CNS Spectrums
March 10, 2026
Halima Faisal, Gia Han Le, Angela T H Kwan et al.
Background: Anhedonia and reward-processing deficits are core features of major depressive disorder (MDD) that respond poorly to traditional antidepressants.Ketamine has rapid antidepressant effects, yet its neurofunctional actions within reward circuits remain unclear.We synthesized human neuroimaging evidence on ketamine-related modulation of reward circuitry and implications for...
CNS Spectrums
August 12, 2025
Gia Han Le, Sabrina Wong, Stavroula Bargiota et al.
3 citations
G protein-coupled receptors (GPCRs) are involved in many physiological and pathophysiological processes. Conventional pharmacological models categorize the typology of pharmacologic ligands as agonists or antagonists. Biased agonism is a relatively newer pharmacodynamic characteristic that has potential to optimize therapeutic efficacy while minimizing adverse effects in psychiatric and...
CNS Spectrums
June 30, 2025
Jose-Manuel Quintero, Rosa-Helena Bustos, Sharon Lechtig-Wassermann et al.
6 citations
Ketamine, originally synthesized in 1962, has gained increasing attention due to its rapid and sustained antidepressant effects in treatment-resistant depression (TRD). Unlike traditional antidepressants, ketamine acts on multiple neurotransmitter systems, including NMDA receptor antagonism and AMPA receptor potentiation, offering a novel mechanism for mood regulation. Beyond psychiatry,...
CNS Spectrums
January 30, 2025
Steve O'Brien, David Nutt
5 citations
This chapter explores the complex and controversial path of MDMA-assisted therapy (MDMA-AT) for treating post-traumatic stress disorder (PTSD) and other behavioral disorders. It covers MDMA's history from research to recreation to medicine, the pivotal trials, and the challenges faced by researchers. Despite recent setbacks for the clinical application of MDMA, the chapter argues that it holds...
CNS Spectrums
January 17, 2025
Roger S McIntyre, Gregory W Mattingly, Yordan Godinov et al.
9 citations
Esketamine nasal spray (ESK) is approved in combination with an oral antidepressant (OAD) for the treatment of adults with treatment-resistant depression (TRD); however, direct comparisons with atypical antipsychotics for TRD are limited. This secondary analysis of the ESCAPE-TRD study compared rates of remission and response, and improvements in depressive symptoms over time, between ESK and...
CNS Spectrums
2025
Emma O’leary, Seetal Dodd, Stephen M Stahl
Psychoactive substances, known for their acute impact on perception and cognition, are gaining attention for their potential therapeutic applications. Many of these substances are plant-derived with deep-rooted histories of use in non-medical contexts, where they have been viewed as either tools for social cohesion or sources of discord, depending on cultural and societal contexts. This review...
CNS Spectrums
2025
Mathieu Fradet, Cecelia Kelly, Anna Donnelly et al.
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CNS Spectrums
2025
Ana Rodríguez Lorente, María Pilar Campos-Navarro, Ángela Gil Montoya et al.
Abstract Objectives This proof-of-concept study aimed to assess the impact of intranasal esketamine (ESK-IN) in brain volume and neurofilament light chain (sNfL) over 6-months in patients with treatment resistant depression (TDR). Methods Seven TRD patients received ESK-IN while continuing oral antidepressants. Clinical evaluations were conducted at baseline, 1, 3, and 6 months, with MRI scans...
CNS Spectrums
December 12, 2024
Alberto Carrara
2 citations
This article presents a comprehensive neuroethical framework that seeks to deepen our understanding of human consciousness and free will, particularly in the context of psychiatric and neurological disorders. By integrating insights from neuroscience with philosophical reflections on freedom and personal identity, the paper examines how various states of consciousness from interoception to...
CNS Spectrums
December 1, 2024
Mathieu Fradet, Carlton M Kelly, Anna Donnelly et al.
10 citations
Psilocybin therapy has recently emerged as a promising new treatment for depression and other mental health disorders. This chapter summarizes the most recent data on its safety and efficacy. The delivery of psilocybin therapy and its subjective effects are also presented. Furthermore, this chapter outlines our current understanding of psilocybin's pharmacology and neurobiological effects....
CNS Spectrums
December 1, 2024
Mauro Scala, Chiara Fabbri, Paolo Fusar‐poli et al.
8 citations
The revival of psilocybin in psychopharmacological research heralds a potential paradigm shift for treating mood and anxiety disorders, and other psychiatric conditions beyond the psychotic spectrum. This critical review evaluates current evidence on psilocybin's efficacy, juxtaposing potential benefits with the practical aspects of psychedelic-assisted psychotherapy (PAP) and the...
CNS Spectrums
November 21, 2024
Elena Koning, Elvina M Chu, Elisa Brietzke
5 citations
Psychedelics are a group of psychoactive substances that alter consciousness and produce marked shifts in sensory perception, cognition, and mood. Although psychedelics have been used by indigenous communities for centuries, they have only recently been investigated as an adjunctive therapeutic tool in psychotherapy. Since the early twentieth century, psychedelic-assisted psychotherapy has been...
CNS Spectrums
November 20, 2024
Rafael Guimarães Dos Santos, Jaime Eduardo Cecilio Hallak
13 citations
Ayahuasca is a botanical hallucinogen traditionally used for therapeutic and ritual purposes by indigenous groups from Northwestern Amazonian countries such as Brazil, Peru, Colombia, and Ecuador. Ayahuasca is made by the decoction of two plants, which are rich in the 5-HT1A/2A partial agonist dimethyltryptamine or DMT (from the leaves of the Psychotria viridis bush) and β-carbolines such as...
CNS Spectrums
November 20, 2024
Angela T H Kwan, Moiz Lakhani, Gurkaran Singh et al.
4 citations
Inadequate response to first- and second-line pharmacological treatments for psychiatric disorders is commonly observed. Ketamine has demonstrated efficacy in treating adults with treatment-resistant depression (TRD), with additional off-label benefits reported for various psychiatric disorders. Herein, we performed a systematic review and meta-analysis to examine the therapeutic applications...
CNS Spectrums
October 31, 2024
Sabrina Wong, Gia Han Le, Angela T H Kwan et al.
10 citations
Postpartum depression (PPD), now referred to as perinatal depression, is a prevalent and debilitating mood disorder that reduces health-related quality of life (HRQoL) and psychosocial functioning. Esketamine, which is efficacious in adults with treatment-resistant depression and individuals with depression and suicidality, is also analgesic in pain management during childbirth labour. Herein,...
CNS Spectrums
October 1, 2024
Angela T.H. Kwan, Roger S. McIntyre
AbstractObjectiveDextromethorphan/bupropion (DXM/BUP) received Food and Drug Administration (FDA) approval for the treatment of adults with major depressive disorder (MDD) in August 2022. This combination is not known to have abuse liability and is not currently scheduled by the Drug Enforcement Administration (DEA). Notwithstanding, dextromethorphan is a drug of abuse. Herein, we sought to...
CNS Spectrums
June 1, 2024
Jennifer Kern Sliwa, Ronaldo R Naranjo, Ibrahim Turkoz et al.
5 citations
To examine the effect of esketamine nasal spray (ESK) plus newly initiated oral antidepressant (OAD) versus OAD plus placebo nasal spray (PBO) on the association between Montgomery-Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) scores in adults with treatment-resistant depression (TRD). Data from TRANSFORM-1 and TRANSFORM-2 (two similarly designed,...
CNS Spectrums
April 1, 2023
Amanda Jones, Roger S McIntyre, Mark Jacobsen et al.
AbstractBackgroundTreatments for MDD that can improve both overall depressive and anhedonic symptoms are urgently needed.AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity being developed for MDD. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of...
CNS Spectrums
April 1, 2023
Amanda Jones, Caroline Streicher, Shawn Alter et al.
AbstractBackgroundIn STAR*D, following non-remission with an SSRI, remission rates for second-line treatments were ~ 25%, regardless of the switch strategy employed. Antidepressants with novel mechanisms may improve outcomes in MDD. AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) is a novel, oral, investigational, NMDA receptor antagonist with multimodal activity. The dextromethorphan...
CNS Spectrums
April 1, 2023
Amanda Jones, Caroline Streicher, Shawn Alter et al.
AbstractBackgroundAXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational, NMDA receptor antagonist with multimodal activity being developed for MDD. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.MethodsAXS-05 was...
CNS Spectrums
April 1, 2023
Amanda Jones, Caroline Streicher, Shawn Alter et al.
AbstractBackgroundInnovative therapies to treat individuals with MDD, especially those with comorbid anxiety, are urgently needed.AXS-05 (dextromethorphan HBr 45 mg-bupropion HCl 105 mg) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion...
CNS Spectrums
July 29, 2022
Ibrahim Turkoz, Oliver Lopena, Giacomo Salvadore et al.
6 citations
Abstract Objective To assess the likelihood of attaining response/remission of depressive symptoms with esketamine nasal spray (ESK) plus standard of care (SoC) vs placebo nasal spray (PBO) plus SoC at 4 weeks in patients with major depressive disorder and active suicidal ideation with intent (MDSI) without early response. Methods A post hoc analysis of pooled data from ASPIRE I and ASPIRE II...
CNS Spectrums
July 11, 2022
Seetal Dodd, Trevor R. Norman, Harris A. Eyre et al.
61 citations
Abstract Psilocybin is a tryptamine alkaloid found in some mushrooms, especially those of the genus Psilocybe. Psilocybin has four metabolites including the pharmacologically active primary metabolite psilocin, which readily enters the systemic circulation. The psychoactive effects of psilocin are believed to arise due to the partial agonist effects at the 5HT2A receptor. Psilocin also binds to...
CNS Spectrums
September 30, 2021
Xénia Gonda, Péter Döme, Joanna C. Neill et al.
77 citations
Abstract Treatment of major depressive disorder (MDD) including treatment-resistant depression (TRD) remains a major unmet need. Although there are several classes of dissimilar antidepressant drugs approved for MDD, the current drugs have either limited efficacy or are associated with undesirable side effects and withdrawal symptoms. The efficacy and side effects of antidepressant drugs are...
CNS Spectrums
April 1, 2021
Steve Best, Dan G. Pavel, Natalie Haustrup
1 citation
AbstractBackgroundRepetitive transcranial magnetic stimulation (rTMS) is a safe, effective and non-invasive treatment for many psychiatric illnesses, including treatment-resistant depression (TRD). Ketamine, an NMDA receptor antagonist, is also an effective antidepressant. This retrospective review examined the clinical benefits of combining these two established treatments for patients...