Synthetic Cannabinoids, Synthetic Cathinones and Salvia Divinorum Basic Chemistry and Lab Analysis
Acknowledgements Synthetic Cannabinoids and Natural Highs Workshop Sponsored by: Midwestern Association of Forensic Scientists Miami Valley Regional Crime Laboratory Dayton, Ohio April 4 and 5, 2011 • “Synthetic Cannabinoids” - Jason Nawyn - US Army Lab • “Salvia Divinorum” - Pam Smith - Retired DEA Chemist
Synthetic Cannabinoids
Synthetic Cannabinoids Spice Silver Spice Gold Spice Diamond Spice Arctic Synergy Spice Tropical Synergy Spice Egypt K2 Sence Yucatan Fire Smoke ChillX Highdi’s Almdrohner
Gorillaz Skunk Genie Galaxy Gold Space Truckin Solar Flare Moon Rocks Blue Lotus Aroma Scope Earth Impact
Synthetic Cannabinoids • Components – Herbal plant material – Psychoactive chemicals - synthetic cannabinoids sprayed on to the herbal matter
Synthetic Cannabinoids • Formulators will change their product to skirt the law. • Formulators of these products can utilize any of a number of synthetic cannabinoids to spray on the herbal material. • The specific synthetic cannabinoid used on any particular product (i.e.: Spice or K-2) could be changed at any time by the formulator.
Synthetic Cannabinoids • Attempts to control or regulate the new synthetic cannabinoids is problematic on a number of fronts: – Because of the structural dissimilarities between the synthetic cannabinoids, using the Controlled Substances Analog Act will most likely, have little success. – Standards for most of these compounds are not available. – Mass spectral analysis of many of these compounds will be difficult if not impossible. – Many of these compounds have multiple positional isomers. – Control of specific products is impractical since the composition of these products can change from batch to batch both qualitatively and quantitatively.
Synthetic Cannabinoids • Synthetic Cannabinoid Agonists ≡ “Synthetic Cannabinoids” – Definition: Agonist - A chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance. – Many of which are not actually cannabinoids in structure – Synthetic Cannabinoids are CB1 receptor agonists – CB1 receptors in the brain mediate the psychoactive effects of THC – Synthetic Cannabinoids mimic the effects of THC
Synthetic Cannabinoids • Synthetic cannabinoid receptor agonists fall into 7 major groups: 1. 2. 3. 4. 5. 6. 7.
Naphthoylindoles Naphthylmethylindoles Naphthoylpyrroles Naphthylmethylindenes Phenylacetylindoles Cyclohexylphenols Dibenzopyrans (classical cannabinoids)
Synthetic Cannabinoids • Naming of chemical compounds (i.e.: JWH compounds, HU compounds, etc.) When compounds are synthesized they are often uniquely named based on whomever synthesized the compound. – JWH, for John W. Huffman @ Clemson University – HU, for Hebrew University – CP compounds were developed by Pfizer.
R4 O C
1
R3
3
2
R2
1
N R1
Naphthoylindoles
Naphthoylindoles Compounds ∆9-THC JWH-007 JWH-018 JWH-019 JWH-048 JWH-073 JWH-080 JWH-081 JWH-082 JWH-098 JWH-122 JWH-149 JWH-181 JWH-182 JWH-193 JWH-198 JWH-200 JWH-210 JWH-213 JWH-? JWH-387 JWH-394 JWH-398 JWH-412 AM2201
R1 Pentyl Pentyl Hexyl Pentyl Butyl Butyl Pentyl Hexyl Hexyl Pentyl Pentyl Pentyl Pentyl MPE MPE MPE Pentyl Pentyl Butyl Pentyl Pentyl Pentyl Pentyl Fluoropentyl
R2 Methyl H H Methyl H H H H H H Methyl Methyl H H H H H Methyl H H Methyl H H H
R3 H H H H H Methoxy Methoxy Methoxy Methoxy Methyl Methyl Propyl Propyl Methyl Methoxy H Ethyl Ethyl H Br Br Cl F H
R4 H H H Methyl H H H H H H H H H H H H H H H H H H H H
Ki 10.2 2.9 2.9 9.8 10.7 8.9 7.6 1.2 5.3 4.5 0.69 5 1.3 0.65 6 10 42 0.46 1.5 8.9 1.2 2.8 2.3 7.2
Affinity Constant (Ki) • A measure of the potency of the cannabinoids Low values are most potent, higher values have lower potency.
1
R3
CH2
3
2
R2
1
N R1
Naphthylmethylindoles
Naphthylmethylindoles Compounds JWH-175 JWH-184 JWH-185 JWH-199
R1 Pentyl Pentyl Pentyl MPE
R2 H H H H
R3 H Methyl Methoxy Methoxy
Ki 22 23 17 20
O C
1
3
2
R2
1
N R1
Naphthoylpyrroles
Naphthoylpyrroles Compounds JWH-145 JWH-146 JWH-147 JWH-292 Unnamed JWH JWH-030 JWH-307 JWH-368 JWH-369 JWH-370
R1 Pentyl Heptyl Hexyl Pentyl Propyl Pentyl Pentyl Pentyl Pentyl Pentyl
R2 Phenyl Phenyl Phenyl Methoxyphenyl H H 2-Fluorophenyl 3-Fluorophenyl 2-Chlorophenyl 2-methylphenyl
Ki 14 21 11 29 >1000 87 7.7 16 7.9 5.6
R4
CH
1
R3
3
2
R2
1
R1
Naphthylmethylindenes
Naphthylmethylindenes Compounds JWH-176 Compound #7 Compound #8
R1 Pentyl MPE MPE
R2 H H Methyl
Ki 26 2.7 2.9
O R2
C
1
3
2
R1
1
N C5H11
Phenylacetylindoles
Phenylacetylindoles Compounds JWH-203 JWH-204 JWH-249 JWH-250 JWH-251 JWH-302 JWH-305 JWH-306 JWH-311
R1 H Methyl H H H H Methyl Methyl H
R2 2-Chlorophenyl 2-Chlorophenyl 2-Bromophenyl 2-Methoxyphenyl 2-Methylphenyl 3-Methoxyphenyl 2-Bromophenyl 2-Methoxyphenyl 2-Fluorophenyl
Ki 8 13 13 11 29 17 15 25 23
OH OH
R2 R1 Cyclohexylphenols
Cyclohexylphenols Compounds CP-55,940 CP-47,497 CP-47,497 VII CP-47,497 XI* CP-47,497 XII CP-47,497 XVI
R1 1,1-Dimethylheptyl 1,1-Dimethylheptyl 1,1-Dimethyloctyl 1,1-Dimethylheptyl 1,1-Dimethylheptyl 1,1-Dimethylheptyl
* C1-α-OH analog of XII
R2 Hydroxypropyl H H Methyl Methyl Hydroxybutyl
Ki 0.34 9.4 4.7 6.2 7.7 1.6
R2 OH
A
O
R1
Dibenzopyrans (classical cannabinoids)
Dibenzopyrans (classical cannabinoids) Compounds HU-210 HU-211 unnamed unnamed unnamed ∆9-THC ∆8-THC
R1 1,1-Dimethylheptyl 1,1-Dimethylheptyl 1,1-Cyclopropylheptyl 1,2-Dimethylheptyl 1,1-Dimethylheptyl Pentyl Pentyl
R2 Hydroxymethyl Hydroxymethyl Methyl Methyl Methyl Methyl Methyl
Ki 0.06 >100 0.44
