Serotonin receptors, also known as 5-hydroxytryptamine (5-HT) receptors, are a diverse family of G protein-coupled and ligand-gated ion channel receptors that mediate the physiological effects of the neurotransmitter serotonin. These receptors are widely distributed throughout the central and peripheral nervous systems, where they regulate numerous processes...
The investigators wish to investigate neurobiological effects of serotonin 2A receptor modulation in healthy volunteers, contrasting effects of an agonist (psilocybin) and an antagonist (ketanserin). Magnetic resonance imaging (MRI) and positron emission tomography (PET) will be used as neuroimaging tools. This project applies an experimental medicine strate...
"Iracema comes with the pot full of the green liquor. The shaman decrees the dreams to each warrior and distributes the wine of jurema, which carries the brave Tabajara to heaven." José de Alencar, in his poetic novel “Iracema” (1865)1. IntroductionThe "wine of jurema", used in ancient Brazilian shamanic rituals, is rich in N,N-dimethyltryptamine (DMT), a na...
Psilocybin has shown promise as a novel pharmacological intervention for treatment of depression, where post-acute effects of psilocybin treatment have been associated with increased positive mood and decreased pessimism. Although psilocybin is proving to be effective in clinical trials for treatment of psychiatric disorders, the information processing mecha...
Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut mic...
Alzheimer's disease (AD) stands as a formidable neurodegenerative ailment and a prominent contributor to dementia. The scarcity of available therapies for AD accentuates the exigency for innovative treatment modalities. Psilocybin, a psychoactive alkaloid intrinsic to hallucinogenic mushrooms, has garnered attention within the neuropsychiatric realm due to i...
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...
Psilocybin, and its metabolite psilocin, induces psychedelic effects through activation of the 5-HT2A receptor. Psilocybin has been proposed as a treatment for depression and anxiety but sometimes induces anxiety in humans. An understanding of mechanisms underlying the anxiety response will help to better develop therapeutic prospects of psychedelics. In the...
Abstract Current treatments for alcohol use disorder (AUD) show large heterogeneity in response and thus limited effectiveness and high relapse rates. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in ...
The desire to find a gold-standard therapy for depression is still ongoing. Developing one universal and effective pharmacotherapy remains troublesome due to the high complexity and variety of symptoms. Over the last decades, the understanding of the mechanism of pathophysiology of depression and its key consequences for brain functioning have undergone sign...
Psychedelic substances have gained significant attention in recent years for their potential therapeutic effects on various psychiatric disorders. This review delves into the intricate cellular neurobiology of psychedelics, emphasizing their potential therapeutic applications in addressing the global burden of mental illness. It focuses on contemporary resea...
Effects of serotonin 2A/1A receptor stimulation by psilocybin on alcohol addicted patients: a randomized double-blind placebo-controlled study Two billion people globally consume alcohol, leading in 2016 to 2.8 million deaths (5.2% of all deaths) and 99.2 million Disability Adjusted Life Years (DALYs) lost (4.2% of all DALYs). Of all the diseases, conditions...
The serotonergic psychedelic psilocybin shows efficacy in treating neuropsychiatric disorders, though the mechanism(s) underlying its therapeutic effects remain unclear. We show that a similar psychedelic tryptamine, N,N-dipropyltryptamine (DPT), completely prevents audiogenic seizures (AGS) in an Fmr1 knockout mouse model of fragile X syndrome at a 10 mg/kg...
Background: Psychedelic drug experiences are shaped by current-moment contextual factors, commonly categorized as internal (set) and external (setting). Potential influences of past environments, however, have received little attention. Aims: To investigate how previous environmental stimuli shaped the experiences of patients receiving ketamine for treatment...
Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds of the patients are prone to relapse of symptoms or are completely ineffective in antidepressant treatment. The recent ...
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...
The clinical evaluation of hallucinogens and other small molecules, conventionally termed psychedelics, has seen a dramatic increase in the past 5 years. Several key clinical trials recently demonstrated the potential efficacy of these compounds in treating a variety of mental health conditions including depression, anxiety, and substance use disorders. Conc...
BACKGROUND: Psychedelics are an increasingly active area of research and pharmaceutical development. This includes abuse potential assessment to better understand their pharmacological mechanisms and effects and guide controlled substance regulation. Psychedelics pose challenges to abuse assessments to ensure valid, reliable, and generalizable outcomes and s...
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...
The psychedelic 5-HT2A receptor (5HT2AR) agonist psilocybin (or the active metabolite psilocin) has emerged as potential useful drug for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. However, the mechanisms responsible for such effects remain incompletely characterized. We aimed to study in vitro pharmacological profile and i...
