Cannabis use during pregnancy is increasing, often to alleviate stress and anxiety, yet the impact of prenatal cannabis exposure alone, or in combination with psychosocial stress on maternal regulation and downstream offspring neurodevelopment remains unclear. Here, we developed a translational rodent model combining prenatal Δ⁹-tetrahydrocannabinol (THC) exposure with chronic psychosocial...
Translational PsychiatryApril 21, 2026Paul A Parcon, Amanda Bardhoshi, Amanda Olsen-Dufour et al.
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is a robust, rapid-acting antidepressant whose molecular effects have not been fully elucidated. Phosphodiesterase-4 (PDE4), which terminates cyclic adenosine monophosphate (cAMP) activity, may underlie antidepressant response. In particular, previous studies found that whole brain binding of the positron emission tomography (PET)...
Prolonged obesity induces enduring structural changes within neural circuits that contribute to maintaining the body at an elevated/obese body weight. These circuits regulate various mechanisms which can inhibit extreme or persistent weight loss. Therefore, a potential therapeutic strategy to facilitate weight loss is to promote structural plasticity within the brain. Psychedelic compounds,...
This study aimed to evaluate the long-term effectiveness and safety of esketamine in adults with Major depressive disorder (MDD), focusing on suicide-related events, all-cause mortality, and major adverse cardiovascular events (MACEs). This target-trial simulation used the TriNetX Global Collaborative Network. Adults (≥ 18 years) with MDD who received either esketamine or a conventional...
N,N-dimethyltryptamine (DMT) is a serotonergic psychedelic that produces short-lived peak effects when administered intravenously as a bolus dose. Initial trials suggested therapeutic effects of DMT in depressive disorders. However, systematic data on dose-dependent pharmacokinetics and acute effects of intravenous bolus DMT administration are currently lacking. We used a double-blind,...
Ketamine holds promise for the treatment of post-traumatic stress disorder (PTSD), but challenges remain in delivery and sustained effects. This controlled study evaluates a novel intranasal formulation, employing AmyloLipid nanovesicles (ALN) to enhance ketamine’s therapeutic efficacy in a predator-scent stress (PSS) rat model of PTSD. A total of 130 rats underwent PSS or sham-PSS exposure,...
Postoperative depression adversely influences breast cancer patients' clinical outcomes. Our prior study demonstrated that intraoperative esketamine ameliorated postoperative depression in breast cancer patients, yet the underlying neural mechanism remains incompletely understood. We performed a double-blind randomized controlled trial in 35 breast cancer patients with preoperative depressive...
Treatment-resistant depression (TRD) accounts for approximately 30% of major depressive disorder cases and has been characterized by altered functional connectivity within and between the Default Mode (DMN) and Frontoparietal networks (FPN). Ketamine can be an effective treatment for TRD, and its antidepressant response has been associated with alterations in resting state functional...
IMPORTANCE: As psychedelic-assisted therapies gain clinical legitimacy, their cultural portability remains underexamined. While promising results have emerged from trials on existential distress in life-limiting illness, most protocols reflect Euro-American values. The expansion of these therapies calls for a pivot toward cultural humility and renewed attention to what constitutes a "good...
Translational PsychiatryFebruary 19, 2026Luís Carlos Pereira, Wigínio Gabriel Lira-Bandeira, Andréa Silva Medeiros-Bandeira et al.
Major depressive disorder remains a debilitating mental health disorder affecting millions worldwide, with growing prevalence among adolescents. Recent studies highlight the critical role of the somatosensory cortex in the neuropathology of depression, including structural alterations that impair cortical function. This study investigates the prophylactic effects of ayahuasca, a classic...
Internet gaming disorder (IGD) has been recognized as a serious mental illness and is often accompanied by depression (IGD-D). An ideal treatment strategy should have effects on both the conditions. Mindfulness meditation (MM) has attracted substantial attention for the treatment of psychiatric diseases; however, its effects on IGD-D and the underlying mechanisms remain unknown. A total of 70...
The serotonergic psychedelic psilocybin induces neural plasticity and profoundly alters consciousness. The benzodiazepine midazolam blunts neural plasticity and induces conscious sedation and amnesia at low doses. In our recent open label pilot study, we administered oral psilocybin (25 mg) along with intravenous midazolam at doses allowing a full psychedelic experience while blunting memory...
Clinical investigations into the therapeutic actions of psilocybin have been the focus of much attention in recent years as duly cited in the manuscript.The authors of the present manuscript discuss potential targets through which psilocybin may help prevent suicide using computational network pharmacology coupled with molecular docking investigations.Unfortunately, the manuscript contains the...
Major depressive disorder (MDD) remains a leading cause of disability worldwide, with current treatments limited by delayed onset and low efficacy. The serotonergic psychedelic N,N-dimethyltryptamine (DMT) has shown rapid antidepressant effects in early clinical studies, yet its mechanisms and efficacy remain poorly characterized in established models of depression. Here, we evaluated the...
Comparing treatments for severe and medication-resistant depression is essential for guiding clinical decision-making. In this meta-analysis, we investigate the efficacy of electroconvulsive therapy (ECT) compared to ketamine for the treatment of major depressive disorder (MDD) and address the discrepant results of prior meta-analyses. We systematically searched PubMED (MEDLINE), Embase, and...
Patients with preexisting sleep disorders face a significantly increased risk of postoperative sleep disturbance (PSD) due to heightened sensitivity to surgical stress, anesthesia, and hospital-related environmental factors. There is a critical unmet need for effective prophylactic medications to prevent PSD, as current treatment options are limited and often inadequate. This study investigated...
Socioeconomic hardship (SES-H) is a known risk factor for adolescent suicidal thoughts and behaviors (STB). This study examined sleep health as a pathway linking SES-H to suicide risk and evaluated the moderating role of Default Mode Network (DMN) coherence. Data came from three waves of the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,878). Increased SES-H predicted greater...
Auditory verbal hallucinations [AVH] are one of the most common psychopathological symptoms in psychosis and schizophrenia [SZ]. While various studies demonstrate the neuronal features of AVH in specific regions and networks including changes in structural and functional connectivity, the relation of their neuronal topography to the organization or structure of the subjects' experience, i.e....
Treatment-resistant depression (TRD) is associated with worse clinical outcomes and longer course of illness. However, TRD is more difficult to model in animal phenotypes, suggesting that other experimental and translational models must be considered to properly address and research novel therapeutics. Reelin, an endogenous glycoprotein downregulated in depression, has shown rapid...
Translational PsychiatryNovember 17, 2025Noah Stapper, Lindsay L Benster, Sahit Menon et al.1 citation
Suicidal ideation (SI) is associated with increased morbidity and is one of the main modifiable risk factors for suicide. While initial evidence indicates the efficacy of several treatments for SI, most treatments were not developed to specifically target SI and are often associated with side effects or high relapse rates. Limited understanding of the neurophysiological basis of SI has hindered...
The meta-analysis of the 11-dimensional Altered States of Consciousness (11D-ASC) included three studies that contained duplicated data from other papers: Duerler et al. (2021), Lewis et al. (2017), and Preller et al. (2017). When these studies are removed from the analysis, the results are generally similar to the previously reported findings. Out of 33 comparisons (3 doses x 11 dimensions)...
Abstract Recent clinical trial data suggests that ratings on depression scales are lowered after psilocybin therapy compared to placebo, though it is unclear what neuropsychological mechanisms underpin these effects. This study compared psilocybin, with an established antidepressant, escitalopram, to investigate whether there are shared or distinct effects on emotional information processing....
In the originally published version of this article, Figure 4 contained an error in the RNA-seq analysis. During data processing, the subtraction order for the treatment groups was inadvertently reversed (vehicle was subtracted from psilocybin-treated samples, instead of psilocybin-treated from vehicle). This error affected the plotted log fold-change values but does not alter the...
BACKGROUND: Over the past ten years, several psychedelic compounds, including tryptamines like lysergic acid diethylamide/LSD, psilocybin, ayahuasca, and dimethyltryptamine/DMT, have been tested in clinical trials for a range of psychiatric conditions, such as anxiety and depression. While these compounds are relatively available for treatment, ketamine and its S(+) enantiomer, esketamine, are...
Translational PsychiatryOctober 31, 2025Kristin L Dawson, Athena May Jean M. Carangan, Jessica Klunder et al.2 citations
Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are debilitating psychiatric conditions associated with poor health outcomes similarly observed in non-pathological aging. Ketamine is a dissociative anesthetic and NMDA receptor antagonist with demonstrated rapid reduction in symptoms associated with Treatment Resistant Depression (TRD) and PTSD. Ketamine's effects on...