Psychopharmacology
May 19, 2015
R. Joules, O. Doyle, A. J. Schwarz et al.
77 citations
Ketamine, which blocks N-methyl-D-aspartate receptors (NMDARs), robustly alters functional connectivity in the human brain, shifting patterns from cortex-centered to subcortex-centered connections. This effect was detected with 87.5% accuracy compared to saline. Pre-treatment with risperidone strongly modulated the connectivity changes (81.25% accuracy), whereas lamotrigine did not (43.75% accuracy). The differential modulation suggests the connectivity effects stem primarily from NMDAR blockade rather than downstream glutamate release. No such differential effect was seen in measures of brain response amplitude, underscoring the value of connectivity analysis for understanding how drugs affect the brain.
Cortex; a journal devoted to the study of the nervous system and behavior
April 1, 2014
Quinton Deeley, David A Oakley, Eamonn Walsh et al.
75 citations
Involuntary movements in neuropsychiatric disorders and culturally influenced dissociative states, such as delusions of alien control and spirit possession, involve distinct brain processes. Using fMRI in 15 highly hypnotically susceptible volunteers, suggestions modelled different experiences of loss of self-control: external personal control (like delusions of control), internal personal control (like spirit possession), and impersonal control by a machine (technical delusions). Brain activity and connectivity varied across these conditions.
PloS one
January 1, 2013
Quinton Deeley, Eamonn Walsh, David A Oakley et al.
48 citations
Voluntary control and awareness of movement are central to selfhood and responsibility, yet can be lost in neuropsychiatric syndromes and dissociative states like spirit possession. Using suggestion and fMRI in 15 highly hypnotically suggestible subjects, loss of perceived control of movements was linked to reduced connectivity between the supplementary motor area (SMA) and motor regions. Reduced awareness of involuntary movements corresponded with less activation in parietal cortices and insula. These results suggest the sense of voluntary control may critically depend on SMA coupling with motor systems, offering a neural basis for narrowed awareness in pathological and culturally influenced dissociative phenomena.
Nature medicine
July 24, 2025
Luke A Jelen, David J Lythgoe, James M Stone et al.
29 citations
Blocking the opioid system with naltrexone reduced both the brain glutamate response and the antidepressant effect of ketamine in adults with major depressive disorder. In a double-blind crossover study of 26 adults, naltrexone before ketamine infusion attenuated the rise in glutamate+glutamine relative to N-acetylaspartate in the anterior cingulate cortex and lessened the drop in depression scores the next day. The opioid system modulates ketamine's acute brain effects and subsequent mood improvement, suggesting interactions between glutamate and opioid systems may inform new depression treatments.
Journal of psychopharmacology (Oxford, England)
June 20, 2025
Mutahira Qureshi, Daniel Silman, Romayne Gadelrab et al.
3 citations
A single dose of immediate-release oral ketamine (40–240 mg) was safe and generally well-tolerated in healthy adults, with no unexpected safety signals or discontinuations due to side effects. Eighty mild or moderate treatment-emergent adverse events occurred after ketamine doses, most commonly dissociation, dizziness, and headache, while only five occurred after placebo. Dissociation events increased with higher doses. Ketamine and its metabolites showed dose-proportional pharmacokinetics. Transient mood and dissociation changes appeared one hour after dosing and resolved within about four hours. These results support further investigation of oral ketamine capsules for treatment-resistant depression.
Neuroscience and biobehavioral reviews
July 1, 2026
Marcus J Glennon, Catherine I V Bird, Prateek Yadav et al.
2 citations
Setting up a psychedelic research study involves a long, arduous, and Kafkaesque process with many unstandardised challenges. These complexities challenge existing assumptions about psychiatric prescribing, the placebo effect, and definitions of selfhood. This review brings together major UK psychedelic research teams to formalise these unique considerations, addressing sociocultural, political, legal, pharmacological, safety, study design, and experiential facets. It identifies continuing areas of debate and provides a practical, experience-based guide with recommendations for policymakers and future researchers intending to set up a psychedelic study or clinical trial.
The American journal of psychiatry
June 1, 2026
Luke A Jelen, Owen O'Daly, Fernando O Zelaya et al.
2 citations
Ketamine increased blood flow in specific brain regions (subgenual, pregenual, and dorsal anterior cingulate cortices) in adults with major depressive disorder, and this effect was not blocked by the opioid blocker naltrexone. However, naltrexone did disrupt the relationships between blood flow changes and both acute subjective effects and antidepressant response. The blood flow changes aligned with patterns of opioid and glutamate receptor distribution, suggesting that ketamine's effects involve interactions among multiple neurotransmitter systems.
bioRxiv : the preprint server for biology
June 12, 2026
Timothy Lawn, Johan Nakuci, Steve Cr Williams et al.
Spatial overlap among brain receptor maps derived from PET imaging can distort analyses that model multiple receptors together. Using test-retest fMRI data, the authors show that as more receptors are included in a multivariate model, the reliability of the resulting functional connectivity networks decreases, and this degradation is driven by collinearity among the receptor maps. A univariate approach, modeling each receptor independently, produces more reliable networks and, in a study comparing LSD to placebo, better captured the known role of the 5HT-2A receptor. Spatial collinearity is a fundamental constraint on multivariate molecular-enriched network estimation, and univariate modeling is recommended as a more robust default.
Translational psychiatry
May 12, 2026
Linda Bryant, Laith Alexander, Sergio Mena et al.
A machine-learning model using structural brain scans predicted which adults with treatment-resistant depression would respond to a single ketamine infusion. The model, trained on 99 participants, achieved 72% balanced accuracy in the discovery sample and 60% in two independent groups, with performance dropping to chance in a saline-treated control group. Greater gray matter volume in frontal regions predicted response, while greater cerebellar volume predicted non-response. The findings suggest that pre-treatment brain structure may help guide personalized treatment decisions for ketamine therapy.