BACKGROUND: Obsessive-compulsive disorder (OCD) is a common and disabling condition. A large proportion of patients fail to respond to first-line treatment with serotonin reuptake inhibitors either selective serotonin reuptake inhibitors (SSRIs) or clomipramine. Preliminary evidence suggests psilocybin, a serotonin receptor agonist, might be efficacious. We ...
ImportancePsilocybin has demonstrated rapid and sustained antidepressant efficacy, with acute-phase effect sizes often more than double those for conventional antidepressants. However, concerns have been raised that high rates of functional unblinding in combination with trial participants with positive expectations of psychedelic use might bias treatment ou...
Introduction: Many Veterans who experienced blast-related traumatic brain injuries (TBIs) in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop chronic cognitive and PTSD-related behavioral traits tha...
The use of drugs with psychedelic and dissociative effects for the treatment of psychiatric illnesses has become increasingly popular in recent years. However, few trials have been conducted to determine the efficacy of these agents in the specific setting of treatment-resistant major depressive disorder (MDD) in older adults. In this paper, we review notabl...
In this study, we provide the first study to integrate molecular and functional neuroimaging during psychedelic drug effects in humans. Using simultaneous PET-MRI technology, we describe multiple brain actions of lysergic acid diethylamide (LSD) in healthy volunteers. We quantify the occupancy of LSD at cerebral serotonin 2A receptors and show that LSD incre...
Depression and anxiety are disabling and high incidence mental disorders characterized by phenotypic heterogeneity. Currently available treatments show severe limitations. Thus, there is an urgent need for effective treatments in this population. In the search for novel rapid-acting antidepressants, the psychedelic psilocybin has emerged as a promising thera...
Millions worldwide suffer from chronic pain, a complex condition often accompanied by depression and anxiety, highlighting the urgent need for innovative treatments. Classic psychedelics, including psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), primarily act on serotonin 5-HT2A receptors and have emerged as potential modulato...
Neurological and psychiatric disorders are considered one of the major problems of today's societies and cause many individual and social problems. Current treatments are effective, but due to their burdens, there is always an effort to introduce novel treatments. Psychedelics, a diverse group of psychoactive compounds, including LSD, psilocybin, DMT, MDMA, ...
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 ...
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 ...
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...
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...
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...
