Pharmacology, biochemistry, and behavior
June 30, 2026
Lucie Ladislavová, Viera Kútná, Kristýna Mazochová et al.
Chronic microdosing of psilocin (0.05 or 0.075 mg/kg) in adult male Wistar rats over five weeks did not alter locomotor activity, depressive-like behavior, sociability, or novelty seeking, and did not increase cell proliferation in the dentate gyrus of the hippocampus. A small anxiogenic effect was detected in the Elevated Plus Maze. The findings suggest that, under this dosing schedule, psilocin microdosing produces limited behavioral effects and does not enhance hippocampal progenitor proliferation.
Asian Journal of Medical Sciences
June 30, 2026
Raja Suhail Shounthoo, Ajaiz Rasool, Athar Un Nisa Quraishi et al.
Ketamine, a dissociative anesthetic developed in the 1960s, is experiencing a resurgence as a treatment for depression and pain. Unlike standard antidepressants that target monoamine systems, ketamine works by modulating glutamate, a key neurotransmitter, and enhancing synaptic plasticity. It shows rapid antidepressant effects in treatment-resistant depression and effectiveness for both acute and chronic pain. However, significant concerns remain about long-term safety, lack of standardized protocols, and potential for misuse. This review examines ketamine's expanding roles in anesthesia, psychiatry, and pain medicine, highlighting its mechanisms, clinical uses, safety issues, and gaps in current evidence.
J Psychopharmacol
June 28, 2026
In a mouse model of posttraumatic stress disorder, a single dose of psilocybin reduced fear responses to a conditioned cue measured 1, 6, and 7 days later. Psilocybin also reversed the fear conditioning-induced reductions in neuroplasticity in the hippocampus and medial prefrontal cortex, increasing dendritic branches and spine density, upregulating GluR1 and synapsin-1, enhancing brain-derived neurotrophic factor and mammalian target of rapamycin signaling, and promoting neurogenesis. These results suggest that psilocybin may have therapeutic potential for PTSD and other disorders involving fear memory by restoring neuroplasticity in these brain regions.
Zenodo (CERN European Organization for Nuclear Research)
June 28, 2026
Giulio Ruffini, Francesca Castaldo
Immersive algorithmic art may enhance neural plasticity through the same computational mechanism as psychedelics: sustained, structured prediction-error signaling. The brain's modeling engine generates predictions of sensory input; mismatches drive model updating via synaptic plasticity. Algorithmic art maximizes these errors while keeping stimuli in a compressible, emotionally rewarding "Goldilocks zone," creating a self-reinforcing loop of engagement, prediction error, plasticity, model updating, and positive valence. The hypothesis is formalized within Kolmogorov Theory, connected to the REBUS model, and supported by convergent evidence from psychedelic neuroimaging and predictive-coding electrophysiology. A translational pathway combining closed-loop EEG-driven algorithmic art with cognitive behavioral therapy for adolescent depression is outlined.
Zenodo (CERN European Organization for Nuclear Research)
June 24, 2026
Ramiro Solis
The brain's ability to rewire itself declines with age, but why remains unclear. This paper examines whether the compound N,N-dimethyltryptamine (DMT) helps maintain neuroplasticity, and whether its decline contributes to age-related loss of cognitive flexibility. DMT promotes synaptic growth and neurogenesis in animals, and levels are reportedly highest during development. However, evidence is mixed: one study finds DMT concentrations comparable to serotonin, while another finds it undetectable in rat brain. DMT's affinity for the sigma-1 receptor is three orders of magnitude higher than physiological concentrations, and a key finding about intracellular 5-HT2A receptor binding has not been replicated. The paper does not claim the hypothesis is established, but proposes a research program to test whether DMT depletion causes lost plasticity or is incidental.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Zhen Xuen Brandon Low
Autism Spectrum Disorder involves social-communication deficits, cognitive rigidity, and atypical sensory processing, with current drugs providing only limited relief. Dysregulated serotonin signaling, impaired neuroplasticity, and chronic neuroimmune activation are central features. Serotonergic psychedelics like psilocybin and LSD, which act as 5-HT2A receptor agonists, may relax overly rigid cortical priors, reopen critical periods for social learning, and recalibrate neural circuits. They enhance synaptic plasticity via BDNF and mTOR signaling, modulate cortical oscillations, and suppress neuroinflammation. Systems-level frameworks suggest these compounds induce less constrained brain states that counteract hyper-segregated connectivity in ASD. Preclinical and early human studies report improvements in sociability, sensory responsiveness, and behavioral flexibility, but rigorous clinical trials are needed to establish safety and efficacy.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Agnieszka Bysiek, Izabela Szpręgiel, Adam Wojtas et al.
Two doses of psilocybin (0.6 mg/kg, given subcutaneously seven days apart) reversed anhedonia, produced antidepressant-like effects in the forced swim test, and reduced anxiety in the light/dark box, elevated plus maze, and open field tests in rats exposed to chronic unpredictable mild stress. Psilocybin also increased hippocampal neurogenesis, shown by higher numbers of BrdU-positive, DCX-positive, and Ki-67-positive cells in stressed animals. Stress-induced reductions in brain-derived neurotrophic factor (BDNF) expression appeared linked to normalization of hypothalamic-pituitary-adrenal (HPA) axis activity. The findings highlight psilocybin-induced neuroplasticity as a key mechanism for its antidepressant and anxiolytic effects.
Clinical drug investigation
June 13, 2026
Angel Prabakar
Ketamine provides rapid antidepressant effects for treatment-resistant depression by blocking NMDA receptors, which triggers glutamatergic signaling that promotes synaptic plasticity and neurogenesis. This review synthesizes preclinical and clinical evidence on how these neuroplastic changes unfold over hours to days, linking molecular mechanisms like BDNF signaling and mTOR pathway activation to improvements in mood, motivation, cognition, and functional outcomes. It emphasizes the temporal trajectory of ketamine's effects and offers a plasticity-centered model to integrate neuroscience with clinical psychiatry, while identifying gaps in translational research for optimizing fast-acting antidepressants.
Pharmacological Reports
June 12, 2026
Wojciech Ziemichód, Natalia Kajka, Klaudia Kister et al.
AMPA receptors, a key component of the glutamatergic system, are linked to the rapid antidepressant effects and synaptic plasticity observed after ketamine administration. Positive allosteric modulators of AMPA receptors, called AMPAkines, prolong receptor channel opening, enhance excitatory neurotransmission, and upregulate brain-derived neurotrophic factor (BDNF). Preclinical studies consistently show antidepressant-like effects of low-impact AMPAkines, which have a favorable safety profile compared to high-impact compounds that carry seizure risk. Preliminary clinical trials support these findings but are limited in scope. Significant translational hurdles remain, including a narrow therapeutic window, suboptimal pharmacokinetic properties, and limited predictive validity of animal models.
Neurosci Biobehav Rev
June 7, 2026
Ketamine's rapid anti-suicidal effects may stem from a unified mechanism that addresses both psychological pain (psychache) and neuroplasticity. The proposed rescue-repair model suggests ketamine first alleviates intense emotional distress by modulating brain circuits involved in mood and cognition, then promotes neural repair and connectivity changes that sustain symptom relief. This framework integrates psychological and neurobiological perspectives, offering a more complete explanation for how a single drug can quickly reduce suicidal thoughts while also fostering long-term brain health.
Translational psychiatry
June 5, 2026
Samaneh Ahmadian-Moghadam, Shiva Roshan-Milani, Ehsan Saboory
Psilocybin-induced neuroplasticity could theoretically modulate stress-related neurodevelopmental risk pathways relevant to ADHD, but this remains a speculative hypothesis rather than an evidence-based intervention. Preclinical studies in non-ADHD models show psilocybin can induce rapid synaptic plasticity, alter cortical excitatory-inhibitory dynamics, and reverse stress-associated alterations. Human clinical trials in mood, trauma-related, and substance use disorders demonstrate durable changes in emotional regulation, cognitive flexibility, and brain network organization—processes overlapping with ADHD neural systems. Emerging preliminary, largely self-reported studies suggest potential benefits for inattention, impulsivity, and emotional dysregulation. Key mechanistic uncertainties and ethical considerations, especially for vulnerable populations, are emphasized as critical constraints on translation.
Zenodo (CERN European Organization for Nuclear Research)
June 5, 2026
Mark Nicolas
Most psychedelic research focuses on brain changes during the acute drug experience, but important changes also occur afterward. Ibogaine, studied only in the post-acute period, produces lasting reductions in neural signal complexity, shifts toward slower brain waves, decreased beta and gamma power, slowed peak alpha frequency, and improved cognitive inhibition lasting weeks. Similar post-acute changes from classical psychedelics suggest a shared stabilization phase. The Neural Attunement Model formalizes this post-acute phase as an organized, low-noise window for stabilizing neuroplasticity, specifying three convergent features and testable predictions. Ibogaine's long half-life and diverse pharmacological actions may extend this window, making it an empirical anchor for a regime that may generalize to other interventions.
Biomedicines
June 1, 2026
Masaru Tanaka
Antidepressant efficacy, especially for rapid-acting agents like ketamine and esketamine, depends on coordinated phases of synaptic plasticity and neuronal excitability. Induction occurs through NMDAR and AMPAR signaling, consolidation involves TrkB, eEF2K, and SV2A to stabilize changes, and maintenance relies on intrinsic excitability governed by Kv7, HCN, and GIRK potassium channels that prevent relapse. The proposed Induction-Consolidation-Maintenance (ICM) framework links these phases to distinct therapeutic windows and candidate biomarkers such as SV2A PET, EEG, and fMRI, offering a hypothesis-generating roadmap for future studies rather than validated clinical tools.
Asian journal of psychiatry
June 1, 2026
Hariprasad Ganapathy Vijayakumar, Varsha Shamanna, Harsh Pathak et al.
1 citation
In a 69-year-old man with chronic multi-therapy resistant bipolar depression, combining intravenous ketamine three times per week with sequential theta burst stimulation led to complete remission that persisted at a two-year follow-up. The patient had previously failed numerous antidepressants, mood stabilizers, electroconvulsive therapy, and standalone brain stimulation. Clinical improvement was measured by a drop in the Hamilton Depression Rating Scale from 15 to 8 and eventually to remission. Electroencephalography showed corrected dysregulated brain activity patterns, suggesting changes in short-term adaptive plasticity. This combination may offer a treatment path for patients who do not respond to standard therapies.
Cureus
June 1, 2026
Hoi Ki Cheung, Ngo Cheung
A 26-year-old woman with severe contamination-focused obsessive-compulsive disorder (OCD) that persisted despite standard treatments showed meaningful improvement after a glutamatergic augmentation strategy using dextromethorphan, piracetam, and L-glutamine, combined with CYP2D6-inhibiting antidepressants. Over nine months, bathing time decreased from about 1.5 hours to about 30 minutes, and ritual preoccupation reduced by 20-30%. Mood, energy, motivation, and daily functioning improved, and passive suicidal ideation resolved temporarily. Residual cleaning symptoms remained at home. The case is hypothesis-generating and not evidence of regimen-specific efficacy; larger controlled studies are needed.