Brain aging (BA) processes are complex, often affect multiple systems, and frequently lead to cognitive decline and increased susceptibility to insults. BA appears to be a primary risk for the development of many prominent neurodegenerative pathologies. The US Census Bureau predicts that the aging population (65+) will represent a greater proportion of the U...
Known for their capacity to alter perception and consciousness, psychedelics are increasingly being explored for therapeutic applications in treating conditions such chronic pain, major depressive disorder, and post-traumatic stress disorder.1,2 Despite historical stigmas and legal restrictions, recent changes in legislation and the United States Food and Dr...
"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...
In the contemporary landscape of psychiatric medicine, critical advancements have been noted in the utilization of psychoactive substances such as hallucinogens, 3,4-methylenedioxymethamphetamine (MDMA), and ketamine for the treatment of severe mental health disorders. This review provides a detailed evaluation of these substances, focusing on their mechanis...
One of the main causes of misery and incapacity is chronic pain, which is frequently linked to psychological issues. Psychedelic substances are drugs that can exert a psychological effect on patients. Psychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin, exert their action mainly via activation of the serotonin-2A (5-HT2A).1 In a trial to u...
Introduction Since the last edition of the Black Book, several innovative agents have been approved or are poised to be approved in the coming year. These include novel antidepressants, the first muscarine agonist for the treatment of schizophrenia, the first psychedelic which may be approved for the treatment of PTSD (Post Traumatic Stress Disorder), and th...
Data on medication interactions with psychedelics are limited. Here we present what may be the first published report of a hypertensive emergency following the combination of psilocybin mushrooms with a monoamine oxidase inhibitor (MAOI). A42-year-old man with treatment-resistant major depressive disorder took 1 g of Psilocybe cubensis mushrooms, while presc...
There is controversy about a causal role of serotonin (5-HT) in depression, some arguing that there is no proof for impaired brain 5-HT function in depressed patients. Major depressive disorder comes with multiple endophenotypes; not surprisingly classical antidepressants (tricyclics, MAO inhibitors, SSRIs, SNRIs) are not universally effective. Most antidepr...
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...
The use of psychoactive substances for ritual, spiritual and medicinal purposes stretches back into prehistory and has been a common feature of many diverse cultures and societies globally. Psychedelics, with their unique ability to amplify feelings of connectedness and openness, may have also served as tools for promoting tribal cohesion and trust in ancien...
Abstract Major depressive disorder (MDD) is one of the most disabling psychiatric disorders in the world. First-line treatments such as selective serotonin reuptake inhibitors (SSRIs) still have many limitations, including a resistance to treatment in 30% of patients and a delayed clinical benefit that is observed only after several weeks of treatment. Incre...
Background: Psychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including conditions that have not benefited from prior interventions. The latter half of the twentieth century marked a revolution in the treatment of depression, anxiety, and psy...
Background: Psychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including conditions that have not benefited from prior interventions. The latter half of the twentieth century marked a revolution in the treatment of depression, anxiety, and psy...
Pathophysiology of depression is related with reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well under-stood, but clinical studies have shown that administration of the fast-acting antidepressant keta-mine reversed the decrease in hippocampus and amygdala volume in depressed pat...
Alzheimer's disease (AD), the most common form of senile dementia, is poised to place an even greater societal and healthcare burden as the population ages. With few treatment options for the symptomatic relief of the disease and its unknown etiopathology, more research into AD is urgently needed. Psychedelic drugs target AD-related psychological pathology a...
Introduction Psilocybin is one of the most extensively studied psychedelic drugs with a broad therapeutic potential. Despite the fact that its psychoactivity is mainly attributed to the agonism at 5-HT2A receptors, it has high binding affinity also to 5-HT2C and 5-HT1A receptors and indirectly modulates the dopaminergic system. Psilocybin and its active meta...
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...
Analogues of 4-phosphoryloxy- N,N -dimethyltryptamine (psilocybin) are being sold on recreational drug markets and developed as potential medications for psychedelic-assisted therapies. Many of these tryptamine-based psilocybin analogues produce psychedelic-like effects in rodents and humans primarily by agonist activity at serotonin 2A receptors (5-HT2A ). ...
Psychedelics alter consciousness and may have potential for drug development. As psychedelics are likely therapeutically active, it is important to study their effects and mechanisms using preclinical models. Here, we examined the effects of phenylalkylamine and indoleamine psychedelics on locomotor activity and exploratory behaviour using the mouse Behaviou...
