The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression.

Objective: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

Methods: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support.

Impressions about harm are formed rapidly and then refined, modulated by serotonin.

Attributing motives to others is a crucial aspect of mentalizing, can be biased by prejudice, and is affected by common psychiatric disorders. It is therefore important to understand in depth the mechanisms underpinning it. Toward improving models of mentalizing motives, we hypothesized that people quickly infer whether other's motives are likely beneficial or detrimental, then refine their judgment (classify-refine).

The impact of antidepressant discontinuation prior to treatment with psilocybin for treatment-resistant depression.

It has been suggested that the recent use and discontinuation of antidepressant drugs compromises the action of psilocybin. As evidence is only available from small or uncontrolled samples, this post hoc analysis investigated this using data from the largest, phase II, randomized controlled trial of psilocybin treatment to date. Data from 233 participants with treatment-resistant depression (TRD) who received 25 mg, 10 mg, or 1 mg of investigational drug COMP360 psilocybin (a proprietary, pharmaceutical-grade synthetic psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.

Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication.

Psilocybin is being investigated as a treatment in adults with treatment-resistant depression (TRD). Withdrawal from serotonergic antidepressant drugs is a common prerequisite for taking part in trials of psilocybin due to the possibility of ongoing antidepressant drugs altering the psychedelic effect. This phase II, exploratory, international, fixed-dose, open-label study explored the safety, tolerability, and efficacy of a synthetic form of psilocybin (investigational drug COMP360) adjunct to a selective serotonin reuptake inhibitor in participants with TRD.

Unblinding and demand characteristics in the treatment of depression.

Blinding of treatment allocation in clinical trials in psychiatry is regarded as an ideal. The potential impact of unblinding chimes with a general concern for psychological research: so-called demand characteristics can undermine confidence in findings from experimental and clinical studies. Scepticism can result in nihilism.