4-Hydroxytryptamines such as psilocin and its prodrug psilocybin are of considerable current interest for innovative antidepressant and other neuropsychiatric treatments. We here present a synthetic route towards 4-hydroxytryptamines displaying a high versatility for SAR exploration at the aliphatic nitrogen. The core concept is to apply HATU-mediated amide ...
Opioid-related overdose deaths have reached record high levels, and novel treatments for opioid use disorder (OUD) are needed. The three United States Food and Drug Administration (FDA)-approved medications for OUD function primarily at the mu-opioid receptor. While these remain the gold-standard treatment for OUD, they have shortcomings and treatment option...
Several species of fungi, collectively known as 'psychedelic fungi', produce a range of psychoactive substances, such as psilocybin, ibotenic acid, muscimol and lysergic acid amides. These substances interact with neurotransmitter receptors in the human brain to induce profound psychological effects. These substances are found across multiple fungal phyla, i...
Ketamine has transformed depression treatment by providing therapeutic relief within a single day, unlike monoaminergic antidepressants that require weeks to take effect. Here, we conducted whole-brain screening in mice to compare drug-evoked c-fos expression-acting as a marker of brain activity leading to protein synthesis-dependent forms of plasticity-foll...
This study examined patient perspectives on psilocybin therapy, specifically their acceptance and views on the therapeutic benefits of both hallucinogenic and non-hallucinogenic forms. A cross-sectional survey was conducted among psychiatric patients aged 18-65 at a community mental health center, assessing their attitudes, knowledge, and acceptance of psilo...
Psychedelics have emerged as a promising treatment for mental health disease, and the therapeutic potential of psilocybin and lysergic acid diethylamide (LSD) is presently being pursued in numerous clinical trials. This has prompted a search for novel agents with more specific pharmacological activities than the rather promiscuous classical psychedelics. Her...
Psilocybin (active compound of "magic mushrooms") is a prototypical psychedelic substance that acts via agonism on serotonin (5-HT) 2A receptors. Psilocybin is rapidly metabolized into its active metabolite psilocin. Psilocybin is currently under investigation as potential treatment for various neuropsychiatric disorders. Psilocybin is also widely used for r...
BACKGROUND: The psychedelic psilocybin has been posited as efficacious for the treatment of depression. However, the potential link between the intensity of acute psychedelic effects and long-term therapeutic outcomes remains undiscovered. Moreover, the impact of classical antidepressant drugs that modulate serotonergic activity on psilocybin's effects is a ...
To design therapeutic trials and select the most appropriate substance and dose for an indication, a detailed understanding of clinical pharmacology is crucial. In recent years, several studies have explored the human pharmacology of different psychedelics and 3,4-methylendioxymethylamphetamin (MDMA). This chapter summarizes pharmacological characteristics o...
Psilocybin, a serotonergic psychedelic, has emerged as a promising treatment for a range of mental health conditions, including anorexia nervosa. Recent insights from animal models and human imaging studies suggest psilocybin enhances cognitive flexibility and modifies reward processing - two core processes disrupted in anorexia nervosa. Both cognitive flexi...
RATIONALE: The head twitch response (HTR) is a spontaneously occurring behavior in mice that is increased in frequency by serotonergic psychedelics. The mouse HTR is often used as a proxy for psychedelic-like drug effects, but limited information is available about sex differences in HTRs evoked by various classes of psychedelics (i.e., phenethylamines, lyse...
The interplay between psychedelics, such as psilocybin, lysergic acid diethylamide (LSD) and dimethyltryptamine (DMT), and sleep is an emerging area, but their impact on sleep remains relatively underexplored. This viewpoint provides a perspective on how psychedelics may alter sleep phases, dreaming, and their potential therapeutic applications for sleep dis...
This is an interventional, parallel arm assignment treatment study in individuals with Major Depressive Disorder (MDD). Each individual will be treated with a single dose of pimavanserin or placebo plus a single dose of psilocybin. Evaluations will be taken before dosing and following dosing at several timepoints up to 5 weeks post-dosing. In this study, the...
Depressive disorders continue to pose a major clinical challenge worldwide, particularly given the high prevalence and increasing number of treatment-resistant cases. Over the past decade, advances in research have elucidated the antidepressant potential of psilocybin and other 5-HT₂A receptor agonists in patients with major depressive disorder (MDD) and tre...
BACKGROUND: Opioid use disorder (OUD) is a debilitating health condition that is associated with significant morbidity and mortality in the U.S. While preliminary studies have demonstrated that psilocybin is associated with lowered odds of OUD, current research in this domain suffers from a lack of investigation into the impact of race/ethnicity on this asso...
In a thought-provoking Genomic Press interview, Dr. Michael Wheeler emerges as a brilliant scientific innovator at the intersection of neuroscience and immunology. As an Assistant Professor at Harvard Medical School and an investigator at Brigham and Women's Hospital, Wheeler's groundbreaking research explores how brain-immune communication shapes our behavi...
Abstract Major depressive disorder (MDD) is a leading cause of disability that affects over 300 million people globally. Despite multiple antidepressant trials, approximately one-third of MDD patients remain symptomatic, progressing to treatment-resistant depression (TRD). This persistence possibly is due to the multifaceted etiology of TRD, encompassing bio...
Background Cluster headache is an excruciating condition for which standard treatments are usually insufficient. Evidence has accumulated that serotonergic psychedelic indoleamines including psilocybin and LSD can be effective in preventing attacks. Methods In this case series, nine patients with episodic and chronic cluster headache that didn’t respond to c...
