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...
Abstract Background Traditionally associated with recreational and spiritual uses, psychedelics have gained attention in psychotherapy for their therapeutic potential. Functioning as potent 5-hydroxytryptamine (5HT) agonists, these compounds have demonstrated the ability to enhance neural plasticity by activating serotoninergic and glutamatergic systems. Des...
Substance use disorder (SUD) is common in psychiatric patients and has a negative impact on health and well-being. However, SUD often goes untreated, and there is a need for psychiatrists, of all specialties, to address this pervasive clinical problem. In this review, the authors' goal is to provide a resource that describes treatments for SUD, using neurosc...
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...
This work utilized fMRI to assess the influence of the psychedelics, Psilocybin, a serotonergic agonist, and Salvinorin-A, a kappa-opioid receptor (KOR) agonist, on functional connectivity (FC) in non-human primates. We used a seed-based FC analysis, probing regions of interest associated with psychedelic hallucinogens. Our findings highlight the overlapping...
Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propag...
Entheogens, a class of psychoactive substances with profound cultural and religious significance, have been utilized for centuries across diverse traditions for healing, spiritual exploration, and communication with the divine. Their historical usage spans continents, from the pre-Columbian Americas to traditional African practices and Ayurvedic medicine in ...
Psychedelics have traditionally been used for spiritual and recreational purposes, but recent developments in psychotherapy have highlighted their potential as therapeutic agents. These compounds, which act as potent 5-hydroxytryptamine (5HT) agonists, have been recognized for their ability to enhance neural plasticity through the activation of the serotonin...
Classical serotonergic psychedelics such as lysergic acid diethylamide or the naturally occurring compounds psilocybin and mescaline produce profound changes in mood, thought, intuition, sensory perception, the experience of time and space, and even the experience of self. Research examining psychedelic compounds has had a complex and turbulent evolution. Ma...
Natural psychedelic compounds are emerging as potential novel therapeutics in psychiatry. This review will discuss how natural psychedelics exert their neurobiological therapeutic effects, and how different neurotransmission systems mediate the effects of these compounds. Further, current therapeutic strategies for depression, and novel mechanism of action o...
Clinical trials of pharmacological approaches targeting the core features of autism have failed. This is despite evidence from preclinical studies, genetics, post-mortem studies and correlational analyses linking peripheral and central markers of multiple candidate neurochemical systems to brain function in autism. Whilst this has in part been explained by t...
To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotrans...
Psilocybin has been shown to be a powerful, long-lasting antidepressant in human clinical trials and in rodent models. Although rodents have commonly been used to model psychiatric disorders, Drosophila have neurotransmitter systems similar to mammals and many comparable brain structures involved in similar behaviors. The forced swim test (FST), which has be...
Current medications have not been effective in reducing the prevalence of mental illness worldwide. The prevalence of illnesses such as treatment-resistant depression has increased despite the widespread use of a broad set of psychopharmaceuticals. Transcranial magnetic stimulation and ketamine therapy are making great strides in improving treatment-resistan...
Rapid-acting antidepressants disprove the dogma that antidepressants need several weeks to become clinically effective. Ketamine, the prototype of a rapid-acting antidepressant, is an N-methyl-D-aspartate (NMDA) receptor blocking agent. A single i.v. application of ketamine induces rapid changes in glutamatergic neurotransmitter systems, leading to preferent...
It is well established that a wide range of drugs of abuse acutely boost the signaling of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, where norepinephrine and epinephrine are major output molecules. This stimulatory effect is accompanied by such symptoms as elevated heart rate and blood pressure, more rapid breathing, in...
Anorexia Nervosa (AN) is a major health problem with one of the highest mortalities and treatment costs of any psychiatric condition. Cognitive behavioural therapy (CBT) is currently the most widely used treatment for AN in adults but provides remission rates ≤ 50%. Treatment drop-out is exceedingly high and those that persevere with treatment often relapse,...
This review illustrates the relevance of shamanism and its evolution under effects of psilocybin as a framework for identifying evolved aspects of psychedelic set and setting. Effects of 5HT2 psychedelics on serotonin, stress adaptation, visual systems and personality illustrate adaptive mechanisms through which psychedelics could have enhanced hominin evolu...
Mounting evidence suggests safety and efficacy of psychedelic compounds as potential novel therapeutics in psychiatry. Ketamine has been approved by the Food and Drug Administration in a new class of antidepressants, and 3,4-methylenedioxymethamphetamine (MDMA) is undergoing phase III clinical trials for post-traumatic stress disorder. Psilocybin and lysergi...
This "Designer Drugs 2.0" issue of Clinical Pharmacology & Therapeutics focuses on novel psychoactive substances, primarily cannabinoids and cathinones, and the repurposing of established psychoactive compounds (e.g., modafinil, psilocybin, lysergic acid diethylamide, and 3,4-methylenedioxymethamphetamine) that simultaneously offer new pharmacotherapies and ...
