Functional effects of synthetic cannabinoids versus Δ9 -THC in mice on body temperature, nociceptive threshold, anxiety, cognition, locomotor/exploratory parameters and depression.

Synthetic cannabinoids are psychoactive substances designed to mimic the euphorigenic effects of the natural cannabis. Novel unregulated compounds appear once older compounds become illegal. It has been previously reported that synthetic cannabinoids are different than Δ9 -tetrahydrocannabinol (Δ9 -THC) as they have chemical structures unrelated to Δ9 -THC, different metabolism and, often, greater toxicity. This study aimed to investigate the effects of three novel synthetic cannabinoids and pure Δ9 -THC on body temperature, nociceptive threshold, anxiety, memory function, locomotor and exploratory parameters, and depression. We performed a battery of behavioural and motor tests starting 50 minutes post i.p. injection of each drug to adult ICR mice. The synthetic cannabinoids that were used are AB-FUBINACA, AB-CHMINACA and PB-22. All synthetic cannabinoids and Δ9 -THC caused hypothermia, but only Δ9 -THC induced a clear antinociceptive effect. All synthetic cannabinoids and Δ9 -THC caused decreased anxiety levels, spatial memory deficits and decreased exploratory behaviour as measured in the elevated plus maze, Y-maze and staircase paradigm, respectively. However, all synthetic cannabinoids but not Δ9 -THC demonstrated decreased locomotor activity in the staircase test. Moreover, only AB-FUBINACA and Δ9 -THC affected the gait balance and grip strength of the mice as was assessed by the latency time to fall from a rod. In the forced swimming test, PB-22 caused elevated depression-like behaviour while AB-FUBINACA induced a reversed effect. These results suggest varied effects among different synthetic cannabinoids and Δ9 -THC. Further studies are needed to characterize the overall effects and differences between these synthetic cannabinoids and Δ9 -THC.

Discrimination between closely related synthetic cannabinoids by GC-Cold-EI-MS.

Gas chromatography thermal-electron ionization mass spectrometry (GC-EI-MS) is an established method for the identification of mind-altering substances and is routinely used by forensic laboratories. However, some commonly analyzed drugs of abuse, relating to the synthetic cannabinoids receptor agonist group (SCs), pose a challenge for this conventional technique. As the molecular cation radicals of many excited SCs are labile within the ion source, the relative abundance of the molecular ions obtained by the GC-EI-MS is often too small to allow discrimination of structurally related drugs. In contrast, the cold-electron ionization (cold-EI) method allows the enhancement and clear identification of the molecular ions, while maintaining the ability to compare unknown analytes with comprehensive mass spectrum libraries. This technique was explored for mass-spectrometric identification and unambiguous differentiation of 15 emerging synthetic cannabinoids found on the drug market in Israel and elsewhere. The current method was demonstrated to discriminate pairs of closely related SCs: FUB-PB-22 and FDU-PB-22, and 5F-PB-22 and NM-2201. In addition, the dependence of the molecular ion enhancement on the cold-EI parameters was examined. Finally, analysis of SCs from seized street samples provided by the Israeli police demonstrates the enhanced identification power of GC-cold-EI-MS.