Serotonergic psychedelics induce profound alterations in consciousness, giving rise to an altered state commonly referred to as the psychedelic state. The entropic brain hypothesis proposes that brain entropy (i.e., the degree of uncertainty in the distribution of brain states) is elevated during the psychedelic state, as well as in other states characterized by an expanded breadth of...
Although research on psychedelics (hallucinogenic serotonin 2 A or 5-HT2A agonists) has shown initial promise in ameliorating a range of psychiatric conditions, the mechanisms by which psychedelics promote therapeutic benefits have yet to be elucidated. Researchers have posited enhancements in cognitive flexibility as a transdiagnostic mechanism through which psychedelics could disrupt...
Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented...
Abstract In their recent case report article, Peck and colleagues suggested that two patients recovered dissociated traumatic memories during psilocybin treatment for anorexia nervosa. These case reports are of clinical and scientific interest and confirm that psychedelics may induce vivid memory-like experiences. However, the reports warrant scrutiny. Here, based on what is known about...
Ayahuasca is an Amazonian brew with 5-HT2A-dependent psychedelic effects taken by religious groups globally. Recently, psychedelics have been shown to impair the formation of recollections (hippocampal-dependent episodic memory for specific details) and potentially distort memory while remembering. However, psychedelics spare or enhance the formation of familiarity-based memory...
Posttraumatic stress disorder (PTSD) is a psychiatric disorder with defining abnormalities in memory, and psychedelics may be promising candidates for the treatment of PTSD given their effects on multiple memory systems. Most PTSD and psychedelic research has investigated memory with fear conditioning and extinction. While fruitful, conditioning and extinction provide a limited model of the...
As research on psychedelics (hallucinogenic serotonin receptor 2A agonists) progresses, it is important to delineate the reliability of supposedly unique effects across this drug class. One such effect is how psychedelics impair the formation (i.e., encoding) of hippocampal-dependent recollections (retrieval of specific details) while potentially enhancing the encoding of cortical-dependent...
Psychedelics are recognised for their potential to re-orient beliefs. We propose a model of how psychedelics can, in some cases, lead to false insights and thus false beliefs. We first review experimental work on laboratory-based false insights and false memories. We then connect this to insights and belief formation under psychedelics using the active inference framework. We propose that...
Psychedelics (hallucinogenic 5-HT2A agonists such as psilocybin) are gaining recognition for their potential to treat a range of conditions, including anxiety-related psychopathology. Despite early promising results, the mechanisms by which psychedelic therapy alleviates anxiety are not well understood. Here, we review neural and cognitive mechanisms underlying anxiety-related psychopathology...
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 reanalyzed episodic memory confidence...
In recent years, psychedelics have generated considerable excitement and interest as potential novel therapeutics for an array of conditions, with the most advanced evidence base in the treatment of certain severe and/or treatment-resistant psychiatric disorders. An array of clinical and pre-clinical evidence has informed our current understanding of how psychedelics produce profound...
Psychoactive drugs modulate learning and emotional processes in ways that could impact their recreational and medical use. Recent work has revealed how drugs impact different stages of processing emotional episodic memories, specifically encoding (forming memories), consolidation (stabilizing memories), and retrieval (accessing memories). Drugs administered before encoding may preferentially...
Background: Emerging literature suggests that classic psychedelics may have efficacy in treating mood and substance use disorders in humans. This has raised questions regarding the primary therapeutic mechanism of these compounds. Here, we hypothesize that the reversal of and resilience against learned helplessness may be an important driver of the therapeutic mechanisms of classic...
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, we raise several issues with this...
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 researchers, review the 42 research...
Psilocybin has shown promise for the treatment of mood disorders, which are often accompanied by cognitive dysfunction including cognitive rigidity. Recent studies have proposed neuropsychoplastogenic effects as mechanisms underlying the enduring therapeutic effects of psilocybin. In an open-label study of 24 patients with major depressive disorder, we tested the enduring effects of psilocybin...
Abstract Classic psychedelic drugs such as psilocybin and lysergic acid diethylamide (LSD) have recaptured the imagination of both science and popular culture, and may have efficacy in treating a wide range of psychiatric disorders. Human and animal studies of psychedelic drug action in the brain have demonstrated the involvement of the serotonin 2A (5-HT2A) receptor and the cerebral cortex in...
Abstract Psychedelic substances produce unusual and compelling changes in conscious experience that have prompted some to propose that psychedelics may provide unique insights explaining the nature of consciousness. At present, psychedelics, like other current scientific tools and methods, seem unlikely to provide information relevant to the so-called “hard problem of consciousness,” which...
Abstract Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum . Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled...
With the increasing prevalence of legal cannabis use and availability, there is an urgent need to identify cognitive impairments related to its use. It is widely believed that cannabis, or its main psychoactive component Δ9-tetrahydrocannabinol (THC), impairs working memory, i.e., the ability to temporarily hold information in mind. However, our review of the literature yielded surprisingly...
Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli. However, no study has investigated the long-term, enduring impact of psilocybin on negative affect and associated brain function....
With the growing acceptance of cannabis use, it is crucial to understand the drug's effects on episodic memory accuracy and distortion. We investigated the impact of the administration of Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on a context-based memory illusion. In a double-blind, placebo-controlled, within-subjects design, healthy infrequent cannabis...
Abstract With the increasing prevalence of legal cannabis use and availability, there is an urgent need to identify cognitive impairments related to its use. It is widely believed that cannabis, or its main psychoactive component Δ 9 -tetrahydrocannabinol (THC), impairs working memory, i.e., the ability to temporarily hold information in mind. However, our review of the literature yielded...