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Psychedelic Drugs and Beyond
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Psychedelic Drugs and Beyond

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 November 2022) | Viewed by 24852

Special Issue Editors

Prof. Dr. Philippe De Deurwaerdere

E-Mail Website
Guest Editor
Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5287), 33076 Bordeaux CEDEX, France
Interests: monoamines; neurochemistry; addiction; Parkinson's disease; schizophrenia; neuropharmacology; mood disorders
Special Issues, Collections and Topics in MDPI journals
Dr. Franck Vandermoere

E-Mail Website
Guest Editor
IGF - Institut de Génomique Fonctionnelle, CNRS UMR 5203, Inserm U1191, Université de Montpellier, 141, rue de la Cardonille, 34094 Montpellier CEDEX 5, France
Interests: psychedelics; 5-HT2A receptors

Special Issue Information

Dear Colleagues,

Dissociative drugs, encompassing psychedelic, hallucinogenic drugs, have been the object of numerous studies to better understand their mechanisms of action. Recurrent targets of research include the N-methyl-D-aspartate glutamatergic receptors for ketamine or phencyclidine and the serotonin 2A receptor (5-HT2A receptor) subtype for serotonergic hallucinogenic drugs, including LSD25, psilocin, and mescalin, although this list can easily be implemented with kappa receptors and salvinorin-A. Interest in these molecules surpasses their powerful action on consciousness, as a growing volume of clinical and experimental data indicate their possible use in a variety of conditions including mood disorders. Some of these compounds, namely ketamin, LSD25, and psilocine, have been used in the treatment of depression, with a rapid onset action lasting for days to weeks.

It changes the “perception” we have on these powerful molecules, but their mechanism of action remains elusive. Difficulties in this field include the synthesis of new compounds and docking studies, the functional selectivity towards intracellular signalling pathways, the dimerization of receptors, addressing specific locations of neurons/glial cells, the electrophysiological responses on neurons, the short- versus long-term cell responses, their effects on neurotrophic factors, their action on specific circuits and/or neurotransmitters, and the integrative brain responses.

The purpose of this Special Issue is to collect original research articles and reviews that concern the mechanism of action of these fascinating drugs. Contributions from different fields of research are welcomed in addition to the pure molecular aspects.

Prof. Dr. Philippe De Deurwaerdere
Dr. Franck Vandermoere
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • 5-HT2A receptors
  • NMDA receptors
  • kappa receptors
  • pharmacology
  • molecular pathway
  • system interaction
  • consciousness
  • mood disorders
  • psychedelics

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Published Papers (3 papers)

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Research

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14 pages, 2978 KiB  
Communication
Transcriptomic Analysis of Glycosylation and Neuroregulatory Pathways in Rodent Models in Response to Psychedelic Molecules
by Anup M. Oommen, Katherine J. Roberts, Lokesh Joshi and Stephen Cunningham
Int. J. Mol. Sci. 2023, 24(2), 1200; https://doi.org/10.3390/ijms24021200 - 7 Jan 2023
Cited by 2 | Viewed by 2540
Abstract
The potential for psychedelic molecules in impacting cognitive flexibility has long been supported and acknowledged across scientific reports. In the current study, an approach leveraging knowledge-based gene-set information analysis has been adopted to explore the potential impact of psychedelic molecules on both glycosylation, [...] Read more.
The potential for psychedelic molecules in impacting cognitive flexibility has long been supported and acknowledged across scientific reports. In the current study, an approach leveraging knowledge-based gene-set information analysis has been adopted to explore the potential impact of psychedelic molecules on both glycosylation, (a post-translational modifications (PTM)) and on neuro-regulatory pathways. Though limitations and restrictions rise from the scarcity of publicly available ‘omics’ data, targeted analysis enabled us to identify a number of key glycogenes (Hexb, Hs6st2, Col9a2, B3gat2, Mgat5, Bgn) involved the structural organization of extracellular matrix and neuroprotective factors (Kl, Pomc, Oxt, Gal, Avp, Cartpt) which play vital roles in neuron protection, development as well as synaptic stability. In response to psychedelic molecules, we found that these genes and associated pathways are transcriptional altered in rodent models. The approach used indicates the potential to exploit existing datasets for hypothesis generation and testing for the molecular processes which play a role in the physiological response to psychedelic molecule effects. These reported findings, which focused on alterations in glycogenes and neuro-regulatory factors may provide a novel range of biomarkers to track the beneficial, as well as potential toxicological effects of psychedelic molecules. Full article
(This article belongs to the Special Issue Psychedelic Drugs and Beyond)
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20 pages, 3013 KiB  
Article
Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior
by Adam Wojtas, Agnieszka Bysiek, Agnieszka Wawrzczak-Bargiela, Zuzanna Szych, Iwona Majcher-Maślanka, Monika Herian, Marzena Maćkowiak and Krystyna Gołembiowska
Int. J. Mol. Sci. 2022, 23(12), 6713; https://doi.org/10.3390/ijms23126713 - 16 Jun 2022
Cited by 45 | Viewed by 10900
Abstract
Clinical studies provide evidence that ketamine and psilocybin could be used as fast-acting antidepressants, though their mechanisms and toxicity are still not fully understood. To address this issue, we have examined the effect of a single administration of ketamine and psilocybin on the [...] Read more.
Clinical studies provide evidence that ketamine and psilocybin could be used as fast-acting antidepressants, though their mechanisms and toxicity are still not fully understood. To address this issue, we have examined the effect of a single administration of ketamine and psilocybin on the extracellular levels of neurotransmitters in the rat frontal cortex and reticular nucleus of the thalamus using microdialysis. The genotoxic effect and density of glutamate receptor proteins was measured with comet assay and Western blot, respectively. An open field test, light–dark box test and forced swim test were conducted to examine rat behavior 24 h after drug administration. Ketamine (10 mg/kg) and psilocybin (2 and 10 mg/kg) increased dopamine, serotonin, glutamate and GABA extracellular levels in the frontal cortex, while psilocybin also increased GABA in the reticular nucleus of the thalamus. Oxidative DNA damage due to psilocybin was observed in the frontal cortex and from both drugs in the hippocampus. NR2A subunit levels were increased after psilocybin (10 mg/kg). Behavioral tests showed no antidepressant or anxiolytic effects, and only ketamine suppressed rat locomotor activity. The observed changes in neurotransmission might lead to genotoxicity and increased NR2A levels, while not markedly affecting animal behavior. Full article
(This article belongs to the Special Issue Psychedelic Drugs and Beyond)
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Review

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14 pages, 661 KiB  
Review
Esketamine and Psilocybin—The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review
by Dominika Psiuk, Emilia Magdalena Nowak, Natalia Dycha, Urszula Łopuszańska, Jacek Kurzepa and Marzena Samardakiewicz
Int. J. Mol. Sci. 2022, 23(19), 11450; https://doi.org/10.3390/ijms231911450 - 28 Sep 2022
Cited by 13 | Viewed by 10147
Abstract
This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment—psilocybin and esketamine. The former is a naturally occurring psychedelic. The latter was invented in the laboratory exactly 60 years ago. Although the substances [...] Read more.
This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment—psilocybin and esketamine. The former is a naturally occurring psychedelic. The latter was invented in the laboratory exactly 60 years ago. Although the substances were controversial in the past, recent studies indicate the potential of those substances as novel antidepressant agents. The PubMed/MEDLINE database was used to identify articles for systematic review, using the following search terms: (depression) AND (psilocybin) OR (ketamine). From 617 items, only 12 articles were obtained in the final analyses. Three articles were devoted to psilocybin in depression treatment and nine to esketamine. In most studies, esketamine showed a significant reduction in both depressive symptoms and suicidal ideation shortly after intake and after a month of treatment compared to baseline and to standard-of-care antidepressant agents. Psilocybin’s antidepressive effects occurred one day after intake and after 6–7 weeks of treatment and were maintained for up to 6 or 8 months of follow-up. One study indicated that psilocybin’s effects are comparable with and may be superior to escitalopram treatment. Both esketamine and psilocybin demonstrated rapid and long-term effects in reducing depression symptoms and, after overcoming some limitations, may be considered as novel antidepressant agents in future. Full article
(This article belongs to the Special Issue Psychedelic Drugs and Beyond)
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