Forensic profiling of synthetic and semi-synthetic cannabinoids in legal cannabis products in Italy.

Semi-synthetic cannabinoids (SSCs) have recently emerged on the new psychoactive substances (NPS) market, alongside the availability of cannabidiol (CBD)-enriched products with low-Δ9-tetrahydrocannabinol (Δ9-THC). SSCs are typically produced by chemical modification of CBD and Δ9-THC, unlike synthetic cannabinoids (SCs), and pose additional challenges for forensic toxicology and public health. The aim of the present study is to provide empirical data on the presence and approximate amounts of SSCs and SCs in low-Δ9-THC products, available online from Italian websites. Twenty-six products, including cannabis flowers, vape-liquids and resins, were purchased between September 2024 and January 2026. Products were analyzed at the Institute of Legal Medicine of Bologna, Italy, by gas chromatrography mass spectrometry (GC-MS) and high-resolution mass spectrometry (HRMS), providing quantitative percentages of Δ9-THC, CBD and approximate amounts of SSCs or SCs. All samples contained CBD (median 7.8%) and Δ9-THC (median 0.4%), including 2 samples with Δ9-THC > 0.6%. H4CBD was the most frequently detected SSC (23.1% of all samples), followed by Δ9-THCP (19.2%) and Δ8-THCP (15.4%). SCs were detected in 4 products, consisting of EDMB-4en-PINACA in 3 cases (11.5% of samples). HRMS enabled confirmation of SSCs when approximated GC-MS amounts exceeded 0.25%. Overall, 92.3% of products were mislabelled. Our results highlight the chemical complexity and widespread mislabelling of legal cannabinoid products circulating on the Italian market. A coordinated response, including improved analytical methods, standardized testing and continued market surveillance, is needed to properly respond to the evolving landscape of SCs and SSCs in consumer products.