Sept 28, 2021: What is “Spice” and Why is it Not Just Marijuana?

What is spice and how did it originate?

Synthetic cannabinoids (SCB), also known as K2 or “spice”, are compounds created to stimulate the endogenous cannabinoid receptors with the potential for therapeutic administration. In the early 2000s, SCBs became popular to obtain "legal highs" sold under brand names such as Spice and K2, in part due to their ability to escape detection by standard cannabinoid screening tests.1


Differences in mechanism of action between THC and “Spice”

Although both Δ-tetrahydrocannabinol (THC) and SCBs stimulate the same receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), studies have shown that SCBs are associated with higher rates of toxicity and hospital admissions than natural cannabis. This may be due to SCBs being direct full agonists of the cannabinoid receptors, whereas THC is a partial agonist.


Clinical Response

SCBs produce physiological and psychoactive effects similar to THC, but with greater intensity, causing medical and psychiatric emergencies. In vitro and animal studies reveal the pharmacological effects of SCB are 2-100 times more potent than THC (including analgesic, anti-seizure, weight-loss, anti-inflammatory, and anti-cancer growth effects.)1 The 10 most common adverse effects in adolescents are tachycardia (41.6%), drowsiness/lethargy (24.3%), agitation/irritability (16.4%), vomiting (13.1%), hallucinations/delusions (11.5%), nausea (8.5%), confusion (8.2%), hypertension (7.5%), chest pain (6.9%) and dizziness/vertigo (5.2%).3


Treatment in Overdose

Acute intoxication of SCBs requires supportive care and observation. Most common treatments are IV fluids and observation. Benzodiazepines can be administered to treat psychomotor agitation and seizures; antiemetics for nausea; and haloperidol for acute psychosis.3


Take away points

  1. SCBs are popular drugs of abuse that have many variable names, structures, and clinical effects.
  2. SCBs are more toxic than natural cannabinoids and the clinical effects are unpredictable.
  3. SCBs are often used with other illicit drugs. Patients who test positive for other drugs of abuse should be asked about recent use of SCBs. However, these drugs are not usually detected with routine assays for cannabinoids.

Prepared by Lindsay Kokoska, DO, PEM 2nd year Fellow, LeBonheur Children’s Hospital





  1. Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend. 2014 Nov 1;144:12-41. doi: 10.1016/j.drugalcdep.2014.08.005. Epub 2014 Aug 18. PMID: 25220897; PMCID: PMC4253059.


  1. Fantegrossi WE, Moran JH, Radominska-Pandya A, Prather PL. Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Δ(9)-THC: mechanism underlying greater toxicity? Life Sci. 2014 Feb 27;97(1):45-54. doi: 10.1016/j.lfs.2013.09.017. Epub 2013 Sep 29. PMID: 24084047; PMCID: PMC3945037.


  1. Mills B, Yepes A, Nugent K. Synthetic Cannabinoids. Am J Med Sci. 2015 Jul;350(1):59-62. doi: 10.1097/MAJ.0000000000000466. PMID: 26132518.


Last week’s Question addressed snake envenomation and administration of Crofab in pregnant women.  Dr. Cosby Stone (Assistant Professor in Allergy/Immunology,

VUMC Drug Allergy Research) sent the following comments:


One important tidbit from the allergists that might help providers who are administering CroFab would be to screen the history for the possibility of alpha-gal allergy prior to administration, and in the event of possible alpha-gal, to have rescue medications at the bedside when giving it. 


CroFab is an ovine derived antibody and does contain alpha-gal as an allergen, see reference 1.  Because people who are in the woods getting snake bites are also people who are in the woods getting tick bites, this allergy can coexist in a small subset of the same population, and may predict at least some of the folks who will react to CroFab.   


We've seen one case at Vanderbilt where someone with a preexisting allergy to alpha-gal did have a reaction to CroFab administration. 


Reference 1: α-Gal on Crotalidae-polyvalent Fab antivenom (CroFab): Investigating the relevance to immediate hypersensitivity reactions.  This paper shows that alpha-gal is present in the drug, and might contribute to reactions.


Reference 2:  Cases are reported where preexisting alpha-gal and a reaction to CroFab happened in the same person.


Beyond that, I'm sure we could come up with a desensitization protocol if we needed it in the event of someone having a bite and needing CroFab with known alpha-gal allergy. ( End of Dr Stone’s comments.)


Always appreciate comments sent to us by the experts who are willing to share.  


I am interested in any questions you would like answered in the Question of the Week. Please email me with any suggestion at


Donna Seger, MD

Executive Director

Tennessee Poison Center

 Poison Help Hotline: 1-800-222-1222