Psychedelic drugs acting as 5-hydroxyptryptamine 2A receptor (5-HT2AR) agonists have shown promise as viable treatments of psychiatric disorders, including obsessive-compulsive disorder. The marble burying test is a test of compulsive-like behavior in mice, and psychedelics acting as 5-HT2AR agonists can reduce digging in this test. We assessed the 5-HT2R contribution to the mechanisms of two...
Pilot studies have hinted that serotonergic psychedelics such as psilocybin may relieve depression, and could possibly do so by promoting neural plasticity. Intriguingly, another psychotomimetic compound, ketamine, is a fast-acting antidepressant and induces synapse formation. The similarities in behavioral and neural effects have been puzzling because the compounds target distinct molecular...
Abstract 4-Bromo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25B-NBOMe) is a hallucinogen exhibiting high binding affinity for 5-HT 2A/C serotonin receptors. In the present work, we investigated its effect on dopamine (DA), serotonin (5-HT), acetylcholine (ACh), and glutamate release in the rat frontal cortex, striatum, and nucleus accumbens. Hallucinogenic activity, impact on cognitive...
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 lysergic acid diethylamide (LSD) are being...
The 5-HT2A receptor is thought to be the primary target for psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and other serotonergic hallucinogens (psychedelic drugs). Although a large amount of experimental work has been conducted to characterize the pharmacology of psilocybin and its dephosphorylated metabolite psilocin (4-hydroxy-N,N-dimethyltryptamine), there has been little systematic...
Psilocybin has in some studies shown promise as treatment of major depressive disorder and psilocybin therapy was in 2019 twice designated as breakthrough therapy by the U.S. Food and Drug Administration (FDA). A very particular feature is that ingestion of just a single dose of psilocybin is associated with lasting changes in personality and mood. The underlying molecular mechanism behind its...
While interest in psychedelic drugs in the fields of psychiatry and neuroscience has re-emerged in recent last decades, the general understanding of the effects of these drugs remains deficient. In particular, there are gaps in knowledge on executive functions and goal-directed behaviors both in humans and in commonly used animal models. The effects of acute doses of psychedelic lysergic acid...
4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a potent serotonin (5-HT) receptor agonist with hallucinogenic properties. The aim of our research was to examine the role of the 5-HT2A, 5-HT2C and 5-HT1A serotonin receptor subtypes in 25I-NBOMe hallucinogenic activity and its effect on dopamine (DA), 5-HT and glutamate release in the rat frontal cortex. Hallucinogenic...
Abstract It has been reported that serotonergic hallucinogens like lysergic acid diethylamide (LSD) induce decreases in functional connectivity within various resting-state networks. These alterations were seen as reflecting specific neuronal effects of hallucinogens and it was speculated that these shifts in connectivity underlie the characteristic subjective drug effects. In this study, we...
BACKGROUND: The glutamatergic modulator ketamine has created a blueprint for studying novel pharmaceuticals in the field. Recent studies suggest that "classic" serotonergic psychedelics (SPs) may also have antidepressant efficacy. Both ketamine and SPs appear to produce rapid, sustained antidepressant effects after a transient psychoactive period. METHODS: This review summarizes areas of...
The hypothesis of monoaminergic deficiency has long dominated the conceptual framework for the development of new antidepressant strategies, but the limits of conventional antidepressant treatments targeting monoaminergic signaling have motivated the search for new antidepressant pathways. The success of ketamine in the management of depressive disorders has provoked a renewed interest in...
Abstract Background Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the...
A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT2 family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (−)-(1R,2S)-configuration. Screening for affinity at...
Abstract Objective To conduct a systematic review of modern‐era (post‐millennium) clinical studies assessing the therapeutic effects of serotonergic psychedelics drugs for mental health conditions. Although the main focus was on efficacy and safety, study characteristics, duration of antidepressants effects across studies, and the role of the subjective drug experiences were also reviewed and...
A series of N-benzylated-5-methoxytryptamine analogues was prepared and investigated, with special emphasis on substituents in the meta position of the benzyl group. A parallel series of several N-benzylated analogues of 2,5-dimethoxy-4-iodophenethylamine (2C-I) also was included for comparison of the two major templates (i.e., tryptamine and phenethylamine). A broad affinity screen at...
Non-competitive N-methyl-D-aspartate/glutamate receptor (NMDAR) antagonism has been considered to play important roles in the pathophysiology of schizophrenia. In spite of severe neuropsychiatric adverse effects, esketamine (racemic enantiomer of ketamine) has been approved for the treatment of conventional monoaminergic antidepressant-resistant depression. Furthermore, ketamine improves...
New psychoactive substances (NPS) appear on the recreational market on a monthly basis, with unclear toxicology, resulting in an increasing number of fatalities. Identification of drug targets and potencies is crucial for understanding and treating intoxications and for scheduling processes. In this study 60 NPS and metabolites belonging to opioids, cannabinoids and serotonergic hallucinogens...
Abstract Psychedelic drugs, including lysergic acid diethylamide and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be...
Background: Psilocybin is a serotonergic psychedelic with psychoactive effects mediated by serotonin 2A receptor (5-HT2AR) activation. It produces an acute psychedelic altered state of consciousness with a unique phenomenology that can be temporally characterized by three intensity phases: onset of psychoactive effect, a peak plateau and return to normal consciousness. Aims: We evaluated...
With a rise in the incidence of autoimmune diseases (AiD), health care providers continue to seek out more efficacious treatment approaches for the AiD patient population. Classic serotonergic psychedelics have recently been gaining public and professional interest as novel interventions to a number of mental health afflictions. Psychedelics have also been shown to be able to modulate immune...