The glutamatergic system, particularly N-methyl-D-aspartate (NMDA) receptors, has long been a significant focus of research into new strategies for treating depression, and the clinical success of ketamine, an NMDA receptor antagonist, has been a significant breakthrough. In parallel, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, another key component of the...
Suicide, the individual desire to take one's own life, at whose core lies the unbearable psychological pain Shneidman called psychache, is a uniquely human experience. Unlike depression, suicidality has no preclinical analog. Suicidality and chronic depression, long treated as a single clinical entity, are increasingly recognized as partly separable in neurobiology and treatment response....
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition in which prenatal stress and long-lasting disruptions of excitatory-inhibitory (E/I) balance have been implicated as key vulnerability factors. Although established pharmacological and behavioral treatments are effective for many individuals, they are not universally successful and do not directly target...
Dominant psychedelic frameworks have been developed primarily from acute-phase neuroimaging and emphasize transient network reconfiguration during the drug state. Less attention has been given to the post-acute period, during which consequential electrophysiological and clinical changes may unfold. Ibogaine, whose human evidence is restricted to the post-acute window, provides a particularly...
Substance use and behavioral addictions are escalating on a global scale. The Global Burden of Disease Study underscores a rising impact on disability-adjusted life years attributable to substance use. This challenge influences families, communities, healthcare infrastructure, and legal systems; nevertheless, the majority of individuals suffering from substance use disorders face challenges in...
Introduction MM120 (lysergide D-tartrate, a formulation of LSD) is under development as a potential treatment for generalized anxiety and major depressive disorders. How psychedelic drugs interact at the TrkB receptor, a key target of neuroplasticity, is not reported. Objectives The study evaluated binding and functional activity of known serotonergic psychedelic compounds and SRI fluoxetine at...
Long-chain polyunsaturated fatty acids (LC-PUFAs) are crucial for brain development, with ω-3 species supporting neuronal membrane architecture, synaptogenesis and cognitive maturation, and ω-6 species linking lipid metabolism to neuronal signalling via the endocannabinoid system (ECS), the network of receptors, lipid mediators, and enzymatic pathways that orchestrate neurodevelopmental...
A proportion of patients with obsessive-compulsive disorder (OCD) continue to experience disabling symptoms despite standard serotonergic treatment, antipsychotic augmentation, and psychological input. Contamination-focused OCD can be especially persistent when rituals are embedded in the home environment and reinforced by family patterns. Recent work has drawn attention to glutamatergic...
Asian Journal of PsychiatryJune 1, 2026Hariprasad Ganapathy Vijayakumar, Varsha Shamanna, Harsh Pathak et al.1 citation
Treatment resistance in bipolar depression is one of the most challenging clinical conditions to treat in psychiatry. We present a case of an elderly gentleman with chronic Multi-Therapy Resistant Bipolar Depression (MTRBD), where ketamine, a preferential NMDAR blocker on cortical GABAergic interneurons, is used adjunctively with sequential theta burst stimulation (sTBS) to achieve remission....
Major depressive disorder remains a leading cause of disability, and decades of monoamine-centered pharmacology have yielded delayed and often incomplete relief. Rapid-acting antidepressants reshaped the field by linking swift symptom improvement to glutamatergic plasticity, yet durable benefit depends on how newly reconfigured circuits are stabilized and tuned. This review synthesizes evidence...
Brain StimulationMay 21, 2026Lucas Dwiel, Mackenzi L. Prina, Elise Bragg et al.
A leading theory for how psychedelics are able to produce robust clinical improvement and preclinical behavioral changes is that psychedelics act through neuroplastic mechanisms to induce lasting structural and functional alterations in neural circuits. However, psychedelics produce these effects across wide swaths of the brain. Based on our prior work, we hypothesized that engaging a specific...
First-line dictionary definitions of ‘plasticity’ describe it as the ability (of a thing) to be shaped or molded; we call this ‘plasticity proper’. In neuroscience, however, ‘neural plasticity’ or ‘neuroplasticity’ is defined as an induced change in brain function or structure. These two plasticities are not the same. Several (but not all) popular biomarkers of neuroplasticity index part of an...
Pranayama, the Yogic discipline of regulated breathing, has evolved from a spiritual practice into a scientifically recognized method for supporting mental and neurological health. This chapter examines its neuroplastic potential by outlining effects on major brain regions and networks, while summarizing key Pranayama techniques and their physiological signatures. Evidence indicates...
The clinical trial NCT03866252 investigates the antidepressant effects of lysergic acid diethylamide (LSD) in 61 patients with major depressive disorder (MDD) randomized to low-dose LSD (LD-LSD; 2 × 25 μg) or moderate-to-high-dose LSD (HD-LSD; 100 μg followed by 200 μg) 4 weeks apart. Although the trial reports positive clinical outcomes, underlying mechanisms remain unclear. Here, we test...
NeurorehabilitationMay 1, 2026Paul Olowoyo, Adefolarin Malomo, Kehinde Adigun et al.
BackgroundSpirituality is an essentially universal human experience and is incorporated into concepts of health and well-being in many cultures. The spiritual domain of quality of life, spared in the disability paradox, may be harnessed for recovery through internal adaptation and coping skills. This can help the individual attain his/her full potential while optimizing health-related quality...
Background/Objectives: Mindfulness-based interventions (MBIs) have been linked to psychological and cognitive benefits, yet evidence for their impact on brain structure remains sparse. Neuroimaging suggests MBIs may alter gray matter volume (GMV), density (GMD), and cortical thickness (CT). The purpose of this scoping review was to investigate structural neuroplasticity following MBIs. Methods:...
Depression is driven by dysfunction in discrete neural circuits, but a deeper understanding of the underlying molecular and synaptic mechanisms is needed to guide the development of therapeutics. Here, we decipher the mechanisms of action of the fast-acting antidepressant ketamine to enable the identification of G protein-coupled receptor (GPCR) antidepressant targets. We find that the...
Background/Objectives: Major depressive disorder (MDD) remains a leading cause of disability worldwide and exhibits substantial biological heterogeneity that is not adequately captured by current symptom-based diagnostic systems. While the classical monoamine hypothesis has historically guided antidepressant development, it does not fully account for variability in treatment response, delayed...
Journal of Psychoactive DrugsApril 23, 2026Brayan Jonas Mano-Sousa, Maria Clara Gama Fontes, Ana Clara Anacleto Gonçalves et al.
Suicide, particularly in treatment-resistant depression (TRD), remains a pressing global health issue, with over 700,000 annual deaths. Existing treatments often have limited efficacy and delayed onset, creating a need for rapid-acting interventions. Ayahuasca, a traditional Amazonian psychedelic, has shown potential for rapidly reducing suicidal ideation. Our systematic review evaluated the...
ElifeApril 21, 2026Colin Bredenberg, Fabrice Normandin, Blake Richards et al.
Classical psychedelics induce complex visual hallucinations in humans, generating percepts that are coherent at a low level, but which have surreal, dream-like qualities at a high level. While there are many hypotheses as to how classical psychedelics could induce these effects, there are no concrete mechanistic models that capture the variety of observed effects in humans, while remaining...