1. Copyright Notice
This presentation is copyrighted by the Psychopharmacology Institute.
Subscribers can download it and use it for professional use.
The contents of the presentation may be modified, but the Psychopharmacology Institute logo must remain visible in all slides.

2. Synthetic Cannabinoids: Epidemiology, Clinical Manifestations, and Practical Diagnostic Aspects
David A. Gorelick, M.D., Ph.D., DLFAPA
Professor of Psychiatry
University of Maryland School of Medicine

3. Epidemiology 2017 Global Drug Survey Lifetime use 5.8% 77.8%
Past-year use
1.1%
60%
Global Drug Survey Available at content/themes/globaldrugsurvey/results/GDS2017_key-findings-report_final.pdf. Accessed 02/20/2018.
United Nations Office on Drugs and Crime, World Drug Report United Nations publication, Sales No. E.17.XI.6). Available at Accessed 02/20/2018.

4. Survey: US High School Seniors
Current use of synthetic cannabinoids
2.9%
Use on at least 3 different days
49.7%
Global Drug Survey Available at content/themes/globaldrugsurvey/results/GDS2017_key-findings-report_final.pdf. Accessed 02/20/2018.
United Nations Office on Drugs and Crime, World Drug Report United Nations publication, Sales No. E.17.XI.6). Available at Accessed 02/20/2018.

5. Trends in Synthetic Cannabinoid Use
2016
Prevalence of past-year use in 12th graders
12% 4%
Synthetic cannabinoid users also use plant cannabis. 

6. Clinical Manifestations
Little high-quality data on their human safety or toxicity 
More associated with serious medical and psychiatric problems than plant cannabis
Winstock, A., Lynskey, M., Borschmann, R., & Waldron, J. (2015). Risk of emergency medical treatment following consumption of cannabis or synthetic cannabinoids in a large global sample. Journal of Psychopharmacology, 29(6),

7. 2017 Global Drug Survey X 5 Current/past-year synthetic cannabis users
Sought emergency medical treatment
3.2%
0.6%

8. Retrospective Case Series: Results
Psychotic symptoms
77.1%
55.5%
Agitation
57.1%
27.3%
Psychotic disorder diagnosis
82.8%
49.8%
Mood disorder diagnosis
17.1%
45.5%
Winstock, A., Lynskey, M., Borschmann, R., & Waldron, J. (2015). Risk of emergency medical treatment following consumption of cannabis or synthetic cannabinoids in a large global sample. Journal of Psychopharmacology, 29(6),

9. Synthetic Cannabinoid Intoxication and Withdrawal
More intense
Longer lasting
Pharmacologic differences between synthetic cannabinoids and plant-derived cannabis 
Plant cannabis contains cannabidiol, which counteracts the effects of THC.

10. Synthetic Cannabinoids Effects
Desired subjective effects
Undesired effects
Synthetic Cannabinoids Effects
Anxiety
Euphoria
Increased appetite
Sedation
Dizziness
Relaxation
Conjunctival redness
Tachycardia
Monte, A. A., Calello, D. P., Gerona, R. R., Hamad, E., Campleman, S. L., Brent, J., ... & ACMT Toxicology Investigators Consortium. (2017). Characteristics and treatment of patients with clinical illness due to synthetic cannabinoid inhalation reported by medical toxicologists: a ToxIC Database study. Journal of Medical Toxicology, 13(2),  
Müller, H. H., Kornhuber, J., & Sperling, W. (2016). The behavioral profile of spice and synthetic cannabinoids in humans. Brain research bulletin, 126, 3-7.
Tait, R. J., Caldicott, D., Mountain, D., Hill, S. L., & Lenton, S. (2016). A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clinical Toxicology, 54(1), 1-13.

11. More Intense Effects + CB1 Stupor Prolonged psychosis
Increased muscle tone
Muscle pain

12. Life-Threatening Medical Complications
Nausea and vomiting
Hypertension
Seizures
Cardiac arrhythmias
Rhabdomyolysis
Hyperventilation
Acute myocardial infarction
Acute renal failure
Apnea
Monte, A. A., Calello, D. P., Gerona, R. R., Hamad, E., Campleman, S. L., Brent, J., ... & ACMT Toxicology Investigators Consortium. (2017). Characteristics and treatment of patients with clinical illness due to synthetic cannabinoid inhalation reported by medical toxicologists: a ToxIC Database study. Journal of Medical Toxicology, 13(2),  
Müller, H. H., Kornhuber, J., & Sperling, W. (2016). The behavioral profile of spice and synthetic cannabinoids in humans. Brain research bulletin, 126, 3-7.
Tait, R. J., Caldicott, D., Mountain, D., Hill, S. L., & Lenton, S. (2016). A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clinical Toxicology, 54(1), 1-13.

13. Cannabinoid intoxication syndrome
Diagnosis of Intoxication
Cannabinoid intoxication syndrome
Collateral
informants
History
Drug
samples
Paraphernalia
Packaging
Monte, A. A., Calello, D. P., Gerona, R. R., Hamad, E., Campleman, S. L., Brent, J., ... & ACMT Toxicology Investigators Consortium. (2017). Characteristics and treatment of patients with clinical illness due to synthetic cannabinoid inhalation reported by medical toxicologists: a ToxIC Database study. Journal of Medical Toxicology, 13(2),  
Tait, R. J., Caldicott, D., Mountain, D., Hill, S. L., & Lenton, S. (2016). A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clinical Toxicology, 54(1), 1-13.

14. Diagnosis is often made by exclusion.
Confirmed by
sophisticated and expensive assay methods
Results are delayed several days
False negative results possible due to novel chemical structures
Monte, A. A., Calello, D. P., Gerona, R. R., Hamad, E., Campleman, S. L., Brent, J., ... & ACMT Toxicology Investigators Consortium. (2017). Characteristics and treatment of patients with clinical illness due to synthetic cannabinoid inhalation reported by medical toxicologists: a ToxIC Database study. Journal of Medical Toxicology, 13(2),  
Tait, R. J., Caldicott, D., Mountain, D., Hill, S. L., & Lenton, S. (2016). A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clinical Toxicology, 54(1), 1-13.

15. Clinical Manifestations Warranting a High Index of Suspicion
(1) Conjunctival redness
(2) Sudden onset of otherwise unexplained psychosis
(3) Sudden onset of otherwise unexplained cognitive impairment, such as disorientation or disorganized speech
Monte, A. A., Calello, D. P., Gerona, R. R., Hamad, E., Campleman, S. L., Brent, J., ... & ACMT Toxicology Investigators Consortium. (2017). Characteristics and treatment of patients with clinical illness due to synthetic cannabinoid inhalation reported by medical toxicologists: a ToxIC Database study. Journal of Medical Toxicology, 13(2),  
Tait, R. J., Caldicott, D., Mountain, D., Hill, S. L., & Lenton, S. (2016). A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clinical Toxicology, 54(1), 1-13.

16. Clinical Manifestations Warranting a High Index of Suspicion
(4) Sudden onset of otherwise unexplained kidney, neurological (seizure), or cardiovascular problems, such as chest pain, tachycardia, arrhythmia, or hypertension
(5) Typical signs and symptoms of cannabis intoxication when the drug test is negative for THC or cannabis
Monte, A. A., Calello, D. P., Gerona, R. R., Hamad, E., Campleman, S. L., Brent, J., ... & ACMT Toxicology Investigators Consortium. (2017). Characteristics and treatment of patients with clinical illness due to synthetic cannabinoid inhalation reported by medical toxicologists: a ToxIC Database study. Journal of Medical Toxicology, 13(2),  
Tait, R. J., Caldicott, D., Mountain, D., Hill, S. L., & Lenton, S. (2016). A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clinical Toxicology, 54(1), 1-13.

17. Synthetic Cannabinoid Brand Names
No distinctive cannabis odor
Spice and K2
Black Mamba
Bliss
Bombay Blue
Genie
Joker
Kush
Kronic
Zohai
~ 700 different brand names identified
Image:

18. Useful Resources US Drug Enforcement Administration (DEA) www.dea.gov
US National Institute on Drug Abuse (NIDA)

19. Physical and neurological
Clinical laboratory testing
Complete blood count
Review of systems
Electrolytes
Blood chemistry
Medical evaluation
12-lead electrocardiogram
Physical and neurological
examination
Imaging (e.g., brain imaging) 
Monte, A. A., Calello, D. P., Gerona, R. R., Hamad, E., Campleman, S. L., Brent, J., ... & ACMT Toxicology Investigators Consortium. (2017). Characteristics and treatment of patients with clinical illness due to synthetic cannabinoid inhalation reported by medical toxicologists: a ToxIC Database study. Journal of Medical Toxicology, 13(2),  
Tait, R. J., Caldicott, D., Mountain, D., Hill, S. L., & Lenton, S. (2016). A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clinical Toxicology, 54(1), 1-13.

20. Key Points
The diagnosis is often made by history and/or presence of typical cannabis intoxication signs, such as conjunctival redness, in the absence of a drug test positive for THC. 
Synthetic cannabinoids are not detected by routine drug screening tests.
Diagnosis is suggested by sudden onset of unexplained psychosis; cognitive impairment; or kidney, neurological, or cardiovascular problems.

21. Next Presentation Management of Intoxication and Withdrawal