IntroductionMescaline (3,4,5-trimethoxyphenethylamine) is one of the oldest hallucinogens, with evidence of use dating back 5700 years. Mescaline is a naturally occurring alkaloid found in cacti, mainly in the peyote cactus (Lophophora williamsii) and in the cacti of the Echinopsis genus. Since the prohibition of psychoactive substances in the early 70s, res...
Post-traumatic stress disorder (PTSD) is a devastating psychiatric disorder afflicting millions of people around the world. Characterized by severe anxiety, intrusive thoughts, pervasive nightmares, an assortment of somatic symptoms, associations with severe long-term health problems, and an elevated risk of suicide, as much as 40-70% of patients suffer from...
A striking feature of psychedelics is their ability to increase attribution of truth and meaningfulness to specific contents and ideas experienced, which may persist long after psychedelic effects have subsided. We propose that processes underlying conferral of meaning and truth in psychedelic experiences may act as a double-edged sword: while these may driv...
Background Synapses and spines are central in major depressive disorder (MDD) pathophysiology, recently highlighted by ketamine’s and psilocybin’s rapid antidepressant effects. The Bayesian brain and interoception perspectives formalize MDD as being “stuck” in affective states constantly predicting negative energy balance. We examined how synaptic atrophy re...
Despite distinct classes of psychoactive drugs producing putatively unique states of consciousness, there is surprising overlap in terms of their effects on episodic memory and cognition more generally. Episodic memory is supported by multiple subprocesses that have been mostly overlooked in psychopharmacology and could differentiate drug classes. Here, we r...
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...
Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for trea...
IntroductionTreatment outcomes for PTSD with current psychological therapies are poor, with very few patients achieving sustained symptom remission. A number of authors have identified physiological and immune disturbances in Post Traumatic Stress Disorder (PTSD) patients, but there is no unifying hypothesis that explains the myriad features of the disorder....
Serotonin 2A receptor (5-HTR) agonist "classic psychedelics" are drawing increasing interest as potential mental health treatments. Recent work suggests psychedelics can exert persisting anxiolytic and antidepressant effects lasting up to several months after a single administration. Data indicate acute subjective drug effects as important psychological fact...
RationaleMemory plays a central role in the psychedelic experience. The spontaneous recall and immersive reliving of autobiographical memories has frequently been noted by researchers and clinicians as a salient phenomenon in the profile of subjective effects of classic psychedelic drugs such as psilocybin, LSD, and ayahuasca. The ability for psychedelics to...
Psychedelic drugs, including the serotonin 2a (5-HT2A) receptor partial agonist psilocybin, are receiving renewed attention for their possible efficacy in treating a variety of neuropsychiatric disorders. Psilocybin induces widespread dysregulation of cortical activity, but circuit-level mechanisms underlying this effect are unclear. The claustrum is a subco...
Introduction Psilocybin (PSI) has persistent antidepressant efficacy in human trials. We have shown one dose of PSI to significantly decrease depressive-like behavior in male Wistar-Kyoto (WKY) rats for at least five weeks without losing efficacy. However, the outcome assay we used to evaluate depressive-like behavior, the forced swim test (FST), has been cr...
BackgroundIn the past few years, the issue of 'microdosing' psychedelics has been openly discussed in the public arena where claims have been made about their positive effect on mood state and cognitive processes such as concentration. However, there are very few scientific studies that have specifically addressed this issue, and there is no agreed scientifi...
psilocybin; depression; terminal cancer; CME; CNE: psilocybin; depression; terminal cancer; CME; CNEPsilocybin is a naturally occurring alkaloid found in more than 200 species of mushrooms. This compound, which was first isolated by the Swiss chemist Albert Hofman in 1959, is the active constituent of psychedelic mushrooms which are thought to have been util...
In recent years, the scientific study of meditation and psychedelic drugs has seen remarkable developments. The increased focus on meditation in cognitive neuroscience has led to a cross-cultural classification of standard meditation styles validated by functional and structural neuroanatomical data. Meanwhile, the renaissance of psychedelic research has she...
ObjectivesClassic psychedelics (serotonin 2A receptor agonists) and dissociative hallucinogens (NMDA receptor antagonists), though differing in pharmacology, may share neuropsychological effects. These drugs, however, have undergone limited direct comparison. This report presents data from a double-blind, placebo-controlled within-subjects study comparing th...
BackgroundNatural speech analytics has seen some improvements over recent years, and this has opened a window for objective and quantitative diagnosis in psychiatry. Here, we used a machine learning algorithm applied to natural speech to ask whether language properties measured before psilocybin for treatment-resistant can predict for which patients it will ...
The prefrontal cortex (PFC) plays a strong role in the execution of executive tasks such as working memory. It is thought to exert top-down control over sensory regions, and integrate information from both external stimuli, and internal computation, such as choice and expectation (1-3). The anterior cingulate cortex (ACC) is a region of the PFC known to rece...
BackgroundA resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or 'classical' psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,Ndimethyltryptamine), and ayahuasca - a betacarboline- and dimethyltryptamine (DMT)-containi...
