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November 2024 - UNODC EWA: New evolution of “semi-synthetic” cannabinoids

Vienna, Austria – November 2024: A series of new cannabinoids with structural similarities to cannabinoids that occur naturally in the cannabis plant has emerged in recent years. They have become known as “semi-synthetic” cannabinoids on the illicit drug markets. “Semi-synthetic” cannabinoids suggest that these substances were manufactured from naturally occurring cannabinoids, however some structural properties indicate that not all substances under this group name were derived from CBD or THC.[1]

The term “semi-synthetic” used here describes the phenomenon of emergence of these structurally related but heterogenous group of new cannabinoids on illicit drug markets and the caveats on their synthesis mentioned in the footnote 1 should be noted. 

Of 40 synthetic cannabinoids identified in seized material and reported to the UNODC EWA between 2022 and 2024*, 18 belong to this new series of “semi-synthetic” cannabinoids (see list in Table 1-3). Among these 18 substances, ten derivatives of delta-8-THC and delta-9-THC have been identified. Five of these 18 cannabinoids were reported for the first time in 2022 (Table 1), ten in 2023 (Table 2) and three in 2024 (Table 3).

Table 1: “Semi-synthetic” cannabinoids reported to UNODC EWA - Year of first report 2022:

 

Source: UNODC Early Warning Advisory on New Psychoactive Substances, October 2024.
Note: For more chemical information on these substances, please click here.


Table 2: “Semi-synthetic” cannabinoids reported to UNODC EWA - Year of first report 2023:


Source: UNODC Early Warning Advisory on New Psychoactive Substances, October 2024.
Note: For more chemical information on these substances, please click here.


Table 3: “Semi-synthetic” cannabinoids reported to UNODC EWA -
Year of first report 2024*:



Source: UNODC Early Warning Advisory on New Psychoactive Substances, October 2024.
Note: For more chemical information on these substances, please click here. *Data collection for 2024 is still ongoing.


Up to October 2024, these 18 “semi-synthetic” cannabinoids have been reported predominantly from Europe, with a smaller number of reports coming from North and South America. Hexahydrocannabinol (HHC) is the most widely reported substance with reports from 34 countries and territories in total from 2022-2024*, followed by Hexahydrocannabiphorol and Tetrahydrocannabidiol (H4-CBD) each with reports from 17 and 15 countries and territories respectively, over the period 2022-2024* (see Figure 1). Hexahydrocannabinol (HHC) was first reported in 2022 and was subject to critical review at the 47th Expert Committee on Drug Dependence of the WHO (ECDD), held from 14 to 18 October 2024.


Figure 1: Top 5 “semi-synthetic” cannabinoids reported to UNODC EWA in 2022-2024*, by number of countries/territories reporting



Source: UNODC Early Warning Advisory on New Psychoactive Substances, October 2024.
Note: For more chemical information on these substances, please click here. *Data collection for 2024 is still ongoing.


As “semi-synthetic” cannabinoids have only recently emerged in drug products, there is a lack of robust, well-controlled studies on their pharmacological activity, toxicology, and potential for producing harmful effects. In UNODC EWA, there is new updated pharmacological information on delta-8-Tetrahydrocannabinol acetate and delta-9-Tetrahydrocannabinol acetate.

The emergence of new substances can pose significant challenges to Member States. To assist the work of law enforcement, forensic drug testing and toxicology laboratories, UNODC provides analytical information on NPS in the UNODC EWA as well as assistance in the areas of quality assurance, provision of manuals and guidelines, field detection and handheld devices, together with training in the UNODC laboratory in Vienna and in the field.

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[1]
Some of the “semi-synthetic” cannabinoids could be derived from plant-based CBD (and some also from THC) through a relatively simple chemical process. There are indications that these substances (such as Hexahydrocannabinol (HHC)) are manufactured in clandestine laboratories from CBD. However, additional substances have emerged, which share some structural similarities but also show structural differences such as a longer alkyl carbon chain. These differences suggest that they were not derived from CBD but synthesized from other precursor chemicals. Therefore, the group name “semi-synthetic” may be misleading, as some of the substances are structurally more diverse and likely are manufactured using purely synthetic means.
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For more information, please see:

UNODC, Beyond plants: semi-synthetics diversify the cannabis market. Smart Forensics Update Vol. 1, May 2024.

UNODC, The challenge of New Psychoactive Substances - A technical update (United Nations publication, 2024)

UNODC, Recommended methods for the Identification and Analysis of Synthetic Cannabinoid Receptor Agonists in Seized Materials (September 2020).

UNODC, Recommended methods for the identification and analysis of cannabis and cannabis products (March 2022).

UNODC EWA news:  September 2024 - WHO: Seven new psychoactive substances and one medicine under critical review by 47th Expert Committee on Drug Dependence

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