BackgroundPsilocybin is being studied for use in treatment-resistant depression.MethodsIn 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 en...
Background: Therapeutic administration of psychedelic drugs has shown significant potential in historical accounts and in recent clinical trials in the treatment of depression and other mood disorders. A recent randomized double-blind phase-IIb study demonstrated the safety and efficacy of COMP360, COMPASS Pathways’ proprietary synthetic formulation of psilo...
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...
RationaleA general feeling of disconnection has been associated with mental and emotional suffering. Improvements to a sense of connectedness to self, others and the wider world have been reported by participants in clinical trials of psychedelic therapy. Such accounts have led us to a definition of the psychological construct of 'connectedness' as 'a state ...
Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the subacute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10 mg and 25 mg, 7 d apart) in patients with treatment-resistant depression. Function...
Background: Across psychotherapeutic frameworks, the strength of the therapeutic alliance has been found to correlate with treatment outcomes; however, its role has never been formally assessed in a trial of psychedelic-assisted therapy. We aimed to investigate the relationships between therapeutic alliance and rapport, the quality of the acute psychedelic e...
Background: Anorexia nervosa (AN) is a serious and life-threatening psychiatric condition. With a paucity of approved treatments, there is a desperate need for novel treatment avenues to be explored. Here, we present (1) an overview of the ways through which Public Patient Involvement (PPI) has informed a trial of psilocybin-assisted therapy for AN and (2) a...
Clinical research into serotonergic psychedelic drugs including psilocybin, LSD and N,N-DMT (e.g., in ‘ayahuasca’) is expanding rapidly and clinical trials across a range of psychiatric conditions have shown promising efficacy, with larger trials ongoing. Resting-state functional magnetic resonance imaging (fMRI) has emerged as a brain imaging strategy commo...
Abstract Importance Psilocybin therapy shows antidepressant potential; our data link its antidepressant effects to decreased brain network modularity post-treatment. Objective To assess the sub-acute impact of psilocybin on brain activity in patients with depression. Design Pre vs post-treatment resting-state functional MRI (fMRI) was recorded in two trials:...
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...
This paper formulates the action of psychedelics by integrating the free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under psychedelics (REBUS) and the anarchic brain, founded on the principle that-via their entropic effect on spontaneous cortical activity-psychedelics work to relax the precision of high-level pri...
Introduction: It is a basic principle of the "psychedelic" treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that th...
RationaleRecent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy.ObjectivesHere, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression.MethodsTwenty patients (six females) with (mostly) severe, unipolar, treat...
Plant-based psychedelics, such as psilocybin, have an ancient history of medicinal use. After the first English language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aids to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial ...
BackgroundPsilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defences.AimsTo test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiog...
