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2. Synthetic Cannabinoids: History, Chemistry, and Pharmacology
David A. Gorelick, M.D., Ph.D., DLFAPA
Professor of Psychiatry
University of Maryland School of Medicine

3. Definition and History
CB1
Synthetic cannabinoids
Agonists at the cannabinoid CB1 receptor
Synthetic marijuana
Spice K2
Fake weed
Bind more tightly than THC

4. THC + CB1 Subjective high Dry mouth Sedation Rapid heart rate
Increased appetite (“munchies”)
Conjunctival redness

5. First produced (research tools) Abuse was first identified
Mid
2000s
1950s
2009
2015
First produced (research tools)
Abuse was first identified
NFLIS identified 2 different synthetic cannabinoids 
Increased to
84 different compounds

6. The Appeal of Synthetic Cannabinoids
Not detected by routine drug screening tests
Conveniently purchased over the internet or in local convenience stores
Perceived as legal, natural, or harmless 
Cost comparable to plant cannabis
Ford, B. M., Tai, S., Fantegrossi, W. E., & Prather, P. L. (2017). Synthetic pot: not your grandfather’s marijuana. Trends in pharmacological sciences, 38(3),

7. Chemistry and Pharmacology
125+ different synthetic cannabinoids 
8 chemical structural categories

8. Early Synthetic Cannabinoids
Name
Synthesized by
JWH-018
JWH-073
John Huffman
HU-208
HU-210
Hebrew University
AM-694
Alexandros Makriyannis CP
Pfizer
WIN
Sterling-Winthrop
U.S. Drug Enforcement Administration, Diversion Control Division. (2016). Synthetic Cannabinoids and Synthetic Cathinones Reported in NFLIS, 2013–2015. Springfield, VA:
U.S. Drug Enforcement Administration.

9. US NFLIS 2013 to 2015 AB-CHMINACA 10.89% XLR11 11.69% AB-FUBINACA
39.12%
U.S. Drug Enforcement Administration, Diversion Control Division. (2016). Synthetic Cannabinoids and Synthetic Cathinones Reported in NFLIS, 2013–2015. Springfield, VA:
U.S. Drug Enforcement Administration.

10. All known synthetic cannabinoids are illegal at the US federal level.
Schedule 1 of the Controlled Substances Act
U.S. Drug Enforcement Administration, Diversion Control Division. (2016). Synthetic Cannabinoids and Synthetic Cathinones Reported in NFLIS, 2013–2015. Springfield, VA:
U.S. Drug Enforcement Administration.

11. Binds at least 100 times more tightly Partial agonist
CB1
Activates receptor more strongly
Full agonist
CB2
No significant action
Partial agonist
Half-life
Longer
Active metabolites
Ford, B. M., Tai, S., Fantegrossi, W. E., & Prather, P. L. (2017). Synthetic pot: not your grandfather’s marijuana. Trends in pharmacological sciences, 38(3),

12. Inactive non cannabis plant material
Sold as plant material
Inactive non cannabis plant material
Widely varying doses of synthetic cannabinoids
Different response each time
Ford, B. M., Tai, S., Fantegrossi, W. E., & Prather, P. L. (2017). Synthetic pot: not your grandfather’s marijuana. Trends in pharmacological sciences, 38(3),

13. Marketed as: Herbal highs Vaporized Resins Incense E-cigarettes
Liquids
Room deodorizer
Vaping
“Not for human consumption”
Ford, B. M., Tai, S., Fantegrossi, W. E., & Prather, P. L. (2017). Synthetic pot: not your grandfather’s marijuana. Trends in pharmacological sciences, 38(3),

14. Key Points
Synthetic cannabinoids activate the cannabinoid CB1 receptor much more strongly than plant-derived THC.
Intoxication and withdrawal syndromes may be more intense and longer lasting than those associated with plant cannabis.
Synthetic cannabinoids are typically smoked or inhaled after vaporization, known as vaping.

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