(1)H Nuclear Magnetic Resonance: A Future Approach to the Metabolic Profiling of Psychedelics in Human Biofluids?

While psychedelics may have therapeutic potential for treating mental health disorders such as depression, further research is needed to better understand their biological effects and mechanisms of action when considering the development of future novel therapy approaches. Psychedelic research could potentially benefit from the integration of metabonomics by proton nuclear magnetic resonance ((1)H NMR) spectroscopy which is an analytical chemistry-based approach that can measure the breakdown of drugs into their metabolites and their metabolic consequences from various biofluids. We have performed a systematic review with the primary aim of exploring published literature where (1)H NMR analysed psychedelic substances including psilocin, lysergic acid diethylamide (LSD), LSD derivatives, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and bufotenin. The second aim was to assess the benefits and limitations of (1)H NMR spectroscopy-based metabolomics as a tool in psychedelic research and the final aim was to explore potential future directions. We found that the most current use of (1)H NMR in psychedelic research has been for the structural elucidation and analytical characterisation of psychedelic molecules and that no papers used (1)H NMR in the metabolic profiling of biofluids, thus exposing a current research gap and the underuse of (1)H NMR. The efficacy of (1)H NMR spectroscopy was also compared to mass spectrometry, where both metabonomics techniques have previously shown to be appropriate for biofluid analysis in other applications. Additionally, potential future directions for psychedelic research were identified as real-time NMR, in vivo (1)H nuclear magnetic resonance spectroscopy (MRS) and (1)H NMR studies of the gut microbiome. Further psychedelic studies need to be conducted that incorporate the use of (1)H NMR spectroscopy in the analysis of metabolites both in the peripheral biofluids and in vivo to determine whether it will be an effective future approach for clinical and naturalistic research.