1H 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 (1H 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 1H 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 1H 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 1H NMR in psychedelic research has been for the structural elucidation and analytical characterisation of psychedelic molecules and that no papers used 1H NMR in the metabolic profiling of biofluids, thus exposing a current research gap and the underuse of 1H NMR. The efficacy of 1H 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 vivo1H nuclear magnetic resonance spectroscopy (MRS) and 1H NMR studies of the gut microbiome. Further psychedelic studies need to be conducted that incorporate the use of 1H 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.

Bibliometric Analysis of Academic Journal Articles Reporting Results of Psychedelic Clinical Studies

After a decades long period of investigational dormancy, there is renewed interest in employing psychedelics as treatments for mental illness and addiction. The academic journals, journal articles, academic institutions, and countries that have helped sustain clinical psychedelic research and the evolution of the literature on clinical studies of psychedelic compounds have only been minimally investigated. Therefore, in we conducted a bibliometric analysis of clinical studies of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), ayahuasca, dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), ibogaine, mescaline, 3,4-methylenedioxymethamphetamine (MDMA), and psilocybin published from 1965-2018. Our search revealed 320 articles published across 106 journals. After a nearly quarter century lull between the 1970s and 1990s, publications in this area have resurged over the last two decades and continue on an upward trajectory, with most clinical studies now focusing on LSD, MDMA, and psilocybin. A subanalysis of the ten most cited articles in psychedelic research prior to 2010 and afterwards demonstrated a shift from research on risks of psychedelics, primarily those of MDMA, to research on therapeutic applications, predominantly those of psilocybin. We also conducted network analyses of inter-country collaborations in psychedelic research, which suggested that psychedelic researchers in the United Kingdom have more diverse international collaborations.

Co-design of Guidance for Patient and Public Involvement in Psychedelic Research

Within the context of scientific research, patient and public involvement (PPI) is defined as research performed “with” or “by” patients and members of the public, rather than “to,” “about”, or “for” them. When carried out systematically and thoughtfully, PPI has the potential to strengthen the quality and impact of research by fostering accountability, transparency, and relevance. There exist numerous guidelines, frameworks and tools for supporting PPI, however, these do not account for the unique challenges faced in psychedelic research. This paper describes the co-design of guidance intended to help build, evaluate and improve PPI in psychedelic research. A steering group was formed to design and run a co-design workshop alongside public collaborators. Insights from this workshop were analyzed and refined into a comprehensive and readily usable guide for planning PPI specific to the field of psychedelic research. Core values emerging from the process focused on the essential importance of trust, learning, purpose and inclusivity. It is hoped that this guidance will be a starting point for incorporating PPI in future psychedelic research, so that it can grow and adapt as this burgeoning field of research progresses.

Research abuses against people of colour and other vulnerable groups in early psychedelic research

There is a growing resurgence in the study of psychedelic medicines for the treatment of mental health and substance use disorders. However, certain early investigations are marred by questionable research methods, abuses against research participants, and covert Central Intelligence Agency financial involvement. The purpose of this study was to understand how and to what extent people of colour and other vulnerable populations, specifically, individuals who were incarcerated or incapacitated due to mental health issues (inpatients with psychotic disorders), were exploited during the first wave of psychedelic research in the USA (1950–1980). To do so, we reviewed available empirical publications according to current ethical standards. Variables of interest included race and ethnicity of participants, population vulnerability, drug administration conditions, informed consent and undue influence. Our findings draw attention to the history of research abuses against people of colour in Western psychedelic research. In light of these findings, we urge a call-to-action to current psychedelic researchers to prioritise culturally inclusive and socially responsible research methods in current and future studies.

Spirituality

‘Spirituality’ examines the import of psychedelic evidence for the philosophical project of naturalising spirituality. This chapter argues that psychedelic research vindicates the claim that there are transformative experiences and practices that can legitimately be called ‘spiritual’ and are compatible with adherence to a naturalistic worldview. The existential transformation afforded by some psychedelic experiences provides a paradigm for naturalistic spirituality: the temporary suspension of our default, self-referential mode of cognition, making available experiences of connectedness and feelings of wonder and awe. Jerome Stone (2012) has reviewed recent philosophical work on naturalistic spirituality and extracted some core ideas: notably (i) that spirituality is about connection, aspiration, and asking the Big Questions, and (ii) that these are all ways of overcoming the limitations of the ordinary sense of self. This chapter argues that psychedelic evidence supports these claims, as well as the further claim that such experiences and practices are independent of non-naturalistic metaphysical ideations.