Cayman's Forensic Division chemists synthesize reference standards and collaborate with Ghent University researchers to rapidly characterize OXIZID synthetic cannabinoids.  

In July 2021, China banned several common synthetic cannabinoid core scaffolds to control the manufacturing and trafficking of these substances. Clandestine chemists promptly pursued alternative core scaffolds to subvert these control measures, which resulted in the emergence of novel synthetic cannabinoids with "legal" core structures on the recreational drug market. OXIZIDs, a new class of emerging synthetic cannabinoids, possess an alternative core scaffold that circumvents these new regulations.

Many compounds once developed as therapeutic agents or tools to study the endocannabinoid system have been repurposed by clandestine chemists for recreational drug use. Developed as a treatment for neuropathic pain, MDA-19 ("BZO-HEXOXIZID"), a previously known CB₂ receptor agonist, represents the prototypical scaffold of OXIZID synthetic cannabinoids. The recent emergence of this compound and its derivatives as novel psychoactive substances (NPS) necessitates a systematic naming system. "MDA" in the name "MDA-19" is an homage to its development at MDAnderson Cancer Center. Now that this substance has been co-opted for recreational drug use, the name could easily be mistaken as an abbreviation for "methylenedioxyamphetamine".

To avoid confusion caused by ambiguous abbreviations, Cayman Chemical and NPS Discovery at the Center for Forensic Science Research and Education (CFSRE) established a systematic naming convention for these emerging compounds that is structurally informative and parallels existing synthetic cannabinoid NPS nomenclature. We propose that MDA-19 and its analogs be referred to as "OXIZIDs", which represents the OXoIndoline core and aZIDe linker scaffold that defines this scaffold. Like other synthetic cannabinoids, head and tail groups along the OXIZID scaffold are abbreviated following the commonly used naming scheme. Following this system, we have named MDA-19 and its derivatives as follows:

Click Here to Access the Downloadable Guide to OXIZID Systematic Naming

Synthetic cannabinoids, also referred to as synthetic cannabinoid receptor agonists (SCRAs), are typically designed to mimic the psychoactive properties of ∆⁹-tetrahydrocannabinol (∆⁹-THC) and activate CB₁ receptors, which are largely expressed in the CNS. Activation of the CB₂ receptor, which is expressed primarily on immune cells, is devoid of psychoactive effects. Until recently, little has been known about the activity of OXIZIDs at CB₁ and CB₂ receptors.

A new study by Deventer and coworkers published in Drug Testing and Analysis assessed the potency and efficacy of BZO-HEXOXIZID, BZO-POXIZID, 5F-BZO-POXIZID, BZO-4en-POXIZID, and BZO-CHMOXIZID at CB₁ and CB₂ receptors with β-arrestin2 recruitment assays.

• For both CB₁ and CB₂ receptors, the rank order potency of these OXIZIDs was found to be: BZO-CHMOXIZID > 5F-BZO-POXIZID > BZO-POXIZID > BZO-4en-POXIZID > BZO-HEXOXIZID
  
• These OXIZIDs acted as potent CB₂ receptor partial agonists and were found to be full agonists at CB₁ receptors, albeit with less potency compared to CB₂ receptors. 
  
• All OXIZIDs showed clear selectivity for CB₂ over CB₁ receptors except BZO-POXIZID.
• The OXIZIDs tested herein were less potent at CB₁ receptors than the reference compounds CP 55,940 and JWH 018.

The lead author, Marie Deventer, recently commented that "At the Laboratory of Toxicology at Ghent University, Belgium, we closely monitor new drug trends, with a particular focus on new synthetic opioids and synthetic cannabinoid receptor agonists. Building on a readily existing fruitful partnership with the Forensic Chemistry Division of Cayman Chemical Company, we were able to act promptly and characterize this new OXIZID class of synthetic cannabinoid receptor agonists. The rapid availability of reference materials is key for labs like ours, who perform both chemical and pharmacological characterization of newly emerging compounds. This allows us to quickly investigate these compounds, only shortly after their first appearance on the market, which is important to contribute to a more comprehensive knowledge on the ever-changing cannabinoid market and to allow risk prioritization."

Donna M. Iula, Ph.D., Vice President of Forensic Chemistry at Cayman Chemical, said, "When broad structural-class regulatory actions are implemented, we typically see the emergence of replacement scaffolds on the designer drug scene. One of the challenges that follows is not knowing what the pharmacology, toxicology, or analytical profile of those new substances look like. My team at Cayman Chemical is committed to partnering with research organizations to gather and disseminate this critical information. We were fortunate to be able to collaborate with NPS Discovery at the Center for Forensic Science Research and Education (CFSRE) on a standardized naming mechanism for this new OXIZID class as well as the Laboratory of Toxicology at Ghent University, Belgium to study the biological activity of these emerging NPS."

Read the Article Here

Cayman keeps abreast of new analogs appearing in forensic casework and/or on the grey market and can quickly provide reference standards in response to emerging NPS. Below are the reference standards used in this publication. Reference materials and analytical standards for many more synthetic cannabinoids can be found here.

Reference Standards Used in this Publication

MDA 19 (aka BZO-HEXOXIZID)
BZO-POXIZID
5-fluoro BZO-POXIZID
BZO-4en-POXIZID
BZO-CHMOXIZID
(–)-CP 55,940
JWH 018

Download or request a physical copy of our Laboratory Guide for Synthetic Cannabinoid Identification and Naming

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