Our hominin ancestors inevitably encountered and likely ingested psychedelic mushrooms throughout their evolutionary history. This assertion is supported by current understanding of: early hominins' paleodiet and paleoecology; primate phylogeny of mycophagical and self-medicative behaviors; and the biogeography of psilocybin-containing fungi. These lines of ...
Potent psychedelic drugs such as LSD and psilocybin are implicated in a multitude of cognitive and perceptual alterations. Through the mediation of serotonergic 5-HT2 receptors, distortion of the self is a common effect of these drugs. The self is usually referred to as an entity comprising physical and psychological attributes that are coherent within our s...
The high symptomatic and biological heterogeneity of major depressive disorder (MDD) makes it very difficult to find broadly efficacious treatments that work against all symptoms. Concentrating on single core symptoms that are biologically well understood might consist of a more viable approach. The Research Domain Criteria (RDoC) framework is a trans-diagno...
Objective: Recent clinical trials have demonstrated that psilocybin may have strong antidepressant effects, and may be effective in the treatment of depressive disorders when embedded in a psychotherapeutic protocol (psilocybin-assisted psychotherapy; PAP). However, despite promising results, the mechanism(s) that may be responsible for the antidepressant ef...
IntroductionMental illness has a chronic course of illness with a number of clinical manifestations. Affected individuals experience significant functional, emotional, cognitive, and/or behavioral impairments. The growing prevalence of mental illness has been associated with significant social and economic costs. Indeed, the economic burden of mental illness...
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...
Anorexia nervosa (AN) has the highest mortality rate of any psychiatric disease, yet available pharmacological treatments are largely ineffective due, in part, to an inadequate understanding of the neurobiological drivers that underpin the condition. The recent resurgence of research into the clinical applications of psychedelic medicine for a range of menta...
The efficacy of psychedelic-assisted therapies for mental disorders has been attributed to the lasting change from experiential avoidance to acceptance that these treatments appear to facilitate. This article presents a conceptual model that specifies potential psychological mechanisms underlying such change, and that shows substantial parallels between psyc...
Serotonin is a key neuromodulator known to be involved in brain development, perception, cognition, and mood. However, unlike as with dopamine for example, a compelling unified theory of brain serotonin function has not yet been established. This is likely due to the exceptional complexity of the serotonin system, with its 14+ receptors, over twice the numbe...
RationaleDisruption of auditory event-related evoked potentials (ERPs) P300 and mismatch negativity (MMN), electrophysiological markers of attentive and pre-attentive cognitive processing, is repeatedly described in psychosis and schizophrenia. Similar findings were observed in a glutamatergic model of psychosis, but the role of serotonergic 5-HT2A receptors...
Users of psychedelic drugs often report that their sense of being a self or 'I' distinct from the rest of the world has diminished or altogether dissolved. Neuroscientific study of such 'ego dissolution' experiences offers a window onto the nature of self-awareness. We argue that ego dissolution is best explained by an account that explains self-awareness as...
Objective: Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus than the general population, and even first-episode, drug-naive (FEDN) patients with schizophrenia have shown a higher prevalence of impaired glucose tolerance (IGT) than the general population. We aimed to investigate the prevalence of abnormal glucose tolerance after glu...
The psychological state elicited by the classic psychedelics drugs, such as LSD and psilocybin, is one of the most fascinating and yet least understood states of consciousness. However, with the advent of modern functional neuroimaging techniques, the effect of these drugs on neural activity is now being revealed, although many of the varied phenomenological...
Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve qu...
The involvement of the serotonin system in the pathophysiology of schizophrenia has been elucidated by experiments with hallucinogens. Application of a hallucinogen to humans leads to changes in perception, cognition, emotions, and induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In rodent studies, their acute administration affe...
Despite the widespread application of drug modelling in psychiatric research, the relative value of different models has never been formally compared in the same analysis. Here we compared the effects of five drugs (cannabis, psilocybin, amphetamine, ketamine and alcohol) in relation to psychiatric symptoms in a two-part subjective analysis. In the first par...
Increasing evidence from neuroimaging and behavioral studies suggests that functional disturbances within cortico-striato-thalamic pathways are critical to psychotic symptom formation in drug-induced and possibly also naturally occurring psychoses. Recent basic and clinical research with psychotomimetic drugs, such as the N-methyl-D-aspartate (NMDA) glutamat...
