European journal of psychotraumatology
December 1, 2026
V Ursule Taujanskaite, Sunjeev K Kamboj
A 6-item short form of the Clinician Administered Dissociative States Scale (CADSS-SF) was developed using data from three studies of nitrous oxide in 229 healthy volunteers, then validated in 80 separate participants. The single-factor scale, composed of derealization and depersonalization items, showed excellent model fit and internal consistency (omega = 0.87), correlated strongly with the full 19-item CADSS (r ≥ 0.88), and moderately with a measure of psychotomimesis (r = 0.63). The CADSS-SF enables rapid, repeated assessment of dissociation during drug intoxication without disrupting the experience, but primarily captures derealization and depersonalization and requires further validation beyond drug-induced dissociation in healthy populations.
European journal of psychotraumatology
December 1, 2026
Maud Rothärmel, Lila Mekaoui, François Kazour et al.
1 citation
In a retrospective study of 22 adults with treatment-resistant depression and comorbid post-traumatic stress disorder who received esketamine nasal spray, trauma re-experiencing episodes occurred during treatment sessions. For 16 patients (72.7%) these episodes disappeared as sessions progressed. Treatment was stopped for 6 patients (27.3%) due to re-experiencing. Among those who continued esketamine, depression response rate was 45.5% and remission 22.7%; PTSD improvement rate was 45.5% and remission 18.2%. The findings suggest esketamine can be safely administered in this comorbid population and that trauma re-experiencing does not prevent clinical improvement.
European journal of psychotraumatology
December 1, 2026
Philip Gerrans, Hugh McGovern, Jakob Hohwy et al.
Complex post-traumatic stress disorder (C-PTSD) involves lasting difficulties with emotions, self-concept, and relationships, beyond typical PTSD symptoms. This review proposes a neurocognitive explanation based on predictive processing and self-modelling, focusing on how the brain's insula integrates bodily signals, emotions, and self-awareness. The authors suggest that C-PTSD arises from maladaptive predictions shaped by prolonged interpersonal trauma, leading to unstable self-regulation. They examine MDMA-assisted psychotherapy as one intervention that may temporarily alter emotional salience, trust, and self-related thinking. The framework generates testable hypotheses about self-modelling in C-PTSD and offers guidance for developing treatments that target affective regulation and self-referential processing.
Journal of affective disorders
November 1, 2026
Dian-Jeng Li, Tien-Wei Hsu, Te-Chang Changchien et al.
Patients with major depressive disorder who are prescribed esketamine have higher rates of comorbid substance use disorders compared to those treated with antidepressants or repetitive transcranial magnetic stimulation. Among esketamine users, those with a substance use disorder face greater risks of self-harm, suicide attempt, emergency visits, hospitalization, and mortality. The findings indicate a prescription bias toward patients with comorbid substance use disorders and highlight the need for careful monitoring and specialized care for this population.
Journal of affective disorders
November 1, 2026
Tse-Hwei Choo, Hanga C Galfalvy, John G Keilp et al.
A midazolam-controlled trial of intravenous ketamine for suicidal depressed patients found that ketamine rapidly reduced suicidal ideation within 24 hours. An exploratory analysis measured saliva cortisol awakening response at baseline and 24 hours after infusion. Waking cortisol significantly increased 24 hours after ketamine treatment. The increase in waking cortisol from baseline to post-infusion showed a small to medium, nonsignificant correlation with decreased suicidal ideation. These preliminary results, pending replication, align with evidence that moderate cortisol increases may enhance stress-resilience.
Journal of affective disorders
November 1, 2026
Lindsay L Benster, Jordan N Kohn, Benjamin Wade et al.
In a real-world comparison of two FDA-approved treatments for treatment-resistant depression, intranasal esketamine led to faster improvement than repetitive transcranial magnetic stimulation (rTMS). Over 90 days, esketamine patients responded a median of 36 days versus 49 days for rTMS, and suicidal ideation resolved more quickly (median 9 vs. 26 days). However, by about 90 days, overall response and remission rates were similar between the groups (68.8% and 45.2% for esketamine; 59.4% and 40.1% for rTMS), suggesting a difference in speed rather than ultimate effectiveness. For rTMS, slower response was predicted by comorbid anxiety and benzodiazepine use, while former tobacco use predicted faster response. No such predictors were found for esketamine.
Journal of affective disorders
November 1, 2026
Carlton M Kelly, Mathieu Fradet, Catherine M Bostian et al.
A single 25-mg dose of psilocybin with psychological support was associated with sustained improvements in anxiety, quality of life, functioning, and PTSD symptoms in 15 veterans with treatment-resistant depression. Anxiety scores dropped 59% from baseline at three weeks and remained lower through 12 months. Quality of life increased 24% and functional impairment decreased 46% at three weeks, though these effects were no longer statistically significant after accounting for concurrent improvements in depression. PTSD symptom reductions were observed at all timepoints. Acute subjective experiences did not correlate with treatment response. The study is limited by its small sample and open-label design.
Neuropharmacology
September 15, 2026
Taisiia Prosvirova, Wiktoria Podolecka, Jacek Wróbel et al.
Ketamine rapidly reorganizes fast brain rhythms differently across cortical networks. In freely moving rats, neocortical gamma power increased broadly, while the olfactory bulb showed suppressed gamma alongside robust high-frequency oscillations (HFO; 130-180 Hz). Local blockade of non-NMDA glutamate receptors in the olfactory bulb suppressed ketamine-enhanced HFO in the bulb, ventral striatum, and prefrontal cortex without affecting neocortical gamma, indicating separate circuit mechanisms. Within the bulb, a kainate receptor antagonist markedly reduced HFO, while AMPA receptor blockade had minimal effect. Blocking GABA-A receptors reduced HFO power while increasing gamma power, showing that fast inhibition is necessary for HFO expression. The findings suggest that tonic kainate-dependent depolarization recruits interneurons to generate an inhibitory network rhythm that drives HFO propagation through olfactory-limbic circuits.
Journal of affective disorders
September 15, 2026
Rutger Boesjes, Claudia Oosterveld, Jeanine Kamphuis et al.
1 citation
Ketamine and its enantiomers show rapid antidepressant effects for major depressive disorder and bipolar disorder, but responses vary widely. This systematic review of 26 studies (1694 participants) found that ketamine treatment is linked to improved subjective sleep quality. Preliminary evidence suggests that baseline sleep disturbances and early sleep improvements may predict antidepressant response. Some studies also indicate beneficial effects on objective sleep and circadian rhythmicity, but this finding is tentative due to few published articles. The authors call for more research on objective circadian measures and potential synergy with chronotherapies.
Psychiatry research
September 1, 2026
Isis Lunsky, Gilmar Gutierrez, Xena Wang et al.
Postpartum depression (PPD) is common and harmful if untreated, with few effective prevention strategies. Ketamine and esketamine are rapid-acting antidepressants showing promise for PPD. This review searched five databases for peer-reviewed randomized controlled trials, pilot studies, and observational studies examining ketamine or esketamine for PPD prevention during pregnancy or postpartum, for both cesarean and vaginal deliveries. A network meta-analysis and narrative synthesis were used. Thirty-six studies were identified; five included vaginal delivery, thirty included cesarean section, and one did not specify delivery mode. Results suggested that ketamine and esketamine were well tolerated and may reduce PPD risk. However, data quality was low to very low, so results should be interpreted cautiously. More high-quality studies are needed.
Neuroscience and biobehavioral reviews
September 1, 2026
Jeremy I Skipper, Daniel R Lametti, David W Green
Aberrations in inner speech are linked to psychotic symptoms such as thought insertion and auditory verbal hallucinations, which may arise from failures in prediction and source monitoring. Normally, efference copies of speech motor commands suppress auditory responses to self-generated input; if suppression malfunctions, predicted auditory input becomes perceptually salient. Impaired self-monitoring regions (e.g., anterior cingulate cortex) may cause inner speech to be misattributed as external. Neuroimaging meta-analyses of neurotypical participants and psychosis spectrum participants showed increased activity in motor-related regions (e.g., ventral premotor cortices) and decreased grey matter in auditory cortices and ACC. These regions form distinct, inversely coupled audiomotor networks, supporting the proposal that psychotic symptoms derive from hyperactivation in inner speech regions producing insufficiently suppressed efference copy signals.
Neuropsychopharmacol Rep
September 1, 2026
Daisuke Ibi, Rika Takaba, Keisuke Yoshida et al.
In a mouse model of social defeat stress, the serotonin 5-HT2A receptor mediates the ability of psilocin to restore deficits in social behavior. Mice repeatedly subjected to social defeat stress showed reduced social interaction, and treatment with psilocin reversed this impairment. The therapeutic effect of psilocin was blocked by a 5-HT2A receptor antagonist and absent in mice lacking the 5-HT2A receptor, indicating that this receptor is necessary for the prosocial action of psilocin. These findings suggest that the 5-HT2A receptor is a key target for psilocin's effects on social behavior deficits caused by chronic stress.
Experimental neurology
September 1, 2026
Javier Calleja-Conde, Víctor Echeverry-Alzate, Marina Sanz-Sancristóbal et al.
In a preclinical model of Parkinson's disease, the compound N,N-dimethyltryptamine (DMT), the main psychoactive ingredient in ayahuasca, reduced neuroinflammation and preserved neurons in the nigrostriatal pathway. Treated animals also showed improvements in behavior. These results suggest DMT may have disease-modifying potential for Parkinson's disease, a progressive neurodegenerative disorder marked by loss of dopaminergic neurons and chronic inflammation, for which current treatments only relieve symptoms.
Psychiatry research
September 1, 2026
Valerio Ricci, Andrea Paggi, Giovanni Martinotti et al.
In patients with cannabis-induced first-episode psychosis, dissociative symptoms—especially depersonalization and derealization—are strong independent predictors of poor functional recovery over 24 months. Among 72 patients, three recovery trajectories emerged: Rapid Recovery (34.7%, GAF +29.1 points), Gradual Recovery (40.3%, GAF +15.7 points), and Persistent Impairment (25.0%, GAF +4.7 points). A symptom-function discrepancy occurred in 31.9% of patients, where psychotic symptoms improved but functioning did not; these patients had higher baseline dissociation scores (33.8 vs. 18.1). Dissociation mediated 35% of cannabis's negative effect on functional outcomes. A high-risk subgroup (22%) with elevated dissociation, depression, and continued cannabis use showed minimal improvement despite treatment. Routine dissociation assessment and targeted interventions may improve outcomes.
Journal of affective disorders
September 1, 2026
Nesreen Sedeek, Carley Rivers, Lucas Williamson et al.
Ketamine's rapid antidepressant effects in treatment-resistant depression are linked to changes in brain activity, but previous studies have been hard to compare due to differences in imaging techniques, analysis methods, and timing. A review combining fMRI and PET studies found that ketamine-related effects commonly appear in subcortical brain regions, with more variable effects in cortical areas like the prefrontal and anterior cingulate cortices. Network-level patterns suggest involvement of the default-mode, ventral attention, and visual systems. These findings are hypothesis-generating and highlight the need for future studies that harmonize methods to directly connect circuit changes to molecular mechanisms and clinical outcomes.
Journal of affective disorders
August 15, 2026
Michał Walaszek, Wiesław Jerzy Cubała, Zofia Kachlik et al.
Anhedonia, a core symptom of major depressive disorder linked to poor outcomes, may be reduced by ketamine. In a retrospective analysis of 34 inpatients with treatment-resistant depression receiving short-term ketamine as an add-on to standard care, 16 patients (47.1%) did not respond to treatment, defined as less than a 50% reduction on the Snaith-Hamilton Pleasure Scale. Non-responders were more likely to be single, had fewer lifetime depressive episodes, and lower rates of prior substance use disorder. These factors suggest that psychosocial and demographic characteristics influence anhedonia treatment outcomes, supporting a personalized approach to mood disorder treatment.
International immunopharmacology
August 1, 2026
Jinghua Zhao, Ruxin Zhang, Jiarui Pan et al.
The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) reduces depression-like behavior in mice by suppressing neuroinflammation and neuronal pyroptosis. In experiments with male C57BL/6J mice and PC12 cells, HNK lowered expression of NLRP3, caspase-1, GSDMD, and interleukin-1β at both protein and mRNA levels, lessened neuronal injury, and reduced lactate dehydrogenase release. Transcriptomic analysis identified Vcam1 as a key differentially expressed gene. Overexpressing Vcam1 increased pyroptosis markers, while HNK reduced Vcam1 expression; knocking down Vcam1 had opposite effects. HNK thus attenuates LPS-induced pyroptosis and neuroinflammation partly by downregulating the Vcam1/caspase-1/IL-1β pathway, offering insights for depression treatment.
Journal of affective disorders
August 1, 2026
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
2 citations
In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.
Psychiatry research. Neuroimaging
August 1, 2026
Kengo Yonezawa, Shinichiro Nakajima, Shuhei Shibukawa et al.
In patients with treatment-resistant depression, higher baseline levels of magnetic substances in the right nucleus accumbens and the left amygdala, measured by brain imaging, predicted a greater reduction in specific depressive symptoms after repeated ketamine infusions. The study included 17 Japanese patients and used a double-blind, randomized placebo-controlled design followed by an open-label phase. Baseline magnetic susceptibility in the right nucleus accumbens correlated with improvement in retardation symptoms, while baseline R2* in the left amygdala correlated with improvement in vegetative symptoms. These brain markers may help predict which patients will benefit from ketamine treatment.
Journal of pharmacological sciences
August 1, 2026
Natsuko Hitora-Imamura, Yuki Nishida, Koki Kawazoe et al.
Mice exposed to three weeks of corticosterone showed increased conflict behavior in a three-compartment task, specifically by prolonging action initiation, without signs of anhedonia. Ketamine reduced conflict in control mice but not in corticosterone-treated mice, indicating that chronic stress abolishes ketamine's anticonflict effect. The findings suggest that chronic stress biases conflict-related decision-making and disrupts mechanisms that normally respond to ketamine.
Brain research bulletin
August 1, 2026
Rui Dong, Jiaxin Liu, Yumei Shen et al.
In a mouse model of trigeminal neuralgia (TN) that also shows anxiety-like behavior, esketamine (ES) given for five days dose-dependently reduced pain and anxiety. TN caused damage to neurons in the hippocampus and increased levels of the necroptosis pathway proteins RIPK1, RIPK3, and MLKL. ES treatment reversed these changes, protecting neurons and restoring dendritic spines. Adding a necroptosis activator blocked ES's effects, confirming that ES works by inhibiting the RIPK1/RIPK3/MLKL pathway. The findings highlight necroptosis as a key mechanism linking TN pain to emotional disorders and suggest ES could be repurposed as a treatment for both pain and anxiety in TN.
Journal of pain and symptom management
August 1, 2026
Paul Noufi, Joshua B Borris, Danielle Chammas et al.
Ketamine and esketamine offer rapid antidepressant effects, with intravenous ketamine producing moderate-to-large improvements within 1–24 hours that last one to two weeks, and a number needed to treat of three in the first week. Esketamine nasal spray shows similar early efficacy and is FDA-approved for treatment-resistant depression and major depression with suicidal ideation. Evidence specific to people with serious illnesses is limited to perioperative cancer trials and small open-label studies, showing short-term reductions in depressive symptoms and suicidal ideation but not addressing long-term management. Safety is generally favorable, with transient dissociation, hypertension, and somnolence as common adverse effects. Rigorous psychiatric trials in serious illness are lacking.
Journal of affective disorders
August 1, 2026
Ching-Hua Julie Lee, Yunzhe Qian, Weiqun Yu et al.
Compared with injectable ketamine, esketamine was linked to higher risks of suicidal ideation (24% increase), generalized anxiety disorder (55% increase), insomnia (25% increase), and cardiac arrest (57% increase). Compared with oral antidepressants in treatment-resistant depression, esketamine was associated with lower risks of suicidal ideation (11% decrease), suicide attempt (29% decrease), and generalized anxiety disorder (18% decrease), but a higher risk of cardiac arrest (109% increase). Injectable ketamine showed a more favorable safety and effectiveness profile than esketamine. Head-to-head clinical trials are needed to validate these findings.
The International journal on drug policy
August 1, 2026
Myfanwy Graham, Yimin Ge, Rosalie Liccardo Pacula et al.
1 citation
An estimated 19% of adults in Canada, the United States, Australia, and New Zealand have used psilocybin, LSD, MDMA, or ketamine at some point in their lives. Psilocybin was the most commonly used substance, with lifetime use highest in Canada (16.3%), followed by the US (13.0%) and New Zealand (12.1%), and lowest in Australia (7.8%). Among those who had ever used a psychedelic, 10-20% had asked their medical provider about medical use, and over a third of past-year users reported experiencing an adverse health effect. Past-month use was low across all countries. Consumer interest in therapeutic use has outpaced clinical trials and therapeutic provisions, and many people use these substances outside regulated pathways, which may increase the risk of adverse events.