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Advances in the Pharmacology of Depression and Mood Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 31 May 2026 | Viewed by 357

Special Issue Editor


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Guest Editor
Team P3TN, INCIA, CNRS UMR 5287, Bâtiment BBS, 2 rue du Dr Hoffmann-Martinot, 33076 Bordeaux, France
Interests: neuropharmacology; serotonergic system; antidepressant research; rapid antidepressant treatments, neuroplasticity; hippocampus; brain circuitries
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Special Issue Information

Dear Colleagues,

Recently, the field of depression and mood disorders has been characterized by the emergence of several new avenues of research. This development mainly began with studies showing that ketamine, administered at a low, subanaesthetic dose, can relieve the symptoms of some depressed patients with an impressive rapidity of action when compared to the canonical classes of antidepressant molecules. This discovery paved the way for new hypotheses, and subsequently a number of innovative concepts have been developed, especially for the purpose of achieving fast-acting treatments. One of the most illustrative examples probably resides in the current trials conducted with other psychedelic drugs, such as LSD or psylocibin. Additional paths of research have arisen, including the role played by the different types of glutama-tergic receptors in the regulation of neurotransmission and synaptic plasticity within brain regions involved in mood control. Still, in parallel, researchers have also focused on the serotonergic (5-HT) system, more classically studied, and new targets have been identified among the different 5-HT receptors (e.g., the 5-HT4 and 5-HT6 types).

Due to this conceptual development, the theories that have been proposed up to this point to address the neuropharma-cology of depression and mood disorders, such as the “plastic hypothesis” or “the serotonergic/aminergic theory”, need to be revisited and/or challenged. For instance, the role played by 5-HT and other monoamines in the therapeutic poten-tial of psychedelics remains virtually unknown, and, similarly, the ability of 5-HT pharmacological agents to modulate the neuroplastic and circuit changes induced by these same compounds has not yet been studied. This Special Issue welcomes both research papers and reviews addressing these points by proposing new mechanisms of action and/or hypotheses. Studies presenting potential new targets are also encouraged. 

Dr. Guillaume Lucas
Guest Editor

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Keywords

  • new antidepressants
  • rapid antidepressant action
  • ketamine in depression
  • glutamatergic antidepressants
  • psychedelics in depression
  • 5-HT receptors as targets for antidepressant research
  • neu-roplasticity and antidepressant action

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Published Papers (1 paper)

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Review

48 pages, 4777 KB  
Review
Predictors of the Effectiveness of Psychedelics in Treating Depression—A Scoping Review
by James Chmiel and Filip Rybakowski
Int. J. Mol. Sci. 2026, 27(5), 2202; https://doi.org/10.3390/ijms27052202 - 26 Feb 2026
Viewed by 194
Abstract
Psychedelic-assisted therapies (PATs) can produce rapid and sustained antidepressant effects, yet variability in response remains substantial. Identifying predictors and moderators is essential for optimising patient selection, preparation, and delivery. To map and synthesise the evidence on the predictors of antidepressant response to classic/serotonergic [...] Read more.
Psychedelic-assisted therapies (PATs) can produce rapid and sustained antidepressant effects, yet variability in response remains substantial. Identifying predictors and moderators is essential for optimising patient selection, preparation, and delivery. To map and synthesise the evidence on the predictors of antidepressant response to classic/serotonergic psychedelics administered with psychotherapeutic support in adults with depressive disorders, including treatment-resistant depression. Following PRISMA-ScR principles, we conducted a scoping review of major biomedical and psychology databases (PubMed (MEDLINE), Embase, PsycINFO, and Web of Science) and trial registries (searches September–October 2025), supplemented by reference-list screening. We included randomised trials, open-label studies, and naturalistic cohorts reporting associations between candidate predictors (baseline traits/clinical features, set/setting variables, acute in-session phenomenology, and biological measures) and validated depression outcomes. We charted study characteristics, analytic approaches (including moderation/mediation where available), and indicators of robustness (e.g., adjustment for overall intensity, preregistration, external validation). A total of 48 studies were included in the review. Across study designs, process-level features during the dosing session were the most consistent correlates of antidepressant improvement. Greater emotional breakthrough, mystical/unitive experiences, and ego dissolution-linked reappraisal/insight generally predicted larger and more durable symptom reductions, whereas anxiety-dominant or dysphoric states tended to attenuate benefit, often independent of overall subjective intensity. Set and setting—particularly a stronger therapeutic alliance and music experienced as resonant—predicted both the emergence of therapeutically salient acute experiences and downstream clinical gains. Baseline moderators showed smaller and mixed effects: PTSD comorbidity sometimes weakened trajectories; extensive prior psychedelic exposure was associated with smaller incremental gains; demographics were typically uninformative. Converging biological findings associated better outcomes with markers consistent with increased neural flexibility and plasticity (e.g., less segregated network dynamics; EEG indices), alongside peripheral changes implicating neurotrophic, inflammatory, and HPA axis pathways. Current evidence suggests that antidepressant response in PATs is driven less by static patient characteristics and more by what occurs during dosing and how the context shapes that experience. Optimising preparation, alliance, and music; facilitating emotional breakthrough and meaning making; and mitigating anxious dysregulation are actionable levers. Future trials should harmonise measures, pre-specify and validate moderators/mediators, intensively sample in-session experience and physiology, and report benefits and harms more consistently. Full article
(This article belongs to the Special Issue Advances in the Pharmacology of Depression and Mood Disorders)
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