NeuroImage
April 4, 2019
Ottavia Dipasquale, Pierluigi Selvaggi, Mattia Veronese et al.
79 citations
A double-blind, placebo-controlled study combined resting-state fMRI with a molecular atlas of serotonin receptors to examine how MDMA alters functional connectivity. Using the REACT method, the researchers found that MDMA-induced connectivity changes were specifically linked to brain regions rich in the serotonin transporter (5-HTT) and the 5-HT1A receptor, the drug's primary targets. Changes in 5-HT1A-enriched maps correlated with MDMA blood levels, while changes in 5-HT2A-enriched maps correlated with spiritual experiences reported by participants. The approach shows that MDMA's effects on brain connectivity can be explained by the distribution of its serotonergic targets, offering a new way to characterize psychoactive compounds.
Psychopharmacology
March 24, 2022
Timothy Lawn, Ottavia Dipasquale, Alexandros Vamvakas et al.
48 citations
LSD alters functional connectivity in the brain in ways that depend on its interactions with multiple serotonin and dopamine receptors, not only the 5-HT2A receptor. By analyzing brain scans from 15 participants, researchers found that LSD-induced changes in connectivity linked to different receptors corresponded to different subjective effects: serotonin-related receptors were predominantly associated with perceptual changes, while dopamine-related receptors were more tied to alterations in selfhood and cognition. These patterns were distinct, with similar relationships appearing within each receptor family but not between them. The findings suggest that LSD's full effects involve a broader set of receptors than previously emphasized.
Journal of Neuroscience
November 19, 2018
Anthony S. Gabay, Matthew J. Kempton, James Gilleen et al.
40 citations
MDMA increases cooperative behavior, but only when interacting with trustworthy partners. In a double-blind, placebo-controlled crossover study, 20 male participants received 100 mg MDMA or placebo and played an iterated Prisoner's Dilemma with opponents who varied in cooperation. MDMA enhanced cooperation with trustworthy opponents (odds ratio = 2.01) but not untrustworthy ones. MDMA specifically improved recovery from, not the impact of, breaches in cooperation. Brain activity increased in regions linked to social cognition, including precentral and supramarginal gyri, superior temporal cortex, central operculum/posterior insula, and supplementary motor area. Trust ratings did not change. The effect of MDMA on social decision-making depends on the context of the other person's behavior.
Translational Psychiatry
December 3, 2023
Laith Alexander, Peter C. T. Hawkins, Jennifer W. Evans et al.
26 citations
Ketamine's antidepressant effects involve changes in brain connectivity that depend on which part of the anterior cingulate cortex (ACC) is examined. In a double-blind, placebo-controlled crossover trial, patients with treatment-resistant depression and healthy volunteers received intravenous ketamine or placebo. Two days later, resting-state functional connectivity between ACC subregions and other brain areas differed between groups. Changes in perigenual ACC connectivity to the insula correlated with improved depression scores. Subgenual ACC connectivity was most altered by ketamine compared to placebo, and changes in its connectivity to other ACC subregions and the ventral striatum correlated with reduced anhedonia. Accurate ACC segmentation is needed to understand ketamine's effects.
Frontiers in Psychiatry
July 3, 2018
Joseph M. Barnby, Mitul A. Mehta
18 citations
The therapeutic potential of psilocybin, a psychedelic compound, is increasingly recognized in psychiatry, but its effects depend heavily on the context of use, known as 'set and setting.' This opinion article argues that the psychotherapeutic framework—including the relationship with therapists and the preparation and integration process—is as important as the drug itself for achieving positive outcomes. The authors suggest that neglecting the therapeutic context risks reducing psilocybin to a mere biological intervention, undermining its full potential for psychological healing and personal insight. The piece calls for careful integration of psychotherapeutic principles into psychedelic treatment models.
bioRxiv (Cold Spring Harbor Laboratory)
December 19, 2019
J.M. Barnby, Vaughan Bell, Quinton Deeley et al.
4 citations
preprint
Dopamine transmission influences social attributions related to paranoia, but not the salience of paranormal or other beliefs. In a double-blind, placebo-controlled experiment, 27 healthy men received either L-DOPA (150 mg), haloperidol (3 mg), or placebo across three sessions. Haloperidol reduced attributions of harmful intent in a Dictator Game, while L-DOPA reduced such attributions only in fair conditions. Haloperidol unexpectedly increased attributions of self-interest for opponents' decisions. No changes occurred in belief salience for politics, religion, science, morality, or the paranormal. These results suggest dopamine selectively affects social inferences linked to paranoia, independent of mood or skepticism.
Wellcome Open Research
April 22, 2025
Matthew Butler, Catherine Bird, Carolina Maggio et al.
3 citations
Functional neurological disorder (FND) is a common, debilitating condition linked to abnormal brain networks, dissociation, interoception, and motor agency. This open-label neuroimaging protocol will administer 25 mg of oral psilocybin with psychological support to 24 people with chronic FND. Resting-state and task-based functional MRI sequences will be compared before and after psilocybin. Additional measures include interoception, somatisation, illness perceptions, suggestibility, and dissociation. Participants will be followed for three months. The study aims to probe mechanisms underlying FND and assess the safety and feasibility of psychedelic administration with psychological support in this population.
Journal of psychopharmacology (Oxford, England)
June 16, 2026
Alice Caulfield, Matthew Butler, Mitul A. Mehta
Psychedelics show promise for treating neuropsychiatric conditions, but their Schedule 1 status creates regulatory and economic hurdles for research. Rigorous human mechanistic studies are needed to understand how psychedelics produce therapeutic effects. This article offers practical guidance on study design, legislation, and drug sourcing, based on the authors' experience setting up non-clinical studies in the UK. The guidance aims to help researchers navigate the complex process of establishing human psychedelic studies, with some content applicable to investigator-initiated studies more broadly.
BJPsych Open
June 1, 2025
Anna Borissova, Allan H. Young, Mitul A. Mehta et al.
In interviews with seven people who had previously received ketamine for treatment-resistant depression, participants were motivated by hope for symptom improvement and a desire to support depression research. They described feeling more open and involved after ketamine and thought it could enhance therapy sessions. They suggested clearer communication that mood changes may not last, providing audiovisual materials to prepare for the infusion experience, and offering check-ins between sessions plus a final session for referrals and support. These insights informed a planned feasibility randomized controlled trial comparing intravenous ketamine plus behavioral activation (n=20) against midazolam plus behavioral activation (n=20) for major depressive disorder with anhedonia.
arXiv Preprint Archive
March 28, 2025
Marcus J. Glennon, Catherine I. V. Bird, Prateek Yadav et al.
Setting up a psychedelic study is a long and complex process that presents unique challenges not yet standardized. This review brings together major UK research teams to formalize these considerations, identify ongoing debates, and provide a practical guide for researchers and policymakers. It addresses challenges to existing assumptions about psychiatric prescribing, the placebo effect, and definitions of selfhood. The paper can be read end-to-end or used as a manual with sections for specific needs.