Objective: To synthesize the neurobiological basis of brain-resetting effects of psilocybin and identify neuroimaging correlates of psilocybin response in depressed patients.Data Sources: MEDLINE(R), Embase, APA PsycINFO, Cochrane, and CINAHL were systematically searched on June 3, 2022, with no date restrictions using the following string: (psilocybin) AND ...
Psilocybin, a naturally occurring hallucinogenic component of magic mushrooms, has significant psychoactive effects in both humans and rodents. But the underlying mechanisms are not fully understood. Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a useful tool in many preclinical and clinical trials to investigate ps...
Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in se...
Imaging studies of treatment-resistant depression (TRD) have examined brain activity, structure, and metabolite concentrations to identify critical areas of investigation in TRD as well as potential targets for treatment interventions. This chapter provides an overview of the main findings of studies using three imaging modalities: structural magnetic resona...
BackgroundMusic listening is a staple and valued component of psychedelic therapy, and previous work has shown that psychedelics can acutely enhance music-evoked emotion.AimsThe present study sought to examine subjective responses to music before and after psilocybin therapy for treatment-resistant depression, while functional magnetic resonance imaging (fMR...
BackgroundPsilocin, the neuroactive metabolite of psilocybin, is a serotonergic psychedelic that induces an acute altered state of consciousness, evokes lasting changes in mood and personality in healthy individuals, and has potential as an antidepressant treatment. Examining the acute effects of psilocin on resting-state time-varying functional connectivity...
IntroductionAlcohol use disorder is a difficult-to-treat psychiatric disorder and a major burden on public health. Existing treatment efficacy is moderate, and relapse rates are high. Preliminary findings suggest that psilocybin, a psychedelic compound, can safely and reliably occasion highly meaningful experiences that may spur a positive change in drinking...
Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain's c...
A recent paper in Nature Medicine found that psilocybin therapy in patients with depression decreased brain network modularity (measured with task-free functional magnetic resonance imaging), an effect supposedly not found with the selective serotonin reuptake inhibitor S-citalopram. This decrease in network modularity also correlated with depression. Here, ...
The purpose of this study is to investigate the prophylactic effects of psilocybin in chronic cluster headache. Subjects will receive a low dose of psilocybin during 3 sessions spaced by one week. Subjects will maintain a headache diary prior to, during, and after the administrations in order to document headache frequency, intensity and duration. Subjects w...
Chronic cluster headache (CCH) is an excruciating disorder of unknown pathophysiology, but hypothalamic dysfunction has been implicated. CCH is difficult to treat but on a case-basis, the psychedelic compound psilocybin is said to have beneficial effects. In this first-ever clinical trial ( NCT04280055 ), we evaluate in a small open-label study of CCH patien...
BackgroundClassic psychedelics, such as psilocybin and LSD, and other serotonin 2A receptor (5-HT2AR) agonists evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been hypothesized to underlie these effects, which is supported by some functional MRI (fMRI) studies. These studies have treated the thalamus as a unitary...
Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used strategy to identify psychedelic-induced changes in neural pathways in clinical and healthy populations. Here we, a large group of psychedelic imaging resea...
The main goal is to compare the antidepressant effects of psilocybin and ketamine in patients with TRD versus the antidepressant inactive substance midazolam. The primary endpoint will be the antidepressant effect on the Montgomery- Asberg Depression Rating Scale (MADRS) 24 hours after treatment, the key secondary endpoints being the duration of antidepressa...
Effects of serotonin 2A/1A receptor stimulation by psilocybin on mood and emotion processing in major depressive disorder: a randomized double-blind placebo-controlled study Major depressive disorder (MDD) is one of the world's greatest contributor to the global burden of disease and MDD affects around 17% of the Swiss population (Tomonaga et al. 2013). It i...
The use of psilocybin as treatment for major depressive disorder (MDD) has been examined as a promising alternative to traditional first-line options. We reviewed existing literature to provide a synthesis of the extant neuroimaging observations with psilocybin, and to identify putative therapeutic targets for target engagement studies with psilocybin, and p...
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...
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 ...
Depression is highly prevalent and represents the leading cause of global disability and primary contributor to overall global burden of disease. Several lines of evidence from early-phase experimental trials suggest that serotonergic psychedelics, particularly psilocybin, with therapeutic support show great promise in the treatment of depression with large ...
Background Psilocin, the neuroactive metabolite of psilocybin, is a serotonergic psychedelic that induces an acute altered state of consciousness, evokes lasting changes in mood and personality in healthy individuals, and has potential as an antidepressant treatment. Examining the acute effects of psilocin on resting-state dynamic functional connectivity imp...
