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Molecular Psychiatry

ISSN 1476-5578

87 papers in the library · 4,043 citations · publishing 2005-2026

Papers

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Improved implicit self-esteem is associated with extended antidepressant effects following a novel synergistic intervention.

Molecular Psychiatry November 1, 2024 H Nur Eken, Crystal Spotts, Benjamin Panny et al. 1 citation

In a previously published randomized controlled trial, automated self-association training (ASAT), a novel digital intervention, was found to extend the rapid antidepressant effect of a single infusion of ketamine for at least 30 days. In this secondary analysis, we aimed to understand the potential role of implicit self-esteem in the combined antidepressant effect of ketamine and ASAT...

Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats

Molecular Psychiatry October 21, 2024 Gabriele Floris, Mary Tresa Zanda, Konrad Dabrowski et al. 19 citations

Abstract Preclinical and human studies indicate psilocybin may reduce perseverant maladaptive behaviors, including nicotine and alcohol seeking. Such studies in the opioid field are lacking, though opioids are involved in >50% of overdose deaths. Psilocybin is an agonist at the serotonin 2A receptor (5-HT 2A R), a well-documented target for modulation of drug seeking, and evidence suggests 5-HT...

Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming

Molecular Psychiatry October 11, 2024 Michal Brownstien, Michal Lazar, Alexander Botvinnik et al. 23 citations

Abstract Obsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches. Mice that carry a homozygous deletion of the SAPAP3 gene (SAPAP3 KO) manifest a phenotype of excessive self-grooming, tic-like head-body twitches...

Oral esketamine in patients with treatment-resistant depression: a double-blind, randomized, placebo-controlled trial with open-label extension.

Molecular Psychiatry September 1, 2024 Sanne Y Smith-Apeldoorn, Jolien K E Veraart, Jeanine Kamphuis et al. 23 citations

About one-third of patients with depression do not achieve adequate response to current treatment options. Although intravenous and intranasal administrations of (es)ketamine have shown antidepressant properties, their accessibility and scalability are limited. We investigated the efficacy, safety, and tolerability of generic oral esketamine in patients with treatment-resistant depression (TRD)...

Ketamine's mechanism of action with an emphasis on neuroimmune regulation: can the complement system complement ketamine's antidepressant effects?

Molecular Psychiatry September 1, 2024 Brandi Quintanilla, Carlos A. Zarate, Anilkumar Pillai 17 citations

Over 300 million people worldwide suffer from major depressive disorder (MDD). Unfortunately, only 30-40% of patients with MDD achieve complete remission after conventional monoamine antidepressant therapy. In recent years, ketamine has revolutionized the treatment of MDD, with its rapid antidepressant effects manifesting within a few hours as opposed to weeks with conventional antidepressants....

Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain.

Molecular Psychiatry July 1, 2024 Orr Shahar, Alexander Botvinnik, Amit Shwartz et al. 37 citations

Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or "full spectrum" (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL). We compared the effects...

Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms

Molecular Psychiatry April 27, 2024 Kyna Conn, L K Milton, K Huang et al. 44 citations

Abstract Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plausible that psilocybin could...

Targeting metaplasticity mechanisms to promote sustained antidepressant actions.

Molecular Psychiatry April 1, 2024 Kyle A Brown, Todd D Gould 45 citations

The discovery that subanesthetic doses of (R, S)-ketamine (ketamine) and (S)-ketamine (esketamine) rapidly induce antidepressant effects and promote sustained actions following drug clearance in depressed patients who are treatment-resistant to other therapies has resulted in a paradigm shift in the conceptualization of how rapidly and effectively depression can be treated. Consequently, the...

Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties

Molecular Psychiatry March 14, 2024 Pol Puigseslloses, Gabriel Ketsela, Nicola Weiss et al. 23 citations

Abstract Recent studies have sparked renewed interest in the therapeutic potential of psychedelics for treating depression and other mental health conditions. Simultaneously, the novel psychoactive substances (NPS) phenomenon, with a huge number of NPS emerging constantly, has changed remarkably the illicit drug market, being their scientific evaluation an urgent need. Thus, this study aims to...

Lasting dynamic effects of the psychedelic 2,5-dimethoxy-4-iodoamphetamine ((±)-DOI) on cognitive flexibility

Molecular Psychiatry February 6, 2024 Merima Šabanović, Alberto Lazari, Marta Blanco-Pozo et al. 17 citations

Abstract Psychedelic drugs can aid fast and lasting remission from various neuropsychiatric disorders, though the underlying mechanisms remain unclear. Preclinical studies suggest serotonergic psychedelics enhance neuronal plasticity, but whether neuroplastic changes can also be seen at cognitive and behavioural levels is unexplored. Here we show that a single dose of the psychedelic...

High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin

Molecular Psychiatry January 17, 2024 Dotan Braun, Ayelet M Rosenberg, Elad Rabaniam et al. 32 citations

Abstract Serotonergic psychedelics are emerging therapeutics for psychiatric disorders, yet their underlying mechanisms of action in the brain remain largely elusive. Here, we developed a wide-field behavioral tracking system for larval zebrafish and investigated the effects of psilocybin, a psychedelic serotonin receptor agonist. Machine learning analyses of precise body kinematics identified...

Synergistic psychedelic - NMDAR modulator treatment for neuropsychiatric disorders.

Molecular Psychiatry 2024 Uriel Heresco-Levy, Bernard Lerer 17 citations

Modern research data suggest a therapeutic role for serotonergic psychedelics in depression and other neuropsychiatric disorders, although psychotomimetic effects may limit their widespread utilization. Serotonergic psychedelics enhance neuroplasticity via serotonin 2 A receptors (5HT2AR) activation and complex serotonergic-glutamatergic interactions involving the ionotropic glutamate...

DNA methylation and the opposing NMDAR dysfunction in schizophrenia and major depression disorders: a converging model for the therapeutic effects of psychedelic compounds in the treatment of psychiatric illness.

Molecular Psychiatry November 1, 2023 L. Taylor Flynn, Wen-Jun Gao 14 citations

Psychedelic compounds are being increasingly explored as a potential therapeutic option for treating several psychiatric conditions, despite relatively little being known about their mechanism of action. One such possible mechanism, DNA methylation, is a process of epigenetic regulation that changes gene expression via chemical modification of nitrogenous bases. DNA methylation has been...

Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics.

Molecular Psychiatry September 1, 2023 Alaina M Jaster, Javier González-Maeso 50 citations

Psychedelics, also known as classical hallucinogens, have been investigated for decades due to their potential therapeutic effects in the treatment of neuropsychiatric and substance use disorders. The results from clinical trials have shown promise for the use of psychedelics to alleviate symptoms of depression and anxiety, as well as to promote substantial decreases in the use of nicotine and...

Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats.

Molecular Psychiatry September 1, 2023 Kat F. Kiilerich, Joe Lorenz, Malthe B. Scharff et al. 48 citations

Psilocybin (a classic serotonergic psychedelic drug) has received appraisal for use in psychedelic-assisted therapy of several psychiatric disorders. A less explored topic concerns the use of repeated low doses of psychedelics, at a dose that is well below the psychedelic dose used in psychedelic-assisted therapy and often referred to as microdosing. Psilocybin microdose users frequently report...

Neuroimaging in psychedelic drug development: past, present, and future.

Molecular Psychiatry September 1, 2023 Matthew B. Wall, Rebecca Harding, Rayyan Zafar et al. 39 citations

Psychedelic therapy (PT) is an emerging paradigm with great transdiagnostic potential for treating psychiatric disorders, including depression, addiction, post-traumatic stress disorder, and potentially others. 'Classic' serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), which have a key locus of action at the 5-HT2A receptor, form the main focus of this...

Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study.

Molecular Psychiatry September 1, 2023 Thomas Desmidt, Paul-Armand Dujardin, Frédéric Andersson et al.

Nitrous oxide (N2O) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP). Thirty participants (20 with a major...

Reducing default mode network connectivity with mindfulness-based fMRI neurofeedback: a pilot study among adolescents with affective disorder history.

Molecular Psychiatry June 1, 2023 Jiahe Zhang, Jovicarole Raya, Francesca Morfini et al. 65 citations

Adolescents experience alarmingly high rates of major depressive disorder (MDD), however, gold-standard treatments are only effective for ~50% of youth. Accordingly, there is a critical need to develop novel interventions, particularly ones that target neural mechanisms believed to potentiate depressive symptoms. Directly addressing this gap, we developed mindfulness-based fMRI neurofeedback...

Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies

Molecular Psychiatry January 20, 2023 Jie Guo, Di Qiu, Han-Wen Gu et al. 46 citations

Ketamine, a commonly used general anesthetic, can produce rapid and sustained antidepressant effect. However, the efficacy and safety of the perioperative application of ketamine on postoperative depression remains uncertain. We performed a meta-analysis to determine the effect of perioperative intravenous administration of ketamine on postoperative depression. Randomized controlled trials...

Taking subjectivity seriously: towards a unification of phenomenology, psychiatry, and neuroscience.

Molecular Psychiatry 2023 Evan J. Kyzar, George H Denfield 62 citations

Nearly all psychiatric diseases involve alterations in subjective, lived experience. The scientific study of the biological basis of mental illness has generally focused on objective measures and observable behaviors, limiting the potential for our understanding of brain mechanisms of disease states and possible treatments. However, applying methods designed principally to interpret objective...

Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation.

Molecular Psychiatry 2023 Gilly Wolf, Sandeep Singh, Karin Blakolmer et al.

Schizophrenia is a widespread psychiatric disorder that affects 0.5-1.0% of the world's population and induces significant, long-term disability that exacts high personal and societal cost. Negative symptoms, which respond poorly to available antipsychotic drugs, are the primary cause of this disability. Association of negative symptoms with cortical atrophy and cell loss is widely reported....

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators

Molecular Psychiatry September 7, 2022 Rebecca B Price, Nicholas Kissel, Andrew Baumeister et al. 80 citations

Abstract Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar...

Magical thinking in individuals with high polygenic risk for schizophrenia but no non-affective psychoses—a general population study

Molecular Psychiatry May 3, 2022 Aino Saarinen, Leo‐Pekka Lyytikäinen, Jarmo Hietala et al. 22 citations

A strong genetic background for psychoses is well-established. Most individuals with a high genetic risk for schizophrenia, however, do not develop the disorder. We investigated whether individuals, who have a high genetic risk for schizophrenia but no non-affective psychotic disorders, are predisposed to develop milder forms of deviant thinking in terms of magical thinking. Participants came...

Comments to pharmacological and behavioral divergence of ketamine enantiomers by Jordi Bonaventura et al.

Molecular Psychiatry February 17, 2022 Guang Chen, G. Mannens, Marlies de Boeck et al. 14 citations

antidepressant ef fi cacy without dissociative effects ” . Open-label study results cannot be used to establish ef fi cacy, partly because they increase the expectancy biases of both the rater and the patient, and even patients with treatment-resistant depression have shown large placebo effect sizes in trials involving various treatment modalities [17]. Thus, as indicated by Bonaventura et al.,...

Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of (R)-ketamine

Molecular Psychiatry November 24, 2021 W. Yao, Qianqian Cao, Shilin Luo et al. 208 citations

(R,S)-ketamine elicits rapid-acting and sustained antidepressant actions in treatment-resistant patients with depression. (R)-ketamine produces longer-lasting antidepressant effects than (S)-ketamine in rodents; however, the precise molecular mechanisms underlying antidepressant actions of (R)-ketamine remain unknown. Using isobaric Tag for Relative and Absolute Quantification, we identified...