MOJ Toxicology How Present Synthetic Cannabinoids Can Help Predict Symptoms in the Future Submit Manuscript | http://medcraveonline.com Abbreviations: SCs: Synthetic Cannabinoids; Δ-9-THC: Delta- 9-TetraHydraCannabinol; UHPLC: Ultra High Performance Liquid Chromatography; DAD: Photodiode Array; MS: Mass Spectrometry. GC: Gas Chromatography; DART: Direct Analysis in Real Time; TOF: Time of Flight Spectrometry; NMR: Nuclear Magnetic Resonance; ATR: Attenuated Total Resonance; FTIR: Fourier Transform Infrared Spectrometry; TIC: Total Ion Chromatogram; LC-MS/MS: Liquid Chromatography Tandem Mass Spectrometry; CNS: Central Nervous System; LOD: Limit of Detection, LOQ: Limit of Quantitation; ULOL: Upper Limit of Linearity; DUID: Driving Under the Influence of Drug; HLM: Human Liver Microsomes; HPM: Human Pulmonary Microsomes; CES 1: Carboxylesterase 1 Introduction Synthetic cannabinoids (SCs) are synthetic compounds sprayed on herbal products and have spread worldwide since 2004. Many of these compounds, more specifically l-valinamides and l-tert-leucinamides, are often characterized as part of the third, fourth and fifth generation of synthetic cannabinoids. There are many street names for herbal like compounds which are sprayed with these compounds, referred to as “Spice” such as Spice Diamond, Spice Gold, Spice Arctic Energy, Magic, Voodoo and Yucatan Fire. Such drugs are easily obtainable via the Internet, in smoke shops, and street markets. To evade law enforcement, these herbal incense products are often labeled “not for human consumption”. Despite this, many countries have entered many synthetic cannabinoids to schedule 1 [1,2]. Initial reports of synthetic cannabinoids (SCs) in Unites States were in November 2008. In December 2008, German forensic laboratories initially identified JWH–018 and cannabicyclohexanol (CP–47,497 C8 homologue). The synthetic cannabinoids are frequently applied on plant material and inhaled. In January 2010, the popularity of these cannabinoids and their associated products appeared to have increased in the United States [3]. Numerous SCs have been identified as adulterants, which have been seized by law enforcement. JWH–018, JWH–073, JWH–200, CP– 47,497, and CP–47,497 C8 homologues were the first SCs identified as being abused. New generations of synthetic cannabinoids quickly emerged to evade law enforcement. After various laws were passed in the United States, different generations of SCs emerged varying only by slight modifications in structure. Some recent SCs include AB–CHMINACA and AB-PINACA. These substances are commonly marketed under the guise of being a ‘‘legal high’’ with a disclaimer of ‘‘not for human consumption’’. Law enforcement, Volume 2 Issue 1 - 2016 1 Consultant, The Forensic Sciences, USA 2 Post-Doctoral Fellowship, Texas Southern University, USA & Toxicologist, Ministry of Justice, Egypt 3 Professor, Barbara Jordan-Mickey Leland School of Public Affairs, Texas Southern University, USA *Corresponding author: Ashraf Mozayani, Executive Director of Forensic Science and Professor, Barbara Jordan- Mickey Leland School of Public Affairs, Texas Southern University, USA, Tel: 17132526556; Email: Received: October 22, 2015 | Published: February 17, 2016 Mini Review MOJ Toxicol 2016, 2(1): 00029 Abstract New synthetic cannabinoids appear regularly in the illicit drug market, often in response to legal restrictions. These compounds are characterized by increasing binding affinities (Ki) to CB1 and CB2 receptors. Increasing affinity to CB receptors can occur by substitution of a halogen on the terminal position of the pentyl chain of the classical synthetic cannabinoids. Fluorination of the aliphatic side chain of established cannabinoid agonists is a popular pathway of modifying existing active drugs and synthesizing novel drugs to increase potency. Biological impacts of these compounds that have been reported include seizures, body temperature losses that may lead to cardiac distress, as well as cases reporting delirium and severe neural incapacities. These symptoms have been reported in case reports with evidence that like their cannabinoid counterparts, these compounds distribute post-mortem into a variety of tissues, especially adipose tissue. Researchers have detected and identified certain synthetic cannabinoid compounds on botanicals using a variety of separation and detection systems such as GC-FID and GC-MS, as well as LC-MS/MS and NMR. Researchers have utilized a variety of chromatographic methods including LC MS/MS, to identify the parent compounds, their metabolites and structural analogs in biological samples such as urine and blood. The aim of this review is to spotlight the newer generations of synthetic cannabinoids with a more powerful affinity towards the cannabinoid receptors to continue to help researchers and clinicians further predict symptoms as well as future compounds and treatments. Keywords: Synthetic Cannabinoids; CHMINACA; Tissue Culture; LCMS/MS; TOF; GC-MS; GC-FID; Case reports