Benzodiazepines were discovered in the 1950s and were rapidly adopted as prescription medicines for the treatment of a variety of conditions, such as anxiety or use as sedatives. However, the increase in popularity of benzodiazepines, along with their addictive properties, also led to an increase in the misuse and abuse of these compounds. 

Novel designer benzodiazepines (DBZD) and novel synthetic opioids (NSO) continue to emerge on the illicit novel psychoactive substance (NPS) market. Given this trend, and the continuing rise in benzodiazepine prescriptions, the likelihood for benzodiazepines to appear in toxicological samples alongside synthetic opioids is high. Understanding the synthesis and analytical interpretation of both NPS classes can help prepare forensic toxicologists for the appearance of unknown compounds in their casework.

Mitragynine is an indole-based alkaloid and is one of the main psychoactive constituents in the Southeast Asian plant Mitragyna speciosa, commonly known as kratom. It is an atypical opioid that is typically consumed as a part of kratom for its pain-relieving and euphoric effects and has also been researched for its use to potentially manage symptoms of opioid withdrawal and as a treatment for alcohol use disorder (AUD). More recently, analogs of mitragynine have begun to appear in the unregulated consumer marketplace and some are readily available in gas stations and vape shops in products branded as "7-hydroxymitragynine" or "7OH" causing heightened concern due to studies showing that 7-hydroxy mitragynine and mitragynine pseudoindoxyl (the rearrangement product of 7-hydroxy mitragynine) are more potent opioid agonists, exceeding that of mitragynine on the order of 10x and 100x, respectively.

Listen as Nathan Layle and Camille Waston-Gooden, synthetic chemists at Cayman Chemical, explain more about the history, pharmacology, metabolism, semi-synthetic modifications, and new emerging analogs of Mitragynine.

Presented as part of the CFSRE's 2026 Current Trends in Seized Drug Analysis Symposium.

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To cite this application note: Franckowski, R., Gregerson, M., Calati, K., et al. Creating Custom Cannabis CRM Mixtures: Forty-seven Phytocannabinoids, One HPLC Method. Application Note, Cayman Chemical (2025).

Semi-synthetic cannabinoids (SSCs) represent an emerging class of Novel Psychoactive Substances (NPSs) that are often advertised and sold as legal. SSCs can be described as partially synthetic materials that are derived from natural components of the Cannabis Sativa L. plant, such as Cannabidiol (CBD). New studies on the in-vivo and in-vitro metabolism of SSC’s, such as Δ¹⁰-THC, Δ^6a,10a-THC, and HHC, are emerging, which detail the similarities and differences seen to natural phytocannabinoid like Δ⁹-THC.

• Mass Spectrum of Etonitazene and Tips for Interpretation
• Common Mass Spec Fragments
• Common Nitazene Naming Conventions
• Nitazene Metabolism
  

The goal of this monograph is to identify the probable metabolites of the newly emerging semi-synthetic cannabinoids Δ¹⁰-THC and Δ^6a,10a-THC using human liver microsomes (HLMs) and high-resolution mass spectrometry. The metabolism of Δ⁹-THC with HLMs was also investigated to provide forensic toxicologists a comparative understanding of the key fragments needed for identification.

This monograph was updated on April 18th, 2025, to provide clarification on the interpretation of the (6aR,9R)-Δ¹⁰-THC metabolite at R.T. 14.16 minutes in Figure 8. 

To cite this monograph: Bassman, J.R., Layle, N.K., Gregerson, M.C., et al. Δ⁹-THC, Δ¹⁰-THC, and Δ^6a,10a-THC. Cayman NPS Metabolism Monograph Issue 3 (2025). 

Following China's generic structural class ban of several sub-classes of synthetic cannabinoids in 2021, the NPS/designer-drug landscape continues to evolve to evade regulation. As new structural variations appear on the grey market, another new phenomenon is the emergence of 'DIY' semi-finished kits. These semi-finished kits provide the end-user with non-regulated precursors enabling the user to finish the synthesis themselves to the desired synthetic cannabinoid of choice. Because the end-user often does not have the appropriate engineering and quality controls in place, drug substances on the illicit market are commonly contaminated with unreacted chemical precursors.  Several of these tail-less penultimate precursors have been detected on the grey market since late 2021.

Listen in as Holly Pierzynski, Cayman's Manager of Forensic Novel Psychoactive Substance Research, discusses several emerging synthetic cannabinoids, their precursors, synthesis, and byproducts from the synthesis. This presentation also highlights Cayman's new application note, "GC Separation of ADB-BUTINACA from its precursor ADB-INACA". 

Presented as part of the 2024 Midwestern Association of Forensic Scientists Conference in Kansas City, Missouri.

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Key Features

• Coelution of ADB-BUTINACA and its synthetic precursor ADB-INACA makes traditional GC-MS methods difficult for the quantification of these two novel psychoactive substances (NPS). Quantities of these synthetic cannabinoids are distorted if the testing methods are unable to resolve the two substances in analyzed samples.
• A new GC method for the separation of ADB-BUTINACA from its precursor ADB-INACA offers a reliable and robust solution for identifying this DEA Schedule I compound.

To cite this application note: Pierzynski, H.G., Liu, J., Calati, K.B., et al. GC separation of ADB-BUTINACA from its precursor ADB-INACA. Application Note, Cayman Chemical (2024).

Production of certified reference materials (CRMs) is prescribed by the conformity assessment standard ISO 17034:2016. Creating multi-component mixtures can present arduous challenges to ensure these criteria are met.