The Hamas-led attack in southern Israel on October 7, 2023 was one of the deadliest terror attacks in history, resulting in 1,182 fatalities, over 4,000 wounded, and 251 taken hostage1. The Nova festival, an 18-hour rave held in the Gaza Envelope region, suffered the highest casualties in the attack, with over 370 killed. For the Nova attendees, the highligh...
The serotonin 2C receptor (5-HT2C) is a G protein-coupled receptor implicated in multiple physiological and psychological processes and has been investigated as a therapeutic target for neuropsychiatric conditions such as obesity, drug abuse, and depression. With renewed interest in serotonergic psychedelics for treating depression, 5-HT2C may contribute to ...
BackgroundMajor depressive disorder (MDD) is a significant public health concern, and current treatments often have limitations in effectiveness and adherence. Psilocybin, a psychedelic compound found in certain mushrooms, is being explored as a potential treatment for depression. It primarily acts through the serotonin 5-HT2A receptor but interacts with 5-H...
Dementia is a progressive neurodegenerative disease which is characterised by cognitive decline, memory loss, and behavioural changes. Patients suffering from dementia often experience emotional distress, sadness and depression which also impacts the wellbeing of their caregivers. Recent research has explored the potential of psychedelics, such as psilocybin...
BACKGROUND AND AIMS: Drug discrimination procedures have made important contributions to the pre-clinical investigation of psychedelic drugs, such as psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). One of the most important being to highlight the critical role of central 5-HT2A rece...
Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses serotonin receptors, and is suggested to play a role in the ability of psilo...
Novel phenalkylamines and tryptamines such as psilocybin demonstrate promising nontraditional pharmacological profiles for treating psychiatric syndromes. Structural modifications yield functional selectivity at 5-HT receptors, mitigating hallucinogenic risk while preserving therapeutic efficacy. This study integrates receptor and behavioral data to support ...
Depression prevalence is markedly elevated in oncological patients, particularly among head and neck cancer (HNC) cohorts, who face twice the prevalence of major depressive disorder (MDD) compared to other cancer populations. MDD in this context independently predicts poorer clinical outcomes and increased morbidity. HNC management often involves acute surgi...
Abstract Background We have designed a novel psychedelic-derived compound (HBL20017) characterized by high functional efficacy at 5-HT2A, 5-HT1A, and 5-HT2C receptors. We assessed its hallucinogenic properties and its potential for OCD treatment on the marble burying test (MBT) and in mice homozygous for deletion of the Synapse Associated Protein 3 (SAPAP3) ...
Abstract Background Major depressive disorder (MDD) is a multifactorial and heterogeneous disorder that affects around 280 million individuals worldwide, with approximately 80 million experiencing treatment-resistant depression (TRD). Neuronal hypotrophy and axon hypomyelination in the prefrontal cortex (PFC) are hallmark features of MDD, highlighting the ne...
Abstract Background Obsessive-compulsive disorder (OCD) is associated with significant personal suffering and functional impairment. At least a third of OCD patients do not respond to conventional treatments. There is a substantial anecdotal literature suggesting that psychedelic agents, specifically psilocybin and psilocybin-containing psychedelic mushroom ...
Depression, a common mental disorder, affects people at different stages of life.Classic antidepressant treatment is generally effective, however, it is prolonged.Nonetheless, numerous patients who undergo various classic antidepressant therapies still suffer from depression.Therefore, the search for novel medications is essential.In this review, we explore ...
Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impression...
The resurgence of psychedelic-assisted psychotherapy marks a pivotal evolution in mental health treatment, challenging traditional paradigms by integrating compounds such as psilocybin, LSD, MDMA, and ketamine into clinical practice. Historically marginalized due to regulatory and societal concerns, these agents are now gaining recognition for their unique n...
The classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT2A serotonin receptor (5-HT2AR). Recent clinical studies have suggested that classical psychedelics may additionally have therapeutic potential for many neuropsychiatric conditions including depression, anxiety,...
Background and Hypothesis Visual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; e.g., Parkinson’s disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; e.g., psilocybin and mescaline). While these classes of VH differ in etiology, shared pathways are suggested by overlapping phenomenology and neural mechanisms. ...
Traumatic brain injury (TBI) is a significant global health challenge, with limited effective treatments for its acute and chronic consequences. TBI is characterized by neuroinflammation, oxidative stress, impaired neuroplasticity, imbalances in neurotransmission, and cell death - factors that contribute to the development of neurological and psychiatric dis...
Major depressive disorder is a debilitating condition, with many patients unresponsive to conventional monoaminergic antidepressants. Rapid-acting antidepressants such as ketamine and psilocybin offer promising alternatives, relieving symptoms within hours. Ketamine, an NMDA receptor antagonist, and psilocybin, a serotonergic psychedelic primarily targeting ...
Background/Objectives: Hallucinogenic substances such as psilocybin, psilocin, ergometrine, ergotamine, and lysergic acid diethylamide (LSD) have been demonstrated to enhance the force of contraction (FOC), in part due to the phosphorylation of phospholamban in human atrial preparations via 5-HT4 serotonin receptors and/or H2 histamine receptors. However, wh...
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...