Semi-synthetic cannabinoids: Recent developments, analytical challenges and strategic responses

Area of Science:

• Forensic Chemistry
• Toxicology
• Pharmacology
• Public Health

Background:

• Semi-synthetic cannabinoids (SSCs) are novel psychoactive substances designed to mimic delta-9 tetrahydrocannabinol (THC).
• Produced from cannabidiol (CBD), SSCs are marketed as legal cannabis alternatives, rapidly expanding in the European new psychoactive substances (NPS) landscape.
• Over 30 SSC compounds are under monitoring by the European Union Drugs Agency (EUDA), with hexahydrocannabinol (HHC) being an early example.

Purpose of the Study:

• To highlight the challenges posed by the rapid emergence and proliferation of SSCs in the NPS market.
• To underscore the limited knowledge regarding the pharmacological, toxicological, and metabolic profiles of SSCs.
• To emphasize the analytical difficulties in detecting and identifying SSCs due to market innovation and product variability.

Main Methods:

• Monitoring of emerging SSC compounds by the EUDA and its associated networks.
• Analysis of consumer products (vapes, edibles, herbal products) for SSCs and contaminants.
• Review of reported acute poisonings linked to SSC use across EU countries.
• Development of analytical tools and reference libraries (e.g., EUDA-JRC GC-MS library).

Main Results:

• SSCs are widely available, often mislabelled, and contain undeclared substances, leading to increased acute poisonings.
• Analytical challenges include rapid market evolution, lack of certified reference materials, isomeric compounds, and complex product matrices.
• Forensic and toxicological laboratories face difficulties in detection and identification due to these evolving threats.

Conclusions:

• Coordinated efforts, including information sharing, best practices, and collaborative research, are crucial for laboratories to address SSC threats.
• Investment in research, test-purchasing, and toxicological studies is essential for understanding and mitigating SSC risks.
• EUDA initiatives, such as the Early Warning System (EWS) and a dedicated network of laboratories, aim to enhance response capabilities.