Disrupted excitation-inhibition (E/I) balance involving GABA and glutamate (Glu) is implicated in the pathophysiology of depression. Ketamine, an NMDA receptor antagonist with rapid antidepressant properties, may modulate this balance, yet proton magnetic resonance spectroscopy (¹H-MRS) studies report inconsistent findings regarding the direction, magnitude, and timing of neurochemical effects....
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...
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....
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...
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
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...
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...
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...
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...
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...
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...
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...
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...
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...
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...