European Archives of Psychiatry and Clinical Neuroscience
February 20, 2020
G. C. Leal, I. D. Bandeira, F. S. Correia-Melo et al.
257 citations
A single intravenous infusion of arketamine (0.5 mg/kg) rapidly reduced depression severity in seven people with treatment-resistant depression. The Montgomery–Åsberg Depression Rating Scale score fell from an average of 30.7 before infusion to 10.4 after one day, a mean drop of 20.3 points. Dissociative side effects were nearly absent. The findings suggest arketamine may produce fast-onset and sustained antidepressant effects with a favorable safety profile, as previously observed in animals, but controlled trials are needed to confirm.
European Archives of Psychiatry and Clinical Neuroscience
April 18, 2016
Kenji Hashimoto, Takeharu Kakiuchi, Hiroyuki Ohba et al.
125 citations
Esketamine, but not R-ketamine, reduces dopamine D2/3 receptor binding availability in the monkey striatum, indicating that esketamine triggers dopamine release in this brain region. This dopamine release may underlie the psychotomimetic side effects of esketamine. R-ketamine, in contrast, does not affect striatal dopamine D2/3 binding, consistent with its proposed safer profile as a rapid antidepressant. The findings suggest a neurochemical difference between the two ketamine enantiomers that could explain their distinct side-effect profiles.
European Archives of Psychiatry and Clinical Neuroscience
January 24, 2019
Claire M. Gorey, Lauren Kuhns, Eleni Smaragdi et al.
118 citations
Adolescence is a period of both risk and resilience regarding the harms of cannabis use. This systematic review examined whether age (adolescent vs. adult) moderates the relationship between cannabis exposure and cognition, drawing on both human and animal studies. The review does not offer a conclusive answer but generates four hypotheses: general executive functioning appears more impaired in adolescent frequent users than in adult frequent users; age effects may be strongest among very heavy and dependent users; craving and inhibitory control may not decrease as much post-intoxication in adolescents; and adolescents' vulnerability to reduced learning following cannabis use may not persist after sustained abstinence. If confirmed, these hypotheses could inform policy and prevention.
European Archives of Psychiatry and Clinical Neuroscience
February 27, 2024
Kenji Hashimoto
51 citations
The relationship between mystical experiences and antidepressant effects of ketamine and classic psychedelics like psilocybin is debated. Ketamine can cause dissociative symptoms such as out-of-body experiences, while psychedelics often produce hallucinogenic experiences like a sense of unity. Clinical studies indicate that dissociative symptoms from ketamine or esketamine are not directly linked to their antidepressant properties. The antidepressant potential of arketamine, which lacks dissociative side effects, remains unproven in large-scale trials. Activation of the serotonin 5-HT2A receptor is crucial for psychedelics' hallucinogenic effects, but its role in antidepressant action is unclear. This article examines whether mystical experiences enhance antidepressant outcomes.
European Archives of Psychiatry and Clinical Neuroscience
February 14, 2023
Kenji Hashimoto
40 citations
Cognitive impairment is common in psychiatric disorders like schizophrenia, major depressive disorder, and bipolar disorder, and current medications do not improve it. The drug (R,S)-ketamine, a rapid antidepressant, may improve cognitive impairment in patients with these conditions, even though it causes cognitive impairment in healthy people. Its component arketamine shows more potent antidepressant-like effects than esketamine in rodents and may improve cognitive deficits induced by phencyclidine or maternal immune activation in mice. The article proposes arketamine as a potential treatment for cognitive impairment in psychiatric disorders and discusses the possible role of the gut-microbiome-brain axis.
European Archives of Psychiatry and Clinical Neuroscience
January 12, 2022
Matti Gärtner, Anne Weigand, Milan Scheidegger et al.
13 citations
Ketamine's rapid antidepressant effects involve the glutamatergic system. A multimodal imaging study of 23 healthy volunteers used resting state fMRI and proton magnetic resonance spectroscopy to examine links between metabolic and functional brain changes during intravenous ketamine infusion. The pregenual anterior cingulate cortex (pgACC) was the focus. Functional connectivity changed from the pgACC to the right frontal pole and anterior mid cingulate cortex (aMCC). Absolute glutamate and glutamine concentrations in the pgACC did not differ significantly from baseline. Stronger pgACC activation during ketamine was linked to lower glutamine concentration, and reduced connectivity between pgACC and aMCC was related to increased pgACC activation and reduced glutamine.
European Archives of Psychiatry and Clinical Neuroscience
November 7, 2023
Ana-Maria Iorgu, Andrei-Nicolae Vasilescu, Natascha Pfeiffer et al.
2 citations
Psilocybin, unlike S-ketamine and MK-801, does not induce neuronal damage in the retrosplenial cortex of rats. Both S-ketamine and psilocybin are rapid-acting antidepressants that increase glutamate signalling and cortical hyperexcitation, but S-ketamine is known to cause neurotoxicity (Olney's lesions) in the retrosplenial cortex. Using immunohistochemical whole-brain mapping for heat shock protein 70 (HSP70) in rats, no HSP70-positive neurons were detected in the retrosplenial cortex of psilocybin-treated animals, whereas S-ketamine and MK-801 produced such markers. This suggests psilocybin may be safer for clinical use regarding neuronal damage.
European Archives of Psychiatry and Clinical Neuroscience
March 28, 2026
Yves Martins Varela, Vagner Deuel De O. Tavares, Luiza Macedo Delgado et al.
1 citation
Cognitive-behavioral therapies are being combined with psychedelic substances such as ketamine, psilocybin, and MDMA to treat mental disorders, but the way they are integrated varies widely across studies. A systematic review of 9 clinical trials involving 283 patients found that traditional cognitive behavioral therapy was the most common approach, used in 6 studies, while mindfulness-based cognitive therapy and acceptance and commitment therapy were each used in 2 and 1 studies respectively. The timing of therapy relative to the psychedelic experience—before, during, or after—also differed. The findings highlight the need for more consistent research to clarify how these therapeutic models are best implemented.
European Archives of Psychiatry and Clinical Neuroscience
June 23, 2026
Ilaria Bufalari, Lilya Abergel, Andrea Zagaria et al.
People with Maladaptive Daydreaming (MD)—compulsive, immersive daydreaming that disrupts daily life—report higher levels of dissociation and altered body awareness compared to those without MD. In a survey of 137 Italian-speaking adults, those with MD scored higher on dissociation, especially absorption and depersonalization, and lower on three aspects of interoception: attention regulation, body listening, and trusting bodily sensations. Network analyses placed maladaptive daydreaming as a central link between dissociation and interoception. The findings suggest that MD may involve using daydreaming to escape uncomfortable bodily states, and that improving interoception through interventions like mindfulness could help address MD and its dissociative features.
European Archives of Psychiatry and Clinical Neuroscience
June 5, 2026
Luis Sobrino-Conde, Antonio Arjona, Emma Osorio-Iriarte et al.
People with psychosis can be grouped into biotypes based on underlying pathological features rather than traditional diagnostic categories. One biotype (cluster 1) involves severe cognitive deficits, while another (cluster 2) involves moderate cognitive deficits. In a study of 113 patients, those in cluster 1 reported significantly more anomalous self-experiences—disturbances in the sense of self—than both healthy controls and cluster 2 patients. Cluster 2 patients showed only slight differences from controls. These findings suggest that severe disruptions in self-experience are a key feature of the biotype characterized by marked cognitive impairment, brain structure changes, and higher negative symptoms.
European Archives of Psychiatry and Clinical Neuroscience
August 19, 2020
Stéphanie Lefebvre, É. Very, Renaud Jardri et al.
People with schizophrenia have a higher visual detection threshold than healthy controls, meaning they need stronger visual input to become consciously aware of it. Brain imaging showed that during conscious vision, patients failed to activate occipital areas as strongly as controls; during unconscious vision, they failed to activate a widespread network; and during the moment of becoming conscious of a visual stimulus, they failed to activate the anterior cingulate cortex.
European Archives of Psychiatry and Clinical Neuroscience
July 14, 2018
K. Hashimoto, Chun Yang
The NMDAR antagonist (R,S)-ketamine is considered a major advance in depression treatment, but safety concerns about repeated infusions persist. (R)-ketamine shows greater potency and longer-lasting antidepressant effects than esketamine in animal models, without psychotomimetic side effects or abuse potential in rodents. Esketamine infusions cause dopamine release in monkeys and psychotomimetic symptoms in humans, suggesting a link. Phase 2 trials of intranasal esketamine found rapid reduction of depression and suicidality, with a dose-response relationship, but effects did not differ from placebo after 4 weeks in one trial. Phase 3 results were mixed: esketamine outperformed placebo in adults but not in patients 65 and older. Abuse potential remains a concern.