. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (2...
RATIONALE: Our study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed l...
The extent of changes in functional connectivity (FC) within functional networks as a common feature across hallucinogenic drug classes is under-explored. This work utilized fMRI to assess the dissociative hallucinogens Psilocybin, a classical serotonergic psychedelic, and Salvinorin-A, a kappa-opioid receptor (KOR) agonist, on resting-state FC in nonhuman p...
Preclinical and human studies indicate psilocybin may reduce perseverant maladaptive behaviors, including nicotine and alcohol seeking. Such studies in the opioid field are lacking, though opioids are involved in more >50% of overdose deaths. Psilocybin is an agonist at the serotonin 2A receptor (5-HT2A R), a well-documented target for modulation of drug see...
The use of psilocybin to treat alcohol use disorder is very promising, but its mechanisms of action remain poorly understood. We combined behavioural, pharmacological and gene expression analyses to decipher the mechanisms of action of psilocybin, for the first time, when injected into the brain. Male Long Evans rats underwent chronic operant ethanol self-ad...
BACKGROUND: Psilocybin offers new hope for treating mood disorders due to its rapid and sustained antidepressant effects, as standard medications require weeks or months to exert their effects. However, the mechanisms underlying this action of psilocybin have not been identified. AIMS: To investigate whether psilocybin has rapid and sustained antidepressant-...
This pilot study investigated psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder (AUD). Participants were recruited from a phase II, randomized, double-blind, placebo-controlled clinical trial investigating psilocybin-assisted therapy (PAT) for the treatment of AUD (NCT02061293). Eleven adult p...
Abstract Novel treatment strategies are needed to overcome some of the current challenges related to treatment resistance and treatment latency within the psychiatric field. Recently, psilocybin has shown promise as a novel treatment of major depressive disorder. A single dose of psilocybin is associated with lasting changes in personality and mood. In paral...
Modern research data suggest a therapeutic role for serotonergic psychedelics in depression and other neuropsychiatric disorders, although psychotomimetic effects may limit their widespread utilization. Serotonergic psychedelics enhance neuroplasticity via serotonin 2 A receptors (5HT2AR) activation and complex serotonergic-glutamatergic interactions involvi...
Functional magnetic resonance imaging (fMRI) is increasingly used to non-invasively study the acute impact of psychedelics on the human brain. While fMRI is a promising tool for measuring brain function in response to psychedelics, it also has known methodological challenges. We conducted a systematic review of fMRI studies examining acute responses to exper...
ABSTRACT Intracellular calcium (Ca 2+ ) is ubiquitous to cell signaling across all biology. While existing fluorescent sensors and reporters can detect activated cells with elevated Ca 2+ levels, these approaches require implants to deliver light to deep tissue, precluding their noninvasive use in freely-behaving animals. Here we engineered an enzyme-catalyz...
In this review paper, we delve into the potential applicability of psilocybin - a naturally synthesized psychedelic substance found within select species of fungi, as a prospective avenue for depression treatment. Depression, a widespread psychological malady affecting countless individuals across the globe, often proves stubborn against existing treatment m...
Introduction Despite emerging evidence suggesting the efficacy of psilocybin in the treatment of mood disorders such as depression, the exact mechanisms by which psilocybin is able to elicit these antidepressant effects remains unknown. Objectives As the use of psilocybin as a treatment modality for depression has garnered increasing interest, this study aim...
Evidence suggests that psilocybin has therapeutic benefit for treating depression. However, there is little consensus regarding the mechanism by which psilocybin elicits antidepressant effects. This systematic review summarizes existing evidence. Ovid MEDLINE, EMBASE, psychINFO, and Web of Science were searched, for both human and animal studies, using a com...
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...
Introduction: Psilocybin has shown long-lasting antidepressant effects in preclinical and clinical trials, but the mechanisms responsible are unclear. As both passive coping strategies and pattern separation deficits are characteristics of major depression, we used adult female rats subjected to adolescent chronic restraint stress (aCRS) to investigate the e...
AIM: Psilocin is an active metabolite form of psilocybin and exerts psychoactive effects. Recent studies suggest that psilocin may have regulatory effects on abuse drugs, but the mechanisms remain unclear. In this study, we want to explore the effects of psilocin on methamphetamine (METH)-induced alterations of behavior in mice and its molecular mechanisms. ...
Interest in the therapeutic potential of serotonergic psychedelic compounds including psilocybin has surged in recent years. While human clinical research suggests psilocybin holds promise as a rapid and long-lasting antidepressant, little is known about how its acute mechanisms of action mediate enduring alterations in cognition and behavior. Human neuroima...
Summary Psilocin, the active compound in Psilocybe sp. mushrooms, is a serotonergic psychedelic that has recently gained renewed interest due to its potential as a therapeutic tool. Despite promising clinical findings, the underlying signaling mechanisms and brain region-specific effects of psilocin and other psychedelic drugs remain unclear. Psilocin, like ...
