Nature Medicine
August 6, 2026
James Rucker, Tim Mantingh, Jess Kerr-Gaffney et al.
1 citation
Psilocybin-assisted therapy may be a promising new treatment for treatment-resistant depression. We examined the feasibility of administering a single 25-mg dose of psilocybin or placebo with psychological support in a randomized controlled trial design with 6 weeks of follow-up. A two-arm, double-blind, randomized, placebo-controlled feasibility trial was conducted at one National Health...
The American journal of psychiatry
June 1, 2026
Luke A. Jelen, Owen O'Daly, Fernando O Zelaya et al.
2 citations
Accumulating evidence suggests that the opioid system may modulate ketamine's rapid antidepressant effects. The objective of this study was to test whether opioid system modulation via naltrexone alters ketamine's acute effects on regional cerebral blood flow (rCBF) in major depressive disorder (MDD), and whether these changes relate to symptom measures and map onto receptor density profiles....
Journal of psychopharmacology (Oxford, England)
May 29, 2026
Elliot Hampsey, Kirsty Martin, Michail Kalfas et al.
Despite renewed investigations into classical psychedelic compounds, their pharmacokinetic profiles remain incompletely understood. This systematic review collated data from healthy adult volunteers on the pharmacokinetic properties of lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), mescaline, and 5-methoxy-N,N-dimethyltryptamine (5-MEO-DMT). We identified 32 eligible...
The International Journal of Neuropsychopharmacology
October 1, 2025
Igor D. Bandeira, Luke A. Jelen, Jason M Tucciarone et al.
4 citations
Igor D Bandeira, MD, PhD, Luke A Jelen, MD, PhD, Jason M Tucciarone, MD, PhD, Boris D Heifets, MD, PhD, Carolyn I Rodriguez, MD, PhD, Alan F Schatzberg, MD
Nature Medicine
July 24, 2025
Luke A. Jelen, David J Lythgoe, James Stone et al.
29 citations
We investigated the potential role of the opioid system in modulating glutamatergic effects of ketamine administration in major depressive disorder. Twenty-six adults with major depressive disorder participated in a double-blind crossover study, receiving oral placebo or 50 mg naltrexone before an intravenous infusion of 0.5 mg per kg ketamine. Brain glutamatergic activity in the anterior...
BJPsych Open
May 10, 2024
Luke A. Jelen, Rupert McShane, Allan H. Young
7 citations
In this editorial, we emphasise the efficacy and challenges of using ketamine in treatment-resistant depression. We highlight the need for comprehensive evidence-based guidelines to manage the use of both licensed and off-licence ketamine formulations and discuss recent efforts by Beaglehole et al to develop ketamine guidelines in New Zealand. We finally advocate for national registries to...
medRxiv
December 11, 2022
Hannah Hartland, Kimia Mahdavi, Luke A. Jelen et al.
22 citations
Background: Ketamine may be effective in treating symptoms of anxiety, but the time profile of ketamine’s anxiolytic effect is ill-defined. This systematic review and meta-analysis investigated the anxiolytic effect of ketamine at different time points across a range of clinical settings. Methods: Electronic databases were searched to capture randomised control trials measuring the anxiolytic...
The New England journal of medicine
November 3, 2022
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
1,095 citations
Psilocybin is being studied for use in treatment-resistant depression. In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the...
Psychopharmacology
September 5, 2022
Matthew Butler, Luke A. Jelen, James Rucker
91 citations
Modern psychedelic research remains in an early phase, and the eventual introduction of psychedelics into clinical practice remains in doubt. In this piece, we discuss the role of blinding and expectancy in psychedelic trials, and place this in a broader historical and contemporary context of blinding in trials across the rest of healthcare. We suggest that premature and uncritical promotion...
Neuroscience & Biobehavioral Reviews
May 10, 2021
Laith Alexander, Luke A. Jelen, Mitul A. Mehta et al.
79 citations
The subdivisions of the anterior cingulate cortex (ACC) - including subgenual, perigenual and dorsal zones - are implicated in the etiology, pathogenesis and treatment of major depression. We review an emerging body of evidence which suggests that changes in ACC activity are critically important in mediating the antidepressant effects of ketamine, the prototypical member of an emerging class of...
Journal of Psychopharmacology
December 20, 2020
Benjamin Illingworth, Declan J Lewis, Andrew T Lambarth et al.
47 citations
Rationale: Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials. Objective: To review the use of MDMA-assisted psychotherapy in treatment-resistant PTSD. Methods: Systematic searches of four databases were conducted from...
Journal of Psychopharmacology
November 6, 2020
Luke A. Jelen, Allan H. Young, James Stone
244 citations
The discovery of the rapid antidepressant effects of the dissociative anaesthetic ketamine, an uncompetitive N-Methyl-D-Aspartate receptor antagonist, is arguably the most important breakthrough in depression research in the last 50 years. Ketamine remains an off-label treatment for treatment-resistant depression with factors that limit widespread use including its dissociative effects and...
Depression and Anxiety
July 5, 2020
N. Weston, Damian Gibbs, Catherine Bird et al.
38 citations
INTRODUCTION: In this paper, we systematically review literature from 1940 to 2000 relating to the combined use of psychological therapies and psychedelic drugs in the treatment of ICD-10 anxiety disorders. METHODS: The databases Ovid MEDLINE(R), PsycINFO, and Multidisciplinary Association for Psychedelic Studies (MAPS) were searched for case reports and trials involving humans in the treatment...
Journal of Psychopharmacology
November 18, 2016
James Rucker, Luke A. Jelen, Sarah Kalen Flynn et al.
187 citations
Unipolar mood disorders, including major depressive disorder and persistent depressive disorder (dysthymia), confer high rates of disability and mortality and a very high socioeconomic burden. Current treatment is suboptimal in most cases and there is little of note in the pharmaceutical development pipeline. The psychedelic drugs, including lysergic acid diethylamide and psilocybin, were used...