Psilocybin has been shown to induce fast and sustained symptoms improvements across various psychiatric conditions, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed be...
The past decade has seen a huge increase in clinical research with psychedelic drugs and 3,4-methylenedioxymethamphetamine (MDMA), which have revealed great potential for treating mental health conditions. Given this progress in research, as well as the current unmet clinical need of millions of patients, in 2023, the Australian Therapeutic Goods Administrat...
In recent decades, the psychedelic psilocybin has been studied as a potential treatment for major depressive disorder (MDD), offering an alternative to traditional antidepressants. However, the brain changes underlying the clinical effects of different interventions remain unclear. Here, we investigated the effects of psilocybin and a conventional antidepres...
Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown. In an exploratory, placebo-controlled, within-subjects, electroencephalography (EEG), and magnetic resonance imaging (MRI) study in 28 healthy, entirely psychedelic-naive participants...
Psilocybin, a classic psychedelic compound, has garnered renewed interest as a potential treatment for various psychiatric disorders. This review provides a comprehensive overview of psilocybin's history, recent clinical evidence, ongoing clinical trials, neuroimaging findings, and regulations. Historically used in spiritual and healing rituals, psilocybin w...
Depressive disorders continue to pose a major clinical challenge worldwide, particularly given the high prevalence and increasing number of treatment-resistant cases. Over the past decade, advances in research have elucidated the antidepressant potential of psilocybin and other 5-HT₂A receptor agonists in patients with major depressive disorder (MDD) and tre...
Background Patients with Major Depressive Disorder (MDD) have more dysfunctional attitudes and pessimism than healthy individuals and these biases are correlated with depression severity. Psilocybin has demonstrated sustained remission in MDD. Methods Secondary analysis of a two-arm, randomized controlled trial ( ClinicalTrials.gov Identifier: NCT03429075 ) ...
Psilocybin has been shown to induce fast and sustained improvements in mental well-being across various populations, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed b...
Psychedelic drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT2A receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinat...
Psychedelic therapy (PT) is an emerging paradigm with great transdiagnostic potential for treating psychiatric disorders, including depression, addiction, post-traumatic stress disorder, and potentially others. 'Classic' serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), which have a key locus of action at the 5-HT2A receptor...
We conducted a meta-analysis using individual participant data from three, two-dose psilocybin trials for depression (N = 102) with the aim of assessing the risk of symptom worsening. Clinically significant symptom worsening occurred for a minority of participants in the psilocybin and escitalopram conditions (∼10%) and for a majority of participants in the ...
Psilocybin therapy is an emerging intervention for depression that may be at least as effective as standard first-line treatments i.e., Selective Serotonin Reuptake Inhibitors (SSRIs). Here we assess neural responses to emotional faces (fear, happy, and neutral) using Blood Oxygen-Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) in two gro...
This theoretical article revives a classical bridging construct, canalization, to describe a new model of a general factor of psychopathology. To achieve this, we have distinguished between two types of plasticity, an early one that we call 'TEMP' for 'Temperature or Entropy Mediated Plasticity', and another, we call 'canalization', which is close to Hebbian...
ObjectivesTo perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis.DesignReanalysis of a two-arm double-blind placebo controlled trial.ParticipantsFifty-nine patients w...
BackgroundMajor depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression.AimsTo assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive disorder.Meth...
Over the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The...
Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy br...
Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following psychedelic therapy. Brain responses ...
BackgroundPsilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking.MethodsIn a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, a selective sero...
