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Some Assembly Required: Emerging Synthetic Cannabinoids Webinar Highlights

Article from 2024-11-06

Holly Pierzynski, manager of the forensic novel psychoactive substance research department within the Forensic Chemistry Division at Cayman Chemical, discussed the emergence of synthetic cannabinoid precursors. The proliferation of do-it-yourself (DIY) kits is resulting in mixtures that can complicate forensic analysis, as they can share the same characteristic EI-MS base peaks, leading to potential misidentification. We have summarized the key takeaways from this webinar below.


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DIY Semi-Finished Kits

Synthetic precursors are being sold online in DIY kits that are one reaction away from final synthetic cannabinoid products.

These DIY semi-finished kits provide precursors for the synthesis of synthetic cannabinoids, enabling the user to finish the synthesis themselves to avoid federal and international regulations. Many of these DIY semi-finished kits are being offered on illicit direct-to-user sites and discussed on internet forums.

Because of the versatility of the reactions employed, the synthetic precursors in these DIY kits can be used to synthesize many common synthetic cannabinoids.

Synthesis of Indole & Indazole Synthetic Cannabinoid Precursors

There are several synthetic pathways to obtain synthetic cannabinoids. Two common pathways may follow route A or route B. Both routes produce the same final product either with the addition of the tail piece for route A or the addition of the amine head group for route B.

Route A

Route A starts with the indole or indazole carboxylic acid and with the addition of the amine head group yields the following precursor I, which is one step behind the finished product. These types of precursors appear to be the most popular showing up in casework.

Route B

Route B starts with the indole or indazole carboxylic acid and with the addition of the tail piece first, precursor II is obtained, which is also one step behind the finished product. Importantly, these precursors may also be produced as metabolites during synthetic cannabinoid metabolism and may be encountered in toxicological casework.

In summary, route A yields the amine head group precursor, and route B produces the tail group precursor. Both routes will produce the final product upon the addition of either the tail group or head group, respectively.

The precursors that appear to be most abundant in current casework are those involved in route A.

Indole Route A Precursors

Indole precursors contain a single nitrogen atom in their structure, and a benzene ring bonded to a pyrrole ring. The following indole precursors may be encountered in casework.

1'-Naphthoyl Indole

  • A precursor to several synthetic cannabinoids such as the classic synthetic cannabinoid JWH 018.

 

2-(2-Chlorophenyl)-1-(1H-indol-3-yl)ethanone

  • A precursor to JWH 203 that was identified in DIY kits in the Russian Federation in 2023.

 

(1H-Indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone

  • A precursor to several synthetic cannabinoids such as the classic synthetic cannabinoids UR-144 and XLR11.

 

ADB-IATA

  • A precursor to ADB-FUBIATA, which emerged in 2021.

 

MDMB-ICA

  • Identified in the United States in Fall 2023.
  • Found in samples containing MDMB-PICA.
  • Our lab saw GC-MS unknowns of MDMB-PICA in August and October 2023 from the Pennsylvania area.


MDMB-ICA is also a precursor for other synthetic cannabinoids, as shown below.

Indazole Route A Precursors

Indazole precursors contain two nitrogen atoms in their structure, and a benzene ring bonded to a pyrazole ring.

Several indazole synthetic cannabinoid precursors may be encountered in forensic and toxicological casework. Notably, ADB-5Br-INACA and MDMB-5Br-INACA started to appear on the market in 2021 and 2022. Both of these precursors were unique in that it marked the emergence of synthetic cannabinoids containing a bromine at the 5 position.

CUMYL-INACA

  • A precursor to the synthetic cannabinoid 5-fluoro CUMYL-PINACA, which emerged in 2020.

 

ADB-5Br-INACA

  • First reported by RESPONSE 2 Project in December of 2021.
  • Detected in seized samples from Scottish prisons and Belgian customs in late 2021.
  • A January 2022 report from the European Union Drugs Agency (EUDA), formerly known as the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), described ADB-5Br-INACA in an off-white powder in Hungary and in blotters from Turkey.
  • Reportedly emerged in the United States in Q1 2022, but our lab saw GC-MS unknowns from Pennsylvania, New Jersey, Indiana, and Texas from Q4 2021 into Q1 2022.
 
MDMB-5Br-INACA

  • First reported by the EUDA in April of 2022 following its detection in a beige powder from Switzerland.
  • Often detected as a mixture with ADB-5Br-INACA, especially in samples from Scottish prisons and Belgian customs in late 2021.
  • Detected in New Zealand in August 2022.
  • Our lab saw GC-MS unknowns from Illinois, Florida, Texas, Pennsylvania, Ohio, Turkey, and the Republic of Mauritius throughout 2022 and into 2023.

 

ADB-5'Br-BUTINACA

  • First reported in June 2022 by the EUDA in samples from Hungary.
  • Detected between May and June 2022 in forensic casework in the United States.
  • Detected between October and December of 2022 in Scottish prisons.
  • Our lab observed GC-MS unknowns predominantly from the Pennsylvania area in 2022.

 

ADB-5'Br-PINACA

  • First reported by EUDA in August 2022.
  • The Public Health Agency of Sweden released a report in October 2022 following seizure in Portugal.
  • Detected in the United States in 2023.
  • Our lab observed a GC-MS unknown from France and its presence on direct-to-user sites in 2023.

 

MDMB-INACA

  • First reported by EUDA in August 2022.
  • Emerged in the United States in April 2023.
  • Appeared in samples alongside MDMB-4en-PINACA and MDMB-BUTINACA.


MDMB-INACA can be used to synthesize many synthetic cannabinoids. If the reaction is incomplete, MDMB-INACA has the potential to show up in samples of the desired finished product.

MDMB-5Me-INACA

  • Emerged on the market in November 2023.
  • Our lab has not seen any synthetic cannabinoid with a tail piece that has incorporated this precursor as of Q3 2024.

ADB-INACA

  • First detected in the United States in November 2022.
  • A precursor to several synthetic cannabinoids, and may coelute with finished product, creating analytical challenges.


ADB-INACA is a precursor to several synthetic cannabinoids, as shown below.


A New Synthetic Cannabinoid or Coelution?

ADB-INACA may coelute with the finished product, creating an analytical challenge. Starting in late 2022, Cayman received requests for assistance identifying a new synthetic cannabinoid. These unknowns were submitted from agencies in Texas, Arkansas, Pennsylvania, Kentucky, Illinois, and Turkey.

Based on the mass spectra, we noticed several similarities with ADB-BUTINACA and ADB-INACA. We concluded that it was possible ADB-INACA was coeluting with ADB-BUTINACA.

Due to the number and frequency of unknown requests and several inquiries on methods to help differentiate them, our ISO department developed a GC method for the separation of ADB-BUTINACA from its precursor ADB-INACA.

View the Application Note


Bis-Alkylated Byproducts

MDMB-INACA can also form bis-alkylated byproducts that may be encountered in casework. MDMB-INACA is typically reacted with a base to add the tail piece group. If the base is strong, it may hydrolyze the methyl ester, yielding the acid product. Hence, the tail piece group is added not only to the indazole nitrogen but also to the acid group, resulting in the bis-alkylated byproducts 4en-PDMB-4en-PINACA and 5F-PDMB-5F-PINACA.


New Synthetic Cannabinoids to Look Out For


3-TMS-ADB-PRINACA

  • Identified in Germany, seized by Bavarian State Police in November 2022.

3-TMS-CUMYL-PRINACA

  • Identified in plant material seized by Swedish customs in March 2023.
  • Found in smoking herbal mixtures called the "Joker".

 

Forensic Tools & Resources

Cayman has a wide range of reference standards for synthetic cannabinoid precursors and finished products.

View All Synthetic Cannabinoid Precursors Available from Cayman

View All Synthetic Cannabinoids Available from Cayman

Synthetic Cannabinoid Identification & Naming Lab Wall Poster

View common synthetic cannabinoid MS fragments and synthetic cannabinoid naming conventions in this guide for drug identification and naming.

Download or Request a Physical Copy

Cayman Spectral Library

Our spectral library is a free-of-charge, searchable GC-MS spectral database containing 70EV EI MS data of hundreds of Cayman's emerging forensic drug standards.

Access the Library


GC-MS Drug Identification Tool

Search unknowns by formula weight, base peak, or 2nd base peak ion.

Try the GC-MS Drug Identification Tool

Our team is available to help the forensic community identify unknown substances within their casework without charge.

Need help identifying your unknown? Send your data to techserv@caymanchem.com.

Synthetic Cannabinoid Flipbook

Identify drugs of abuse that share common head, core, and tail pharmacophores with known synthetic cannabinoids.

View the Synthetic Cannabinoid Flipbook


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