Biocompatible SPME Probes for in Vivo and ex Vivo Profiling of Endo- and Phytocannabinoids in Blood and Brain Samples: Metabolism, Pharmacokinetics, and Analytical Challenges

In recent years, there has been increasing interest in research on the endocannabinoid system, which plays a crucial role in maintaining physiological homeostasis. This system includes CB1 and CB2 receptors, endogenous ligands such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and enzymes involved in their metabolism. Endocannabinoids, lipid-based neurotransmitters derived from omega-6 fatty acids, regulate processes such as memory, motor activity, energy balance, and appetite control. In addition to these endogenous compounds, plant-derived cannabinoids (phytocannabinoids), such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), interact with the endocannabinoid system. These molecules exert pharmacological effects, including analgesic and neuroprotective actions, and are metabolized primarily in the liver by CYP450 isoenzymes following oral administration. A key step in studying endo- and phytocannabinoids involves their isolation and quantification. However, their low stability, adsorption tendency, and trace-level presence in biological matrices require highly sensitive analytical methods. In this study, biocompatible probes were used for solid-phase microextraction (SPME) of endo- and phytocannabinoids from blood (in vivo) and brain samples (ex vivo) of rats after the administration of capsules containing CBD or THC rich plant material. SPME coupled with liquid chromatography–tandem mass spectrometry (LC-MS/MS) facilitated efficient isolation and monitoring of AEA, 2-AG, CBD, THC, and their metabolites up to 6 hrs after administation of cannabis-based medicines. The obtained results provided important insights into the pharmacokinetic profiles of THC and CBD, as well as temporal variations in endocannabinoid levels in blood and brain tissue. These findings contribute to a better understanding of cannabinoid metabolism and their mechanisms of action, supporting further research into their potential therapeutic applications in medicine.