reported here

are consistent with those of previous studies in the United States

and Europe [29,30]. The emergence of the ‘‘2C’’ and NBOMe

hallucinogenic drugs listed in Table 1 began in 2010 and no clear

preference for any particular compound in this series has yet been

observed (data not shown).

In summary, JWH-018, AM2201, JWH-210, XLR11, MDPV,

Fig. 5. Abundance of most common synthetic cannabinoid and stimulant

methylone, and pentedrone represent the primary active con-

compounds. The formulations of synthetic cannabinoid compounds changed

during the surveillance period, where JWH-018 initially represented the synthetic stituents of new designer drug products identiﬁed as part of this

cannabinoid present in 100% of products but gradually declined such that, by the study. The sale, distribution, and use of these designer drugs are

end of 2012, the chemically distinct synthetic cannabinoid XLR11 was present in

associated with both population and universities. Speciﬁc drug

the majority of cases.

formulations are complex and highly unpredictable, despite the

general notion that vegetable material found in K2 or Spice

regulatory actions. In 2010 and most of 2011, MDPV and products contain synthetic cannabinoids and bath salt powders are

methylone were the most common designer stimulant compound formulated with designer stimulants. Results presented here

detected. By mid-2011, the compound pentedrone became more demonstrate that end users of designer drug products cannot

prevalent, which may coincide with the placement of MDPV and accurately and consistently predict their ‘‘high’’. For unknown

methylone into Schedule I of the Controlled Substances Act that reasons, the popularity of synthetic cannabinoids is much greater

same year. All of these most prevalent stimulant constituents – than the other, new designer drugs recently regulated. Synthetic

MDPV, methylone, and pentedrone – are analogs of the cathinone cannabinoid composition is inﬂuenced by regulations, whereas the

422 K.A. Seely et al. / Forensic Science International 233 (2013) 416–422

[12] B.R. Martin, R. Jefferson, R. Winckler, J.L. Wiley, J.W. Huffman, P.J. Crocker,

designer stimulant compounds are not changed by regulatory

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Conﬂict of interest

[16] A.B. Schneir, J. Cullen, B.T. Ly, Spice girls: synthetic cannabinoid intoxication, J.

Emerg. Med. 40 (2010) 296–299.

All of the authors are without declaration of interest, including [17] K. Tomiyama, M. Funada, Cytotoxicity of synthetic cannabinoids found in Spice

products: the role of cannabinoid receptors and the caspase cascade in the NG

ﬁnancial interests, activities, relationships, and afﬁliations.

108-15 cell line, Toxicol. Lett. 207 (2011) 12–17.

[18] M.H. Baumann, J.S. Partilla, Lehner K.R. Psychoactive, bath salts: not so soothing,

Acknowledgements Eur. J. Pharmacol. 698 (2013) 1–5.

[19] K.R. Lehner, Baumann M.H., Psychoactive ‘bath salts’: compounds, mechanisms,

and toxicities, Neuropsychopharmacology 38 (2013) 243–244.

This work was supported by the Association of Public Health

[20] M.H. Baumann, M.A. Ayestas Jr., J.S. Partilla, J.R. Sink, A.T. Shulgin, P.F. Daley, et al.,

Laboratories [Grant Innovations in Quality Public health Laborato- The designer methcathinone analogs, mephedrone and methylone, are substrates

for monoamine transporters in brain tissue, Neuropsychopharmacology 37

ry Practice] (JHM) and by the Centers for Disease Control (Contract

(2012) 1192–1203.

No. 200-2007-21729) (JHM).

[21] M.H. Baumann, J.S. Partilla, K.R. Lehner, E.B. Thorndike, A.F. Hoffman, M. Holy,

et al., Powerful cocaine-like actions of 3,4-Methylenedioxypyrovalerone (MDPV),

a principal constituent of psychoactive ‘bath salts’ products, Neuropsychophar-

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