Present and future of metabolic and metabolomics studies focused on classical psychedelics in humans

Nov 9, 2023Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Current and future research on metabolism and chemical markers in humans using classic psychedelics

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Abstract

Metabolic studies have robustly established the main metabolites for classical psychedelics.

Psychedelics may induce a marked altered state of consciousness.
Further investigation is needed to understand their biological effects and mechanisms of action in humans.
Metabolomics studies could help clarify the biological processes underlying the psychedelic state.
Metabolic and metabolomics research progresses at different speeds, with metabolites well-established but metabolic alterations needing further exploration.
Integration of metabolomics and pharmacokinetics may enhance understanding of the therapeutic role of psychedelics.

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Psychedelics are classical hallucinogen drugs that induce a marked altered state of consciousness. In recent years, there has been renewed attention to the possible use of classical psychedelics for the treatment of certain mental health disorders. However, further investigation to better understand their biological effects in humans, their mechanism of action, and their metabolism in humans is needed when considering the development of future novel therapeutic approaches. Both metabolic and metabolomics studies may help for these purposes. On one hand, metabolic studies aim to determine the main metabolites of the drug. On the other hand, the application of metabolomics in human psychedelics studies can help to further understand the biological processes underlying the psychedelic state and the mechanisms of action underlying their therapeutic potential. This review presents the state of the art of metabolic and metabolomic studies after lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT) and β-carboline alkaloids (ayahuasca brew), 5-methoxy-DMT and psilocybin administrations in humans. We first describe the characteristics of the published research. Afterward, we reviewed the main results obtained by both metabolic and metabolomics (if available) studies in classical psychedelics and we found out that metabolic and metabolomics studies in psychedelics progress at two different speeds. Thus, whereas the main metabolites for classical psychedelics have been robustly established, the main metabolic alterations induced by psychedelics need to be explored. The integration of metabolomics and pharmacokinetics for investigating the molecular interaction between psychedelics and multiple targets may open new avenues in understanding the therapeutic role of psychedelics.

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Present and future of metabolic and metabolomics studies focused on classical psychedelics in humans

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