Herbal Smoking Blends - SPICE • SPICE and other herbal blends have been sold in head shops and on the Internet since 2006 for their cannabis-like intoxication Classes and Structures of Emerging Cannabimimetics • The herbal blends sometimes have a fragrance and Cathinones which could include vanilla, potpourri, spice, blueberry, caramel, and strawberry Arthur Berrier Senior Research Chemist Special Testing and Research Laboratory • The plant materials for the different blends Drug Enforcement Administration have a wide variation in appearance ~ ) D[A Speco0I Tornnr. oncl lle1ea1ch 1.1boratory ~~ Emt!•t;mg Trends Ptobr,1m Herbal Smoking Blends - SPICE Herbal Smoking Blends - SPICE • In late 2008, THC Pharma reported the • K2 enters market in April, 2009 presence of JWH 018, a synthetic cannabimimetic indole in some blends • Interest booms in herbal smoking blends in 2009 • In early 2009, analogues of CP 47,497 (another synthetic cannabinoid) were also • Many new products appeared, typically with found in some blends by the U. of Freiburg JWH 018 and JWH 073 • In early 2009, several European Countries • States begin to control the blends/synthetic control Herbal Blends/JWH 018/CP 47,497 cannabinoids ~) 0(1\ Spr•c:i.11 f~l'.. [1 ng and Rtl~C!'allh l11hor,1to ry ~ ' ) O(I' S1Jec1a l Tl.?sltng amJ RPWJr< h l .1bor,1tory r"::::> Fme rf;mg Trt>nd. Proc;f.101 ~=> [me1eing Tr!>nth P1ogr.i111 Classes of Synthetic Cannabinoids Herbal Smoking Blends - SPICE Observed on Smoking Blends • Products quickly reformulated with new, non­ i) 2-(3-hydroxycyclohexyl)phenol (CP 47,497) controlled synthetic cannabimimetics ii) 3-(1-naphthoyl)indole (JWH 018) iii) 3-(1-naphthoyl)pyrrole • Five of the synthetic cannabimimetics iv) 1-( 1-naphthylmethylene )indene controlled at the Federal level in 2011 v) 3-phenylacetylindole or 3-benzoylindole • Synthetic Drug Abuse Prevention Act of 2012 ~ ) 11[ •\ "' 1,r( 1,-,1 lf'.',..tr11g and [~p Pnrch lJUOrdto1 y ~ \ DE/\ Special Te1 1ing .1nrJ R·~>P<Hrh I abora\Clly r C :> f 1n~~ 1 ,_,1 r\ , Trc11ds P1L)grJm -r.:---::::>J fniPre1ng lrend'.. Progrom Structures o,f the Major Cannabimimetics Observed in 2009 and 2010 - Cannabimimetic Classes Detected First Appearance of JWH Compounds o:rd ~ <3-phenylacolyhndole J 3-11-nuphlhoyl)indole < JWH 203 > JWH 018 \ JWH018 JWH073 JWH 250 ~o CP 47,497 ? 3-beri zoy nllole ( RCS-4 2--{3-hydroxycyclohexyl)phenol CP 47 497 C8 ~ ' ) DtP Special le.::.L1ng an d Research Labor ,1to1 y ~ \ lJEA Sptcial Te,lmg und Re;ca1ch lauoratory r e> Fme1t;111b Tremh PrO!; ICJ!ll S,} f.mergrng lrt:'nd:; Program Cannabimimetics Observed Starting in 2011- More 2011- Introduction of Fluoroalkyl JWH's, Introduction of Fluoroalkyls and the Beginning of Novel Materials Derivatives JWH019 JWH 081 JWH 018 JWH 122 JWH 073 JWH 200 JWH250 AM 2201 CP 47,497 AM694 RCS-4 JWH 018 AM2201 RCS-8 Fluoro version of JWH 018 ~ \ O[A Spec1ul ie:.t1ng ,md Ri:'iearch I ubor(1tory ~ ' ) lJEA Spec1ol Te,t1ng ,1nd Research Laboratory ~-:::::>} r nlt:rbuig lr(•nd~ Progrl'n'1 .-::-c::> fme151ng Trends. Progrilm 2011- Introduction of Novel Materials 2011- Introduction of Novel Materials RCS-4 • Materials identified never reported in scientific or patent literature • Initially named after the website selling it = - RCS-4 - RCS-8 AM67Q RCS-4 JWH081 • Made by changing/modifying known material New ~ ') DI 1\ Special Te:;.t111g anU Re:evrch I il l>0ratorv ~ ',) DEA S1wr:1CJI T~ ~t1ng and Re_,ea1ch Laboratory S I mrrt~mg lr('rah ProgrJm f"'."C > Ernert,1ng T1 en d_, Pro1:11.1m 2011- Introduction of Novel Materials Cannabimimetics Observed Starting in 2012 - RCS-8 Continuation of New Materials and New Classes JWH 019 JWH203 JWH 081 UR 144 JWH 018 JWH 122 A 796,260 JWH 073 JWH200 5FUR144 JWH 250 AM 2201 2NE1 CP 47,497 AM694 STS-135 RCS-4 AKB48 RCS-8 ABOOl JWH 250 RCS-8 New ~ ·) DEA Special Te :.t 1ng and Re~earch LC1bor.lto1y ~ ') DEA Special Testing and Re, h i1rh L..ilioratory ~..::> I rner gmg T1 en ds. Progr a1n ~:> Emerging Trends P1ogrc1m 2012 - Introduction of AKB48 - New Material in 2012 Tetramethylcyclopropyl Materials 0 Ql ~J H cr;N ~ ~ = ~ 0 ~ ~ F ~ A-796.260 U R-14 4 5FUR 14 4 AKB48 A-It l abs A-It l abs New Falls within claims of 2003 World Patent but not given as example ~ ) OlA Special Te~t1ng a nd ke~C'arc h L.1 boratory ~ ~) DEA Special Te::.t111g and Re::.e2. rch l dborato1y ~? [ m er~ rn g T am d ~ Prog ram ;-:;~ E1ne1g111g T1 c nds Progrdm 2012 - Continued Introduction of New 2012 -ABOOl, A New Material Derived Materials from a Combination of Known Compounds ~ AM124B ~ l\K.848 2NE1 STS-135 'low lndole vt=rs1on of AK 940 H 10ro ver&on o( 2NE1 A8 001 New New -:~ JWH~ New ~ ) [JfA '"pf'c1al Te:.t1ng and Re~earch Lalwr ,1to1y ~ J Dfl\ ~pec1a l T<-1tin;: .ind He·.~aich UborJtory ~/ hnt·1 ~ 111 g Trend:. Progrcim r':::::> ( nwrg111g rrends Progr.1m Cannabimimetics Observed Starting in 2013 - 2013 - Introduction of lndazole Continuation of New Materials and New Classes Carboxamides and Derivatives +1111••111 JWH 019 JWH203 MN-25 JWH081 UR 144 AB-FUBINACA JWH018 JWH 122 A 796,260 ADB-FUBINACA = JWH073 JWH 200 5FUR144 PB22 JWH250 AM 2201 2NE1 5FP822 CP 47,497 AM 694 STS-135 8822 RCS-4 AK848 A8PINACA RCS-8 A8001 AD8/CA AB-FUBINACA AB-P!NACA 2009 Pfizer Patent New ~ J DEA Specral Test mg and Reoei1fch Lobo r ~tory ~) DEA Snec•ol Tes t on~ and Re , e,1'ch laborotory f':'Q lmer;;rng hend> Progr<1m S [mer~inc: Trends P1ogr.1m 2013 - Introduction of lndazole 2013 - New Materials Derived From Carboxamides and Derivatives 8-Hydroxyquinoline = = = c6·0tY c6°t9' c6°t9 ~ '-v ~ 88-22 PB-22 5Ff>S..22 New Now Ne~ Esler, Ouifl.uhne ADB-FUBINACA ADBICA 2009 P1izer Patent New ~ \ DEi\ Speual Te:.ting and Rt"'::iea1 ch Laboratory ~ ') DEA 5pccral ieslrng ,ind Re;e,lfch Labor,1tory "'':::::) Emerging T1encls Prog101T"\ S EnH~f t,; 1ng Trend1.. Progrom Designer Cathinones - Designer Cathi nones Changes in the Aromatic Ring Three parts of methcathinone can be modified: Aromatic ring O Alkyl group drH Amine group N'-.... C H3 ' motht111h nooe Armm1tic Alkyl Amine ~) DE1\ <;pecral Te'lrng and Reseorch I <1bor,1tory ~ " [1E1\ SpPcral Te,t111g ar'U RP~:,(?arch L;:iborator { S fmer1;111g Trrntl~ Prngr.1111 ~c:) Cme1 t:;ing T1 f'nd::. P1 r\~1 din Designer Cathinones - Designer Cathinones - Changes in the Alkyl Group Changes in the Amine Group 0 H ~, N-CH 3 O CH3 melhcathinone ethcathinone methcathinone buphedrone 0 H o I\ .,, )I ( N ,,/ '"'r-N 'CH3 ( O CH, ......,:.-· CH, methcathinone methcathinone r<-PPP ~ - ) Dfll Spc<.101 foiling'""' ReseMch l oboroto1y ~\ DEA 5peual Je;tmg and Resea1ch L.1bor,,101y ~ [me1r;11\G frt!tlcl!. ProgrJm ~.::::::>} f:merc,1ng Trends Progr,1m Designer Cathinones - Questions? Changes in All Groups methcathinone MDPV Arthur Berrier [email protected] Just the changes discussed in the last three slides can produce 12 different Cathinone derivatives Drug Enforcement Administration ~) Dfl\ Special Tes11ng onci Rese;;tr.h l.ilm<dlory ~ '\ DEA Spt>c1al feJll1\r; and Re_,earch Laboratory ~::::> fmere,1np, Trends Prngi.:im -, 2:..>) Eine1,;111~ T1enrb Pro~1J111 Outline • Hallucinogens • Plant-Derived Highs - 2C Compounds - Kratom - NBOMe Compounds - Fly Agaric Mushrooms Novel Hallucinogens and - DOX Compounds - Kava Kava - Kanna Plant-Derived Highs • Empathogens - Aminoindanes Emily Dye - APDB Forensic Chemist - APB Special Testing and Research Laboratory Drug Enforcement Administration ~) Drn ~peC1al Te;tmg and H,»earr.h 1.1bor.11ory ~ fmergrng Trends P1ug1um 2C Compounds 2C Compounds Name R1 I R1 • Psychedelic phenethylamines 2C-B H Br 2c-c• Cl 2c-o• H CH, 2C-E"' CH2CH1 2C-F 2C-T-2"' SCH10t, • Synthesized by Alexander Shulgin ZC-T-4" SCH(CH J, 2C-G CH1 CH, 1 - Published in PiHKAL 2C-G-3 (CH,), 2C-T-7 H S{CHzhCH, 2C-G-4 {CH2)4 2C-T-8 SCH 2CH (CH ih 2C-G-N (CH), 2C-T-9 H SC(CH1), 2C-H• H H 2C-T-13 H S(CH 2)20 CH, • 27 known compounds 2c-1• H 2C-T-15 H SCH(CH,J, 2C-N' H NO, 2C-T-17 SCH(CH l)CH2CH1 - Most common: 2C-C, 2C-B, and 2C-I 2C-O H OCH, 2C-T-21 H S(CH 2),F 2C-0-4 H OCH(CH 1J, 2C-TFM CF 2C-P"" H CH2CH2CHJ 1 ~\ DfA <; pec1al Test111g and Research Labor,1tn1v ~ ' ) DEA Special Testing and Re scdrch l dl.Joratory ~} frnerg1ng Trends Program ~J ErY1erg1ng Trench Progr<1m 2C-B-FLY Bromo-DragonFLY 0 CH ~ • Psychedelic phenethylamine • Psychedelic phenethylamine B IH2 0 • Synthesized by Aaron Monte • Synthesized in the lab of David Nichols • Deaths associated with misrepresentation as 2C-B-FLY ~~ ' ) Uri\ Special Testing <ln d Resea1ch Laboratory ~., ' ) DEA SJ> ec1al Testing anci Re~ e arch I aboratory ~_:> [111prg1ng Trends P1 og1 .Jm ~:.:> Eme1 gmg Ti ends Program Mti,.IMKllCM+M-CMM@l,,IWW·'MWWW NBOMe Compounds 258-NB20Me Br OCHJ H H 25N-NB20Me N01 OCH 1 H H 25B -NB30Me Br H OCH1 25N-NB30Me NO, OCH 3 25B-NB40Me Br H OCH1 25N-NB40Me NO, H OCH 1 25C-NB20Me Cl OCH 3 H 2SP-NB20Me CH 2CH 2CH 3 OCH3 • Hallucinogenic phenethylamines 25C-N830Me Cl OCH 1 25P-NB30Me CH;i,CH1CH1 OCH1 H 25C-NB40Me Cl OCH 3 25P-NB40Me CH 2CH 2CH 3 H OCH3 25D-NB20Me CH, OCH1 H 2ST2-NB20Me CH,CH,S OCH, H 25D-NB30Me CH, H OCH3 25T2-NB30Me CH 3CH 2S OCH1 25D-NB40Me ,, ,_y.· CH, OCH, 25T2-NB40Me CH3CH,S H H OCH 1 25E-NB20Me C2Hs OCH 3 H 25T4-NB20Me (CH3 JiCH5 OCHl H • Synthesized by Heim, et al .